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Yueyue Fu,1 Yuling Xing,2 Linlin Yang,3 Jing Liu,2 Huijuan Ma3 1Graduate School of North China University of Science and Technology, Tangshan, People’s Republic of China; 2Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China; 3Department of Endocrinology, the First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of ChinaCorrespondence: Jing Liu, Department of Endocrinology, Hebei General Hospital, Shijiazhuang, People’s Republic of China, Tel +86 13673186039, Email liujing981531@163.com Huijuan Ma, Department of Endocrinology, the First Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China, Tel +86 18032838686, Email huijuanma76@163.comPurpose: To explore the correlation between fasting C-peptide to diabetes duration ratio (FCP/DD) and diabetic peripheral neuropathy (DPN).Methods: The study was conducted on 816 patients with type 2 diabetes (T2DM). Subjects were classified into a diabetic peripheral neuropathy group (DPN, n=408) and a non-diabetic peripheral neuropathy group (NDPN, n=408) depending on the presence of DPN. Collected patients’ baseline data, calculated the FCP/DD ratio, and analyzed the correlation between FCP/DD and DPN.Results: A comparative analysis of general characteristics revealed that the DPN group exhibited higher values for age, DD, proportion of hypertension, proportion of DN, and proportion of DR compared to the NDPN group, Conversely, the DPN group demonstrated lower proportions of eGFR, FCP/DD, FCP, and fatty liver relative to the NDPN group, with all differences achieving statistical significance (P < 0.05). Compared to the high FCP/DD group, the low FCP/DD group exhibited higher values in age, DD, the proportion of DPN, DN, DR, and hypertension, as well as elevated levels of HDL-C and NEUT (P< 0.05). Conversely, the low FCP/DD group demonstrated a lower proportion of patients who smoked and those with fatty liver, along with reduced BMI, ALB, FBG, UA, eGFR, TC, TG, and LDL-C levels (P < 0.05). In patients with T2DM, after adjusting for confounding factors, high levels of FCP/DD were found to be a protective factor for DPN (P < 0.05). The area under the curve of the FCP/DD Model predicting DPN (AUC=0.737) was higher than that of single FCP (AUC=0.587), DD (AUC=0.665).Conclusion: The high FCP/DD ratio was a protective factor for T2DM with DPN. Additionally, the FCP/DD ratio was found to be a better predictor for the occurrence of DPN in T2DM compared to FCP and DD alone.Keywords: Diabetic peripheral neuropathy, type 2 diabetes, FCP/DD

Haibin Zou,1 Fangfang Xi,1 Yuanyuan Fu,1 Jinhui Xu,1 Ping Zhang,1 Dongge Li,2 Heguo Luo1 1Department of Anesthesiology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330006, People’s Republic of China; 2The Third Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, People’s Republic of ChinaCorrespondence: Heguo Luo, Department of Anesthesiology, Jiangxi Provincial People’s Hospital, The First Affiliated Hospital of Nanchang Medical College, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel +86 13807035516, Email ddjy121@163.comPurpose: Ciprofol, a new sedative anesthetic developed in China, offers rapid onset and recovery, reduced injection pain, and stable circulation. However, its effect on blood pressure during anesthesia induction in older adults remains unclear. To compare the effects of propofol and ciprofol on hypotension induced by general anesthesia in older adults.Patients and Methods: This prospective, single-center, double-blind, randomized, controlled clinical study enrolled 117 older adults undergoing surgery. Patients in the ciprofol group (group C) received an intravenous injection of ciprofol (0.3 mg/kg, n=57), while the propofol group (group P) received an intravenous injection of propofol (1.5 mg/kg, n=58). The primary outcome was the incidence of hypotension (mean arterial pressure (MAP) decreased by > 30% from baseline or MAP< 65 mmHg). Secondary outcomes included induction success rate (bispectral index (BIS) value ≤ 60 and Modified Observer’s Assessment of Alertness/Sedation Scale (MOAA/S) score ≤ 1), injection pain, number of drug additions, time to BIS 60, time to eyelash reflex disappearance, blood pressure changes, incidence of hypertension, tachycardia and BIS values before and after administration.Results: The incidence of induced hypotension was 26.3% (15/57) in group C and 48.3% (28/58) in group P (OR=0.383, 95% CI:175– 0.837, P =0.015). Group C had significantly lower injection pain incidence (5.3% vs 20.7%, OR=0.213, 95% CI: 0.057– 0.801, p=0.014). Both groups had a 100% induction success rate, with no significant difference in the number of additional doses. Post-intubation hypertension and tachycardia incidence were not significantly different. Group C showed less blood pressure decrease during induction and a deeper anesthesia level.Conclusion: Compared to propofol, ciprofol reduces the incidence of induced hypotension in older adults and maintains more stable blood pressure during induction. Additionally, ciprofol reduces injection pain and provides a good depth of anesthesia, making it a safe and effective option for anesthesia induction in older adults.Trial Registration ClinicalTrials.gov Identifier: ChiCTR2200066053.Keywords: ciprofol, propofol, bispectral index, BIS, hypotension

Xiang Tang,1,2,&ast; Jinbin Chen,1,2,&ast; Wei Peng,1,2,&ast; Zhoutian Yang,1,2 Li Hu,1,2 Zhiwei Ye,1,2 Yizhen Fu,1,2 Dandan Hu,1,2 Zhongguo Zhou,1,2 Minshan Chen,1,2 Yaojun Zhang,1,2 Jun-Cheng Wang1,2 1State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yaojun Zhang; Jun-Cheng Wang, Department of Liver Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of China, Email zhangyuj@sysucc.org.cn; wangjch@sysucc.org.cnObjection: To report the efficacy and safety of triple combination therapy with bevacizumab plus anti-PD-1 (BP1) or anti-PD-L1 inhibitors (BPL) combined with hepatic arterial infusion chemotherapy (HAIC) as a first-line treatment for initially unresectable hepatocellular carcinoma (uHCC).Methods: In this retrospective study, patients with initially uHCC received either BP1-HAIC or BPL-HAIC as first-line treatment. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR).Results: Between January 2020 and December 2022, a total of 136 patients with initially uHCC received triple combination therapy, with 76 in the BP1-HAIC group and 60 in the BPL-HAIC group. The median PFS for the entire cohort was 11.1 months (95% CI, 8.0– 13.7 months), and the median OS was 22.4 months (95% CI, 21.3- not reached). Comparative analysis revealed no significant differences in PFS (HR, 0.91, P = 0.69) or OS (HR, 0.71, P = 0.31) between the BP1-HAIC and BPL-HAIC groups. The ORR was 46.3% per RECIST v1.1 and 66.9% per mRECIST, with a DCR of 83.1% under both criteria. Common adverse events (AEs) included hypoalbuminemia and elevated aspartate/alanine aminotransferase, with 5.1% (7/136) experienced upper gastrointestinal bleeding. Multivariate Cox analysis identified tumor number and BCLC stage as independent prognostic factors for OS, and tumor number for PFS.Conclusion: Triple combination therapy demonstrated significant therapeutic efficacy and tumor response in initially uHCC. No notable differences in outcomes were observed between the BP1-HAIC and BPL-HAIC groups. AEs were manageable in clinical practice.Keywords: hepatocellular carcinoma, immune checkpoint inhibitor, bevacizumab, hepatic arterial infusion chemotherapy, adverse event

Yaojie Fu,1,&ast; Yujing He,2,&ast; Caixia Zheng,3 Jianyong Zeng,3 Hongjie Ou3 1Emergency Department, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 2Intense Care Unit, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China; 3Department of Infectious Diseases, The First Affiliated Hospital of Xiamen University, Xiamen, Fujian, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hongjie Ou, Department of Infectious Diseases, The First Affiliated Hospital of Xiamen University, No. 10, Shanggu Road, Xiamen, Fujian, 361001, People’s Republic of China, Email ouhongjie@sina.com Yujing He, Intense Care Unit, The First Affiliated Hospital of Xiamen University, No. 10, Shanggu Road, Xiamen, Fujian, 361001, People’s Republic of China, Email heyujing1988@126.comIntroduction: Sepsis remains a significant global health challenge due to its high morbidity and mortality rates. Disseminated Intravascular Coagulopathy (DIC) represents a critical complication of sepsis, contributing to increased mortality and economic burden. Despite various prognostic scoring systems, there is a lack of a specific model for DIC prediction in sepsis patients.Methods: This observational study included 336 sepsis patients. Clinical and laboratory data were collected, and prognoses were defined according to established criteria.Results: We enrolled 336 patients, with 304 in the non-DIC group and 32 in the DIC group. Patients with DIC had notably lower platelet (PLT) and higher levels of prothrombin time (PT), lactate (LAC), and procalcitonin (PCT) compared to those without DIC. Univariate and multivariate analyses identified risk factors associated with the DIC, showing that PLT (OR = 0.985, 95% CI 0.978– 0.993, p < 0.001), PT level (OR = 1.140, 95% CI 1.004– 1.295, p = 0.044), and LAC (OR = 1.101, 95% CI 0.989– 1.226, p = 0.078) were related factors. A risk model was established, and its sensitivity and specificity in predicting DIC among sepsis patients were assessed by comparing it to the SOFA score. The area under the ROC curve for the model was 0.850, while the SOFA score was 0.813. With a model score >− 2.12, the sensitivity for predicting DIC was 84.4%, and the specificity was 75.0%.Conclusion: Our study introduces a predictive model for DIC detection in sepsis patients, emphasizing the need for clinicians to focus on patients with high model scores for timely intervention.Keywords: sepsis, risk model, disseminated intravascular coagulopathy, platelet, mortality

Ying Fu,1,2 Yufeng Zhu,1,3 Feng Zhao,1,2,4 Bingyan Yao,1,2 Yunsong Yu,5 Jun Zhang,1,2 Qiong Chen6 1Department of Clinical Laboratory, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 2Key Laboratory of Precision Medicine in Diagnosis and Monitoring Research of Zhejiang Province, Sir Run Run Shaw Hospital, Hangzhou, Zhejiang Province, People’s Republic of China; 3Department of Clinical Laboratory, Hangzhou Xixi Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China; 4Department of Clinical Laboratory, Zhejiang University Sir Run Run Shaw Alar Hospital, Alar, Xinjiang province, People’s Republic of China; 5Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Hangzhou, Zhejiang Province, People’s Republic of China; 6Department of Clinical Laboratory, Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University, Hangzhou, Zhejiang Province, People’s Republic of ChinaCorrespondence: Qiong Chen; Jun Zhang, Email chenqiong2002@126.com; jameszhang2000@zju.edu.cnObjective: Our aim was to elucidate the resistance mechanisms and assess the combined synergistic and bactericidal activities of aztreonam in combination with ceftazidime/avibactam (CZA), meropenem/vaborbactam (MEV), and imipenem/relebactam (IMR) against Enterobacterales strains producing dual carbapenemases.Methods: Species identification, antimicrobial susceptibility testing and determination of carbapenemase type were performed for these strains. Plasmid sizes, plasmid conjugation abilities and the localization of carbapenemase genes were investigated. Whole-genome sequencing was performed for all strains and their molecular characteristics were analyzed. In vitro synergistic and bactericidal activities of the combination of aztreonam with CZA, MEV and IMR against these strains were determined using checkerboard assay and time-kill curve assay.Results: A total of 12 Enterobacterales strains producing dual-carbapenemases were collected, including nine K. pneumoniae, two P. rettgeri, and one E. hormaechei. The most common dual-carbapenemase gene pattern observed was bla(KPC-2+NDM-5) (n=4), followed by blaKPC-2+IMP-26 (n=3), bla(KPC-2+NDM-1) (n=2), bla(KPC-2+IMP-4) (n=1), bla(NDM-1+IMP-4) (n=1) and bla(KPC-2+KPC-2) (n=1). In each strain, the carbapenemase genes were found to be located on two distinct plasmids which were capable of conjugating from the original strain to the receipt strain E. coli J53. The results of the checkerboard synergy analysis consistently revealed good synergistic effects of the combination of ATM with CZA, MEV and IMR. Except for one strain, all strains exhibited significant synergistic activity and bactericidal activity between 2 and 8 hours.Conclusion: Dual-carbapenemase-producing Enterobacterales posed a significant threat to clinical anti-infection treatment. However, the combination of ATM with innovative β-lactam/β-lactamase inhibitor compounds had proven to be an effective treatment option.Keywords: dual-carbapenemase-producing enterobacterales, β‑lactam/β‑lactamase inhibitor combinations, aztreonam, checkerboard assay, time-kill curve

