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Min Chai,1,* Patajiang Yusufu,2,* Yixin Chen,1 Jiannan Chai,3 Xinran Yang,1 Yuqi Xiao,1 Hongwei Long,4 Dilimulat Maimaiti,2 Dahai Xu1 1Department of Emergency Medicine, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 2Department of Emergency Medicine, Seventh Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3Department of Laboratory, The First Hospital of Jilin University, Changchun, Jilin, People’s Republic of China; 4Department of Neurosurgery, Meihekou Central Hospital, Changchun, Jilin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dahai Xu, Department of Emergency Medicine, The First Hospital of Jilin University, No. 1 Xinmin Street, Chaoyang District, Changchun, Jilin, People’s Republic of China, Tel +8615043032548, Email xudahai0319@jlu.edu.cn Dilimulat Maimaiti, Department of Emergency Medicine, Seventh Affiliated Hospital of Xinjiang Medical University, No. 1986, Qidaowan Road, Shuimogou District, Urumqi City, Xinjiang, People’s Republic of China, Tel +8617704972862, Email 3090760383@qq.comAbstract: Peptoniphilus asaccharolyticus is a gram-positive anaerobic coccus that can cause infections in immunocompromised individuals. P. asaccharolyticus causing empyema has not been reported earlier. Here, we present a novel case of empyema caused by P. asaccharolyticus. A 72-year-old male had a constant fever with difficulty breathing. A chest computed tomography scan revealed infiltration in the right lower lobe and pleural effusion. Following hospital admission, pleural fluid drainage was conducted, and the culture isolated P. asaccharolyticus. Initially treated with piperacillin/tazobactam, the patient experienced excessive thick sputum production, prompting a tracheostomy. Subsequent sputum cultures identified Acinetobacter baumannii. After transitioning to cefoperazone/sulbactam for antibiotic treatment and continued pleural effusion drainage, recovery was achieved. Empyema can be caused by P. asaccharolyticus and further complicated by a secondary infection with A. baumannii. Management should include appropriate antibiotic therapy, pleural drainage, vigilant monitoring, and supportive care. We aim to raise clinicians’ awareness of the potential for P. asaccharolyticus to cause empyema in immunocompromised patients and to provide early treatments, thereby improving morbidity and mortality.Keywords: Peptoniphilus asaccharolyticus, empyema, Acinetobacter baumannii, case report

Jingwen Zhang,1,2,&ast; Guoqiang Zhang,1,2,&ast; JiaJia Wang,1,2,&ast; Yun Xiao,1,2 Xinxin Lu,1,2 Xunhong Lan,1,2 Yan Zhang,1,2 Zhang Dai1,2 1Centre of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China; 2Institute of Infectious Disease, School of Medicine, Xiamen University, Xiamen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Zhang; Zhang Dai, Centre of Clinical Laboratory, Zhongshan Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen, People’s Republic of China, Tel +86-0592-2293046, Email zy1983@xmu.edu.cn; 180219034@qq.comBackground: Nosocomial candidemia is a life-threatening condition, and the incidence has increased in recent years. Thorough epidemiological data is still lacking in China.Methods: A retrospective cohort study was conducted to investigate the patients admitted to Zhongshan Hospital Xiamen University from 1 January 2004 to 31 December 2022. This study included 205 individuals who were diagnosed with candidemia as subjects. Additionally, 303 cases with blood cultures were negative during the same period and were from the same department as a control group. We randomly assigned them to the training and validation groups in a 7:3 ratio. The least absolute shrinkage and selection operator regression, univariate and multivariate logistic regression analyses were used to filtrate independent factors associated with nosocomial candidemia. A nomogram model was established based on the selected variables. Receiver operating characteristic (ROC) curve, calibration plots and decision curve analysis (DCA) were used to evaluate clinical utility.Results: Two hundred and five nosocomial candidemia patients were reported, containing a high proportion of Candida albicans (n = 91,44.39%), followed by Candida parapsilosis (n = 40, 19.51%), Candida tropicalis (n = 37,18.05%), Candida glabrata (n = 23, 11.22%) and Candida guilliermondii (n = 9,4.39%). Multiple organ dysfunction syndrome (OR = 10.372, 95% CI: 4.745– 24.14 P < 0.001), increased urea nitrogen of serum (OR=1.088,95% CI: 1.039– 1.144 P< 0.001), decreased albumin of serum (OR = 0.922 95% CI: 0.850– 0.997 P=0.045), mechanical ventilation (OR=4.074,95% CI: 1.397– 12.77 P=0.012), central venous indwelling catheter (OR=7.422,95% CI: 3.189– 18.41 P< 0.001) and solid tumor (OR = 3.036 95% CI: 1.276– 7.359 P=0.012) were identified as independent risk factors of candidemia. The area under the curve (AUC) of the nomogram model was 0.925 (95% CI: 0.898– 0.952) in the training group and 0.946 (95% CI: 0.881– 0.963) in the validation group. The calibration curve revealed good agreement between the probability and the observed values. DCA indicated that this nomogram might be clinically beneficial.Conclusion: The nomogram including multiple organ dysfunction syndrome, elevated blood urea nitrogen, decreased albumin, mechanical ventilation, central venous indwelling catheter and solid tumor could provide reference value to clinicians for identifying nosocomial candidemia.Keywords: candidemia, risk factors, nomogram model, ROC curve

Xinqiang Liu,1,&ast; Hongguang Ding,2,&ast; Miner Chen,1,&ast; Xusheng Li,2 Yan Xiao,1 Yongli Han,1 Hongke Zeng1 1Department of Intensive Care Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510800, People’s Republic of China; 2Department of Emergency Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, 510800, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongke Zeng, Department of Intensive Care Medicine, Guangdong Provincial People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, No. 106, Zhongshan 2nd Road, Guangzhou, People’s Republic of China, 510080, Tel/Fax +8602083827812-60810, Email zenghongke@gdph.org.cnBackground: Shenfu injection (SF) has demonstrated its potential to enhance cellular immunity and induce clinical regression in patients suffering from sepsis or infectious shock. However, the therapeutic effect of SF on sepsis-induced cognitive dysfunction (SAE) and the mechanisms involved are still unclear. We aimed to investigate the mechanism of SF in mice with SAE.Methods: Sepsis was constructed by caecal ligation and puncture. Mice were injected intraperitoneally with SF or NLRP3 inhibitor. The hippocampus injury of brain tissues was evaluated, and the levels of inflammatory cytokines (IL-1β, IL-18) and NLRP3 and Caspase 1 were measured. The active ingredients of SF were analyzed using network pharmacology, and molecular docking of the active ingredients of SF with NLRP3 and Caspase 1 was performed. BV-2 cells were treated with LPS or norcoclaurine. CCK-8 detected the cell viability, and the levels of inflammatory cytokines and NLRP3 and Caspase 1 were measured.Results: SF and NLRP3 inhibitor increased survival rate and the number of crossing the platform and decreased the escape latency time of sepsis mice. Moreover, SF and NLRP3 inhibitor improved neuronal damage and apoptosis in hippocampus of sepsis mice. In addition, SF and NLRP3 inhibitor reduced the levels of inflammatory cytokines, as well as inflammasomes in sepsis mice. There were 43 active ingredients in SF. Among them, 22 were Renshen and 21 were Fuzi. Renshen and Fuzi, the main active components of SF, form a complex regulatory network with NLRP3 and Caspase 1. (R)-norcoclaurine was most closely bound to NLRP3 with binding energy of − 7.2 kJ·mol− 1, ignavine was most closely bound to Caspase 1 with binding energy of − 8.3 kJ·mol− 1. Norcoclaurine increased the cell viability and decreased inflammation and pyroptosis.Conclusion: SF regulated NLRP3/Caspase 1 through (R)-norcoclaurinee to prevent SAE.Keywords: shenfu injection, NLRP3, caspase 1, pyroptosis, sepsis-associated encephalopathy

Qiang Guo,1,&ast; Yang Xiao,2,&ast; Jing Chu,3 Yu Sun,2 Shaomei Li,3 Shihai Zhang1 1Department of Clinical Laboratory, Anhui Children’s Hospital, Hefei, People’s Republic of China; 2Xuhzou Medical University, Jiangsu, People’s Republic of China; 3Department of Pathology, Anhui Children’s Hospital, Hefei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shihai Zhang, Department of Clinical Laboratory, Anhui Children’s Hospital, Wangjiang Road 39, Hefei, People’s Republic of China, Tel +86– 13856048692, Email zhangshihai888@126.comObjective: This study aims to identify differentially expressed genes (DEGs) in neuroblastoma (NB) through comprehensive bioinformatics analysis and machine learning techniques. We seek to elucidate these DEGs’ biological functions and associated signaling pathways. Furthermore, our objective extends to predicting upstream microRNAs (miRNAs) and relevant transcription factors of pivotal genes, with the ultimate goal of guiding clinical diagnostics and informing future treatment strategies for Neuroblastoma.Methods: In this study, we sourced datasets GSE49710 and TARGET from the GEO and UCSC-XENA databases, respectively. Differentially expressed genes (DEGs) were identified using the R language “limma” package. Subsequent Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of these DEGs were conducted using the “clusterProfiler” package. We employed Weighted Gene Co-expression Network Analysis (WGCNA) to isolate the most significant modules associated with death and MYCN amplification, specifically MEpink and MEbrown modules. These modules were then cross-referenced with the DEGs for further GO and KEGG pathway analyses. LASSO regression analysis, facilitated by the “glmnet” package, was utilized to pinpoint three hub genes. We performed differential analysis on these genes and constructed Receiver Operating Characteristic (ROC) curves for disease diagnosis purposes. Immune infiltration analysis was conducted using the “GSVA” package’s ssGSEA function. Additionally, single-gene Gene Set Enrichment Analysis (GSEA) on the hub gene was carried out based on Reactome and KEGG databases. Upstream miRNA and transcription factors associated with the hub gene were predicted using RegNetwork, with visual representations created in Cytoscape. Furthermore, to validate the three identified markers in neuroblastoma tissues, quantitative Real-Time Polymerase Chain Reaction (qRT-PCR) analysis was conducted.Results: We identified 483 differentially expressed genes (DEGs) in neuroblastoma. These genes predominantly function in protein translation, membrane composition, and RNA transcription regulation, and are implicated in multiple signaling pathways relevant to neurodegenerative diseases. Utilizing LASSO regression analysis, we pinpointed three hub genes: VGF, DGKD, and C19orf52. The Receiver Operating Characteristic (ROC) curve analysis yielded Area Under Curve (AUC) values of 0.751 and 0.722 for VGF, 0.79 and 0.656 for DGKD, and 0.8 and 0.753 for C19orf52, respectively. Our immune infiltration analysis revealed significant correlations among monocytes, follicular helper T cells, and CD4+ T cells. Notably, in the death group, we observed heightened infiltration levels of activated CD4+ T cells, macrophages, and Th2 cells. C19orf52 exhibited a close association with the infiltration of monocytes, CD4+ T cells, and Th2 cells, with P-values less than 0.05. Furthermore, qRT-PCR analysis corroborated the upregulation of VGF in neuroblastoma tissues, further validating our findings.Conclusion: The hub genes (VGF, DGKD, and C19orf52) of neuroblastoma are screened. VGF, one of the hub genes, may have a high diagnostic value and is involved in the immune cell infiltration in neuroblastoma tissue, which may be used as a biomarker for the diagnosis of neuroblastoma and provides a new direction for clinical prognosis prediction and management improvement. Keywords: neuroblastoma, WGCNA, LASSO regression, bioinformatics analysis

Qingyang Yu,1,2 Yuanyuan Cui,1 Shuwen Dong,1 Yanqing Ma,1 Yi Xiao,1 Li Fan,1 Shiyuan Liu1 1Department of Radiology, Changzheng Hospital, Navy Military Medical University, Shanghai, 200003, People’s Republic of China; 2Department of Neurosurgery, Changhai Hospital, Navy Military Medical University, Shanghai, 200433, People’s Republic of ChinaCorrespondence: Shiyuan Liu, Department of Radiology, Changzheng Hospital, Navy Military Medical University, 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Fax +86 2181886012, Email radiology_cz@163.comObjective: Hemifacial spasm (HFS) is a clinical neurosurgical disease, which brain structural alterations caused by HFS remain a topic of debate. We evaluated changes in brain microstructure associated with HFS and observed their relevance to clinical characteristics.Methods: We enrolled 72 participants. T1-weighted structural and diffusion tensor images were collected from all participants using 3.0T magnetic resonance equipment. Voxel-based morphometry (VBM) and tract-based spatial statistics (TBSS) were used to identify changes in gray matter volume (GMV) and disruptions in white matter (WM) integrity. The severity of the spasms was graded using the Cohn scale.Results: VBM analysis revealed that the GMV was significantly reduced in the left Thalamus and increased GMV in the right Cerebellum IV-V of the HFS group. TBSS analysis showed that FA in the left superior longitudinal fasciculus (SLF) of the HFS group was significantly increased. GMV in the thalamus showed a negative correlation with disease duration and Cohn grade, while FA in the left SLF had a positive correlation with both the disease duration and Cohn grade.Conclusion: We identified regions with altered GMV in HFS patients. Additionally, we determined that FA in the left SLF might serve as a significant neural indicator of HFS.Keywords: hemifacial spasm, voxel-based morphometry, diffusion tensor imaging, tract-based spatial statistics, Cohn grading

Yinxue Zhou,1,&ast; Tingyu Wu,2,&ast; Jiaxing Sun,1 Huanhuan Bi,1 Yuting Xiao,1 Yanmei Shao,1 Weizhong Han,1 Hongmei Wang1 1Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China; 2Department of Joint Surgery, The Affiliated Hospital of Qingdao University, Qingdao, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiaxing Sun; Hongmei Wang, Email jiaxing20022001@163.com; dor.whm@163.comBackground: EGFR-TKI resistance poses a significant challenge in the treatment landscape of non-small cell lung cancer (NSCLC), prompting extensive research into mechanisms and therapeutic strategies. In this study, we conduct a bibliometric analysis to elucidate evolving research hotspots and trends in EGFR-TKI resistance, offering insights for clinical interventions and scientific inquiries.Methods: Publications spanning from 1996 to 2024, focusing on EGFR-TKI resistance in NSCLC, were sourced from the Web of Science Core Collection. Utilizing VOSviewer 1.6.19, CiteSpace 6.2. R2, and Scimago Graphica 1.0.35, we analyzed these articles to identify countries/regions and institutions, Journals, publications, key contributors, collaborations, and emerging topics.Results: An analysis of 8051 articles by 38,215 researchers from 86 countries shows growing interest in EGFR-TKI resistance mechanisms. Since 1996, publications have steadily increased, surpassing 500 per year after 2016, with a sharp rise in citations. Research articles make up 84% of publications, emphasizing scholarly focus. Global collaboration, especially among researchers in China, the US, and Japan, is strong. Leading institutions like Dana-Farber and Harvard, along with journals such as “Lung Cancer”, are key in sharing findings. Professors Yi-Long Wu and William Pao are prominent contributors. Keyword analysis reveals core themes, including first-generation EGFR-TKIs, emerging agents like osimertinib, and research on the T790M mutation.Conclusion: EGFR-TKI resistance remains a critical issue in NSCLC treatment, driving ongoing research efforts worldwide. Focusing future research on clear identification of resistance mechanisms will guide post-resistance treatment strategies, necessitating further exploration, alongside the validation of emerging drugs through clinical trials. Moreover, “chemo+” treatments following EGFR-TKI resistance require more clinical data and real-world evidence for assessing safety and patient outcomes. As research advances, a multidisciplinary approach will be key to overcoming these challenges. Continued innovation in treatment could greatly enhance patient survival and quality of life.Keywords: EGFR-TKI, resistance, lung cancer, bibliometric, citespace, VOSviewer

Peiran Guo,1,2,&ast; Yuting Tan,1,2,&ast; Li Feng,3 Cui Liu,4 Jin Sun,5 Rong Cheng,1,2 Yanling Xiao,1 Xingxin Zhan,6 Lingjie Yang,1 Zhixia Zhang1 1Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Wuhan University of Science and Technology School of Medicine, Institute of Nursing Research, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, Wuhan, Hubei, People’s Republic of China; 3School of Public Health and Nursing, Hubei University of Science and Technology, Xianning, Hubei, People’s Republic of China; 4Geriatric Hospital Affiliated with Wuhan University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 5Yiling Hospital of Yichang City, Yichang, Hubei, People’s Republic of China; 6School of Public Health, Xinyu University, Xinyu, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhixia Zhang, Tianyou Hospital, Wuhan University of Science and Technology, No. 9, Tujialing, Dingzhiqiao, Wuchang District, Wuhan, Hubei, People’s Republic of China, Tel +8613476805827, Email zzx13476805827@126.comPurpose: The development of “Internet + nursing services” can effectively solve the problem of population aging, and grassroots nurses are the primary providers of such services in rural areas. This study aimed to analyze the factors affecting grassroots nurses’ risk perception of “Internet + nursing services” and construct a predictive model.Patients and Methods: A multicenter cross-sectional study of 2220 nurses from 27 secondary hospitals and 36 community health centers in Hubei Province was conducted from August to December 2023 using a multi-stage cluster sampling method. Information was collected through a structured anonymous questionnaire. A Chi-square test, a Welch t-test, and binary logistic regression analyses were employed to determine independent risk factors for grassroots nurses’ risk perception of “Internet + nursing services”, and a nomogram was constructed. Receiver operating characteristic curves, calibration curves, and decision curves were plotted to evaluate the discrimination, calibration, and clinical effectiveness of the nomogram.Results: A total of 2050 valid questionnaires were collected, demonstrating that 51.95% of grassroots nurses thought that “Internet + nursing services” was a medium-high risk. Age, other sources of income, knowledge about “Internet + nursing services”, personal safety, physical function, occupational exposure, social psychosocial, and time risk (P< 0.05) were independent risk factors for grassroots nurses’ risk perception. The area under the receiver operating characteristic curve of the nomogram was 0.939. The calibration and decision curve analyses demonstrated good calibration ability and clinical application values.Conclusion: The prediction model constructed in this study has good prediction ability. Most grassroots nurses believe that “Internet + nursing services” are risky and influenced by several factors. It is suggested that the government and hospitals should formulate a unified charging standard, improve the safety guarantee, and gradually eliminate the concerns of grassroots nurses.Keywords: grassroots nurse, Internet + nursing services, risk perception, predictive model

Jingying Xu, Yuan Chen, Jianhua Yu, Shourong Liu, Ying Meng, Chaodan Li, Qian Huang, Yunlei Xiao Department of Infectious Diseases, Hangzhou Xixi Hospital, Hangzhou Sixth People’s Hospital, Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Qian Huang; Yunlei Xiao, Department of Infectious Diseases, Hangzhou Xixi Hospital, Hangzhou Sixth People’s Hospital, Hangzhou Xixi Hospital Affiliated to Zhejiang Chinese Medical University, No. 2, Hengbu Street, Liu Xia Town, Xihu District, Hangzhou, 310023, Zhejiang, People’s Republic of China, Tel +8613575746522 ; +8615258639960, Email tcm99hq@163.com; 15258639960@163.comPurpose: Developing countries, invasive Salmonella infections can cause considerable morbidity and mortality. There is a relative lack of data on coinfection with Salmonella in HIV-infected patients in Hangzhou, China.Patients and Methods: In this study, we manually collected case data of patients aged > 18 years with HIV combined with invasive Salmonella infections admitted to Xixi Hospital in Hangzhou from January 2012 to August 2023 by logging into the Hospital Information System, and identified 26 strains of invasive Salmonella using a fully automated microbiological identification system and mass spectrometer. Serotypes were determined using Salmonella diagnostic sera based on the White-Kauffmann-Le Minor scheme. Drug sensitivity tests were performed using the automated instrumental method of the MIC method.Results: A total of 26 HIV-infected patients with invasive Salmonella coinfections were identified over 11 years; Twenty-five of the 26 patients (96.2%) were males, with a mean age of 33.5 years (26.75, 46.75). The most common type of infection was bloodstream infection (92.3%). One patient also had concomitant meningitis and osteoarthritis, followed by pneumonia (7.7%). The presence of multiple bacterial infections or even multiple opportunistic pathogens was clearly established in 7 (26.9%) patients. Three (11.6%) patients were automatically discharged from the hospital with deterioration of their condition, and one (3.8%) patient died. Salmonella enteritidis was the most common serotype in 6 patients (23.2%), and Salmonella Dublin was the most common serotype in 6 patients (23.2%). Drug sensitivity results revealed multidrug resistance in a total of 8 (30.8%) patients.Conclusion: The clinical presentation of invasive Salmonella infection in HIV patients is nonspecific and easily masked by other mixed infections. A CD4+ count < 100 cells/μL and comorbid intestinal lesions may be important susceptibility factors. Salmonella has a high rate of resistance to common antibiotics, and the risk of multidrug resistance should not be ignored.Keywords: Salmonella, invasiveness, HIV, serotype, antibiotic resistance

Jingfei Weng,1,2,&ast; Yuyao Xiao,1,&ast; Jing Liu,3,&ast; Xiaohua Liu,4 Yuqing He,2 Fei Wu,1 Xiaoyan Ni,1 Chun Yang1 1Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Radiology, The Affiliated Traditional Chinese Medicine Hospital, Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Radiology, Fudan University Shanghai Cancer Center, Shanghai, People’s Republic of China; 4Department of Radiology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun Yang; Xiaoyan Ni, Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China, Tel +86 18702135336 ; +86 15201803582, Email dryangchun@hotmail.com; nixiaoyan1103@126.comPurpose: To study the MRI features (based on LI-RADS) and clinical characteristics of P53-mutated hepatocellular carcinoma (HCC) patients.Patients and Methods: This study enrolled 344 patients with histopathologically confirmed HCC (P53-mutated group [n = 196], non-P53-mutated group [n = 148]). We retrospectively evaluated the preoperative MRI features, clinical and pathologic features of the lesions and assigned each lesion according to the LI-RADS. MRI findings, clinical features, and pathologic findings were compared using the Student’s t test, χ 2 test, and multivariable regression analysis.Results: Most HCC patients were categorized as LR-5. On multivariate analysis, the Edmondson–Steiner grade (odds ratio, 2.280; 95% CI: 1.268, 4.101; p = 0.006) and rim enhancement (odds ratio, 2.517; 95% CI: 1.095, 5.784; p = 0.030) were found to be independent variables associated with P53-mutated HCC. In the group of HCC lesions with the largest tumor diameter (LTD) greater than or equal to 10mm and less than or equal to 20mm, enhancing capsule was an independent predictor of P53-mutated HCC (odds ratio, 6.200; 95% CI: 1.116, 34.449; p = 0.037). Among the HCC lesions (20 mm ˂ LTD ≤ 50 mm), corona enhancement (odds ratio, 2.102; 95% CI: 1.022, 4.322; p = 0.043) and nodule-in-nodule architecture (odds ratio, 2.157; 95% CI: 1.033, 4.504; p = 0.041) were found to be independent risk factors for P53 mutation. Among the HCC lesions (50 mm ˂ LTD ≤ 100 mm), diameter (odds ratio, 1.035; 95% CI: 1.001, 1.069; p = 0.044) and AFP ≥ 400 (ng/mL) (odds ratio, 3.336; 95% CI: 1.052, 10.577; p = 0.041) were found to be independent variables associated with P53-mutated HCC.Conclusion: Poor differentiation and rim enhancement are potential predictive biomarkers for P53-mutated HCC, while HCCs of different diameters have different risk factors for predicting P53 mutations.Keywords: liver neoplasms, magnetic resonance imaging, P53-mutated

Hao Wang,1 Yinbo Xiao,1 Yumeng Cai,1 Yang Zhou,1 Longyun Chen,1 Jianbin Guo,2 Xiaohua Shi,1 Zhiyong Liang1 1Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, People’s Republic of China; 2Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, Beijing, 100730, People’s Republic of ChinaCorrespondence: Zhiyong Liang; Xiaohua Shi, Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science & Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, Tel +86 10-69159353 ; +86 10-69159365, Email liangzy@pumch.cn; shixiaohua3762@foxmail.comIntroduction: This study used single-center data to analyze the clinicopathological features of site-specific endometrial cancer.Methods: Patients with endometrial carcinoma who had undergone surgery at Peking Union Medical College Hospital, China, between March 2016 and January 2022 were enrolled. Clinical information and pathological characteristics were summarized, and microsatellite status was analyzed using the immunohistochemical method. Patient prognoses were measured in terms of the rates of overall survival and progression-free survival.Results: The mean patient age was 49 years (ranging: from 25 to 76 years old), and there was no difference in clinicopathological features between endometrioid and type II endometrial carcinoma in LUSC. The ER and PR expression ratios were 80.4% and 64.3%, respectively, in this LUSC cohort, and the MMR deficiency ratio was 33.9%, including 39.6% in endometrioid carcinoma and 15.4% in type II endometrial carcinoma. Combined MSH2&MSH6 loss was more common than combined MLH1&PMS2 being unexpressed (16.1% vs 12.5%), and dMMR patients differed significantly from the pMMR group in terms of vascular invasion (P=0.003). The combination of chemotherapy and radiotherapy did not provide a statistically significant improvement in prognosis compared to chemotherapy alone.Conclusion: The results of this study showed that LUSC patients tended to be younger and their tumors had less expression of hormone markers. The biological behavior of both endometrioid cancer and type II EC may be similar when EC occurs in this area. Furthermore, this type of tumor also showed a higher incidence of vascular invasion, and the combination of chemotherapy and radiotherapy did not provide significant improvement. Thus, successful treatment of LUSC tumors requires aggressive surgical intervention and a more effective postoperative treatment approach.Keywords: endometrial cancer, lower uterine segment, prognosis

Yan-Jun Xiong,&ast; Yu Xiao,&ast; Lei Xie, Lei Gao, Yi Han, Peng-Fei Huang, Shuang Liu, Ya-Xue Liang, Hua Wang Department of Tuberculosis, Anhui Provincial Chest Hospital (Anhui Institute of Tuberculosis Control), Hefei, Anhui, 230022, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Wang, Department of Tuberculosis, Anhui Provincial Chest Hospital (Anhui Institute of Tuberculosis Control), No. 392, Jixi Road, Hefei, Anhui, People’s Republic of China, Tel +86 13395694530, Email 1726553540@qq.comBackground: Linezolid (LZD) is a cornerstone medication in the treatment of drug-resistant tuberculosis (DR-TB). However, it frequently triggers adverse effects such as bone marrow suppression, optic neuropathy, and peripheral neuropathy, all of which can impact treatment outcomes and prognosis. Contezolid (CZD), a novel oxazolidinone antibiotic, exhibits comparable antimicrobial efficacy against Mycobacterium tuberculosis as LZD, but with potentially enhanced safety profiles.Case Presentation: This report presents five cases (Cases 1– 5) of LZD intolerance, wherein CZD served as an effective alternative treatment. In Cases 1– 3, LZD administration resulted in bone marrow suppression, primarily manifested as anemia. Transitioning to CZD therapy led to a rise and stabilization of hemoglobin (HGB) levels in Cases 1– 2, and a return to baseline values in Case 3. In Case 4, CZD treatment alleviated symptoms of LZD-induced peripheral neuritis, although complete resolution was not achieved, hinting at potential irreversibility of this type of peripheral neuropathy. In Case 5, direct CZD anti-TB therapy was initiated for recurrent leukopenia and neutropenia, resulting in no further severe myelosuppression and successful recovery.Conclusion: These case studies suggest that CZD could represent an effective and safe option for anti-TB therapy, especially for patients intolerant to LZD.Keywords: contezolid, linezolid, drug-resistant tuberculosis, myelosuppression, peripheral neuropathy

Xiao-Hong Wu,1,2,&ast; Yu Xiao,3,4,&ast; Xi-Sui Chen5 1Nursing Department, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2School of Nursing, Shantou University Medical College, Shantou, People’s Republic of China; 3Psychosomatic Medical Center, The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 4Psychosomatic Medical Center, The Fourth People’s Hospital of Chengdu, Chengdu, People’s Republic of China; 5Nursing Department, The First Affiliated Hospital of Shantou University Medical College, Shantou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xi-Sui Chen, Email zdfsichuan@126.comObjective: This study aimed to develop the Chinese version of the totally implantable venous access port (TIVAP) self-management behavior scale for patients with cancer to provide a reliable tool for medical staff to judge patients with TIVAP self-management behavior.Methods: This study employed a mixed-method exploratory design. The initial scale was developed through a literature review, expert meetings, and two-round Delphi expert consultation. The reliability indicators included retest reliability and Cronbach’s alpha coefficients. The validity indicators included content, construct, convergent, discriminant, and criterion validity. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were employed for the validity analysis; 22 venous therapy experts participated in the Delphi expert consultation. A total of 500 patients were recruited from two third-class A hospitals in Guangdong Province, China, between July 2020 and January 2021 to test reliability and validity. A convenience sampling method was adopted.Results: The final scale comprised seven dimensions and 29 items. The content validity index (S-CVI) was 0.990. Cronbach’s alpha coefficient and retest reliability of the scale were 0.931 and 0.900, respectively. The EFA results indicated a seven-factor structure, accounting for 65.68% of the total data variance. The results of the CFA showed that the CMIN/DF value was 2.348; the root mean square error of approximation value was 0.06; and the values of comparative fit index, incremental fit index, and Tucker–Lewis index were all > 0.90. The factor loadings for all the items were > 0.50, the composite reliability value was > 0.70, and the average variance extracted (AVE) value was > 0.50. Moreover, all absolute values of the correlation coefficients were less than the square root of the AVE for the seven dimensions. The total scores between the health promoting lifestyle profile-II revise (HPLP-IIR) and CPTSMBS were positively correlated (r = 0.465, p < 0.01).Conclusion: The scale demonstrated good reliability and validity and can be applied in clinical practice to evaluate self-management behavior among patients using a TIVAP.Keywords: totally implantable venous access port, TIVAP, reliability, validity, scale, self-management