Xiaoyun Li,1,&ast; Yuke Fu,2,&ast; Wanjuan Weng,1 Mowei Liu,2 Yan Li1 1Shanghai Institute of Early Childhood Education, Shanghai Normal University, Shanghai, People’s Republic of China; 2Department of Psychology, Trent University, Peterborough, Ontario, Canada&ast;These authors contributed equally to this workCorrespondence: Mowei Liu, Department of Psychology, Trent University, Peterborough, Ontario, K9L 0G2, Canada, Email moweiliu@trentu.ca Yan Li, Shanghai Institute of Early Childhood Education, Shanghai Normal University, No. 100 Guilin Road, Shanghai, 200234, People’s Republic of China, Email liyan@shnu.edu.cnPurpose: Given that mother plays the main nurturing role in a family unit and their unique influence on children’s development, the current study aimed to examine the influence of maternal phubbing on children’s problematic media use and the independent and interactive moderating role of children’s negative affectivity and effortful control.Methods: Participants were 1986 children aged 3 to 6 years in Shanghai, China. Their mothers were asked to complete a series of questionnaires including parental phubbing scale, problematic media use measure, and child behavior questionnaire. To investigate the moderating influence of children’s negative affectivity and effortful control, hierarchical linear regression analyses were conducted using SPSS 24.0. Simple slopes analyses and the Johnson–Neyman technique were further used to depict moderation effects.Results: Maternal phubbing was associated with higher levels of problematic media use in preschool children (β = 0.18, p < .001, [0.14, 0.22]). Children’s negative affectivity acts as a risk factor, exacerbating the adverse effects of maternal phubbing on children’s problematic media use (β = 0.05, t = 2.69, p < 0.05), whereas children’s effortful control acts as a protective factor, buffering the link between maternal phubbing and children’s problematic media use (β = − 0.10, t = − 5.00, p < 0.001).Conclusion: These results suggest that interventions seeking to promote appropriate digital development in preschoolers should take the child’s temperament into account and be complemented by active parental mediation and involvement.Keywords: maternal phubbing, problematic media use, negative affectivity, effortful control, preschoolers

Jiayun Jiang,1 Hui Zhang,1 Jiejuan Lai,1 Shiyu Zhang,1 Yanjiao Ou,1 Yu Fu,2,&ast; Leida Zhang1,&ast; 1Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), Chongqing, People’s Republic of China; 2Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Leida Zhang, Institute of Hepatobiliary Surgery, Southwest Hospital, Third Military Medical University (Army Medical University), No. 30, Gaotanyan Street, Shapingba District, Chongqing, 400038, People’s Republic of China, Email 2518569931@qq.com Yu Fu, Medical Research Institute, College of Pharmaceutical Sciences, Southwest University, No. 2, Tiansheng Road, Beibei District, Chongqing, 400715, People’s Republic of China, Email fuyu2020@swu.edu.cnPurpose: To compare the efficacy and safety of transarterial chemoembolization (TACE) plus lenvatinib and tislelizumab (TACE-Len-T) versus TACE plus lenvatinib (TACE-Len) as the first-line treatment for patients with unresectable hepatocellular carcinoma (uHCC).Patients and Methods: This retrospective study included 136 uHCC patients treated with TACE-Len-T or TACE-Len from January 1, 2021, to June 30, 2023. Clinical outcomes including overall survival (OS), progression-free survival (PFS), tumor response and adverse events (AEs) were compared between the two groups. The risk factors affecting OS and PFS were also analyzed.Results: The median OS and PFS of the TACE-Len-T group were significantly longer than those of the TACE-Len group (Median OS: not reached vs 13.8 months, P< 0.001; Median PFS: 13.0 months vs 2.7 months, P< 0.001). The best overall objective response rate (ORR) was also better with TACE-Len-T treatment (ORR: 72.1% vs 29.4%, P< 0.001), and the disease control rate (DCR) significantly increased in the TACE-Len-T group (88.2% vs 48.5%, P< 0.001). Multivariate analyses revealed that TACE-Len treatment, tumor number > 3, and cTACE were independent risk factors for OS, whereas TACE-Len treatment was the only independent risk factor for PFS. The frequency and severity of AEs in the TACE-Len-T group were comparable to those in the TACE-Len group (any grade: 92.6% vs 91.2%, P=0.753; grade 3 or 4: 33.8% vs 32.3%, P=0.855).Conclusion: TACE-Len-T treatment significantly improved OS, PFS, ORR, and DCR over TACE-Len treatment, with a manageable safety profile in uHCC.Keywords: unresectable hepatocellular carcinoma, transarterial chemoembolization, lenvatinib, tislelizumab, immunotherapy

Lu Huang, Yujing Fu, Jinghong Cao, Jianjun Zhai Department of Obstetrics and Gynecology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, People’s Republic of ChinaCorrespondence: Jianjun Zhai, Department of Obstetrics and Gynecology, Beijing Tongren Hospital, Capital Medical University, NO.1 of Dongjiaominxiang Street, Dongcheng District, Beijing, 100730, People’s Republic of China, Email jianjunzhai0504@163.comObjective: As a common endocrine and metabolic disorder, polycystic ovary syndrome (PCOS) is mostly associated with an obese phenotype. The present research focuses on the clinical significance of miR-379 in obesity-PCOS and attempts to elucidate its potential mechanisms.Methods: Healthy individuals (n = 46), obesity-PCOS (n = 92), and non-obesity PCOS (n = 31) subjects were enrolled. Quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to examine the level of serum miR-379. The receiver operating characteristic (ROC) curve and logistic regressions were applied to reveal the diagnostic significance. Dual luciferase reporters were performed to validate the targeting relationships. And cell count kit (CCK-8) assay was used to detect cell proliferation.Results: Serum miR-379 was highly expressed in PCOS patients (P < 0.05), in especially obesity-PCOS patients. Higher miR-379 was associated with greater body mass index (BMI), higher bioavailable testosterone (bT), and greater insulin resistance (IR). Additionally, miR-379 was an independent risk factor for the development of obesity-PCOS. The sensitivity of miR-379 in identifying patients with obesity-PCOS from healthy or non-obesity-PCSO patients was 81.52% and 72.83%, and the specificity was 86.96% and 80.65%. Semaphorin 3 A (SEMA3A) was identified as a target of miR-379 and was reduced in the patients with obesity PCOS (P < 0.05). Inhibition of miR-375 reduced KGN proliferation, but this reduction was partially restored by silencing of SEMA3A (P < 0.05).Conclusion: Elevated miR-379 assists the diagnosis of obesity-PCOS and regulates the proliferation of KGN by targeting SEMA3A engaged in disease development.Keywords: obesity, PCOS, miR-379, diagnostic, SEMA3A

Zhimei Jiang,1– 3 Yuzhi Fu,1– 3 Hongxin Shen1– 3 1Department of Pharmacy, West China Second University Hospital of Sichuan University, Chengdu, People’s Republic of China; 2Evidence-Based Pharmacy Center, West China Second University Hospital of Sichuan University, Chengdu, People’s Republic of China; 3Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, People’s Republic of ChinaCorrespondence: Hongxin Shen, West China Second University Hospital, Sichuan University, No. 20, Third Section, Renmin South Road, Chengdu, Sichuan, 610041, People’s Republic of China, Email 1103747222@qq.comAbstract: Research for tumor treatment with significant therapy effects and minimal side-effects has been widely carried over the past few decades. Different drug forms have received a lot of attention. However, systemic biodistribution induces efficacy and safety issues. Intratumoral delivery of agents might overcome these problems because of its abundant tumor accumulation and retention, thereby reducing side effects. Delivering hydrogels, nanoparticles, microneedles, and microspheres drug carriers directly to tumors can realize not only targeted tumor therapy but also low side-effects. Furthermore, intratumoral administration has been integrated with treatment strategies such as chemotherapy, enhancing radiotherapy, immunotherapy, phototherapy, magnetic fluid hyperthermia, and multimodal therapy. Some of these strategies are ongoing clinical trials or applied clinically. However, many barriers hinder it from being an ideal and widely used option, such as decreased drug penetration impeded by collagen fibers of a tumor, drug squeezed out by high density and high pressure, mature intratumoral injection technique. In this review, we systematically discuss intratumoral delivery of different drug carriers and current development of intratumoral therapy strategies. Keywords: intratumoral drug delivery, drug carrier, treatment strategy, antitumor therapy

Bingcong Zhao,1,2 Zhigang Li,3 Chuan Shi,4 Yan Liu,5 Yang Sun,3 Bin Li,1,2 Jie Zhang,6 Zhizhong Gong,7 Yuanzheng Wang,8 Xuehong Ma,9 Xinjing Yang,10 Huili Jiang,3 Yuanbo Fu,1,2 Xin Wang,1,2 Yang Li,6 Hengchia Liu,6 Tuya Bao,3 Yutong Fei11– 13 1Department of Acupuncture and Moxibustion, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Beijing Key Laboratory of Acupuncture Neuromodulation, Beijing, People’s Republic of China; 3School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Psychological Assessment Center, Peking University Sixth Hospital, Beijing, People’s Republic of China; 5Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 6Department of Psychosomatic Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 7Division of Medical Affairs, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 8Department of Integrative TCM and Western Medicine, Peking University First Hospital, Beijing, People’s Republic of China; 9Department of Acupuncture & Moxibustion, Dongfang Hospital, the Second Clinical Medical College of Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 10Department of Traditional Chinese Medicine, South China Hospital of Shenzhen University, Shenzhen, People’s Republic of China; 11Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 12Institute of Excellence in Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 13Beijing GRADE Centre, Beijing, People’s Republic of ChinaCorrespondence: Tuya Bao, School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, People’s Republic of China, Email tuyab@263.net Yutong Fei, Centre for Evidence-Based Chinese Medicine, Beijing University of Chinese Medicine, No. 11, Bei San Huan Dong Lu, Chaoyang District, Beijing, 100029, People’s Republic of China, Email feiyt@bucm.edu.cnPurpose: Anxious depression (AD) is a common, distinct depression subtype. This exploratory subgroup analysis aimed to explore the effects of acupuncture as an add-on therapy of selective serotonin reuptake inhibitors (SSRIs) for patients with AD or non-anxious depression (NAD).Patients and Methods: Four hundred and sixty-five patients with moderate-to-severe depression from the AcuSDep pragmatic trial were included in analysis. Patients were randomly assigned to receive MA+SSRIs, EA+SSRIs, or SSRIs alone (1:1:1) for six weeks. AD was defined by using dimensional criteria. The measurement instruments included 17-items Hamilton Depression Scale (HAMD-17), Self-Rating Depression Scale (SDS), Clinical Global Impression (CGI), Rating Scale for Side Effects (SERS), and WHO Quality of Life-BREF (WHOQOL-BREF). Comparison between AD and NAD subgroups and comparisons between groups within either AD or NAD subgroups were conducted.Results: Eighty percent of the patients met the criteria for AD. The AD subgroup had poorer clinical manifestations and treatment outcomes compared to those of the NAD subgroup. For AD patients, the HAMD response rate, remission rate, early onset rate, and the score changes on each scale at most measurement points on the two acupuncture groups were significantly better than the SSRIs group. For NAD patients, the HAMD early onset rates of the two acupuncture groups were significantly better than the SSRIs group.Conclusion: For AD subtype patients, either MA or EA add-on SSRIs showed comprehensive improvements, with small-to-medium effect sizes. For NAD subtype patients, both the add-on acupuncture could accelerate the response to SSRIs treatment. The study contributed to the existing literature by providing insights into the potential benefits of acupuncture in combination with SSRIs, especially for patients with AD subtypes. Due to its limited nature as a post hoc subgroup analysis, prospectively designed, high-quality trials are warranted.Clinical Trials Registration: ChiCTR-TRC-08000297.Keywords: anxious depression, non-anxious depression, acupuncture, SSRIs, subgroup analysis