Yuxin Wang,1,&ast; Xiaona Wang,1,2,&ast; Jinmei Luo,1 Bintao Qiu,3 Rong Huang,1 Yi Xiao1 1Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Respiratory Medicine, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Central Laboratory, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinmei Luo, Department of Pulmonary and Critical Care Medicine, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, 100730, People’s Republic of China, Email palmljm@126.comPurpose: There are currently no ideal indicators for predicting the cardiovascular risk of obstructive sleep apnea (OSA). This study aimed to employ urinary metabolomics to detect early cardiovascular risk in patients with moderate-to-severe OSA.Patients and Methods: Male participants who underwent polysomnography from November 2020 to May 2021 were screened. Clinical data, polysomnography data and urine samples were collected. Untargeted metabolomics analyses of urine were performed. Multivariate analyses and receiver operating characteristic (ROC) curve analyses were subsequently performed to identify potential biomarkers. Associations between metabolites and clinical indicators and cardiovascular risk were examined through linear regression analyses with interaction and mediation analyses.Results: Thirty-six male participants were included in the study, comprising 22 males with moderate-to-severe OSA and 14 age-matched controls, with an average age of 39.6 ± 9.2 years. We identified 65 metabolites in the study, involving pathways including pyrimidine, androgen, estrogen, vitamin B6 and sulfate/sulfite metabolism. Among them, epinephrine sulfate was the most significantly altered metabolite. ROC analyses highlighted that epinephrine sulfate had the highest area under the curve (AUC=0.883) for detecting moderate-to-severe OSA. Epinephrine sulfate was statistically correlated with OSA severity, hypoxia-related indicators (apnea-hypopnea index: r=0.685; oxygen desaturation index: r=0.743, p< 0.0001), arterial stiffness (arterial augmentation index: r=0.361, p=0.031) and long-term cardiovascular risk (Framingham cardiovascular risk: r=0.375, p=0.024). Linear regression analysis revealed that epinephrine sulfate was significantly associated with an increased in the Framingham risk (β = 0.004, 95% CI = 0.000– 0.009, p = 0.049), with the effect partly mediated by systolic blood pressure (27.6%) and not moderated by other factors. Additionally, it also significantly associated with the increased in the arterial augmentation index (β = 0.019, 95% CI = 0.000– 0.037, p = 0.046), with the effect fully mediated by blood pressure and not moderated by other indices statistically.Conclusion: There are significant metabolic pathway alterations in moderate-to-severe OSA patients. Urinary epinephrine sulfate markedly predicts early cardiovascular risk in OSA patients.Keywords: metabolomics, Framingham cardiovascular risk score, epinephrine sulfate, obstructive sleep apnea

Zonglei Chong,1,&ast; Xiaoqian Yang,1,&ast; Xiaoxiao Peng,2 Qiang Zong,3 Hongxing Li,3,&ast; Yilei Xiao1,&ast; 1Liaocheng People’s Hospital, Liaocheng, Shandong, People’s Republic of China; 2Dongying District People’s Hospital, Dongying, Shandong, People’s Republic of China; 3Shengli Oilfield Central Hospital, Dongying, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yilei Xiao, Department of Neurosurgery, Liaocheng People’s Hospital, No. 67 Dongchang West Road, Dongchangfu District, Liaocheng, Shandong Province, 252000, People’s Republic of China, Email yileixiao@163.com Hongxing Li, Department of Neurosurgery, Shengli Oilfield Central Hospital, No. 31 Jinan Road, Dongying, Shandong Province, 257000, People’s Republic of China, Email lihongxing159@126.comAbstract: We report the case of a 53-year-old man who was diagnosed with Holmes tremor and underwent deep brain stimulation of the ventro-intermediate thalamic nucleus and posterior subthalamic area. We assessed the patients’ tremor with the Fahn-Tolosa-Marin Tremor Rating Scale at 1, 3, 6, 12 and 24 months after deep brain stimulation. Deep brain stimulation relieved the patient’s tremor during the 24-month follow-up period.Keywords: deep brain stimulation, Holmes’ tremor, posterior subthalamic area, the ventro-intermediate thalamic nucleus, ventro-intermediate thalamic nucleus

Wenwu Zhang,1,2,&ast; Yuhan Xiao,3,&ast; Xin Zhu,1 Yanxia Zhang,1 Qin Xiang,1 Shunhong Wu,1 Xiaoyu Song,1 Junxiu Zhao,3 Ruanfei Yuan,1 Qiguang Li,1 Bin Xiao,1 Linhai Li1 1Department of Laboratory Medicine, The Affiliated Qingyuan Hospital (Qingyuan People’s Hospital), Guangzhou Medical University, Qingyuan, Guangdong, 511518, People’s Republic of China; 2Department of Laboratory Medicine, Suzhou Municipal Hospital, Affiliated to Nanjing Medical University, Suzhou, 21500, People’s Republic of China; 3School of Public Health, Dali University, Dali, 671000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linhai Li; Bin Xiao, Email mature303@126.com; xiaobin2518@163.comPurpose: Meiotic nuclear division 1 (MND1) is a meiosis-specific protein that promotes lung adenocarcinoma progression. However, its expression and biological function across cancers remain largely unexplored.Patients and Methods: The expression, prognostic significance, mutation status, and methylation profile of MND1 in various cancers were comprehensively analyzed using the TIMER, GTEX, Kaplan-Meier plotter, cBioPortal, and GSCA databases. Additionally, we constructed a PPI network, enrichment analysis and single-cell transcriptomic sequencing to elucidate the underlying mechanism of MND1. Furthermore, we investigated the association between MND1 expression and drug sensitivity using CellMiner. Moreover, we also explored the correlation between MND1 expression and immune infiltration. Finally, we validated the functional role of MND1 in breast cancer through IHC staining, CCK8, EdU, colony formation, and flow cytometry assays.Results: MND1 has been reported to be highly expressed in Pan-cancer, High MND1 expression was significantly associated with poor prognosis in cancers. Additionally, MND1 mutation frequency is high in most cancers, and its expression correlates with methylation. Furthermore, MND1 expression significantly correlates with immune checkpoint blockade (ICB) markers, including PD-L1, PD-1, and CTLA-4. The PPI network reveals interactions between MND1 and PSMC3IP, BRCA1, and BRCA2. Enrichment analysis and single-cell sequencing indicate that MND1 positively correlates with cell cycle. ROC curve reveals favorable diagnostic efficacy of MND1 in breast cancer. In vitro, MND1 overexpression promotes breast cancer cell proliferation and increases the expression of key cell cycle regulators (CDK4, CDK6, and cyclin D3), accelerating the G1/S phase transition and leading to abnormal breast cancer cell proliferation. The immunohistochemical analysis revealed a robust expression of MND1 in breast cancer tissues, exhibiting a significant positive correlation with PD-L1 and FOXP3.Conclusion: MND1 is an oncogene and may serve as a biomarker for cancer prognosis and immunotherapy. Targeting MND1 may be a potential tumor treatment strategy.Keywords: meiosis-specific protein, pan-cancer, prognosis biomarker, immune infiltration, cell cycle

Yuexi Liu,&ast; Qiuying Gu,&ast; Yao Xiao, Xing Wei, Jinlong Wang, Xiaolan Huang, Hua Linghu Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Linghu, Department of Gynecology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China, Email linghuhua@cqmu.edu.cnPurpose: To evaluate Ki67 expression and prognostic value during neoadjuvant chemotherapy (NACT) in advanced epithelial ovarian cancer (EOC).Patients and Methods: 95 patients with advanced EOC receiving NACT followed by interval debulking surgery (IDS) were available for tissue samples from matched pre- and post-therapy specimens. The expression of Ki-67 was evaluated by immunohistochemistry and classified by percentage of stained cells. The optimal cutoff values of the Ki67 were assessed by receiver operating characteristic analysis. Kaplan-Meier analysis, the Log rank test, and Cox regression analysis were carried out to analyze survival.Results: Post-NACT Ki67 was an independent prognostic factor for recurrence by univariate (HR: 1.8, 95% CI: 1.1– 3.0, P-value: 0.023) and multivariate (HR: 1.88, 95% CI: 1.08– 3.26, P-value: 0.025) analysis. Residual disease > 1cm (HR: 2.69, 95% CI: 1.31– 5.54, P-value: 0.0070) and pre-treatment CA125 ≥ 1432 U/mL (HR: 2.00, 95% CI: 1.13– 3.55, P-value: 0.017) were also independent risk factors for progression-free survival (PFS) in multivariate analysis. Post-NACT Ki67 ≥ 20% was an independent risk factor for PFS, however, baseline Ki67 and Ki67 change did not suggest prognostic significance. In patients with high CA125, the median PFS for patients with high postKi67 (median PFS: 15.0 months, 95% CI: 13.4– 16.6 months) was significantly (P-value: 0.013) poorer compared to patients with low postKi67 (median PFS: 30.0 months, 95% CI: 13.5– 46.5 months).Conclusion: Post-NACT Ki67 ≥ 20% was an independent factor associated with poorer PFS in patients with advanced-stage EOC undergoing NACT followed by IDS. The combination of post-NACT Ki67 and pretreatment CA125 could better identify patients with poorer PFS in NACT-administered patients.Keywords: interval debulking surgery, progression-free survival, overall survival, tumor marker

Yongqiang Xiao,1– 3,&ast; Wanqing Chen,4,&ast; Wei Deng,1,&ast; Guoqing Zhu,1 Jin Xie,1 Laihui Luo,1 Liucong Lin,1 Jiahao Tao,1 Zhigao Hu,1 Renfeng Shan1 1Department of General Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of General Surgery, Ganjiang New Area People’s Hospital, Nanchang, Jiangxi, People’s Republic of China; 3Department of General Surgery, Ganjiang New Area Hospital of the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 4Department of Gastroenterology, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhigao Hu; Renfeng Shan, Department of General Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17, Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86-791-88692522, Email 854189568@qq.com; srf1978@126.comPurpose: This study aimed to assess the prognostic significance of alpha-fetoprotein (AFP) response in patients with unresectable hepatocellular carcinoma (u-HCC) who underwent hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab.Methods: A retrospective review was conducted on patients with u-HCC receiving treatment with HAIC combined with lenvatinib and camrelizumab. Early AFP response was defined as a > 20% decrease in AFP within 4 weeks, and AFP response as a > 75% decrease in AFP within 8 weeks. The correlation between early AFP response, AFP response, therapeutic response, overall survival (OS), and progression-free survival (PFS) was investigated.Results: The study included 63 patients. AFP responders exhibited superior objective response rates compared to AFP non-responders, as determined by RECIST v1.1 or mRECIST criteria (45.5 vs. 18.2%, p=0.014, or 81.8 vs. 48.5%, p=0.013). Furthermore, early AFP responders demonstrated prolonged OS (not reached vs. 8.0 months, p< 0.001) and PFS (13.3 vs. 3.0 months, p= 0.018) relative to early AFP non-responders. Similarly, AFP responders exhibited improved OS (not reached vs. 9.0 months, p< 0.001) and PFS (19.3 vs. 5.1 months, p=0.002) compared to AFP non-responders. Multivariate analysis results indicated that both early AFP response and AFP response independently predicted OS [hazard ratio (HR) 2.963, 95% confidence interval (CI) 1.333– 6.585, p=0.008, and HR 6.182, 95% CI 1.780– 21.466, p=0.004] and PFS (HR 2.186, 95% CI 1.107– 4.318, p=0.024, and HR 3.078, 95% CI 1.407– 6.730, p=0.005), serving as significant prognostic values.Conclusion: Early AFP response and AFP response serve as predictive biomarkers for the effectiveness of HAIC combined with lenvatinib and camrelizumab in patients with u-HCC.Keywords: unresectable hepatocellular carcinoma, alpha-fetoprotein, hepatic arterial infusion chemotherapy, lenvatinib, camrelizumab

Weihua Han,1,&ast; Peiyao Zhou,2,&ast; Chun Chen,3,&ast; Chunyang Wu,2 Li Shen,1 Cailing Wan,4 Yanghua Xiao,4 Jiao Zhang,2 Bingjie Wang,1 Junhong Shi,1 Xinru Yuan,1 Haojin Gao,1 Hongxiu Wang,1 Ying Zhou,1 Fangyou Yu1 1Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Cancer Center, Department of Pulmonary and Critical Care Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, People’s Republic of China; 4School of Public Health, Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Zhou; Fangyou Yu, Email 18702195157@163.com; wzjxyfy@163.comBackground: Carbapenem-resistant Klebsiella pneumoniae (CRKP) infections are a great threat to public health worldwide. Ceftazidime-avibactam (CZA) is an effective β-lactam/β-lactamase inhibitors against CRKP. However, reports of resistance to CZA, mainly caused by Klebsiella pneumoniae carbapenemase (KPC) variants, have increased in recent years. In this study, we aimed to describe the resistance characteristics of KPC-12, a novel KPC variant identified from a CZA resistant K. pneumoniae.Methods: The K. pneumoniae YFKP-97 collected from a patient with respiratory tract infection was performed whole-genome sequencing (WGS) on the Illumina NovaSeq 6000 platform. Genomic characteristics were analyzed using bioinformatics methods. Antimicrobial susceptibility testing was conducted by the broth microdilution method. Induction of resistant strain was carried out in vitro as previously described. The G. mellonella killing assay was used to evaluate the pathogenicity of strains, and the conjugation experiment was performed to evaluate plasmid transfer ability.Results: Strain YFKP-97 was a multidrug-resistant clinical ST11-KL47 K. pneumoniae confers high-level resistance to CZA (16/4 μg/mL). WGS revealed that a KPC variant, KPC-12, was carried by the IncFII (pHN7A8) plasmids (pYFKP-97_a and pYFKP-97_b) and showed significantly decreased activity against carbapenems. In addition, there was a dose-dependent effect of blaKPC-12 on its activity against ceftazidime. In vitro inducible resistance assay results demonstrated that the KPC-12 variant was more likely to confer resistance to CZA than the KPC-2 and KPC-3 variants.Discussion: Our study revealed that patients who was not treated with CZA are also possible to be infected with CZA-resistant strains harbored a novel KPC variant. Given that the transformant carrying blaKPC-12 was more likely to exhibit a CZA-resistance phenotype. Therefore, it is important to accurately identify the KPC variants as early as possible.Keywords: carbapenem-resistant Enterobacterales, Klebsiella pneumoniae, ceftazidime-avibactam, KPC-12, carbapenemase

Yi Zhang,1,2,&ast; Zhang-Rui Liang,1,3,&ast; Yang Xiao,4 Yi-Shi Li,4 Bin-Jie Fu,1 Zhi-Gang Chu1 1Department of Radiology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China; 2Department of Radiology, Chongqing Jiangjin Second People’s Hospital, Chongqing Jiangjin Cancer Hospital, Chongqing, 402260, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, People’s Republic of China; 4Department of Respiratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400016, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin-Jie Fu; Zhi-Gang Chu, Department of Radiology, The First Affiliated Hospital of Chongqing Medical, University, 1&num; Youyi Road, Yuanjiagang, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86 18883851162 ; +86 18723032809, Fax +86 23 68811487, Email binjie_fu@163.com; chuzg0815@163.comPurpose: To explore the computed tomography (CT) features of bronchopneumonia caused by pepper aspiration to improve the diagnosis.Materials and Methods: 28 adult patients diagnosed with obstructive pneumonia caused by pepper aspiration from January 2016 to September 2022 were enrolled. The CT characteristics of bronchial changes and pulmonary lesions caused by pepper were analyzed and summarized.Results: Among 28 patients, the most common symptom was cough (26, 92.9%), followed by expectoration (23, 82.1%). Bronchoscopy revealed that peppers were mainly found in the bronchus of the right lower lobe (n = 18, 64.3%), followed by the bronchus of the left lower lobe (n = 5, 17.9%). In combination with bronchoscopy results, the pepper in the bronchus manifested as circular or V/U-shaped high-density, localized soft tissue, and flocculent opacification in 8 (28.6%), 16 (57.1%), and 3 (10.7%) cases on CT images, respectively. The bronchial wall around the pepper was thickened with localized occlusion (n = 19, 67.9%) and stenosis (n = 9, 32.1%). Regarding adjacent bronchi without peppers, extensive wall thickening with stenosis and/or occlusion was found in 23 (82.1%) cases. Distal pulmonary lesions frequently involved two or three segments (21, 75.0%) and mainly presented as patchy consolidation or atelectasis (24, 85.7%).Conclusion: In combination to a history of eating peppers and clinical symptoms, bronchopneumonia caused by pepper should be highly suspected if U/V-shaped and annular high-density or localized soft tissue density is detected in the bronchi of the lower lobes, accompanied by extensive bronchial wall thickening, stenosis, or occlusion, and consolidation or atelectasis in multiple distal lung segments.Keywords: obstructive pneumonia, foreign body, pepper, computed tomography

Xin-Mei Hu,1,&ast; Can-Can Wang,1,&ast; Yu Xiao,1 Yu Liu,1 Hong-Ri Huang,2 Peng Jiang,1 Ying-Kai Wang,1 Yun-Jin Lin,1 Liang-Cheng Li,3 Zhong-Quan Qi1 1Medical College, Guangxi University, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 2Department of Research and Development, Guangxi Taimei Rensheng Biotechnology Co., Ltd, Nanning, Guangxi Zhuang Autonomous Region, People’s Republic of China; 3School of Pharmaceutical Sciences, Xiamen University, Xiamen, Fujian Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhong-Quan Qi, Guangxi University, Da-Xue-Dong Road No. 100, Xixiangtang District, Nanning, Guangxi Zhuang Autonomous Region, 530004, People’s Republic of China, Tel +8613806001271, Email yxyyz@gxu.edu.cn Liang-Cheng Li, Xiamen University, No. 4221-115, Rm 355, Xiang’an District, Xiang’an, Xiamen Fujian Province, 361102, People’s Republic of China, Tel +8618359206906, Email lchli2013@xmu.edu.cnPurpose: In recent years, exosomes have been proved to be used to treat many diseases. However, due to the lack of uniform quality control standards for exosomes, the safety of exosomes is still a problem to be solved, especially now more and more exosomes are used in clinical trials, and its non-clinical safety evaluation is particularly important. However, there is no safety evaluation standard for exosomes at present. Therefore, this study will refer to the evaluation criteria of therapeutic biological products, adopt non-human primates to evaluate the non-clinical safety of human umbilical cord mesenchymal stem cell exosomes from the general pharmacology and immunotoxicity, aiming at establishing a safety evaluation system of exosomes and providing reference for the clinical application of exosomes in the future.Methods: 3.85 × 1012 exosomes derived from human umbilical cord mesenchymal stem cells were injected into cynomolgus monkeys intravenously. The changes of general clinical conditions, hematology, immunoglobulin, Th1/Th2 cytokines, T lymphocytes and B lymphocytes, and immune organs were observed before and within 14 days after injection.Results: The results showed that exosomes did not have obvious pathological effects on the general clinical conditions, blood, coagulation function, organ coefficient, immunoglobulin, Th1/Th2 cytokines, lymphocytes, major organs, and major immune organs (spleen, thymus, bone marrow) of cynomolgus monkeys. However, the number of granulocyte-macrophage colonies in exosomes group was significantly higher than that in control group.Conclusion: To sum up, the general pharmacological results and immunotoxicity results showed that the injection of 3.85 × 1012 exosomes may have no obvious adverse reactions to cynomolgus monkeys. This dose of exosomes is relatively safe for treatment, which provides basis research for non-clinical safety evaluation of exosomes and provides reliable research basis for future clinical application of exosomes.Keywords: exosomes, cynomolgus monkeys, safety, immunotoxicity

Jie Chen,1,&ast; Yan Xiao,2,&ast; Chaofang Yan,1 Xiaoju Li,1 Yafang Zhang,1 Ying Chen,1 Yuan Huang,1 Rui Deng1 1School of Public Health, Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2Foreign Languages Department, Kunming Medical University, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rui Deng; Yuan Huang, Email dengruirita@126.com; huangyuan@kmmu.edu.cnPurpose: With population aging, individuals in underdeveloped areas may experience a higher prevalence of chronic non-communicable diseases (NCDs), a lower level of health-related quality of life (HRQoL), and distinct lifestyles. However, this triadic association remains inadequately studied, particularly regarding the role of health lifestyle. This study aims to examine the relationship between the number of NCDs and HRQoL, while considering the moderating effect of health lifestyle among middle-aged and older adults residing in resource-limited areas.Methods: This cross-sectional study was conducted in Yunnan Province from July to December 2022. Participants completed a self-report questionnaire related to socio-demographic information, NCDs conditions, health lifestyle status, and HRQoL, which was assessed using the EuroQol five-dimension five-level (EQ-5D-5L) scale. Hierarchical regression and simple slope tests were used to examine the moderating effect of health lifestyle.Results: Out of the total 2704 participants, 57.91% presented at least one NCD. The mean scores for health lifestyle and health utility value were 11.109 and 0.944 respectively. The number of NCDs was negatively associated with health utility value, while positively correlated with the health lifestyle score (P< 0.001). The results of hierarchical regression indicated that health lifestyle exerted a negative moderating effect on the relationship between the number of NCDs and HRQoL (β=0.006, P< 0.001), which was also observed for specific health-related behaviors such as sleep duration (β=0.013, P< 0.001), physical examination attendance (β=0.006, P< 0.05) and physical activity (β=0.013, P< 0.001).Conclusion: These findings highlight the crucial role of a healthy lifestyle in attenuating the association between the number of NCDs and HRQoL. Recognizing the potential modulating influence of a healthy lifestyle in this relationship could be pivotal for developing effective interventions for this population, even within resource-constrained rural settings.Keywords: chronic non-communicable diseases, health-related quality of life, health lifestyle, health-related behavior, rural, moderating effect

Yu Xiao,1,2 Liang Liu,3 Ting-ting Chen,4 Zhou Zhang,5 Xiao-hong Wu6 1Psychosomatic Medical Center, The Fourth People’s Hospital of Chengdu, Chengdu, Sichuan Province, 610036, People’s Republic of China; 2Psychosomatic Medical Center, The Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, 610036, People’s Republic of China; 3Department of Urology, Baoding No.1 Central Hospital, Baoding, Hebei Province, 071030, People’s Republic of China; 4Mental Health Center, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610044, People’s Republic of China; 5Department of Gastroenterology, Xiangyang No.1 People’s Hospital, Hubei University of Medicine, Xiangyang, Hubei Province, 441011, People’s Republic of China; 6Nursing Department, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliate Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan Province, 610041, People’s Republic of ChinaCorrespondence: Yu Xiao, The Fourth People’s Hospital of Chengdu, No. 8, Huli West Lane 1, Yingmenkou Road, Chengdu, Sichuan Province, 610036, People’s Republic of China, Tel +86-028-85641749, Email xiaoy3@outlook.comObjectives: Sexual harassment (SH) is a prevalent issue in various professional fields worldwide. The current study aims to investigate the incidence of SH targeting psychiatrists in China and explore its impact on quality of life (QOL).Methods: A consecutive recruitment of 1093 psychiatrists was conducted from 6 hospitals in China. The recorded data included participants’ socio-demographic characteristics, experiences of workplace SH within the previous year, and their QOL. SH comprised verbal harassment, physical harassment, and displaying of sexual organs. The Chinese version of the World Health Organization Quality of Life Brief Version (WHOQOL-BREF) was employed to assess QOL. We compared the demographic characteristics and QOL between the SH group and the non-SH group. Multiple logistic regression analysis was used to identify independent demographic correlates of SH.Results: In total, 13.8% (n = 151) of the psychiatrists reported SH, with 5.8% reporting it once, 4.4% reporting it twice, and 3.6% reporting it three times or more. Psychiatrists who had encountered SH exhibited lower QOL across social, psychological, physical, and environmental domains. Multiple logistic regression analysis revealed that young physicians and those with shorter work experience had a higher likelihood of experiencing SH.Conclusion: The high prevalence of SH among Chinese psychiatrists is of concern. Given its detrimental effects on the well-being of physicians and the quality of medical care they provide, it is crucial to develop specialized employee training programs for this population to effectively manage workplace SH.Keywords: China, psychiatrists, quality of life, mental health professionals, sexual harassment, workplace safety

Yanhua Liu,1,2,&ast; Fuxing Li,1,2,&ast; Youling Fang,2,3 Qiaoshi Zhong,1,2 Yanping Xiao,1,2 Yunwei Zheng,1,2 Junqi Zhu,2,3 Chuwen Zhao,2,3 Xingwei Cao,1,2 Jianqiu Xiong,4 Longhua Hu1,2 1The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Jiangxi, Nanchang, People’s Republic of China; 2Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, People’s Republic of China; 3School of Public Health, Nanchang University, Jiangxi, Nanchang, People’s Republic of China; 4Department of Nursing, the Second Affiliated Hospital of Nanchang University, Jiangxi, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianqiu Xiong, Department of Nursing, The Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Jiangxi, Nanchang, 330006, People’s Republic of China, Email 1773014059@qq.com Longhua Hu, Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Jiangxi, Nanchang, 330006, People’s Republic of China, Email longhuahu@163.comObjective: This research aimed to analyze the clinical characteristics, prognosis, and antimicrobial treatment of bloodstream infections (BSI) caused by Enterobacter cloacae complex (ECC).Methods: The clinical data of patients with bloodstream infections caused by Enterobacter cloacae complex from April 2017 to June 2023 were collected retrospectively. These data were then analyzed in subgroups based on the detection results of extended-spectrum β-lactamase (ESBL), 30-day mortality, and the type of antimicrobial agent used (β-lactam/β-lactamase inhibitor combinations (BLICs) or carbapenems).Results: The proportion of ESBL-producing Enterobacter cloacae complex was 32.5% (37/114). Meanwhile, ICU admission, receiving surgical treatment within 3 months, and biliary tract infection were identified as risk factors for ESBL-producing ECC-BSI. Additionally, immunocompromised status and Sequential Organ Failure Assessment (SOFA) score ≥ 6.0 were identified as independent risk factors of 30-day mortality in patients with ECC-BSI (n = 108). Further analysis in BSI patients caused by non-ESBL-producing ECC revealed that patients treated with BLICs (n = 45) had lower SOFA scores and lower incidence of hypoproteinemia and sepsis compared with patients treated with carbapenems (n = 20). Moreover, in non-ESBL-producing ECC-BSI patients, the univariate Cox regression analysis indicated a significantly lower 30-day mortality rate in patients treated with BLICs compared to those treated with carbapenems (hazard ratios (HR) [95% CI] 0.190 [0.055– 0.662], P = 0.009; adjusted HR [95% CI] 0.106 [0.013– 0.863], P = 0.036).Conclusion: This study investigated the factors influencing the susceptibility to infection by ESBL-producing strains and risk factors for 30-day mortality in ECC-BSI patients. The results revealed that ESBL-negative ECC-BSI patients treated with BLICs exhibited significantly lower 30-day mortality compared to those treated with carbapenems. BLICs were found to be more effective in ECC-BSI patients with milder disease (ESBL-negative and SOFA ≤ 6.0).Keywords: Enterobacter cloacae complex, extended-spectrum β-lactamase, bloodstream infection, risk factors, β-lactam/β- lactamase inhibitor combinations, carbapenems

Chen Yang,1,2,&ast; Wangjun Dong,2,&ast; Jianbo Luo,2 Mengzhao Ma,2 Yeyue Gao,2 Lijie Ni,2 Huixing Liu,2 Chengjun Cha,2 Yangli Xiao,2 Shaoqiang Huang1 1Department of Anesthesia, Obstetrics & Gynecology Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Anesthesia, Yongping County People’s Hospital, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaoqiang Huang, Department of Anesthesia, Obstetrics & Gynecology Hospital, Fudan University, 128&num; Shenyang Road, Shanghai, 200090, People’s Republic of China, Email Drhuangsq@163.comObjective: Alterations in altitude can lead to an augmented requirement for local anesthesia among patients. Nevertheless, the necessity for an elevated dosage of local anesthetic for parturients at moderately high altitudes during spinal anesthesia for cesarean section remains uninvestigated. This up-down sequential study endeavors to determine the ED50 dose of bupivacaine required for spinal anesthesia during cesarean sections at moderately high-altitude.Methods: Thirty singleton parturients at moderately high altitude underwent elective cesarean section under combined spinal-epidural anesthesia. The up-and-down sequential method was employed, starting with an initial dose of 12mg (1.6mL) of 0.75% hyperbaric bupivacaine for the first participant. The dose for the next case was adjusted up or down by 0.75mg based on the effectiveness of the previous participant. Effectiveness was defined as the bilateral sensory block reaching T6 within 15 minutes after spinal anesthesia injection, without the need for additional epidural anesthesia before fetal delivery. The ED50 dose and 95% confidence interval were calculated using the Dixon sequential method and isotonic regression, respectively. The incidence of maternal hypotension, nausea, and vomiting during the study period was also recorded.Results: The ED50 of hyperbaric bupivacaine for spinal anesthesia in cesarean section was calculated as 8.23 mg (95% CI, 6.52– 9.32 mg) using the Dixon up-and-down method. Further validation using isotonic regression yielded a value of 8.39 mg (95% CI, 7.48– 9.30 mg), confirming the accuracy and sensitivity of the conclusion. During the operation, only 6 parturients experienced hypotension, and no adverse reactions such as nausea, vomiting, and shivering were observed.Conclusion: The ED50 dose of 0.75% hyperbaric bupivacaine for spinal anesthesia during cesarean section at moderately high altitude is 8.23 mg, which exceeds the ED50 dose typically required by parturients at low altitude. Comprehensive investigations are warranted to ascertain the ED90 or ED95 dose of local anesthetics for cesarean section at moderately high altitudes, thereby offering enhanced guidance for clinical practice.Keywords: bupivacaine, high altitude, spinal anesthesia, ED50 dose