Xiaoguang Xiao,1 Jianhai Sun,2 Dongsheng Zhang,3 Linjun Li,4 Haibo Zhou,5 Yongjun Li,6 Quan Li,7 Zhongshi He,8 Yang Fu,9 Qiwen Duan,10 Guping Zheng,11 Ze Tang,12 Qian Chu,1,&ast; Yuan Chen1,&ast; 1Department of Oncology, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2Department of Oncology, Hubei Zhongshan Hospital, Wuhan, Hubei, People’s Republic of China; 3Department of Oncology, Suizhou Hospital, Hubei University of Medicine, Suizhou, Hubei, People’s Republic of China; 4Department of Oncology, Hubei Provincial Hospital of Integrated Chinese and Western Medicine, Wuhan, Hubei, People’s Republic of China; 5Department of Oncology, Yichang Central People’s Hospital, Yichang, Hubei, People’s Republic of China; 6Department of Oncology, Yichang Second People’s Hospital, Yichang, Hubei, People’s Republic of China; 7Department of Oncology, Xiangyang Central Hospital, Xiangyang, Hubei, People’s Republic of China; 8Department of Oncology, Xiangyang No 1 People’s Hospital Affiliated to Hubei University of Medicine, Xiangyang, Hubei, People’s Republic of China; 9Department of Oncology, Xiangyang Hospital of Traditional Chinese Medicine, Xiangyang, Hubei, People’s Republic of China; 10Department of Oncology, Taihe Hospital, Shiyan, Hubei, People’s Republic of China; 11Department of Oncology, Xiaogan Central Hospital, Xiaogan, Hubei, People’s Republic of China; 12Department of Oncology, Huangshi Central Hospital, Huangshi, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qian Chu; Yuan Chen, Email qianchu@tjh.tjmu.edu.cn; chenyuantj2023@126.comBackground: Studies have shown that oral oxycontin tablets can be used for opioid titration. The European Society for Medical Oncology (ESMO) guidelines for adult cancer pain recommend opioid titration through the parenteral route, usually the intravenous or subcutaneous route. Patient-controlled subcutaneous analgesia (PCSA) with hydromorphone needs further evaluation for opioid titration. This prospective multicenter study was designed to compare the efficacy and safety of hydromorphone PCSA with oral oxycontin tablets for opioid titration of cancer pain.Patients and Methods: Eligible patients with cancer pain were randomly assigned in a 1:1 ratio to the PCSA group or the oxycontin group for dose titration. Different titration methods were given in both groups depending on whether the patient had an opioid tolerance. The primary endpoint of this study was time to successful titration (TST).Results: A total of 256 patients completed this study. The PCSA group had a significantly lower TST compared with the oxycontin group (median [95% confidence interval (CI)], 5.5[95% CI:2.5– 11.5] hours vs.16.0 [95% CI:11.5– 22.5] hours; p< 0.001). The frequency (median; interquartile) of breakthrough pain (Btp) over 24 hours was significantly lower in the PCSA group (2.5;2.0– 3.5) than in the oxycontin group.(3.0; 2.5– 4.5) (p=0.04). The pain was evaluated by numeric rating scale (NRS) score at 12 hours after the start of titration. The pain score (median; interquartile) was significantly lower in the PCSA versus the oxycontin group (2.5;1.5– 3.0) vs 4.5;3.0– 6.0) (p=0.02). The equivalent dose of oral morphine (EDOM) for a successful titration was similar in both groups (p=0.29), but there was a significant improvement in quality of life (QoL) in both groups (p=0.03). No between-group difference in the incidence of opioid-related adverse effects was observed (p=0.32).Conclusion: Compared with oral oxycontin tablet, the use of PCSA with hydromorphone achieved a shorter titration duration for patients with cancer pain (p< 0.001), without significantly increasing adverse events (p=0.32).Keywords: cancer pain, opioid titration, oxycontin tablets, hydromorphone, patient-controlled subcutaneous analgesia

Zhongfang Yang,1– 4 Hongli Yang,5 Beibei Gong,6 Lin Zhang,7 Yanfen Fu,8 Yan Hu1– 3 1Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, People’s Republic of China; 2School of Nursing, Fudan University, Shanghai, People’s Republic of China; 3Fudan University Centre for Evidence-Based Nursing: A Joanna Briggs Institute Centre of Excellence Department, Fudan University, Shanghai, People’s Republic of China; 4NYU Rory Meyers College of Nursing, New York University, New York, NY, USA; 5Department of Nursing, Yunnan Provincial Hospital of Infectious Disease/Yunnan AIDS Care Center/Yunnan Mental Health Center, Kunming, People’s Republic of China; 6Department of Nursing, The Fourth People’s Hospital of Nanning, Nanning, People’s Republic of China; 7Department of Nursing, Shanghai Public Health Clinical Center, Shanghai, People’s Republic of China; 8School of Nursing, Dali University, Dali, People’s Republic of ChinaCorrespondence: Yan Hu, Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, No. 305 Fenglin Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Email huyan@fudan.edu.cnPurpose: As of the end of 2022, over 20 million women worldwide, aged 15 and above, are living with HIV. Stigma remains a formidable barrier for women living with HIV/AIDS, hindering their access to healthcare and exacerbating health disparities. Indeed, some women living with HIV/AIDS can successfully confront and overcome stigma. There remains a paucity of qualitative research exploring the stigma coping strategies of women living with HIV/AIDS in China. This study was aimed to gain the deeper understanding of stigma experienced by women living with HIV/AIDS and coping strategies.Patients and Methods: We recruited diverse participants using snowball sampling and purposive sampling. Semi-structured personal in-depth interviews were conducted with 30 women living with HIV/AIDS from December 2022 to June 2023. The samples were from four HIV/AIDS designated hospitals. The data were analyzed using the Colaizzi seven-step model.Results: The experiences of stigma among women living with HIV/AIDS included family role (wife/mother/grandmother) collapse and disgusted by family, resignation in being shunned by others, helplessness due to social exclusion, grief at being devaluated, and resentment for experiencing injustice. The coping strategies used to deal with stigma included concealing their conditions, avoiding socialization, and attempting to retaliate against society.Conclusion: Healthcare professionals are recommended to offer women living with HIV/AIDS effective emotional support and guidance to cope with stigma. The study highlights the stigma they face, providing valuable evidence for policymakers. Recommendations emphasize the importance of developing services addressing both physical and psychological needs of women living with HIV/AIDS.Keywords: female, acquired immunodeficiency syndrome, social stigma, Asian, qualitative research

Yang Fu,&ast; Xiao-Qin Huang,&ast; Hang-Bo Qu, Yan Zhi Ge, Xuan-Liang Ru Department of Orthopedics, Zhejiang Hospital, Hangzhou, Zhejiang Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuan-Liang Ru, Department of Orthopedics, Zhejiang Hospital, No. 1229 Gudun Road, Hangzhou, Zhejiang Province, 310013, People’s Republic of China, Tel +86-133-3612-4875, Email zjyyrxl@qq.comBackground: Intervertebral disc degeneration (IVDD) is the main cause of low back pain (LBP), but the specific regulatory factors, pathways and specific molecular mechanisms remain unclear.Methods: We identified and quantitatively analyzed Pfirrmann Grade II (n=3) and Pfirrmann Grade IV (n=3) pulposus samples via MRI. The differential abundance of proteins in the samples was determined and quantitatively analyzed by relative and absolute quantitative analysis of the isotope marker levels combined with the liquid chromatography–tandem mass spectrometry (LC‒MSMS/MS).Results: A total of 70 proteins (30 significantly increased proteins (> 1.2-fold change) and 40 significantly decreased proteins (< 0.8-fold change)) showed different levels among the groups. Kyoto Encyclopedia of Genes and Genomes and Gene Ontology (GO) enrichment analyses and Western blot analysis showed that CYCS, RAC1, and PSMD14 may play important roles in IVDD and that Epstein‒Barr virus infection, viral myocarditis, colorectal cancer, nonalcoholic fatty liver disease (NAFLD) and amyotrophic lateral sclerosis (ALS) are the main pathways involved in IVDD.Conclusion: CYCS, RAC1 and PSMD14 may play important roles in IVDD, and Epstein‒Barr virus infection, viral myocarditis, colorectal cancer, NAFLD and ALS may be the main pathways involved in IVDD.Keywords: TMT, LC‒MS/MS, proteomics, low back pain, nucleus pulposus

Xinyi Long,1 Fangfang Li,1 Sishi Tang,1 Jing Liu,1 Yunfeng Fu,2 Yanhui Feng3 1Department of Hematology, The Third Xiangya Hospital, Central South University, Changsha, 410013, People’s Republic of China; 2Department of Blood Transfusion, The Third Xiangya Hospital of Central South University, Changsha, 410013, People’s Republic of China; 3Department of Oncology, The Third Xiangya Hospital of Central South University, Changsha, 410013, People’s Republic of ChinaCorrespondence: Yanhui Feng, Department of Oncology, The Third Xiangya Hospital, Central South University, No. 138 Tongzipo Road, Yuelu District, Hexi, Changsha, Hunan Province, People’s Republic of China, Tel +86-13549656766, Email fengyanhui900@sohu.comPurpose: Immunological regimens are an important area of research for treating multiple myeloma (MM). Plasma cells play a crucial role in immunotherapy.Patients and Methods: In our study, we used both single-cell RNA sequencing (scRNA-seq) and bulk sequencing techniques to analyze MM patients. We analyzed each sample using gene set variation analysis (GSVA) based on immune-related gene sets. We also conducted further analyses to compare immune infiltration, clinical characteristics, and expression of immune checkpoint molecules between the H-S100A9 and L-S100A9 groups of MM patients.Results: We identified eight subpopulations of plasma cells, with S100A9 plasma cells being more abundant in patients with 1q21 gain and 1q21 diploid. CellChat analysis revealed that GAS and HGF signaling pathways were prominent in intercellular communication of S100A9 plasma cells. We identified 14 immune-related genes in the S100A9 plasma cell population, which allowed us to classify patients into the H-S100A9 group or the L-S100A9 group. The H-S100A9 group showed higher ESTIMATE, immune and stroma scores, lower tumor purity, and greater immune checkpoint expression. Patients with 1q21 gain and four or more copies had the lowest ESTIMATE score, immune score, stroma score, and highest tumor purity. Drug sensitivity analysis indicated that the H-S100A9 group had lower IC50 values and greater drug sensitivity compared to the L-S100A9 group. Quantitative reverse transcription (RT-q) PCR showed significantly elevated expression of RNASE6, LYZ, S100A8, S100A9, and S100A12 in MM patients compared to the healthy control group.Conclusion: Our study has identified a correlation between molecular subtypes of S100A9 plasma cells and the response to immunotherapy in MM patients. These findings improve our understanding of tumor immunology and provide guidance for developing effective immunotherapy strategies for this patient population.Keywords: multiple myeloma, single-cell sequencing, bulk transcription, tumor immune microenvironment, S100A9

Yingda Fu,1 Guangbing Li,1,2 Zichen Feng,1 Jun Liu,2 Xiaoyu Wang,1 Tao Wang,2 Jun Liu1,2 1Department of Hepatobiliary Surgery and Center of Organ Transplantation, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Hepatobiliary Surgery and Center of Organ Transplantation, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of ChinaCorrespondence: Jun Liu, Department of Hepatobiliary Surgery and Center of Organ Transplantation, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong, People’s Republic of China, Email dr_liujun1967@126.comBackground: AMP-activated protein kinase (AMPK) plays a critical role in energy metabolism. Its activation leads to the phosphorylation of downstream proteins such as acetyl-CoA carboxylase (ACC) and sterol regulatory element-binding protein-1 (SREBP1), subsequently inhibiting de novo fatty acid synthesis, thereby reducing intracellular triglyceride accumulation. MC is a compound found in extracts from Zanthoxylum armatum DC plants. Research has shown that MC can inhibit the differentiation of 3T3-L1 adipocytes through the CAMKK2-AMPK pathway. However, the biological effect of MC in HepG2 cells remains unknown.Methods: In this study, we utilized HepG2 cells to establish a model of MAFLD through FFAs stimulation. We investigated the biological effects of MC on HepG2 cells and studied its impact on lipid metabolism. Small interfering RNA was employed to explore the mechanism by which MC activates AMPK. Finally, molecular docking was conducted, establishing a model of the interaction between AMPK and MC.Results: We observed that MC can alleviate triglyceride accumulation in HepG2 cells. We observed the elevated p-AMPK/AMPK, P-ACC/ ACC, and elevated CPT1a after treatment of MC in HepG2 cells. The interference of CAMKK2 mRNA did not impact the ability of MC to phosphorylate AMPK. Compound C attenuates the ability of MC to increase p-AMPK. Molecular docking results led us to hypothesize that MC directly interacts with AMPK, resulting in AMPK phosphorylation and improved lipid accumulation in HepG2 cells.Keywords: AMPK, CAMKK2, FFAs, HepG2, methyl cinnamate, MAFLD