Naya Huang,1,&ast; Yiying Xiao,2,&ast; Wei Chen,1 Xin Wang1 1Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; Key Laboratory of Clinical Nephrology of the NHC (Sun Yat-Sen University) and Guangdong Provincial; Key Laboratory of Nephrology, Guangzhou, 510080, People’s Republic of China; 2School of Medicine, Sun Yat-Sen University, Shenzhen, Guangdong, 518170, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Chen; Xin Wang, Department of Nephrology, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, China; Key Laboratory of Clinical Nephrology of the NHC (Sun Yat-Sen University) and Guangdong Provincial; Key Laboratory of Nephrology, Guangzhou, 510080, People’s Republic of China, Tel +86-20-87766335, Email chenwei99@mail.sysu.edu.cn; wangxin8@mail.sysu.edu.cnBackground: A minor difference in college entrance examination scores can result in vastly different educational resources in China, so it has been debated whether it is the difference in the student population or the difference in educational resources that causes the difference in medical graduates. We aimed to evaluate the effects of entry grades on students’ academic performance under homogeneous educational resources.Methods: Students in grade 2016 with 13-point difference in the average admission scores of 2 medicine schools in Sun Yat-sen University were educated in mixed classes and were taught with the same educators during the 5 years of undergraduate period. The grades, graduation, and postgraduate enrollment rates of the students were compared between the two campuses.Results: The average admission scores for Shenzhen Campus (SZC) students are 13 points lower than those of Guangzhou North Campus (GZNC) (613 points vs 626 points). After 5 years of homogeneous education, comparing the GZNC students with the SZC students, there were no significant differences in the average total score (80.2 ± 4.6 vs 80.0 ± 5.6, P = 0.691), the average compulsory course (78.9 ± 3.4 vs 78.4 ± 6.1, P = 0.438), the average core course score (78.8 ± 7.4 vs 78.7 ± 5.0, P=0.860) and the average clerkship score (85.1 ± 7.2 vs 84.6 ± 2.7, P=0.275). However, the completion rate for SZC was higher than for GZNC (93.94% vs 86.27%, P=0.009). There was no statistical difference in postgraduate enrolment between the two institutions (P=0.758).Conclusion: Given the same educational resources, more medical students with lower entrance scores completed their studies and achieved the same percentage of postgraduate acceptance. This finding suggests that a key component of improving the quality of medical higher education in China may be to further rationalize the allocation of high-quality educational resources, rather than to pursuing students with high entrance examination scores.Key Messages: 1. Undergraduates from two medical schools with different average admission scores were educated with the same resources during the 5-year undergraduate period. After 5 years of homogeneous education, more students with lower entrance scores completed their studies and achieved the same percentage of postgraduate acceptance. 2. The key to improving educational quality is to optimize educational resources, not just to recruit high-scoring students.Keywords: medical education, teaching quality, student quality, education sources

Yulong Xiao,1 Genhao Zhang2 1Department of Medical Laboratory, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Department of Blood Transfusion, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Genhao Zhang, Email smilegenhao@163.comBackground: Pediatric sepsis has a very high morbidity and mortality rate. The purpose of this study was to evaluate diagnostic biomarkers and immune cell infiltration in pediatric sepsis.Methods: Three datasets (GSE13904, GSE26378, and GSE26440) were downloaded from the gene expression omnibus (GEO) database. After identifying overlapping genes in differentially expressed genes (DEGs) and modular sepsis genes selected via a weighted gene co-expression network (WGCNA) in the GSE26378 dataset, pivotal genes were further identified by using LASSO regression and random forest analysis to construct a diagnostic model. Receiver operating characteristic curve (ROC) analysis was used to validate the efficacy of the diagnostic model for pediatric sepsis. Furthermore, we used qRT-PCR to detect the expression levels of pivotal genes and validate the diagnostic model’s ability to diagnose pediatric sepsis in 65 actual clinical samples.Results: Among 294 overlapping genes of DEGs and modular sepsis genes, five pivotal genes (STOM, MS4A4A, CD177, MMP8, and MCEMP1) were screened to construct a diagnostic model of pediatric sepsis. The expression of the five pivotal genes was higher in the sepsis group than in the normal group. The diagnostic model showed good diagnostic ability with AUCs of 1, 0.986, and 0.968. More importantly, the diagnostic model showed good diagnostic ability with AUCs of 0.937 in the 65 clinical samples and showed better efficacy compared to conventional inflammatory indicators such as procalcitonin (PCT), white blood cell (WBC) count, C-reactive protein (CRP), and neutrophil percentage (NEU%).Conclusion: We developed and tested a five-gene diagnostic model that can reliably identify pediatric sepsis and also suggest prospective candidate genes for peripheral blood diagnostic testing in pediatric sepsis patients.Keywords: pediatric sepsis, diagnostic model, ROC curves, WGCNA

Yi Tang,1,&ast; Zhengqi Hu,2,&ast; Zhibin Liu,2 Siling Peng,2 Tiancheng Liu,2 Yaoyuan Xiao,2 Jianqiang Peng,1 Hongwei Pan,1 Zhaofen Zheng,1 Jin He1 1Department of Cardiology, Hunan Provincial People’s Hospital, the First Affiliated Hospital of Hunan Normal University, Clinical Medicine Research Center of Heart Failure of Hunan Province, Hunan Normal University, Changsha, People’s Republic of China; 2Department of Cardiology, Hunan Provincial People’s Hospital, the First Affiliated Hospital of Hunan Normal University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jin He, Email 394929734@qq.comPurpose: The levels of human epididymis protein 4 (HE4) is associated not only with the prognosis of patients with acute heart failure (AHF), but also with chronic kidney disease (CKD). Our study aims to understand the prediction value of HE4 on prognosis in patients with AHF combined with CKD.Patients and Methods: This study prospectively enrolled patients diagnosed with AHF combined with CKD at the Department of Cardiology of Hunan Provincial People’s Hospital from March 2019 to December 2022. Serum levels of HE4 were measured using a chemiluminescence microparticle immunoassay. The endpoint events included heart failure readmission and cardiovascular death.Results: A total of 130 patients with AHF combined with CKD were included in the stud. The median age is 73 years (interquartile range: 65– 79 years). Among the patients, 94 experienced the endpoint events. The multivariable Cox analysis reveals that LnHE4 (HR=2.280, 95% CI 1.300– 3.998, P = 0.004) and age (HR=1.024, 95% CI 1.003– 1.045, P = 0.025) are independent predictors of the endpoint events. The Kaplan-Meier survival curve demonstrates that patients with HE4 levels> 276.15 pmol/L has a significantly higher incidence of endpoint events compared to those with HE4 levels≤ 276.15 pmol/L (Log rank test: χ 2=19.689, P < 0.001). After adjusting for age and gender, the HR is 2.520 (95% CI: 1.626– 3.906, P < 0.001).Conclusion: HE4 is an independent predictor of heart failure readmission and cardiovascular death in patients with AHF combined with CKD.Keywords: Human epididymis protein 4, Acute heart failure, Chronic kidney disease, Prognosis

Yunyu Xiao, Shaofeng Zhang, Qiusheng Ren Department of Anesthesiology, Hangzhou Ninth People’s Hospital, Hangzhou, Zhejiang, 311225, People’s Republic of ChinaCorrespondence: Qiusheng Ren, Department of Anesthesiology, Hangzhou Ninth People’s Hospital, No. 298, Yilong Road, Hangzhou, Zhejiang, 311225, People’s Republic of China, Tel +86 15372085337, Email renqiusheng1971@yahoo.comPurpose of Review: Postoperative analgesia is currently a significant topic in anesthesiology. Currently, the predominant approach for achieving multimodal analgesia involves the utilization of pharmacotherapy and regional anesthesia procedures. The primary objectives of this approach are to mitigate postoperative pain, enhance patient satisfaction, and diminish overall opioid usage. Nevertheless, there is a scarcity of research on the use of remote ischemia preconditioning aimed at mitigating postoperative pain.Recent Findings: Transient stoppage of blood flow to an organ has been found to elicit remote ischemia preconditioning (RIPC), which serves as a potent intrinsic mechanism for protecting numerous organs. In addition to its established role in protecting against reperfusion injury, RIPC has recently been identified as having potential benefits in the context of postoperative analgesia.Summary: In addition to traditional perioperative analgesia, RIPC provides perioperative analgesia and organ protection.Keywords: postoperative pain, remote ischemic preconditioning, inflammation, opioids

Jin Zhang,1,&ast; Yang Xiao,2,&ast; Shuoxin Bai,3 Shaoqian Lin,2 Shuang Du,1 Zhiping Wang4 1Department of Occupational and Environmental Health, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Center for Disease Control and Prevention, Jinan, Shandong, 250021, People’s Republic of China; 3Department of Epidemiology, School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 4School of Public Health, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhiping Wang, School of Public Health, Cheeloo College of Medicine, Shandong University, 44 Wenhuaxi Road, Jinan, Shandong, 250012, People’s Republic of China, Email zhipingw@sdu.edu.cnPurpose: We aimed to examine the association between exercise during pregnancy and preterm birth (PTB).Methods: This study was a baseline survey of the Jinan birth cohort. The study subjects were the mothers one month after giving birth, which were investigated by questionnaires retrospectively containing physical exercise (frequency, time, and primary exercise patterns) during pregnancy and each trimester. Individual time spent on exercise and energy expenditure were assessed based on the questionnaires. PTB was clinically defined as a newborn born on or before the last day of the 37th week. Adjusted odds ratios (OR) were estimated using logistic regression to assess the relationship between exercise during pregnancy and the risk of PTB. Variable selection for the multivariate models was guided by the directed acyclic graph. The median effect was analyzed by the sequential test.Results: The prevalence of PTB in this study was 4.38% (285/6501). The adjusted OR (95% CI) for the risk of PTB related to exercise during pregnancy was 0.74 (0.58– 0.95). During the 1st and 2nd trimesters, the ORs (95% CI) for 2.5 to 7 hours of exercise per week were 0.77 (0.59– 0.99) and 0.74 (0.57– 0.96). During the 3rd trimester, the ORs (95% CI) for 2.5 to 7 hours and more than 7 hours of exercise per week were 0.74 (0.56– 0.96) and 0.65 (0.44– 0.94). After stratifying the subjects, the association was only found among subjects without pregnancy complications. Pregnancy complications partially mediated (52.40%) the relationship between exercise during pregnancy and PTB.Conclusion: Exercise during pregnancy can reduce the risk of PTB for women without pregnancy complications. 2.5 to 7 hours of exercise (like walking) per week may be appropriate in three trimesters of pregnancy, and the time could be extended in the 3rd trimester.Keywords: pregnant women, exercise, trimester, mediation analysis

Despite effective control of HIV replication by antiretroviral therapy (ART), a significant number of people living with HIV (PLWH) fail to achieve complete immune reconstitution and thus are deemed immune non-responders (INRs). Compared with immune responders (IRs) who have restored their CD4 T cell numbers and functions, CD4 T cells from these INRs exhibit prominent mitochondrial dysfunction and premature aging, which play a major role in increasing the incidence of non-AIDS, non-communicable diseases (NCDs). To date, there are no reliable biomarkers that can be used to typify and manage PLWH, especially INRs with non-AIDS NCDs. Growth differential factor-15 (GDF-15) is a transforming growth factor-β (TGF-β) family member known to regulate several biological processes involved in cell aging and stress responses. Since PLWH exhibit premature aging and metabolic dysregulation, here we measured the plasma levels of GDF-15 by ELISA and metabolic proteins by proteomic array and correlated the results with clinical parameters in ART-controlled PLWH (including INRs and IRs) and healthy subjects (HS). We found that GDF-15 levels were significantly elevated in PLWH compared to HS. GDF-15 levels were positively correlated with age and negatively associated with body mass and LDL cholesterol levels in the study subjects. Also, elevated GDF-15 levels were correlated with differential dysregulation of multiple metabolic proteins in PLWH. These results suggest that GDF-15 protein may serve as a biomarker of metabolic dysregulation and aging, and this biomarker will be useful in clinical trials targeting aging and metabolic disorders in ART-treated PLWH.

Yansu Wang,1,&ast; Yiting Xu,1,&ast; Tingting Hu,1 Yunfeng Xiao,2 Yufei Wang,1 Xiaojing Ma,1 Haoyong Yu,1 Yuqian Bao1 1Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai Clinical Center for Diabetes, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, People’s Republic of China; 2Department of Radiology, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yuqian Bao, Department of Endocrinology and Metabolism, Shanghai Sixth People’s Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, 600 Yishan Road, Shanghai, 200233, People’s Republic of China, Tel +86-21-64369181, Fax +86-21-64368031, Email yqbao@sjtu.edu.cnBackground: It has been reported recently that the ratio of uric acid to high-density lipoprotein cholesterol (UHR) is correlated with several metabolic disorders. The present study aimed to investigate the associations of UHR with body fat content and distribution.Methods: This study enrolled 300 participants (58 men and 242 women) aged 18 to 65 years. The levels of serum uric acid and high-density lipoprotein cholesterol were measured by standard enzymatic methods. The overall fat content and segmental fat distribution were assessed with an automatic bioelectrical impedance analyzer. In the population with obesity, the visceral fat area (VFA) and subcutaneous fat area (SFA) were measured using magnetic resonance imaging.Results: Among the study population, 219 individuals (73.0%) were with obesity. The median level of UHR in individuals with obesity was 33.7% (26.2% - 45.9%), which was significantly higher than that in those without obesity [22.6% (17.0% - 34.4%), P < 0.01]. UHR was positively associated with overall fat content and segmental fat distribution parameters (all P < 0.01). In multivariate linear regression analysis, compared with body mass index, waist circumference was more closely associated with UHR (standardized β = 0.427, P < 0.001) after adjusting for confounding factors. Additionally, total fat mass (standardized β = 0.225, P = 0.002) and trunk fat mass (standardized β = 0.296, P = 0.036) were more closely linked to UHR than total fat-free mass and leg fat mass, respectively. In the population with obesity, VFA was independently correlated with UHR (P < 0.01), while SFA was not associated with UHR.Conclusion: UHR was significantly associated with overall fat content and trunk fat accumulation. In the population with obesity, UHR was positively associated with VFA. Attention should be paid to the role of excessive trunk fat mass in the relationship between UHR and metabolic disorders.Keywords: fat distribution, the UHR index, trunk fat mass, visceral fat area

Xiaolu Li,1,&ast; Yizhong Wang,1,2,&ast; Rong Cao,1 Fangfei Xiao,1 Xufei Wang,1 Lin Ye,1 Yongmei Xiao,1 Dan Li,1 Ting Zhang1,2 1Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China; 2Gut Microbiota and Metabolic Research Center, Institute of Pediatric Infection, Immunity and Critical Care Medicine, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yizhong Wang; Ting Zhang, Department of Gastroenterology, Hepatology and Nutrition, Shanghai Children’s Hospital, School of Medicine, Shanghai Jiao Tong University, 355 Luding Road, Shanghai, 200062, People’s Republic of China, Tel/Fax +86 2152976335, Email wangyz@shchildren.com.cn; zhangt@shchildren.com.cnBackground: Our previous study reported a high rate of recurrence in children with Clostridioides difficile (C. difficile) infection (CDI) after conventional antibiotic therapy. Here, we aimed to explore whether metronidazole and vancomycin resistant C. difficile isolates are circulating in pediatric CDI.Methods: Antimicrobial susceptibility testing (AST) using the agar dilution method according to the Clinical and Laboratory Standard Institute (CLSI) were performed on C. difficile isolates collected from children with CDI between 2019 and 2022 at the Shanghai Children’s Hospital. Whole-genome sequencing (WGS) was performed on all C. difficile isolates, and the presence of antibiotic resistance genes (ARGs) were identified using Resfinder and the Comprehensive Antibiotic Resistance Database (CARD). The presence of plasmid pCD-METRO was detected using SRST2 (v0.2.0) against 8 pCD-METRO coding sequences.Results: A total of 50 C. difficile isolates were collected from stools of CDI children. The overall resistance rate on all isolates was 30.00% for metronidazole, 6.00% for vancomycin, 0% for rifaximin, 2.00% for rifampin, 24.00% for meropenem, 100.00% for ceftriaxone and clindamycin, 86.00% for erythromycin, 30.0% for levofloxacin, and 50.0% for tetracycline. Multidrug-resistant (MDR) was presented in 44 isolates (88.00%). Sixteen reported potential ARGs relating with resistance to antibiotic classes of aminoglycoside (AAC(6’)-Ie-APH(2”)-Ia, aad(6), ANT(6)-Ib, APH(2”)-If, APH(3’)-IIIa), lincosamide-clindamycin-erythromycin (ErmB, ErmQ), fluoroquinolones (CdeA), glycopeptides (vanRG), nucleoside (SAT-4), tetracycline (tetM, tetA(P), tetB(P), tetO), and trimethoprim (dfrF) were identified. However, the pCD-METRO plasmid and vanA/B were not detected in any isolates.Conclusion: C. difficile isolates from children with reduced susceptibility to metronidazole and vancomycin are emerging in pediatric CDI in China. The lack of pCD-METRO plasmid and vanA/B associated with reduced antibiotic susceptibility suggests there are additional mechanisms of resistance.Keywords: Clostridioides difficile, antibiotic resistance, metronidazole, vancomycin, children