Jiameng Gao,1,2,&ast; Zhiyuan Zhang,1,2,&ast; Jing Yu,1,2,&ast; Nan Zhang,1,2 Yu Fu,1,2 Xuemei Jiang,1,2 Zheyu Xia,3 Qingqing Zhang,1,2 Zongmei Wen1,2 1Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Shanghai Engineering Research Center of Lung Transplantation, Shanghai, People’s Republic of China; 3School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongmei Wen; Qingqing Zhang, Department of Anesthesiology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, 507 Zhengmin Road, Shanghai, 200433, People’s Republic of China, Tel +86 13761635280 ; +86 13764542055, Email wzm1103@126.com; elfe666@163.comPurpose: Ischemia reperfusion injury (IRI) unavoidably occurs during lung transplantation, further contributing to primary graft dysfunction (PGD). Neutrophils are the end effectors of IRI and activated neutrophils release neutrophil extracellular traps (NETs) to further amplify damage. Nevertheless, potential contributions of NETs in IRI remain incompletely understood. This study aimed to explore NET-related gene biomarkers in IRI during lung transplantation.Methods: Differential expression analysis was applied to identify differentially expressed genes (DEGs) for IRI during lung transplantation based on matrix data (GSE145989, 127003) downloaded from GEO database. The CIBERSORT and weighted gene co-expression network analysis (WGCNA) algorithms were utilized to identify key modules associated with neutrophil infiltration. Moreover, the least absolute shrinkage and selection operator regression and random forest were applied to identify potential NET-associated hub genes. Subsequently, the screened hub genes underwent further validation of an external dataset (GSE18995) and nomogram model. Based on clinical peripheral blood samples, immunofluorescence staining and dsDNA quantification were used to assess NET formation, and ELISA was applied to validate the expression of hub genes.Results: Thirty-eight genes resulted from the intersection between 586 DEGs and 75 brown module genes, primarily enriched in leukocyte migration and NETs formation. Subsequently, four candidate hub genes (FCAR, MMP9, PADI4, and S100A12) were screened out via machine learning algorithms. Validation using an external dataset and nomogram model achieved better predictive value. Substantial NETs formation was demonstrated in IRI, with more pronounced NETs observed in patients with PGD ≥ 2. PADI4, S100A12, and MMP9 were all confirmed to be up-regulated after reperfusion through ELISA, with higher levels of S100A12 in PGD ≥ 2 patients compared with non-PGD patients.Conclusion: We identified three potential NET-related biomarkers for IRI that provide new insights into early detection and potential therapeutic targets of IRI and PGD after lung transplantation.Keywords: ischemia reperfusion injury, neutrophil extracellular traps, lung transplantation, primary graft dysfunction, WGCNA, machine learning

Yanbei Duo,1 Shuoning Song,1 Xiaolin Qiao,2 Yuemei Zhang,3 Jiyu Xu,4 Jing Zhang,5 Zhenyao Peng,6 Yan Chen,2 Xiaorui Nie,2 Qiujin Sun,7 Xianchun Yang,7 Ailing Wang,8 Wei Sun,4 Yong Fu,1 Yingyue Dong,1 Zechun Lu,8 Tao Yuan,1,&ast; Weigang Zhao1,&ast; 1Department of Endocrinology, Key Laboratory of Endocrinology of Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 2Department of Obstetrics, Beijing Chaoyang District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 3Department of Obstetrics, Haidian District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 4Core Facility of Instrument, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine, Peking Union Medical College, Beijing, People’s Republic of China; 5Department of Laboratory, Haidian District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 6Department of Dean’s Office, Haidian District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 7Department of Clinical Laboratory, Beijing Chaoyang District Maternal and Child Health Care Hospital, Beijing, People’s Republic of China; 8National Center for Women and Children’s Health, China CDC, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Yuan; Weigang Zhao, Email t75y@sina.com; xiehezhaoweigang@163.comObjective: Gestational diabetes mellitus (GDM) is a condition of glucose intolerance, which may be accompanied with inflammation. The levels of hematological parameters during pregnancy can reflect inflammatory conditions in pregnant women. This study aims to describe the dynamic change of blood cell parameters from the first trimester (6– 12 weeks of gestation) to the second trimester (24– 28 weeks of gestation) and to investigate the associations of these biomarkers with the risk of GDM.Methods: This study was a prospective double-center study conducted in Beijing, China (clinical trial number: NCT03246295). Hematological parameters were tested four times during the follow-up. Logistic regression analysis and Receiver Operating Characteristic (ROC) curve analysis were used to explore the association and predictive ability of hematological parameters for GDM.Results: There were 258 of 1027 pregnant women in our study developed GDM. Among the 1027 pregnant women, white blood cells (WBC) gradually increased, and red blood cells (RBC), hemoglobin (HGB), and platelet (PLT) tended to decrease from the first trimester to second trimester. After adjusting for confounding factors, higher levels of RBC, HGB, and PLT in both early and middle pregnancy were positively associated with GDM risk, whereas the level of WBC was associated with GDM risk only in early pregnancy. WBC, RBC, HGB, and PLT in early and middle pregnancy were all correlated with fasting insulin (FINS) in early pregnancy.Conclusion: Higher levels of hematological parameters in early and middle pregnancy were associated with glucose metabolism in early pregnancy and the subsequent risk of GDM.Keywords: hematological parameters, gestational diabetes mellitus, inflammation, insulin resistance, prospective study

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

Feifei Sun,1,&ast; Chenjing Wang,1,&ast; Yi Xu,1 Pingping Lin,1 Yaozhong Cao,2 Jiahui Zhang,3 Xin Li,1 Xin Jiang,1 Yao Fu,1 Yu Cao1 1Clinical Trials Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China; 2Clinical Medical Center, Xiuzheng Pharmaceutical Group, Hangzhou, Zhejiang, People’s Republic of China; 3Xiuzheng Bio-Medicine Research Institute, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yu Cao, Clinical Trials Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong, People’s Republic of China, Tel +86 532 82911767, Email caoyu@qdu.edu.cnIntroduction: Hyperuricemia is a disease with abnormal purine metabolism, which leads to the increase of urate concentration. It is an independent risk factor for the occurrence and development of metabolic syndrome, type 2 diabetes, hypertension, cardiovascular disease, chronic kidney disease, and gout. The enzyme urate oxidase can metabolize urate to allantoin, resulting in decreased urate concentrations. Pegylated the urate oxidase can extend half-life and decrease immunogenicity of the protein. This trial aims to evaluate the safety, tolerability, pharmacokinetics(PK), pharmacodynamics(PD) and immunogenicity of a new intravenous PEGylated urate oxidase produced by Xiuzheng Bio-Medicine Research Institute Co., Ltd.Methods and Analysis: A randomized, double-blind, placebo-controlled, phase I, dose escalation study will be conducted in China. In total, 56 subjects will be enrolled in the study, with 24 healthy subjects in the low dose-escalation stage and 32 patients with hyperuricemia in the high dose-escalation stage. There is a bridging between the two stages. Subjects are randomized to PEGylated urate oxidase or the placebo in a 3:1 ratio in each group and followed up for 71 days observation. The primary outcomes include PK, PD, tolerability; the secondary outcomes include safety and immunogenicity.Ethics and Dissemination: The trial is performed abiding by the Declaration of Helsinki, Good clinical practice (GCP) and the guidelines of China National Medical Products Administration (NMPA). Relevant documents, including protocol, informed consent and drug inspection report, are all approved independently by the Medical Ethics Committee of the Affiliated Hospital of Qingdao University. The first subject was enrolled on January 17, 2022.Trial Registration: Clinicaltrials, NCT05226013 (Registered April 2, 2022, Retrospectively registered). ChinaDrugTrials, CTR20211801(Registered July 27, 2021).Keywords: PEGylated urate oxidase, healthy volunteers, patients with hyperuricemia, study protocol

Yajuan Zheng,1,&ast; Peipei Yuan,1,2,&ast; Zhenkai Zhang,1 Yang Fu,1,2 Saifei Li,1 Yuan Ruan,1 Panying Li,1 Yi Chen,1 Weisheng Feng,1– 3 Xiaoke Zheng1– 3 1College of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, 450008, People’s Republic of China; 2The Engineering and Technology Center for Chinese Medicine Development of Henan Province, Zhengzhou, 450046, People’s Republic of China; 3Collaborative Innovation Center for Chinese Medicine and Respiratory Diseases Co-Constructed by Henan province & Education Ministry of P. R. China, Zhengzhou, 450008, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weisheng Feng; Xiaoke Zheng, Email fwsh@hactcm.edu.cn; zhengxk.2006@163.comPurpose: Fatty oil of Descurainia Sophia (OIL) has poor stability and low solubility, which limits its pharmacological effects. We hypothesized that fatty oil nanoparticles (OIL-NPs) could overcome this limitation. The protective effect of OIL-NPs against monocrotaline-induced lung injury in rats was studied.Methods: We prepared OIL-NPs by wrapping fatty oil with polylactic-polyglycolide nanoparticles (PLGA-NPs) and conducted in vivo and in vitro experiments to explore its anti-pulmonary hypertension (PH) effect. In vitro, we induced malignant proliferation of pulmonary artery smooth muscle cells (RPASMC) using anoxic chambers, and studied the effects of OIL-NPs on the malignant proliferation of RPASMC cells and phospholipase C (PLC)/inositol triphosphate receptor (IP3R)/Ca2+ signal pathways. In vivo, we used small animal echocardiography, flow cytometry, immunohistochemistry, western blotting (WB), polymerase chain reaction (PCR) and metabolomics to explore the effects of OIL-NPs on the heart and lung pathological damage and PLC/IP3R/Ca2+ signal pathway of pulmonary hypertension rats.Results: We prepared fatty into OIL-NPs. In vitro, OIL-NPs could improve the mitochondrial function and inhibit the malignant proliferation of RPASMC cells by inhibiting the PLC/IP3R/Ca2+signal pathway. In vivo, OIL-NPs could reduce the pulmonary artery pressure of rats and alleviate the pathological injury and inflammatory reaction of heart and lung by inhibiting the PLC/IP3R/Ca2+ signal pathway.Conclusion: OIL-NPs have anti-pulmonary hypertension effect, and the mechanism may be related to the inhibition of PLC/IP3R/Ca2+signal pathway. Keywords: pulmonary hypertension, PLC/IP3R/Ca2+, nanoparticles, RPASMC, fatty oil

Yan Fu,1,&ast; Hongji Pu,2,&ast; Qun Huang,2,&ast; Peng Qiu,2 Deyin Zhao,3 Yong Cheng1 1Department of Nursing, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Vascular Surgery, Shanghai Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Second Ward of General Surgery, Suzhou Hospital of Anhui Medical University (Suzhou Municipal Hospital of Anhui Province), Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong Cheng; Deyin Zhao, Email cy7107@163.com; 9168722@qq.comIntroduction: Critical limb ischemia (CLI) is a severe condition characterized by inadequate blood flow to the lower extremities, often leading to tissue damage and amputation. CLI is characterized by microcirculatory dysfunction, muscle tissue necrosis, and inflammation. Patients may suffer from the traumatic pain and the increase of plantar pressure, and foot care for patients with CLI has become the “last mile” to improve their life quality. Traditional shoe insoles often lack individual customization, failing to address the unique anatomical needs and hemodynamic characteristics of patients. The study aims to investigate the effects of this innovative intervention on improving the clinical outcomes, and quality of life in CLI patients.Methods and Analysis: This Critical Limb Ischemia Hemodynamic Insole Study is a randomized controlled study performed to explore the effect of a 3D printing insole on foot care of CLI patients. This study recruitment began on November 1, 2021. Patients with CLI confirmed by clinical symptoms and imaging were recruited as the research objects. Participants will be randomly assigned to either the experimental group, which will receive 3D-printed insoles customized based on their hemodynamics, or the control group, which will receive traditionally manufactured insoles. Both groups were followed up for up to 24 months after surgery, including claudication distance, claudication time, pain score, rehospitalization, etc.Trial Registration Number: ChiCTR2100051857.Keywords: 3D printing, insole, hemodynamics, critical limb ischemia