Yanhua Fu,1 Yuanyuan Xiao,2 Tianji Gao,1 Junxiu Zhang,3 Tianjiao Wang1 1Department of Rheumatology, Baoding Hospital of Beijing Children’s Hospital, Baoding, 071000, People’s Republic of China; 2Department of Dermatology, National Center for Children’s Health (Beijing) Children’s Hospital Affiliated to Capital Medical University, Beijing, 100045, People’s Republic of China; 3Department of Dermatology, Baoding Hospital of Beijing Children’s Hospital, Baoding, 071000, People’s Republic of ChinaCorrespondence: Yuanyuan Xiao, Department of Dermatology, National Center for Children’s Health (Beijing) Children’s Hospital Affiliated to Capital Medical University, No. 56 of Nanlishi Road, Xicheng District, Beijing, 100045, People’s Republic of China, Tel +86 10 59612345, Email xiao_yuanyuan23@126.comAbstract: Toxic epidermal necrolysis (TEN) is a type of drug eruption in dermatology emergencies that is rare in clinical practice but has a high mortality rate. The main causes are drug and viral infections. Unfortunately, no expert consensus on treating this disease exists, and a standard therapy is absent. Up to now, glucocorticoids combined with gamma globulin are commonly used in clinical practice, but their efficacy is highly controversial. This study reports on a 7-year-old girl with TEN who did not respond to traditional therapy, such as methylprednisolone combined with gamma globulin, but was finally cured with an additional low-dose etanercept. The results showed that etanercept therapy in paediatric TEN is safe, reliable and worth recommending.Keywords: child toxic epidermal necrolysis, etanercept, glucocorticoids, gamma globulin

Ming Zhou,1,2,&ast; Peng Liu,1,2,&ast; Xiaoqin Yin,1 Caiting Deng,3,4 Yi Xiao,1 Meng Lei,1 Shuo Hu,1 Feifei An,3 Min Zhao1,5,6 1Department of Nuclear Medicine, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Key Laboratory of Biological, Nanotechnology of National Health Commission, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 4Institute of Medical Engineering, Department of Biophysics, School of Basic Medical Science, Health Science Center, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 5Department of Nuclear Medicine, Third Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 6National Clinical Research Center of Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Zhao; Feifei An, Email mzhao1981@csu.edu.cn; anfeifei@xjtu.edu.cnBackground: Sentinel lymph node (SLN) mapping-guided biopsy is crucial for cancer staging and treatment. Optical/nuclide dual-modality imaging agents for mapping SLN are ideal for preoperative planning and intraoperative biopsy, which are enabled by penetration-depth unlimited nuclide imaging and dynamic real-time optical imaging, respectively. However, commonly reported dual-modality imaging agents are composed of novel but safety-unproven materials, making their quick clinical translation challenging. Herein, we report a novel nanoparticle composed of facile hospital-available drugs and isotope for single-photon emission computed tomography (SPECT)/near-infrared (NIR) fluorescence imaging to detect SLNs.Methods: Indocyanine green-human serum albumin (ICG-HSA) nanoparticles (NPs) were synthesized by ICG-induced HSA self-assembly and further 99mTc-labeling via a one-step, facile hospital-available method. After injecting 99mTc-ICG-HSA into the rats’ forepaw pads, the rats’ draining axillary lymph nodes were visualized by preoperative mapping with SPECT/CT and intraoperative biopsy with NIR fluorescence. The axillary lymph nodes of rats were identified by pathology and fluorescent staining after execution. Additionally, its toxicity testing and comparison with 99mTc-sulfur colloid imaging were also explored.Results: The study reported a self-assembled 99mTc-ICG-HSA with a high radiochemical yield (85.6 ± 3.8%). Compared with conventional 99mTc-sulfur colloid, 99mTc-ICG-HSA NPs showed faster SLN identification, higher renal clearance, and lower hepatic retention. Furthermore, NIRF imaging allowed for the accurate visualization of the SLN and guided SLN biopsy intraoperatively. Notably, the 99mTc-ICG-HSA NPs were composed of hospital-available drugs and isotope, which are safe for acute toxicity evaluation by a certified institute.Conclusion: The proposed 99mTc-ICG-HSA NPs are safe and capable of noninvasive SLN identification and biopsy guidance with multi-modal imaging strategies and could be a promising tool for clinically assisted SLN biopsy. Keywords: image-guided surgery, indocyanine green, albumin, fluorescence imaging, near-infrared, single-photon emission computed tomography

Li-Zhi Chen,1,2,&ast; Han-Shu Li,1,2,&ast; Gao-Wei Han,1,2,&ast; Yong Su,1,3 Tian-Zhu Lu,1– 3 Hong-Hui Xie,1,3 Xiao-Chang Gong,1,3 Jin-Gao Li,1,3 Yun Xiao1,3 1NHC Key Laboratory of Personalized Diagnosis and Treatment of Nasopharyngeal Carcinoma, Jiangxi Clinical Research Center for Cancer, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330029, People’s Republic of China, Nanchang, Jiangxi, 330029, People’s Republic of China; 2Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330029, People’s Republic of China; 3Department of Radiation Oncology, Jiangxi Clinical Research Center for Cancer, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330029, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jin-Gao Li; Yun Xiao, Department of Radiation Oncology, Jiangxi Clinical Research Center for Cancer, Jiangxi Cancer Hospital, The Second Affiliated Hospital of Nanchang Medical College, 519 East Beijing Road, Nanchang, Jiangxi, 330029, People’s Republic of China, Tel +86-791-88313632, Fax +86-791-8321742, Email lijingao@hotmail.com; 813898920@qq.comPurpose: This study aimed to assess the prognostic and predictive value of a circulating hematological signature (CHS) and to develop a CHS-based nomogram for predicting prognosis and guiding individualized chemotherapy in non-metastatic nasopharyngeal carcinoma (NPC) patients.Patients and Methods: NPC patients were recruited between January 2014 and December 2017 at the Jiangxi Cancer Hospital. The CHS was constructed based on a series of hematological indicators. The nomogram was developed by CHS and clinical factors.Results: A total of 779 patients were included. Three biomarkers were selected by least absolute shrinkage and selection operator regression, including prognostic nutritional index, albumin-to-fibrinogen ratio, and prealbumin-to-fibrinogen ratio, were used to construct the CHS. The patients in the low-CHS group had better 5-year DMFS and OS than those in the high-CHS group in the training (DMFS: 85.0% vs 56.6%, p< 0.001; OS: 90.3% vs 65.4%, p< 0.001) and validation cohorts (DMFS: 92.3% vs 43.6%, p< 0.001; OS: 92.1% vs 65.5%, p< 0.001). The nomogram_CHS showed better performance than clinical stage in predicting distant metastasis (concordance index: 0.728 vs 0.646). In the low-TRS (total risk scores) group, the patients received RT alone, CCRT and IC plus CCRT had similar 5-year DMFS and OS (p> 0.05). In the middle-TRS group, the patients received RT alone had worse 5-year DMFS (58.7% vs 80.8% vs 90.8%, p=0.002) and OS (75.0% vs 94.1% vs 95.0%, p=0.001) than those received CCRT or IC plus CCRT. In the high-TRS group, the patients received RT alone and CCRT had worse 5-year DMFS (18.6% vs 31.3% vs 81.5%, p< 0.001) and OS (26.9% vs 53.2% vs 88.8%, p< 0.001) than those received IC plus CCRT.Conclusion: The developed nomogram_CHS had satisfactory prognostic accuracy in NPC patients and may individualize risk estimation to facilitate the identification of suitable IC candidates.Keywords: nasopharyngeal carcinoma, circulating hematological signature, induction chemotherapy, distant metastasis-free survival, overall survival

Jinyu Hu,1,&ast; Yuanyi Xiao,1,&ast; Guilin Jiang,2 Xiaorong Hu2 1School of Graduate and Clinical Medicine, Jiangxi University of Chinese Medicine, Nanchang City, People’s Republic of China; 2Department of Clinical Medicine, The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaorong Hu; Guilin Jiang, The Affiliated Hospital of Jiangxi University of Chinese Medicine, Nanchang City, Jiangxi Province, People’s Republic of China, Email 414496410@qq.com; j1333070957788@163.comBackground: Acupuncture is considered an important means of analgesic, which has been widely used in chronic pelvic pain syndrome (CPPS) management and treatment in recent years, published a large number of related documents. However, the relevant literature in this field has not been summarized and quantitatively analyzed. Therefore, this study aims to analyze the hotspots and predicting future research trends of acupuncture on pelvic pain syndrome.Methods: Search for the relevant publications of the web of science database from 2000 to 2022 about the treatment of acupuncture on chronic pelvic pain syndrome. The Citespace software and VosViewer software are used to analyze the visualization of the countries, institutions, authors, keywords and references and references in the literature.Results: A total of 173 publications were included. The annual number of essays gradually showed an overall growth trend over time. Medicine magazine is the most published journal in this field. J UROLOGY and Acupunct Med are the most cited journals and the most influential magazines; The most active and influential country is China, and the most produced institutions are Beijing University of Chinese Medicine; The most produced authors are Liu Zhishun. The most cited and most influential authors are Nickel JC and Armour M; keywords and cited reference analysis show that the quality of life, mechanism research, alternative medicine and electro-acupuncture will be the scientific hotspot of acupuncture treatment for chronic pelvic pain syndrome.Conclusion: This study shows that acupuncture on CPPS is increasingly valued and recognized. The future research hotspots will focus on the effects and mechanisms. In the future, more high-quality animal basic research will be required to explore the exact mechanism of acupuncture on CPPS. In addition, different parameters of acupuncture such as electric-acupuncture, stimulating frequency, duration and strength are also the focus of future research. More clinical trials are required to verify its safety and effectiveness.Keywords: acupuncture, chronic pelvic pain syndrome, bibliometrics, CiteSpace

Yongqiang Xiao,&ast; Guoqing Zhu,&ast; Jin Xie,&ast; Laihui Luo, Wei Deng, Liucong Lin, Jiahao Tao, Zhigao Hu, Renfeng Shan Department of General Surgery, the First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhigao Hu; Renfeng Shan, Department of General Surgery, the First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86-791-88692522, Email 854189568@qq.com; srf1978@126.comPurpose: This study aimed to assess the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in patients with unresectable hepatocellular carcinoma (u-HCC) treated with hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab.Patients and Methods: We conducted a retrospective cohort study involving patients diagnosed with u-HCC who underwent HAIC combined with lenvatinib and camrelizumab. Patients were stratified into two cohorts using the median NLR as the cutoff point. We then assessed treatment response, overall survival (OS), progression-free survival (PFS), and adverse events in these patient groups.Results: Between October 2020 and April 2022, a total of 88 patients were enrolled in the study. The overall cohort exhibited a median PFS of 7.9 months, while the median OS was not reached, and a median NLR of 3.46. Notably, the group with NLR< 3.46 demonstrated significantly superior OS (not reached vs 9.6 months, p = 0.017) and PFS (18.3 vs 5.3 months, p = 0.0015) compared to the NLR≥ 3.46 group. Furthermore, multivariate analysis revealed that an alpha-fetoprotein (AFP) ≥ 400 ng/mL [hazard ratio (HR), 2.133; 95% confidence interval (CI), 1.102– 4.126; p = 0.024], Barcelona Clinical Hepatocellular Carcinoma (BCLC) stage C (HR, 2.319; 95% CI, 1.128– 4.764; p = 0.022), and NLR ≥ 3.46 (HR, 2.35; 95% CI, 1.239– 4.494; p = 0.009) were identified as independent risk factors for OS. Additionally, multivariate analysis demonstrated that AFP ≥ 400 ng/mL, BCLC stage C, and NLR ≥ 3.46 were independent negative factors of PFS.Conclusion: NLR can be associated with outcomes in patients with u-HCC treated with HAIC combined with lenvatinib and camrelizumab.Keywords: unresectable hepatocellular carcinoma, neutrophil-to-lymphocyte ratio, hepatic arterial infusion chemotherapy, lenvatinib, camrelizumab

Shenghua Shen, Yuan Xiao Department of Pulmonary and Critical Care Medicine, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213004, People’s Republic of ChinaCorrespondence: Yuan Xiao, Department of Pulmonary and Critical Care Medicine, The Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, 29 Xinglong Lane, Tianning District, Changzhou, Jiangsu, 213004, People’s Republic of China, Tel +86 13775118679 ; +86 519-88125317, Email yuanyuanxiao12@outlook.comPurpose: This study was to evaluate the association between C-reactive protein (CRP) to albumin (ALB) ratio (CAR) and the risk of mortality in patients with chronic obstructive pulmonary disease (COPD).Methods: In this retrospective cohort study, clinical data were extracted from the National Institutes of Health National Health and Nutrition Examination Survey (NHANES) database between 2007 and 2010. Cox proportional hazard regressions were performed to assess the association between CAR and 5-year mortality in COPD patients. Subgroup analyses were applied to identify the consistency of the association based on the severity of COPD, gender, body mass index (BMI), smoking status, cardiovascular disease (CVD), and chronic kidney disease (CKD), and diabetes. The area under the curve (AUC) of the receiver operator characteristic (ROC) curve analysis was used to evaluate the predictive performance of CAR.Results: A total of 1210 COPD patients were included, of which 110 COPD patients (9.09%) had 5-year mortality. The mean follow-up was 57.76 (0.33) months. A higher CAR was associated with an increased risk of 5-year mortality in COPD patients [hazard ratio (HR): 1.94, 95% confidence interval (CI): 1.07 to 3.50, P =0.029)]. Subgroup analysis showed that the association between CAR and mortality was especially suitable for COPD patients with mild COPD, in COPD patients who were still smoking, in COPD patients with BMI