Jingjie Wu,1 Erxu Xue,1 Siyuan Huang,2 Yujia Fu,3 Dandan Chen,1 Jing Shao,3 Hui Zhang,4 Leiwen Tang,1 Zhihong Ye1 1Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Nursing Department, the First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China; 3School of Nursing, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 4Nursing Department, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of ChinaCorrespondence: Zhihong Ye, Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3rd of East Qingchun Road, Hangzhou, Zhejiang Province, People’s Republic of China, Tel +8613606612119, Email 3192005@zju.edu.cnPurpose: A lack of coordinated care leads to multiple adverse effects for older adults with multimorbidity, including high treatment burdens, adverse health outcomes, reduplicated healthcare service utilization, and catastrophic healthcare expenditure. To foster healthy aging, person-centered integrated care that is responsive to older adults has been proposed by the World Health Organization. The objective of this study was to identify factors that impact the successful implementation of integrated care for older adults with multimorbidity in China.Patients and Methods: From July 2022 to May 2023, 33 healthcare providers and managers involved in the delivery and management of healthcare services for older adults with multimorbidity were recruited from Zhejiang Province, China using purposeful and maximum variation sampling methods. Semi-structured, face-to-face in-depth interviews were conducted by the same interviewer in the participants’ native Chinese language until data saturation was reached. Inductive thematic analysis was used to analyze the data, and then, themes were mapped onto six dimensions using the Rainbow Model of Integrated Care to allow for a comprehensive view of the study’s findings.Results: Eleven themes were generated as facilitators and barriers to integrated care for older adults with multimorbidity in China. These themes include (1) clinical integration: patient-centered care, (2) professional integration: interdisciplinary teams and training, (3) organizational integration: resources and accessibility, (4) system integration: community and funds, incentives, and health insurance, (5) functional integration: electronic health record systems, workforce, and guidelines, and (6) normative integration: shared mission.Conclusion: Guided by the Rainbow Model of Integrated Care, various factors at both micro, meso, and macro levels that impact the implementation of integrated care for older adults with multimorbidity in the Chinese context have been identified in this study. The strategies for future interventions and policies should focus on promoting facilitators and addressing barriers.Keywords: delivery of health care, integrated, aged, older adult, multiple chronic conditions, facilitator, barrier

Jingjie Wu,1,&ast; Hui Zhang,2,&ast; Jing Shao,3 Dandan Chen,1 Erxu Xue,1 Siyuan Huang,4 Yujia Fu,3 Leiwen Tang,1 Zhihong Ye1 1Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Nursing Department, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China; 3Nursing Faculty, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 4Nursing Department, The First Affiliated Hospital of Ningbo University, Ningbo, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhihong Ye, Nursing Department, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, 3th of East Qingchun Road, Hangzhou City, Zhejiang Province, People’s Republic of China, Tel +8613606612119, Email 3192005@zju.edu.cnPurpose: To summarize adverse healthcare outcomes experienced by older adults with multimorbidity and barriers perceived by stakeholders regarding the healthcare systems primarily designed to address individual health conditions. Healthcare elements that aim to provide coordinated, continuous, and comprehensive services for this population were also identified.Patients and Methods: We applied the methodology framework developed by Arksey and O’Malley to guide the review. The three-step search strategy was used to identify relevant English reviews that focused on adverse healthcare outcomes and barriers encountered by older adults with multimorbidity and other stakeholders regarding the single-disease-focused healthcare systems, as well as those concentrated on healthcare elements that aim to provide coordinated, continuous, and comprehensive services for older adults with multimorbidity. Five electronic databases, including PubMed/Medline, CINAHL, Web of Science Core Collection, Cochrane Library, and Embase, were systematically searched from database inception to February 2022. A standardized table was used to extract data. Thematic analysis was then conducted under the guidance of the Rainbow Model of Integrated Care and the Chronic Care Model.Results: Twenty reviews were included in this study. Therapeutic competitions, high healthcare service utilization, and high healthcare costs were three adverse healthcare outcomes experienced by patients. Both patients and healthcare professionals faced various barriers. Other stakeholders, including informal caregivers, healthcare managers, and policymakers, also perceived several barriers. Numerous healthcare elements were identified that may contribute to optimized services. The elements most frequently mentioned included the implementation of shared decision-making, comprehensive geriatric assessments, and individual care plans.Conclusion: This study conducted a comprehensive overview of the current knowledge related to healthcare for older adults with multimorbidity. In the future, it is necessary to develop more coordinated, continuous, and comprehensive healthcare service delivery models based on the healthcare needs of older adults with multimorbidity and the specific characteristics of different countries.Keywords: multiple chronic conditions, aging, healthcare service delivery, long-term care, review

Junli Zhang,1,&ast; Zhenghui Xu,1,&ast; Yu Fu,2,&ast; Lu Chen1,2 1Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China; 2Department of Clinical Nutrition, The Third Affiliated Hospital of Soochow University, Changzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Chen, Department of Endocrinology and Metabolism, The Third Affiliated Hospital of Soochow University, Changzhou, 213003, People’s Republic of China, Tel +86 0519-68870424, Email chenluforever@163.comPurpose: There remains a lack of a machine learning (ML) model incorporating body composition to assess the risk of bone mineral density (BMD) decreases in type 2 diabetes mellitus (T2DM) patients. We aimed to use ML algorithms and the traditional multivariate logistic regression to establish prediction models for BMD decreases in T2DM patients over 50 years of age, and compare the performance of the two methods.Patients and Methods: This cross-sectional study was conducted among 450 patients with T2DM from 1 August 2016 to 31 December 2022. The participants were divided into a normal BMD group and a decreased BMD group. Traditional multivariate logistic regression and six ML algorithms were selected to construct male and female models. Two nomograms were constructed to evaluate the risk of BMD decreases in the male and female T2DM patients, respectively. The ML models with the highest area under the curve (AUC) were compared with the traditional multivariate logistic regression models in terms of discriminant ability and clinical applicability.Results: The optimal ML model was the extreme gradient boost (XGBoost) model. The AUCs of the traditional multivariate logistic regression and the XGBoost models were 0.722 and 0.800 in the male testing dataset, respectively, and 0.876 and 0.880 in the female testing dataset, respectively. The decision curve analysis results suggested that using the XGBoost models to predict the risk of BMD decreases obtained more net benefits compared with the traditional models in both sexes.Conclusion: We preliminarily proved that the XGBoost models outperformed most other ML models in both sexes and achieved higher accuracy than traditional analyses. Due to the limited sample size in the study, it is necessary to validate our findings in larger prospective cohort studies.Keywords: type 2 diabetes mellitus, bone mineral density decrease, prediction model, machine learning, nomogram

Xinli Mu,1,&ast; Jianghong Liang,2,&ast; Linyan Qian,3 Bing Zhou,4 Xuehan Zou,5 Ying Fu,6 Yongze Zhu,2 Xi Li,2 Jiana Shi7 1Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People’s Republic of China; 3Heart Center, Department of Cardiovascular Medicine, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People’s Republic of China; 4Heart Center, Department of Cardiovascular Surgery, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People’s Republic of China; 5Center for General Practice Medicine, Department of Infectious Diseases, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 6Department of Clinical Laboratory, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou, Zhejiang, People’s Republic of China; 7Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital, Hangzhou Medical College), Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xi Li, Laboratory Medicine Center, Department of Clinical Laboratory, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel/Fax +86-571-8589-3267, Email lixi_0611@163.com Jiana Shi, Center for Clinical Pharmacy, Cancer Center, Department of Pharmacy, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China, Tel +86-571-8589-3899, Email shijjnn@126.comAbstract: Infective endocarditis (IE) is a rare disease but with high associated mortality. Currently, the mainstays of diagnosis are still echocardiography and blood cultures. Here, we reported a case of infective endocarditis with negative blood cultures, and blood and aortic valve tissue metagenomic next-generation sequencing (mNGS) results suggested Bartonella henselae. In addition, we obtained the whole genomic sequence of B. henselae ZJBH strain. To our knowledge, this is the first report of B. henselae genomic analysis isolated from clinic in China. Furthermore, we described the whole genome sequencing (WGS) data incorporating all B. henselae from diverse sources worldwide and shed light on underlying risk of B. henselae transmitted between cats and humans.Keywords: infective endocarditis, Bartonella henselae, metagenomic next-generation sequencing

Xu M, Fu Y, Fang Y, et al. Infect Drug Resist. 2019;12:641–653. Page 647, Molecular characteristics of the K. pneumoniae isolates, first paragraph, right column, second sentence from the bottom, the text “The PFGE results showed that the homology of 44 isolates was diverse (Figure 3)” should read “The PFGE results showed that the homology of 44 isolates was diverse (Figure 4)”. Page 648, left column, last sentence, the text “In general, ST11 KPC-2-producing hvKP strains harbored more antibioticresistant genes and less virulence factors when compared with the non-ST11 KPC-2-producing hvKP (Figure 5)” should read “In general, ST11 KPC-2-producing hvKP strains harbored more antibioticresistant genes and less virulence factors when compared with the non-ST11 KPC-2-producing hvKP (Figure 6)”. Page 648, right column, first sentence, the text “Among the 15 KPC-2-producing hvKP strains, 4 strains (KP35, KP37, KP43, and KP44) shared >75% similarity and classified into one cluster (Figure 3), while the remaining 11 strains exhibited distinct genetic relationship” should read “Among the 15 KPC-2-producing hvKP strains, 4 strains (KP35, KP37, KP43, and KP44) shared >75% similarity and classified into one cluster (Figure 4), while the remaining 11 strains exhibited distinct genetic relationship”. Page 649, left column, second paragraph, first sentence, the text “Consistent with the epidemiology trend of K. pneumoniae meningitis in some Asian countries especially in Taiwan,3,4” should read “Consistent with the epidemiology trend of K. pneumoniae meningitis in Taiwan,3,4”. The authors apologize for these errors.

Yiran Fu,1 Weishe Zhang,1,2 Qi Wang,1 Caihong Hu,1 Qi Li,3 Jingrui Huang1 1Department of Obstetrics, Xiangya Hospital Central South University, Changsha, People’s Republic of China; 2Hunan Engineering Research Center of Early Life Development and Disease Prevention, Changsha, People’s Republic of China; 3Reproductive Medicine Center, Xiangya Hospital Central South University, Changsha, People’s Republic of ChinaCorrespondence: Jingrui Huang, Department of Obstetrics, Xiangya Hospital Central South University, 87 Xiangya Road, Changsha, 410008, People’s Republic of China, Email jingruihuang@hotmail.com; huangjingrui@csu.edu.cnIntroduction: To evaluate the methodological quality of diagnosis and treatment guidelines/consensus related to ectopic pregnancy.Materials and methods: Use the “Appraisal of Guidelines and Research and Evaluation” (AGREE II) method to evaluate the differences among the guideline/consensus.Results: We appraised 9 clinical practice guidelines for ectopic pregnancy (9 clinical practice guidelines from 5 countries) including the United States, United Kingdom, Ireland, Canada, and China. The guidelines received the highest scores for clarity of presentation (82.72%) and lowest scores for editorial independence (30.56%). The comprehensive recommendations of the 7 guidelines were Grade B, the other 2 guidelines were Grade C.Conclusion: The overall quality of the ectopic pregnancy guidelines had room for improvement. It is recommended to supplement and improve the four fields of “independence”, “rigor”, “participants” and “application”, especially the “independence” and “application” fields.Keywords: guidelines, ectopic pregnancy, pelvic pain, AGREE II, clinical practice