Ning Zhang,1,&ast; Tong Liu,1,&ast; Jianan Wang,2,&ast; Yingying Xiao,1 Ying Zhang,1 Jun Dai,1 Zhihong Ma,1,3 Donglai Ma4 1School of Basic Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China; 2Graduate School, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China; 3Hebei Key Laboratory of Integrative Medicine on Liver-Kidney Patterns, Shijiazhuang, Hebei, 050200, People’s Republic of China; 4School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihong Ma; Donglai Ma, Hebei University of Chinese Medicine, Xingyuan Road 3, Shijiazhuang, Hebei, 050200, People’s Republic of China, Tel +86 31189926238, Email mazh1969@163.com; mdl_hebei@aliyun.comBackground: Metabolic associated fatty liver disease (MAFLD) is a chronic disease characterized by excessive lipid deposition in the liver without alcohol or other clear liver-damaging factors. AMP-activated protein kinase (AMPK)/silencing information regulator (SIRT)1 signaling pathway plays an important role in MAFLD development. Si-Ni-San (SNS), a traditional Chinese medicine, has shown reducing hepatic lipid deposition in MAFLD rats, however, the underlying mechanisms of SNS are barely understood.Purpose: The aim of this research was to investigate the mechanisms of SNS in reducing hepatic lipid deposition in MAFLD rats by regulating AMPK/SIRT1 signaling pathways.Methods: The components of SNS were determined by high performance liquid chromatography with mass spectrometry (HPLC-MS) analysis. MAFLD rats were induced by high-fat and high-cholesterol diet (HFHCD), and treated by SNS. SNS-containing serum and Compound C (AMPK inhibitor) were used to treat palmitic acid (PA)-induced HepG2 cells. To elucidate the potential mechanism, lipid synthesis-related proteins (SREBP-1c and FAS), fatty acid oxidation (PPARα and CPT-1), and AMPK/SIRT1 signaling pathway (p-AMPK and SIRT1) were assessed by Western blot.Results: SNS improved serum lipid levels, liver function and reduced hepatic lipid deposition in MAFLD rats. SNS-containing serum reduced lipid deposition in PA-induced HepG2 cells. SNS could up-regulate protein expressions of PPARα, CPT-1, p-AMPK and SIRT1, and down-regulate protein expressions of SREBP-1c and FAS. Similar effects of SNS-containing serum were observed in PA-induced HepG2 cells. Meanwhile, Compound C weakened the therapeutic effects of SNS-containing serum on lipid deposition.Conclusion: SNS could reduce hepatic lipid deposition by inhibiting lipid synthesis and promoting fatty acid oxidation, which might be related with activating the AMPK/SIRT1 signaling pathway. This study could provide a theoretical basis for the clinical use of SNS to treat MAFLD.Graphical Abstract: Keywords: Si-Ni-San, MAFLD, lipid deposition, lipid synthesis, fatty acid oxidation, AMPK

Linghang Zhou, Jin Tan, Yuzhe Dai, Keke Zhu, Yanbo Xiao, Dan Wu, Zongkang Wang, Yisi Tan, Yijie Qin Department of Stomatology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of ChinaCorrespondence: Jin Tan, Department of Stomatology, The First Affiliated Hospital of Hunan University of Chinese Medicine, 95 Shaoshan Middle Road, Changsha, Hunan, People’s Republic of China, Email 310176@hnucm.edu.cnPurpose: Arecoline is one of the main toxic components of arecoline to cause oral mucosal lesions or canceration, which seriously affects the survival and life quality of patients. This study analyzed the mechanism of Jiawei Danxuan Koukang (JDK) in alleviating arecoline induced oral mucosal lesions, to provide new insights for the treatment of oral submucosal fibrosis (OSF) or cancerosis.Methods: Metabolomics was applied to analyze the composition of JDK and serum metabolites. The active ingredients of JDK were analyzed by the combined ultra-high performance liquid chromatography and mass spectrometry. The target network of JDK, metabolites and OSF was analyzed by network pharmacology, and molecular docking. Oral mucosal lesions and fibrosis were analyzed by HE and Masson staining. Cell differentiation, proliferation and apoptosis were detected. The expressions of α-SMA, Collagen I, Vimentin, Snail, E-cadherin, AR and NOTCH1 were detected by Western blot.Results: Arecoline induced the gradual atrophy and thinning of rat oral mucosal, collagen accumulation, the increase expressions of fibrosis-related proteins and Th17/Treg ratio. JDK inhibited arecoline-induced oral mucosal lesions and inflammatory infiltration. Arecoline induced changes of serum metabolites in Aminoacyl-tRNA biosynthesis, Alanine, aspartate and glutamate metabolism and Arginine biosynthesis pathways, which were reversed by M-JDK. Quercetin and AR were the active ingredients and key targets of JDK, metabolites and OSF interaction. Arecoline promoted the expression of AR protein, and the proliferation of oral fibroblasts. Quercetin inhibited the effect of arecoline on oral fibroblasts, but was reversed by AR overexpression. Arecoline induced NOTCH1 expression in CAL27 and SCC-25 cells, and promoted cell proliferation, but was reversed by M-JDK or quercetin.Conclusion: JDK improved the arecoline-induced OSF and serum metabolite functional pathway. Quercetin targeted AR protein to improve arecoline-induced OSF. JDK and quercetin inhibited arecoline-induced NOTCH1 protein expression in CAL27 and SCC-25 cells to play an anti-oral cancer role.Graphical Abstract: Keywords: oral submucous fibrosis, Jiawei Danxuan Koukang, arecoline, pharmacology, metabolomics

Xingrui Li,1,&ast; Yue Wang,1,&ast; Denghao Huang,1 Zhonghao Jiang,1 Zhiyu He,1 Maoxuan Luo,2 Jie Lei,1,2 Yao Xiao1– 3 1Oral & Maxillofacial Reconstruction and Regeneration of Luzhou Key Laboratory, the Affiliated Stomatological Hospital of Southwest Medical University, Institute of Stomatology, Southwest Medical University, Luzhou, People’s Republic of China; 2Department of Orthodontics, the Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, People’s Republic of China; 3Department of Chengbei Outpatient, the Affiliated Stomatological Hospital of Southwest Medical University, Luzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yao Xiao; Jie Lei, Email orthoxiaoyao@outlook.com; 1067233579@qq.comAbstract: The critical challenges in repairing oral soft and hard tissue defects are infection control and the recovery of functions. Compared to conventional tissue regeneration methods, nano-bioactive materials have become the optimal materials with excellent physicochemical properties and biocompatibility. Dental-derived mesenchymal stem cells (DMSCs) are a particular type of mesenchymal stromal cells (MSCs) with great potential in tissue regeneration and differentiation. This paper presents a review of the application of various nano-bioactive materials for the induction of differentiation of DMSCs in oral and maxillofacial restorations in recent years, outlining the characteristics of DMSCs, detailing the biological regulatory effects of various nano-materials on stem cells and summarizing the material-induced differentiation of DMSCs into multiple types of tissue-induced regeneration strategies. Nanomaterials are different and complementary to each other. These studies are helpful for the development of new nanoscientific research technology and the clinical transformation of tissue reconstruction technology and provide a theoretical basis for the application of nanomaterial-modified dental implants. We extensively searched for papers related to tissue engineering bioactive constructs based on MSCs and nanomaterials in the databases of PubMed, Medline, and Google Scholar, using keywords such as “mesenchymal stem cells”, “nanotechnology”, “biomaterials”, “dentistry” and “tissue regeneration”. From 2013 to 2023, we selected approximately 150 articles that align with our philosophy.Keywords: nano-material, stem cell, tissue reconstruction, cell differentiation

Zhimin Shen,1,&ast; Shiping Chen,2,&ast; Yiqiang Duan,1 Juan Yu,3 Dayang Pan,4 Jiaxin Dong,1 Shanglong Wang,1 Qizhe Li,1 Yinlong Xiao,1 Xun Yuan1 1Department of Orthopedics, The Affiliated Hospital of Guizhou Medical University, Guiyang City, People’s Republic of China; 2Department of Orthopedics, The No.1 People’s Hospital of Qingzhen, Qingzhen City, People’s Republic of China; 3The Affiliated Stomatological Hospital of Guizhou Medical University, Guiyang City, People’s Republic of China; 4The 4th People’s Hospital of Guiyang, Guiyang City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yiqiang Duan, Department of Orthopedics, The Affiliated Hospital of Guizhou Medical University, No. 28, Guiyijie Road, Guiyang City, Guizhou Province, 550004, People’s Republic of China, Email duanyiqiang0114@163.com Juan Yu, The Affiliated Stomatological Hospital of Guizhou Medical University, No. 9, Beijing Road, Guiyang City, Guizhou Province, 550004, People’s Republic of China, Email 416876483@qq.comObjective: To explore the application value of adjustable skin stretchers for repairing skin wound defects.Methods: Twenty patients with skin defects were included in this study. The largest defect was measured to be 45.4 cm × 13.3 cm (length × width) and the smallest one was 4.4 cm × 3.2 cm (length × width). All patients were subjected to adjustable skin stretchers and the short- and long-term clinical efficacy was evaluated.Results: The wounds of all enrolled patients were healed completely except for one patient with a dorsal foot infection (the patient requested to return to the local county hospital for further treatment), with a total satisfaction of 100%. Postoperative 3-month follow-up showed scar formation, a little local hyperpigmentation, normal skin elasticity, and intact organs of involved cases, thus signifying the significant impact of adjacent joint activities.Conclusion: Adjustable skin stretchers can accurately control the tension on wound margins, breaking the limitation of previous stretchers to provide objective quantitative indicators for clinical application. These stretchers are characterized by high use-value and are worth promoting.Keywords: adjustable skin stretchers, wound-related defects, wound repair

Fei Wu,1,2,&ast; Haitao Sun,1,2,&ast; Zhang Shi,1,2 Changwu Zhou,1– 3 Peng Huang,1,2 Yuyao Xiao,1,2 Chun Yang,1,2 Mengsu Zeng1– 3 1Department of Radiology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Cancer Center, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Shanghai Institute of Medical Imaging, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mengsu Zeng, Department of Radiology, Zhongshan Hospital, Fudan University; Shanghai Institute of Medical Imaging, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86 13501922963, Email zeng.mengsu@zs-hospital.sh.cn Chun Yang, Department of Radiology, Zhongshan Hospital, Fudan University, No. 180 Fenglin Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86 18702135336, Email dryangchun@hotmail.comObjective: To determine the preoperative clinicoradiological factors to predict microvascular invasion (MVI) in patients with resectable multinodular hepatocellular carcinoma (mHCC), and further to establish and validate a stratified risk scoring system.Methods: Two hundred and seventy-three patients with pathologically confirmed mHCC (≥ 2 lesions) without major vascular invasion and biliary tract tumor thrombosis, who underwent preoperative contrast-enhanced MRI and hepatectomy, were consecutively enrolled (training/validation cohort=193/80). Preoperative clinicoradiological variables were collected and analyzed. The multivariable logistic regression was performed to determine the independent predictors of MVI and create a risk score system. The C-index, calibration curve and decision curve were used to evaluate the performance of the risk score. A risk score-based prognostic stratification system was performed in mHCC patients. The risk score system was further verified in the validation cohort.Results: AFP > 400 ng/mL, presence of satellite nodule, mosaic architecture and increased total tumor diameter were independent predictors of MVI while fat in mass was an independent protective factor of MVI. The risk score yielded satisfactory C-index values (training/validation cohort: 0.777/0.758) and fitted well in calibration curves. Decision curve analysis further confirmed its clinical utility. Based on the risk score, mHCC patients were stratified into high-/low-MVI-risk subgroups with significantly different recurrence-free survival (both P < 0.001).Conclusion: The presented risk score incorporating clinicoradiological parameters could stratify mHCC patients into high-risk and low-risk subgroups and predict prognosis in patients with resectable mHCC.Keywords: hepatocellular carcinoma, prognosis, magnetic resonance imaging, statistical model

Yu Gu,1,2,&ast; Pei Li,3,&ast; Yongying Xiao,2 Jiaojiao Zhang,2 Xin Su1,2 1Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Jinling Hospital, Nanjing, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Taikang Xianlin Drum Tower Hospital, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xin Su, Nanjing Drum Tower Hospital, 321 Zhongshan Road, Nanjing, 210008, People’s Republic of China, Email suxinjs@163.comBackground: Pentraxin 3 (PTX3) is an acute-phase protein and an important inflammatory mediator. We hypothesized plasma PTX3 could be a valuable diagnostic biomarker in acute exacerbation of chronic obstructive pulmonary disease (AECOPD).Methods: In this prospective controlled study, 458 COPD patients and 71 healthy controls from May 2019 to December 2020 in two hospitals were enrolled. COPD patients were divided into AECOPD group (n = 173) and stable COPD group (n = 285). AECOPD patients were subdivided into mild or moderate group (n = 43) and severe group (n = 130) based on severity. Plasma PTX3 levels were detected by ELISA.Results: Plasma PTX3 levels were significantly higher in AECOPD (2.8 ng/mL) compared to stable COPD (0.87 ng/mL) and healthy controls (0.83 ng/mL). In the analysis of AECOPD subgroups, plasma PTX3 level of severe group (4.51 ng/mL) was significantly higher than that of mild or moderate group (1.25 ng/mL). Patients with respiratory failure had higher PTX3 than those without respiratory failure. No difference was observed between stable COPD patients and healthy controls. ROC analysis showed that plasma PTX3 had a considerable ability to distinguish AECOPD from stable COPD [AUC: 0.85, 95% CI (0.81– 0.88), P < 0.0001; cut-off 1.25 ng/mL, sensitivity 77.5%, specificity 74%]. AUC of PTX3 was better than CRP regarding diagnosis of AECOPD. Combination of PTX3 and CRP was superior to either of them in diagnosing AECOPD.Conclusion: Plasma PTX3 levels were significantly higher in AECOPD than stable COPD. The level was associated with the severity of exacerbation. Plasma PTX3 has potential value as a biomarker to diagnose and evaluate AECOPD.Keywords: pentraxin 3, AECOPD, diagnosis, severity, C-reactive protein

Wenting Tu,1,&ast; Taohu Zhou,1,2,&ast; Xiuxiu Zhou,1,&ast; Yanqing Ma,3 Shaofeng Duan,4 Yun Wang,1 Xiang Wang,1 Tian Liu,1 HanXiao Zhang,5 Yan Feng,1 Wenjun Huang,2 Xinang Jiang,1 Yi Xiao,1 Shiyuan Liu,1 Li Fan1 1Department of Radiology, Second Affiliated Hospital of Naval Medical University, Shanghai, 200003, People’s Republic of China; 2School of Medical Imaging, Weifang Medical University, Weifang, Shandong, 261053, People’s Republic of China; 3Department of Radiology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital of Hangzhou Medical College, Hangzhou, Zhejiang, 310000, People’s Republic of China; 4GE Healthcare, Precision Health Institution, Shanghai, 210000, People’s Republic of China; 5School of Medical Imaging, Xuzhou Medical University, Xuzhou, Jiangsu, 221018, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shiyuan Liu; Li Fan, Department of Radiology, Second Affiliated Hospital, Naval Medical University, No. 415 Fengyang Road, Shanghai, 200003, People’s Republic of China, Tel +86 21 81886012 ; +86 21 81886018, Fax +86 21 63587668, Email cjr.liushiyuan@vip.163.com; fanli0930@163.comPurpose: This study aimed to screen out computed tomography (CT) morphological features and clinical characteristics of patients with lung cancer to identify chronic obstructive pulmonary disease (COPD). Further, we aimed to develop and validate different diagnostic nomograms for predicting whether lung cancer is comorbid with COPD.Patients and Methods: This retrospective study examined data from 498 patients with lung cancer (280 with COPD, 218 without COPD; 349 in training cohort, 149 in validation cohort) from two centers. Five clinical characteristics and 20 CT morphological features were evaluated. Differences in all variables were assessed between COPD and non-COPD groups. Models were developed using multivariable logistic regression to identify COPD, including clinical, imaging, and combined nomograms. Receiver operating characteristic curves were used to evaluate and compare the performance of nomograms.Results: Age, sex, interface, bronchus cutoff sign, spine-like process, and spiculation sign were independent predictors of COPD in patients with lung cancer. In the training and validation cohorts, the clinical nomogram showed good performance to predict COPD in lung cancer patients (areas under the curves [AUCs] of 0.807 [95% CI, 0.761– 0.854] and 0.753 [95% CI, 0.674– 0.832]); while the imaging nomogram showed slightly better performance (AUCs of 0.814 [95% CI, 0.770– 0.858] and 0.780 [95% CI, 0.705– 0.856]). For the combined nomogram generated with clinical and imaging features, the performance was further improved (AUC=0.863 [95% CI, 0.824– 0.903], 0.811 [95% CI, 0.742– 0.880] in the training and validation cohort). At 60% risk threshold, there were more true negative predictions (48 vs 44) and higher accuracy (73.15% vs 71.14%) for the combined nomogram compared with the clinical nomogram in the validation cohort.Conclusion: The combined nomogram developed with clinical and imaging features outperformed clinical and imaging nomograms; this provides a convenient method to detect COPD in patients with lung cancer using one-stop CT scanning.Keywords: chronic obstructive pulmonary disease, lung cancer, computed tomography, chest imaging, nomogram