Fangfang Yuan,1 Weiqiang Xiao,2 Xiaokun Wang,2 Yuewen Fu,1 Xudong Wei1 1Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University& Henan Cancer Hospital, Zhengzhou, People’s Republic of China; 2Department of Laboratory Science, The Affiliated Cancer Hospital of Zhengzhou University& Henan Cancer Hospital, Zhengzhou, People’s Republic of China;Correspondence: Xudong Wei; Yuewen Fu, Department of Hematology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, People’s Republic of China, Tel +86-371-65587218 ; +86-371-65587027, Email xudongwei@zzu.edu.cn; zlyyfuyuewen1480@zzu.edu.cnObjective: To analyze the clinical characteristics and prognostic risk factors of carbapenem-resistant Pseudomonas aeruginosa (CRPA) bloodstream infections in patients with hematologic malignancies.Methods: Medical records and drug susceptibility data of patients with hematologic malignancies complicated by CRPA bloodstream infections admitted to the Cancer Hospital of Zhengzhou University between January 1, 2018, and December 31, 2022, were retrospectively analyzed.Results: A total of 64 patients were included in the study, with a mortality rate of 37.5% (24/64) at 28 days after the occurrence of CRPA bloodstream infection. In Cox regression analysis, an absolute neutrophil count < 0.5× 109/L at discharge (HR 0.039, 95% CI 0.006 ~ 0.258, p=0.001), admission to the intensive care unit (HR 7.546, 95% CI 1.345 ~ 42.338, p= 0.022), and a higher Pitt bacteremia score (HR 0.207, 95% CI 0.046 ~ 0.939, p = 0.041) were independent risk factors associated with 28-day mortality. Survival analysis showed that patients receiving ceftazidime-avibactam-based (HR 0.368, 95% CI 0.107~ 1.268, p = 0.023) or polymyxin B (HR 2.561, 95% CI 0.721 ~ 9.101, p = 0.015) therapy had a higher survival rate.Conclusion: Patients with hematologic neoplasms had high mortality from CRPA bloodstream infections, and admission to the intensive care unit, higher Pitt bacteremia score (PBS) scores, granulocyte deficiency, and granulocyte deficiency at discharge were independently associated with higher mortality. Early anti-infective treatment with ceftazidime-avibactam or polymyxin B may improve the clinical prognosis of patients.Keywords: Pseudomonas aeruginosa, carbapenem resistance, bloodstream infection, hematologic neoplasm, risk factors

Zhenyun Yang,1,2,&ast; Zili Hu,1,2,&ast; Yizhen Fu,1,2 Dandan Hu,1,2 Zhongguo Zhou,1,2 Minshan Chen,1,2 Yangxun Pan,1,2 Yaojun Zhang1,2 1State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yangxun Pan; Yaojun Zhang, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, People’s Republic of China, Tel +86-20-87343828, Email panyx@sysucc.org.cn; zhangyuj@sysucc.org.cnBackground: Laparoscopic hepatectomy (LH) is more advantageous than open hepatectomy (OH) for hepatocellular carcinoma (HCC). However, surgical methods of conversion resection for patients with HCC have not been compared. We aimed to compare LH with OH for HCC after conversion therapy.Methods: We retrospectively reviewed the data of 334 patients who underwent conversion resection between January 2016 and December 2020 at Sun Yat-sen University, China. Propensity score matching (PSM) of patients in a ratio of 1:2 was conducted, and 62 patients and 121 patients who underwent LH and OH, respectively, were matched.Results: The LH and OH groups differed at baseline in terms of ALT (P=0.008), AFP (P=0.042), largest tumor size (P=0.028), macrovascular invasion (P=0.006), BCLC stages (P=0.021), and CNLC stages (P=0.048). The incidences of postoperative complications before and after PSM were lower in the LH group than in the OH group (P=0.007 and 0.003, respectively). There were no significant differences in the overall survival (OS) and recurrence-free survival (RFS) between the two groups (P=0.79 and 0.8, respectively). According to the multivariable Cox regression analyses, the largest tumor size (P< 0.0001) and tumor number (P=0.004) were significant and independent prognostic factors of OS.Conclusion: In our study, we found that LH is technically feasible and safe in patients after conversion therapy. Compared with OH, LH showed similar OS and RFS and was associated with fewer postoperative complications.Keywords: laparoscopic hepatectomy, open hepatectomy, hepatocellular carcinoma, conversion therapy, propensity score matching

Shuang Xu,1 Yi Fu,2 Dan Xu,1 Shuang Han,1 Mingzhi Wu,3 Xinrong Ju,1 Meng Liu,1 De-Sheng Huang,4,5 Peng Guan4,6 1Library of China Medical University, Shenyang, Liaoning, People’s Republic of China; 2School of Health Management, China Medical University, Shenyang, Liaoning, People’s Republic of China; 3Library of Shenyang Pharmaceutical University, Shenyang, Liaoning, People’s Republic of China; 4Key Laboratory of Environmental Stress and Chronic Disease Control & Prevention (China Medical University), Ministry of Education, Shenyang, Liaoning, People’s Republic of China; 5Department of Intelligent Computing, School of Intelligent Medicine, China Medical University, Shenyang, Liaoning, People’s Republic of China; 6Department of Epidemiology, School of Public Health, China Medical University, Shenyang, Liaoning, People’s Republic of ChinaCorrespondence: De-Sheng Huang; Peng Guan, China Medical University, Shenyang, Liaoning, 110122, People’s Republic of China, Email dshuang@cmu.edu.cn; pguan@cmu.edu.cnBackground: Before the COVID-19 pandemic, tuberculosis is the leading cause of death from a single infectious agent worldwide for the past 30 years. Progress in the control of tuberculosis has been undermined by the emergence of multidrug-resistant tuberculosis. The aim of the study is to reveal the trends of research on medications for multidrug-resistant pulmonary tuberculosis (MDR-PTB) through a novel method of bibliometrics that co-occurs specific semantic Medical Subject Headings (MeSH).Methods: PubMed was used to identify the original publications related to medications for MDR-PTB. An R package for text mining of PubMed, pubMR, was adopted to extract data and construct the co-occurrence matrix-specific semantic types. Biclustering analysis of high-frequency MeSH term co-occurrence matrix was performed by gCLUTO. Scientific knowledge maps were constructed by VOSviewer to create overlay visualization and density visualization. Burst detection was performed by CiteSpace to identify the future research hotspots.Results: Two hundred and eight substances (chemical, drug, protein) and 147 diseases related to MDR-PTB were extracted to form a specific semantic co-occurrence matrix. MeSH terms with frequency greater than or equal to six were selected to construct high-frequency co-occurrence matrix (42 × 20) of specific semantic types contains 42 substances and 20 diseases. Biclustering analysis divided the medications for MDR-PTB into five clusters and reflected the characteristics of drug composition. The overlay map indicated the average age gradients of 42 high-frequency drugs. Fifteen top keywords and 37 top terms with the strongest citation bursts were detected.Conclusion: This study evaluated the literatures related to MDR-PTB drug therapy, providing a co-occurrence matrix model based on the specific semantic types and a new attempt for text knowledge mining. Compared with the macro knowledge structure or hot spot analysis, this method may have a wider scope of application and a more in-depth degree of analysis.Keywords: multidrug-resistant tuberculosis, pulmonary tuberculosis, medication trends, specific semantic types, MeSH tree, pubMR

Hang Dong, Meng Gao, Lu Lu, Rong Gui, Yunfeng Fu Department of Blood Transfusion, the Third Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of ChinaCorrespondence: Yunfeng Fu, Department of Blood Transfusion, the Third Xiangya Hospital, Central South University, Tongzipo Road 138, Changsha, Hunan, 410013, People’s Republic of China, Email fuyunfeng@csu.edu.cnIntroduction: Triple-negative breast cancer (TNBC) is a highly aggressive subtype with a poor prognosis. Current single-agent checkpoint therapy has limited effectiveness in TNBC patients. In this study, we developed doxorubicin-loaded platelet decoys (PD@Dox) for chemotherapy and induction of tumor immunogenic cell death (ICD). By combining PD-1 antibody, PD@Dox has the potential to enhance tumor therapy through chemoimmunotherapy in vivo.Methods: Platelet decoys were prepared using 0.1% Triton X-100 and co-incubated with doxorubicin to obtain PD@Dox. Characterization of PDs and PD@Dox was performed using electron microscopy and flow cytometry. We evaluated the properties of PD@Dox to retain platelets through sodium dodecyl sulfate-polyacrylamide gel electrophoresis, flow cytometry, and thromboelastometry. In vitro experiments assessed drug-loading capacity, release kinetics, and the enhanced antitumor activity of PD@Dox. The mechanism of PD@Dox was investigated through cell viability assays, apoptosis assays, Western blot analysis, and immunofluorescence staining. In vivo studies were performed using a TNBC tumor-bearing mouse model to assess the anticancer effects.Results: Electron microscopic observations confirmed that platelet decoys and PD@Dox exhibited a round shape similar to normal platelets. Platelet decoys demonstrated superior drug uptake and loading capacity compared to platelets. Importantly, PD@Dox retained the ability to recognize and bind tumor cells. The released doxorubicin induced ICD, resulting in the release of tumor antigens and damage-related molecular patterns that recruit dendritic cells and activate antitumor immunity. Notably, the combination of PD@Dox and immune checkpoint blockade therapy using PD-1 antibody achieved significant therapeutic efficacy by blocking tumor immune escape and promoting ICD-induced T cell activation.Conclusion: Our results suggest that PD@Dox, in combination with immune checkpoint blockade therapy, holds promise as a potential strategy for TNBC treatment.Keywords: drug delivery, doxorubicin, immunogenic cell death, immune checkpoint blockade therapy

Tao Xie,1 Rong Huang,1 Daishuo Deng,1 Peipei Tang,2 Yufeng Fu,2 Yulong Zheng,1 Yufeng Wan1 1Department of Respiratory Diseases, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, Jiangsu, People’s Republic of China; 2Institute of Medicinal Biotechnology, Jiangsu College of Nursing, Huai’an, Jiangsu, People’s Republic of ChinaCorrespondence: Yulong Zheng; Yufeng Wan, Department of Respiratory Diseases, The Affiliated Huai’an Hospital of Xuzhou Medical University, Huai’an, Jiangsu, People’s Republic of China, Tel +86 137 7670 7363 ; +86 158 0523 0282, Fax +86 517 8087 1636 ; +86 517 8087 1616, Email ha183@163.com; ggwanyufeng@163.comPurpose: Corticosteroid insensitivity has become a major barrier in the treatment of chronic obstructive pulmonary disease (COPD). It is known that oxidative stress reduces the expression and activity of histone deacetylase (HDAC)-2 by activating phosphoinositide-3-kinase-δ(PI3Kδ)/Akt pathway, which is a common mechanism. The aim of this study was to investigate whether cryptotanshinone (CPT) can improve corticosteroid sensitivity and to investigate the molecular mechanisms by which this occurs.Patients and Methods: Corticosteroid sensitivity in peripheral blood mononuclear cells (PBMCs) collected from COPD patients, or in human monocytic U937 monocytic cells exposed to cigarette smoke extract (CSE), was quantified as the dexamethasone concentration required to achieve 30% inhibition of tumor necrosis factor-α (TNFα)–induced interleukin 8 (IL-8) production in the presence or absence of cryptotanshinone. PI3K/Akt activity (measured as the relative ratio of phosphorylated Akt at Ser-473 to total Akt) and HDAC2 expression levels were determined by western blotting. HDAC activity was evaluated by a Fluo-Lys HDAC activity assay kit in U937 monocytic cells.Results: Both PBMCs in patients with COPD and U937 cells exposed to CSE were found to be insensitive to dexamethasone, accompanied by increased phosphorylated Akt (pAkt) and decreased HDAC2 protein expression. The pretreatment of cryptotanshinone restored their sensitivity to dexamethasone, and simultaneously downregulated the level of phosphorylated Akt and upregulated the level of HDAC2 protein. Pretreatment with cryptotanshinone or IC87114 reversed the decrease in HDAC activity in CSE-stimulated U937 cells.Conclusion: Cryptotanshinone restores corticosteroid sensitivity induced by oxidative stress via inhibition of PI3Kδ and is a potential treatment for corticosteroid-insensitive diseases such as COPD.Keywords: corticosteroid insensitivity, chronic obstructive pulmonary disease, phosphoinositide-3-kinase-δ, histone deacetylase 2, cryptotanshinone

Yiyi Zhu,1 Lingling Wu,2– 5 Shuling Ye,6– 9 Yaoyang Fu,2– 5 Huimin Huang,1 Jianbo Lai,2– 5 Chuan Shi,6– 9 Shaohua Hu1– 5,10 1School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China; 2Department of Psychiatry, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3The Key Laboratory of Mental Disorder’s Management in Zhejiang Province, Hangzhou, People’s Republic of China; 4Brain Research Institute of Zhejiang University, Hangzhou, People’s Republic of China; 5Zhejiang Engineering Center for Mathematical Mental Health, Hangzhou, People’s Republic of China; 6Peking University Sixth Hospital, Beijing, People’s Republic of China; 7Peking University Institute of Mental Health, Beijing, People’s Republic of China; 8NHC Key Laboratory of Mental Health (Peking University), Beijing, People’s Republic of China; 9National Clinical Research Center for Mental Disorders (Peking University Sixth Hospital), Beijing, People’s Republic of China; 10Department of Neurobiology, NHC and CAMS Key Laboratory of Medical Neurobiology, School of Brain Science and Brian Medicine, and MOE Frontier Science Center for Brain Science and Brain-Machine Integration, Zhejiang University School of Medicine, Hangzhou, 310058, People’s Republic of ChinaCorrespondence: Shaohua Hu, School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China, Email dorhushaohua@zju.edu.cn Chuan Shi, Peking University Sixth Hospital, Beijing, 100191, People’s Republic of China, Email shichuan@bjmu.edu.cnBackground: Emotional blunting is prevalent in patients with mood disorders and adversely affects the overall treatment outcome. The Oxford Depression Questionnaire is a validated psychometric instrument for assessing emotional blunting. We aimed to evaluate the reliability and validity of the Chinese version of the ODQ (ODQ) in Chinese patients with mood disorders.Methods: 136 mood disorders patients and 95 healthy control participants were recruited at the First Affiliated Hospital of Zhejiang University, School of Medicine. Patients were assessed using the ODQ, Beck Depression Inventory-II (BDI-II), and Montgomery-Asberg Depression Rating Scale (MADRS). Internal consistency reliability and test-retest reliability were analyzed. Confirmatory factor analysis and correlation analysis were used to evaluate construct and convergent validity.Results: A total of 136 patients with mood disorders and 95 healthy controls participated in this study. Cronbach α values were 0.928 (ODQ-20) and 0.945 (ODQ-26). Test-retest reliability coefficients were 0.798 (ODQ-20) and 0.836 (ODQ-26) (p< 0.05); intraclass correlation coefficient values were 0.777 (ODQ-20) and 0.781 (ODQ-26) (p< 0.01). The score of ODQ was positively correlated with BDI-II and MADRS (r=0.326~0.719, 0.235~0.537, p< 0.01). The differences in the ODQ scores between the patient and control groups were statistically significant.Conclusion: The reliability, structural validity, and criterion validity of the ODQ applied to patients with mood disorders meet the psychometric requirements, and the scale can be used to assess emotional blunting in Chinese patients with mood disorders.Keywords: emotional blunting, Chinese, mood disorder, psychometrics, validation

Chengxuan Liu,1 Weijian Xiong,1 Jing Song,2 Xiaoqin Ouyang,1 Yang Fu3 1Department of Nephrology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, People’s Republic of China; 2Molecular Medicine and Cancer Research Centre, Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Rehabilitation, Chongqing Traditional Chinese medicine Hospital, Chongqing, People’s Republic of ChinaCorrespondence: Yang Fu, Department of Rehabilitation, Chongqing Traditional Chinese Medicine Hospital, No. 6 Panxi Branch Road, Jiangbei District, Chongqing, 400021, People’s Republic of China, Email fuyang@stu.cdutcm.edu.cnIntroduction: The overall survival of patients with high-stage clear cell renal carcinoma (ccRCC) is poor. However, promising molecular-level prognostic marker is still lacking to date.Methods: We systematically evaluated the prognostic potential of immune-related long non-coding RNAs (lncRNAs) in ccRCC. The expressions of lncRNAs were validated in clinical tissues of ccRCC. Functional experiments were performed to investigate the role of lncRNAs in ccRCC.Results: Eight hundred and ninety-three lncRNAs were differentially expressed in ccRCC and compared with normal controls and were screened out using three independent cohorts. Among them, 290 immune-related lncRNAs were identified. We identified a seven-lncRNA signature (LINC01270, FIRRE, RP11-37B2.1, RP11-253I19.3, RP11-438L19.1, RP11-504P24.9, and CTB-41I6.1) associated with the overall survival of late-stage ccRCC patients. Further multivariate Cox analysis using clinical factors as covariates showed that our lncRNA signature was an independent biomarker in training (P < 0.001, Log rank test) and validation cohorts (P = 0.003). The seven lncRNAs were closely related to the major targets (PD-1, PD-L1, and CTLA4) of immune checkpoint blockade drugs, implying that they may have potential value in predicting immunotherapy response. The seven lncRNAs may play an important role in tumor-infiltrating immune cells (eg, T/B cells) and tumor progression through regulating the binding of protein receptors/complexes, as revealed by functional analysis. qRT-PCR showed that LINC01270 was upregulated in ccRCC tissues (n=20) compared with paired normal samples. Functional experiments showed that LINC01270 silencing inhibited the proliferation, invasion, and migration of ccRCC cells.Discussion: In summary, the seven-lncRNA signature has great potential in prognosis for patients with late-stage ccRCC, which could be a novel clinical biomarker. LINC01270 could be a novel therapeutic target of ccRCC.Keywords: long non-coding RNA FIRRE, prognosis, renal cell carcinoma, tumor immune

Yajuan Fu,1,2 Lingbo Xu,1– 3 Hui Zhang,1– 3 Ning Ding,1– 3 Juan Zhang,1– 3 Shengchao Ma,1– 3 Anning Yang,1– 3 Yinjv Hao,1– 3 Yujing Gao,1,2 Yideng Jiang1– 3 1National Health Commission Key Laboratory of Metabolic Cardiovascular Diseases Research, Ningxia Medical University, Yinchuan, People’s Republic of China; 2Ningxia Key Laboratory of Vascular Injury and Repair Research, Ningxia Medical University, Yinchuan, People’s Republic of China; 3School of Basic Medical Sciences, Ningxia Medical University, Yinchuan, People’s Republic of ChinaCorrespondence: Yujing Gao; Yideng Jiang, Email gaoyujing2004@126.com; jydeng@nxmu.edu.cnBackground: Atherosclerosis and type 2 diabetes mellitus contribute to a large part of cardiovascular events, but the underlying mechanism remains unclear. In this study, we focused on identifying the linking genes of the diagnostic biomarkers and effective therapeutic targets associated with these two diseases.Methods: The transcriptomic datasets of atherosclerosis and type 2 diabetes mellitus were obtained from the GEO database. Differentially expressed genes analysis was performed by R studio software, and differential analysis including functional enrichment, therapeutic small molecular agents prediction, and protein–protein interaction analysis were applied to the common shared differentially expressed genes. Hub genes were identified and further validated using an independent dataset and clinical samples. Furthermore, we measured the expression correlations, immune cell infiltration, and diagnostic capability of the three key genes.Results: We screened out 28 up-regulated and six down-regulated common shared differentially expressed genes. Functional enrichment analysis showed that cytokines and immune activation were involved in the development of these two diseases. Six small molecules with the highest absolute enrichment value were identified. Three critical genes (CD4, PLEK, and THY1) were further validated both in validation sets and clinical samples. The gene correlation analysis showed that CD4 was strongly positively correlated with PLEK, and ROC curves confirmed the good discriminatory capacity of CD4 and PLEK in two diseases.We have established the co-expression network between atherosclerosis lesions progressions and type 2 diabetes mellitus, and identified CD4 and PLEK as key genes in the two diseases, which may facilitate both development of diagnosis and therapeutic strategies.Keywords: small molecular agents, immune infiltration, atherosclerosis, diabetes mellitus, inflammation

Yugang Lu,&ast; Qing Zhou,&ast; Yu Fu,&ast; Zongmei Wen, Xin Lv Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongmei Wen; Xin Lv, Department of Anesthesiology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, No. 507 Zhengmin Road, Shanghai, 200433, People’s Republic of China, Tel/Fax +86 21 65115006, Email wzm1103@126.com; xinlvg@126.comPurpose: Simultaneous bilateral pulmonary resection via uniportal video-assisted thoracoscopic surgery (UVATS) was safe and feasible for the treatment of bilateral multiple pulmonary nodules. But, it should be noted that considerable postoperative pain at the bilateral surgical site was a crucial issue. The safety and efficacy of bilateral thoracic paravertebral block (TPVB) have been reported for postoperative analgesia. But, whether bilateral sequential TPVB can be safely and effectively used in simultaneous bilateral UVATS remains unknown. Therefore, this study aimed to determine the analgesic efficacy and safety of bilateral sequential TPVB after simultaneous bilateral UVATS.Study Design and Methods: In this study, 80 participants scheduled for UVATS will be randomly allocated to the bilateral sequential TPVB group (G2) and the control group (G1). The patient of G2 will be performed bilateral TPVB at 2 time-points: before the start of the first side of pulmonary resection and before the start of the contralateral pulmonary resection. G1 will only receive standard analgesia protocol. The primary outcome is the numeric rating scale score during coughing at 24 h postoperatively. The secondary outcomes include the Prince Henry Pain Score scores, sufentanil consumption, postoperative nausea and vomiting, levels of inflammatory factors, and the Quality of Recovery-40 scores at different time points, as well as chronic pain at postoperative day (POD) 90.Discussion: This is the first prospective trial to determine the safety and effectiveness of ultrasound-guided bilateral sequential TPVB for postoperative analgesia following simultaneous bilateral UVATS. This study also intended to evaluate the effect of this intervention on postoperative quality of recovery and inflammation levels. The final results will provide clinical evidence related to bilateral sequential TPVB, and promote the application of that acting as a more appropriate analgesic method for simultaneous bilateral UVATS.Keywords: thoracic surgery, video-assisted, multiple pulmonary nodules, nerve block, pain measurement

Huajie Yang,1,&ast; Zhuohua Wu,2,&ast; Xiang Huang,3,4,&ast; Man Zhang,3 Yu Fu,5 Yijuan Wu,2 Lei Liu,2 Yiheng Li,2 Harry HX Wang5 1School of Health Technology, Guangdong Open University (Guangdong Polytechnic Institute), Guangzhou, People’s Republic of China; 2The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Sanxiang Community Health Service Centre of Zhongshan, Zhongshan, People’s Republic of China; 4Faculty of Medicine, Macau University of Science and Technology, Macau SAR, People’s Republic of China; 5School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Harry HX Wang, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China, Tel +86 20 87330672, Email wanghx27@mail.sysu.edu.cn Yiheng Li, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of China, Tel +86 20 83062721, Email ehengs@qq.comIntroduction: Timely access to emergency treatment during in-hospital care phase is critical for managing the onset of acute ischaemic stroke (AIS), particularly in developing countries. We aimed to explore in-hospital emergency treatment delay and the relation of door-to-needle (DTN) time to ambulance arrivals vs walk-in arrivals.Methods: Data were collected from 1276 Chinese AIS patients admitted to a general, tertiary-level hospital for intravenous thrombolysis. Information on patients’ characteristics and time taken during in-hospital emergency treatment was retrieved from the hospital registry data and medical records. Ambulance arrival was defined as being transported by emergency ambulance services, while walk-in arrival was defined as arriving at hospital by regular vehicle. In-hospital emergency treatment delay occurred when the DTN time exceeded 60 minutes. We performed multivariable logistic regression analysis to explore the association between hospital arrivals (by ambulance vs by walk-in) and treatment delay after adjustment for age, sex, education, marital status, residence, medical insurance, number of symptoms, clinical severity and survival outcome.Results: Over half (53.76%) of patients aged over 60 years. Around one-fifth (20.61%) of patients admitted to hospital through emergency ambulance services, while their counterparts arrived by regular vehicle. Overall, the median time taken from the hospital door to treatment initiation was 86.0 minutes. Patients arrived by ambulance (adjusted odds ratio [aOR] = 1.744, 95% confidence interval [CI] = 1.185– 2.566, p = 0.005), had higher socio-economic status (aOR = 1.821, 95% CI = 1.251– 2.650; p = 0.002), or paid out-of-pocket (aOR = 2.323, 95% CI = 1.764– 3.060; p < 0.001) had an increased likelihood of in-hospital emergency treatment delays.Conclusion: In-hospital emergency treatment delay is common in China, and occurs throughout the entire emergency treatment journey. Having a triage pathway involving hospital arrival by ambulance seems to be more likely to experience in-hospital emergency treatment delay. Further efforts to improve triage pathways may require qualitative evidence on provider- and institutional-level factors associated with in-hospital emergency treatment delay.Keywords: in-hospital emergency treatment, acute ischaemic stroke, treatment delay, hospital arrival, triage pathways