Yunbo Chen,1,2 Yuanyuan Dai,3 Yizheng Zhou,4 Ying Huang,5 Yan Jin,6 Yan Geng,7 Bing Ji,8 Rong Xu,9 Wencheng Zhu,10 Shuyan Hu,11 Zhuo Li,12 Jinhua Liang,13 Yonghong Xiao1,2 1State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou, People’s Republic of China; 3Clinical Laboratory, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, People’s Republic of China; 4Clinical Laboratory, Jingzhou Central Hospital, Jingzhou, People’s Republic of China; 5Clinical Laboratory, First Affiliated Hospital of Anhui Medical University, Hefei, People’s Republic of China; 6Clinical Laboratory, Shandong Provincial Hospital, Jinan, People’s Republic of China; 7Clinical Laboratory, The Second Affiliated Hospital of Xi’an Jiaotong University, Xi’an, People’s Republic of China; 8Clinical Laboratory, Affiliated Hospital of Binzhou Medical College, Binzhou, People’s Republic of China; 9Clinical Laboratory, People’s Hospital of Yichun City, Yichun, People’s Republic of China; 10Clinical Laboratory, Lu’an Civil Hospital, Lu’an, People’s Republic of China; 11Clinical Laboratory, People’s Hospital of Qingyang, Qingyang, People’s Republic of China; 12Clinical Laboratory, The First Affiliated Hospital of Xi’an Medical University, Xi’an, People’s Republic of China; 13Clinical Laboratory, The Affiliated Hongqi Hospital of Mudanjiang Medicine College, Mudanjiang, People’s Republic of ChinaCorrespondence: Yonghong Xiao, The First Affiliated Hospital, School of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou, Zhejiang, 310003, People’s Republic of China, Tel/Fax +86 571 87236421, Email xiao-yonghong@163.comPurpose: Blood cultures (BCs) are essential laboratory tests for diagnosing blood stream infections. BC diagnostic improvement depends on several factors during the preanalytical phase outside of innovative technologies. In order to evaluate the impact of an educational program on BC quality improvement, a total of 11 hospitals across China were included from June 1st 2020 to January 31st 2021.Methods: Each hospital recruited 3 to 4 wards to participate. The project was divided into three different periods, pre-implementation (baseline), implementation (educational activities administered to the medical staff) and post-implementation (experimental group). The educational program was led by hospital microbiologists and included professional presentations, morning meetings, academic salons, seminars, posters and procedural feedback.Results: The total number of valid BC case report forms was 6299, including 2739 sets during the pre-implementation period and 3560 sets during the post-implementation period. Compared with the pre-implementation period, some indicators, such as the proportion of patients who had 2 sets or more, volume of blood cultured, and BC sets per 1000 patient days, were improved in the post-implementation period (61.2% vs 49.8%, 18.56 vs 16.09 sets, and 8.0 vs 9.0mL). While BC positivity and contamination rates did not change following the educational intervention (10.44% vs 11.97%, 1.86% vs 1.94%, respectively), the proportion of coagulase negative staphylococci-positive samples decreased in BSI patients (6.87% vs 4.28%).Conclusion: Therefore, medical staff education can improve BC quality, especially increasing volume of blood cultured as the most important variable to determine BC positivity, which may lead to improved BSI diagnosis.Keywords: blood culture, bloodstream infection, medical education, medical staff, quality improvement

Youling Fang,1,2 Qiaoshi Zhong,1 Yanhui Chen,1 Yaping Hang,1 Xueyao Fang,1 Yanping Xiao,1 Xingwei Cao,1 Hongying Zhu,3 Hong Luo,1 Suqin Peng,1 Shumin Gu,1 Fuxing Li,1 Junqi Zhu,1 Jianqiu Xiong,4 Longhua Hu1 1Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2School of Public Health, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Clinical Laboratory of Ganzhou People’s Hospital, Ganzhou, Jiangxi, People’s Republic of China; 4Department of Nursing, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of ChinaCorrespondence: Longhua Hu; Jianqiu Xiong, Email longhuahu@163.com; 1773014059@qq.comObjective: To analyze the clinical characteristics, outcomes, and risk factors of patients treated with ceftazidime/avibactam, polymyxin, or tigecycline (CPT) compared with those receiving a conventional therapy (CT) (ie, imipenem, levofloxacin, or gentamicin).Methods: A single-center retrospective cohort study included patients with carbapenem-resistant Klebsiella pneumoniae bloodstream infection (CRKP-BSI) treated at one Chinese tertiary hospital between March 2012 and November 2022 was performed. Clinical characteristics, outcomes, and risk factors of patients treated with CPT or CT were compared. Predictors of 30-day mortality of patients with CRKP-BSI were also analysed in our study.Results: Among 184 recruited patients with CRKP-BSI, 39.7% (73/184) were treated with CPT, while 60.3% (111/184) were treated with CT. Compared to patients treated with CT, patients treated with CPT had worse conditions, as evidenced by a higher rate of underlying diseases and invasive procedures; however, they also had a better prognosis and lower rates of 14-day treatment failure (p = 0.024). In addition, univariate analysis and multivariate analysis showed that SOFA score [odds ratio (OR) = 1.310, 95% confidence interval (CI) 1.157– 1.483; p < 0.001] and cold weather (OR = 3.658, 95% CI 1.474– 9.081; p = 0.005) were independent risk factors for 30-day mortality.Conclusion: Compared to CRKP-BSI patients treated with CT, patients treated with CPT had worse conditions but better prognoses. CRKP-BSI occurred more frequently in hot weather; however, higher 30-day mortality was associated with cold weather. A randomized trial is needed to confirm these observational results.Keywords: carbapenem-resistantKlebsiella pneumoniae, polymyxin, tigecycline, ceftazidime/avibactam, bloodstream infection, hot weather, cold weather

Shumin Gu,1,* Jianqiu Xiong,2,* Suqin Peng,1 Longhua Hu,1 Hongying Zhu,3 Yanping Xiao,1 Hong Luo,1 Yaping Hang,1 Yanhui Chen,1 Xueyao Fang,1 Xingwei Cao,1 Youling Fang,1 Fuxing Li,1 Junqi Zhu,1 Qiaoshi Zhong1 1Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Departmentof Nursing, The Second Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 3Clinical Laboratory of Ganzhou People’s Hospital, Ganzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Qiaoshi Zhong, Department of Jiangxi Provincial Key Laboratory of Medicine, Clinical Laboratory of the Second Affiliated Hospital of Nanchang University, Mingde Road No. 1, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86151-8047-5673, Email zhong20000947@sina.comObjective: This study aimed to determine the clinical features, risk factors, and effective antimicrobial therapy for Carbapenem-resistant Acinetobacter baumannii (CRAB) bloodstream infection (BSI).Methods: This was a retrospective analysis of data from patients with CRAB bacteremia in a Chinese tertiary hospital between January 2012 and October 2021. Risk factors, predictors of 30-day mortality, and effective antimicrobial therapy for CRAB BSI were identified using logistic and cox regression analyses.Results: Data from 276 patients with Acinetobacter baumannii (AB) BSI were included, of whom 157 (56.9%) had CRAB BSI. The risk factors that were significantly associated with CRAB BSI included previous intensive care unit (ICU) stay (P < 0.001), immunocompromised status (P < 0.001), cephalosporin use (P = 0.014), and fluoroquinolone use (P = 0.007). The 30-day mortality of the CRAB BSI group was 49.7% (78/157). ICU stay after BSI (P = 0.047), sequential organ failure assessment (SOFA) score ≥ 10 (P < 0.001), and multiple organ failure (MOF) (P = 0.037) were independent predictors of 30-day mortality. Among antibiotic strategies for the treatment of patients with CRAB BSI, we found that definitive regimens containing cefoperazone/sulbactam were superior to those without cefoperazone/sulbactam in reducing the 30-day mortality rate (25.4% vs 53.4%, P = 0.005). After propensity score matching, we observed a significant increase in the 30-day mortality (77.8%vs 33.3%, P = 0.036) in patients receiving tigecycline monotherapy compared to those receiving cefoperazone/sulbactam monotherapy. The mortality rate of patients receiving tigecycline with cefoperazone/sulbactam was also higher than that of patients receiving cefoperazone-sulbactam monotherapy; however, the difference was not significant (28.6%vs 19.0%, P = 0.375).Conclusion: The severity of patient conditions was significantly associated with mortality in patients with CRAB BSI. Those Patients treated with cefoperazone/sulbactam had better clinical prognoses, and tigecycline should be used with caution.Keywords: carbapenem-resistant, Acinetobacter baumannii, bacteremia, tigecycline, cefoperazone/sulbactam

Dengming Lai,1,&ast; Kun Zhu,2,&ast; Sisi Li,3,&ast; Yi Xiao,1 Qi Xu,4 Yisheng Sun,5 Pingping Yao,5 Daqing Ma,6,7 Qiang Shu7 1Department of Neonatal Surgery, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of China; 2Department of Pathology, The Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of China; 3School of Medicine, Hangzhou City University, Hangzhou, People’s Republic of China; 4School of Laboratory Medicine and Bioengineering, Hangzhou Medical College, Hangzhou, People’s Republic of China; 5Key Laboratory of Vaccine, Prevention and Control of Infectious Disease of Zhejiang Province, Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, People’s Republic of China; 6Division of Anaesthetics, Pain Medicine & Intensive Care, Department of Surgery & Cancer, Faculty of Medicine, Imperial College London, Chelsea & Westminster Hospital, London, UK; 7Department of Thoracic and Cardiovascular Surgery, Children’s Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiang Shu, Department of Thoracic and Cardiovascular Surgery, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310052, People’s Republic of China, Tel +86-13906500193, Email shuqiang@zju.edu.cn Dengming Lai, Department of Neonatal Surgery, Children’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310052, People’s Republic of China, Tel +86-13567164728, Email dengming_lai@zju.edu.cnBackground: SARS-CoV-2-induced acute lung injury but its nucleocapsid (N) and/or Spike (S) protein involvements in the disease pathology remain elusive.Methods: In vitro, the cultured THP-1 macrophages were stimulated with alive SARS-CoV-2 virus at different loading dose, N protein or S protein with/without TICAM2-siRNA, TIRAP-siRNA or MyD88-siRNA. The TICAM2, TIRAP and MyD88 expression in the THP-1 cells after N protein stimulation were determined. In vivo, naïve mice or mice with depletion macrophages were injected with N protein or dead SARS-CoV-2. The macrophages in the lung were analyzed with flow cytometry, and lung sections were stained with H&E or immunohistochemistry. Culture supernatants and serum were harvested for cytokines measurements with cytometric bead array.Results: Alive SARS-CoV-2 virus or N protein but not S protein induced high cytokine releases from macrophages in a time or virus loading dependent manner. MyD88 and TIRAP but not TICAM2 were highly involved in macrophage activation triggered by N protein whilst both inhibited with siRNA decreased inflammatory responses. Moreover, N protein and dead SARS-CoV-2 caused systemic inflammation, macrophage accumulation and acute lung injury in mice. Macrophage depletion in mice decreased cytokines in response to N protein.Conclusion: SARS-CoV-2 and its N protein but not S protein induced acute lung injury and systemic inflammation, which was closely related to macrophage activation, infiltration and release cytokines.Keywords: SARS-CoV-2, S protein, N protein, macrophage, cytokine, acute lung injury

Tianshui Niu,1,2,&ast; Lihua Guo,2,&ast; Xiaoyang Kong,2,&ast; Fei He,1 Chuhui Ru,1 Yonghong Xiao2 1Department of Respiratory and Critical Care Medicine, Affiliated Hangzhou Chest Hospital, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of China; 2State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghong Xiao, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang, 310003, People’s Republic of China, Tel/Fax +86 571 87236421, Email xiaoyonghong@zju.edu.cnBackground: Different sequence types of Acinetobacter baumannii (AB) have their own epidemiological characteristics, drug resistance, and toxicity.Methods: AB bloodstream infection (BSI) in the First Affiliated Hospital of Medical College of Zhejiang University from January 2012 to December 2017 were classified by multilocus sequence typing. Clinical data of patients were retrospectively analyzed, drug resistance and toxicity were respectively studied by drug sensitivity and complement killing tests.Results: 247 unduplicated AB strains were collected, and ST191/195/208, the main epidemic dominant strain, accounted for 70.9%. Patients with ST191/195/208 on infection had higher white blood cell (10.8 vs 8.9, p = 0.004), neutrophil% (89.5 vs 86.9, p = 0.005), neutrophil count (9.5 vs 7.1, p = 0.021), D-dimer (6.7 vs 3.8, p = 0.000), total bilirubin (27.0 vs 21.5, p = 0.038), pronatriuretic peptide (324 vs 164, p = 0.042), C-reactive protein (82.5 vs 56.3, p = 0.048), clinical pulmonary infection score (CPIS; 7.33 ± 2.30 vs 6.50 ± 2.72, p = 0.045), and acute physiology and chronic health evaluation-II (APACHE-II; 19.620 ± 5.1850 vs 17.648 ± 6.1251, p = 0.011). Patients with ST191/195/208 had more complications, including pulmonary infection (p = 0.041), septic shock (p = 0.009), and multiple organ failure (p = 0.019). Patients with ST191/195/208 had higher 3 day mortality (24.6% vs 13.9%, p = 0.043), 14 day mortality (46.8% vs 26.8%, p = 0.003), and 28 day mortality (55.0% vs 32.4%, p = 0.001). ST191/195/208 strains had higher drug resistance to most antibiotics, and higher survival rate at 90% normal serum concentration (p < 0.001).Conclusion: ST191/195/208 strains predominate in the hospital and prevails in patients with severe infections with increased multidrug antimicrobial resistance and excessive mortality compared to any other AB stains.Keywords: Acinetobacter baumannii, bloodstream infection, MLST, mortality, toxicity