Ling Yang,&ast; Yu Fu,&ast; Si Li, Chang Liu, Donghua Liu Department of Dermatology and Venereology, First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Donghua Liu, Department of Dermatology and Venereology, First Affiliated Hospital of Guangxi Medical University, No. 6, Shuang Yong Road, Nanning, 530021, People’s Republic of China, Tel +86 13877113417, Email ldhgxmu@163.comPurpose: Neurosyphilis (NS) is a chronic infectious disease associated with Treponema pallidum subsp. pallidum (TP) infection of the central nervous system. The purpose of this study was to offer evidence for the diagnosis and treatment of NS by revealing the detection of TP DNA and CXCL13 concentration in the cerebrospinal fluid (CSF) of HIV-negative syphilis patients.Patients and Methods: This study included 75 syphilis patients. The frequency of TP invasion into the CSF was detected by nested PCR. ELISA was performed to detect CSF CXCL13 concentrations, and ROC analysis was performed to assess diagnostic accuracy. Sociodemographic data, clinical symptoms, and laboratory indices of patients were collected. CSF CXCL13 levels and clinical characteristics of syphilis patients were investigated retrospectively.Results: The detection rate of CSF DNA of TP by nested PCR was 5.3% and 16.7% in HIV-negative syphilis patients and NS patients, respectively. There was a significant difference between the NS and non-NS groups in terms of neurological symptoms, CSF TPPA, CSF TRUST, CSF nucleated cells, CSF protein, and CSF CXCL13 levels (P< 0.05). ROC curve analysis showed that the AUC for CSF CXCL13 levels was 0.906 (95% CI 0.832– 0.981, P < 0.0001), with an optimal critical value of 57.85 pg/mL and sensitivity and specificity of 88.89% and 78.95%, respectively.Conclusion: Nested PCR can be used as an auxiliary diagnosis of NS, and CSF CXCL13 > 60 pg/mL has high sensitivity and specificity for NS patients and non-NS patients. CXCL13 may be a useful marker to distinguish NS from non-NS syphilis in HIV-negative patients.Keywords: neurosyphilis, Treponema pallidum, cerebrospinal fluid, CXCL13

Zili Hu,1,2,&ast; Yu Yuan,3,&ast; Zhiwen Hu,1,2,&ast; Qingbo Liu,4 Yizhen Fu,1,2 Jingyu Hou,1,2 Xuqi Sun,5 Shaoqiang Li,6 Wenbin Duan,7 Minshan Chen1,2 1Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 2Collaborative Innovation Center for Cancer Medicine, State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Guangzhou, 510060, People’s Republic of China; 3Department of Respiratory Medicine, the Second Xiangya Hospital, Central South University, Changsha, 510235, People’s Republic of China; 4Department of Hepatobiliary Surgery, Shunde Hospital, Southern Medical University (The First People’s Hospital of Shunde), Foshan, 528308, People’s Republic of China; 5Department of Hepatobiliary and Pancreatic Surgery, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of China; 6Hepatic Pancreatobiliary Surgery Center, the First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 7Department of Hepatobiliary Surgery, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, 410005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Minshan Chen; Wenbin Duan, Fax ++86-20-87343117 ; +86-20-877557668214, Email chenmsh@sysucc.org; cnduanwenbin0222@163.comBackground: The value of lactate dehydrogenase (LDH) compared with other inflammation-based scores in predicting the outcomes of hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) patients after curative resection remains unknown. This study aims to evaluate the predictive value of LDH and develop novel nomograms to predict postoperative recurrence and survival in these patients.Methods: This study retrospectively collected 1560 patients with HBV-related HCC who underwent curative resection from four institutions in China. In total, 924 patients were recruited from our center and randomly divided into the training cohort (n = 616) and internal validation (n = 308) cohorts. Additionally, 636 patients were selected from three other centers as the external validation cohort. The C index of inflammation-based scores was calculated and compared in the training cohort. Novel models were developed according to multivariable Cox regression analysis in the training cohort and validated in the internal and external validation cohorts.Results: LDH showed a higher C-index than other inflammation-based scores for recurrence survival (RFS, 0.60, 95% CI, 0.58– 0.61) and overall survival (OS, 0.65, 95% CI, 0.63– 0.68). The nomograms of RFS and OS were developed based on tumor diameter, macrovascular invasion, AFP, operative hemorrhage, tumor differentiation, tumor number and LDH and achieved a high C-index (0.78, 95% CI, 0.76– 0.79 and 0.81, 95% CI, 0.79– 0.83), which were remarkably higher than the C-indexes of the five conventional HCC staging systems (0.52– 0.62 for RFS and 0.53– 0.67 for OS). The nomograms were validated in the internal validation cohort (0.77 for RFS, 0.78 for OS) and external validation cohort (0.80 for RFS, 0.81 for OS) and performed well-fitted calibration curves.Conclusion: The two nomograms based on inflammatory markers achieved optimal prediction for RFS and OS of patients with HBV-related HCC after hepatectomy.Keywords: hepatocellular carcinoma, hepatectomy, inflammation-based scores, lactate dehydrogenase, nomogram

Zhenyun Yang,1,2,* Deyao Zhang,1,2,* Huilan Zeng,1,2,* Yizhen Fu,1,2 Zili Hu,1,2 Yangxun Pan,1,2 Jinbin Chen,1,2 Juncheng Wang,1,2 Yaojun Zhang,1,2 Zhongguo Zhou,1,2 Li Xu,1,2 Dandan Hu,1,2 Minshan Chen1,2 1State Key Laboratory of Oncology in South China, Sun Yat-Sen University Cancer Center, Collaborative Innovation Center for Cancer Medicine, Guangzhou, Guangdong, 510060, People’s Republic of China; 2Department of Liver Surgery, Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong, 510060, People’s Republic of China*These authors contributed equally to this workCorrespondence: Dandan Hu; Minshan Chen, Tel +86-20-87343828 ; +86-20-87343117, Fax +86-20-87343585, Email hudd@sysucc.org.cn; chenmsh@sysucc.org.cnPurpose: Inflammatory response is related to tumor progression and patient survival. We aimed to clarify the prognostic value of the inflammation-based scores in intrahepatic cholangiocarcinoma (ICC) patients receiving anti-PD1 therapy.Patients and Methods: A total of 73 patients who received anti-PD-1 therapy from February 2019 to February 2021 were included in the study. Representative inflammation-based prognostic scores, including C-reactive protein (CRP), the platelet-to-lymphocyte ratio (PLR), neutrophil-to-lymphocyte ratio (NLR), lymphocyte-to-CRP ratio (LCR), lymphocyte-to-monocyte ratio (LMR), systemic immune inflammation index (SII), CRP-to-albumin ratio (CAR), prognostic nutritional index (PNI), Glasgow Prognostic Score (GPS), and prognostic index (PI), were assessed for prediction accuracy using Kaplan–Meier survival curves and time-dependent receiver operating characteristic (ROC). All the ten inflammation-based prognostic scores were measured before receiving anti-PD1 therapy.Results: All the ten inflammation-based prognostic scores showed good discriminatory ability in terms of overall survival (OS) (all P < 0.01), the higher the score, the worse the prognosis, while the CRP score was a remarkable independent predictor for OS in multivariate analysis (hazard ratio, 6.032; confidence interval, 2.467– 14.752; P < 0.001). The area under the ROC curve at 6 months, 12 months, 18 months and 24 months consistently demonstrated that the predictive value of the CRP score was superior to other inflammation-based scores.Conclusion: Inflammation-based scores predict the efficacy of anti-PD-1 therapy in patients with ICC and CRP score superior to the other inflammation-based prognostic scores in terms of predictive ability.Keywords: inflammation-based score, intrahepatic cholangiocarcinoma, anti-PD-1 treatment, overall survival, C-reactive protein

Yang Fu, Xiaohua Zhu, Ping Cao, Chen Shen, Xiaowen Qian, Hui Miao, Yi Yu, Hongsheng Wang, Xiaowen Zhai Department of Hematology, National Children’s Medical Center Children’s Hospital of Fudan University, Shanghai, People’s Republic of ChinaCorrespondence: Hongsheng Wang; Xiaowen Zhai, Department of Hematology, National Children’s Medical Center Children’s Hospital of Fudan University, 399 Wanyuan Road, Shanghai, 201102, People’s Republic of China, Tel +86 21 64931123, Fax +86 21 64931901, Email honswang@hotmail.com; xwzhai@fudan.edu.cnPurpose: To analyze the contribution of metagenomic next-generation sequencing (mNGS) in the guidance of clinical treatment and outcomes of infection during myelosuppression among children with hematological and neoplastic diseases.Patients and Methods: The clinical data and results of mNGS assay of febrile patients suspected of infection were retrospectively collected. The characteristics of pathogenic microorganisms and clinical course of myelosuppressed children with hematological diseases were summarized.Results: Our study included 70 patients (45 males) with a median age of 5 years (range: 0.5 to 13 y). During the study period, there were 96 events of suspected infection. According to comprehensive clinical diagnosis, 73 blood infections, 43 pneumonia and 2 urinary tract infections occurred. The positive rate of mNGS was significantly higher than that of traditional microbial detection (83.3% vs 17.7%). The main pathogens detected by mNGS were Pseudomonas aeruginosa, Acinetobacter, human herpesvirus, Candida and Aspergillus. The average duration of fever was 4.9 days and 11.6 days (P < 0.05), and the average cost of anti-infection treatment was RMB ¥ 28,077 and 39,898 (P < 0.05) among children received mNGS within 48 hours and more than 48 hours after the onset of infection symptoms.Conclusion: mNGS contributes to clinical management of children with infection during myelosuppression, especially among patients with negative traditional microbial detection. Early implementation of mNGS in children with symptoms has a tendency to reduce the time of infection, fever and the cost of treatment.Keywords: metagene, pathogenic microorganism, child, hematology and oncology

Yang Fu, Ying-Chao Yan, Xuan-Liang Ru, Hang-Bo Qu Department of Orthopedics, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Hang-Bo Qu, Department of Orthopedics, Affiliated Zhejiang Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Tel +86-153-5571-0890, Email quhb1222@163.comObjective: Chronic low back pain (CLBP) after percutaneous endoscopic transforaminal discectomy (PTED) surgery may be caused by preoperative lumbar microinstability (MI). However, there is a paucity of research on the relationship between lumbar microinstability and chronic low back pain. The purpose of this article is to assess the preoperative radiographic characteristics of patients and evaluate the effects of lumbar microinstability on patient-reported outcomes among single-level lumbar disc herniation (LDH) patients who underwent PTED.Methods: This study retrospectively reviewed the radiographic characteristics of a consecutive series of 127 patients with low back pain and leg pain caused by single-level LDH underwent PTED from August 2018 to March 2021. They were divided into three groups according to the radiographic parameters: the stable group (Group S), the dysfunctional group (Group D), and the microinstability group (Group M). The visual analogue scale (VAS) scores for leg and low back pain and Oswestry Disability Index (ODI) were evaluated preoperatively and postoperatively. Logistic regression analysis was used to identify independent risk factors for CLBP.Results: Compared with Group D and Group S, Group M had the highest ODI scores (P < 0.01) and VAS scores (low back pain) (P < 0.01) after 1 year, while there were no significant differences in the VAS scores for leg pain at different time points after surgery (P > 0.05). In addition, the logistic regression analysis results regarding CLBP revealed that muscle fatty degeneration on MRI (95% CI, 1.20– 8.51, P = 0.02), and facet tropism (95% CI, 1.39 − 11.37, P = 0.01) may be independent risk factors.Conclusion: Patients with lumbar microinstability may have CLBP after PTED, so patients with lumbar microinstability may need to take internal fixation surgery to solve their symptoms.Keywords: chronic low back pain, PTED, microinstability, risk factor

Jing zhao,1,2,&ast; Yu Fu,3,&ast; Yong Wang,1 Mingjia Bao,3 Huiling Li,1 Hongbin Qiu2 1Department of Microbiology, The First Affiliated Hospital of Jiamusi University, Jiamusi, People’s Republic of China; 2Key Laboratory of Microecology-immune Regulatory Network and Related Diseases School of Basic Medicine, Jiamusi University, Jiamusi, People’s Republic of China; 3Department of Microbiology, Center for Disease Control and Prevention of Jiamusi, Jiamusi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence:Hongbin Qiu, Key Laboratory of Microecology-immune Regulatory Network and Related Diseases School of Basic Medicine, Jiamusi University, Jiamusi, People’s Republic of China, Email qhbin63@163.comObjective: To investigate drug resistance and homology of pathogens that can cause infective diarrhea in East Heilongjiang, China, and provide suitable references for the clinical treatment.Methods: The process of isolation and identification of pathogenic bacteria in the faeces and blood of diarrhea patients was conducted. The drug resistance of the isolated pathogenic bacteria was analyzed by VITEK 2 compact drug sensitivity analysis system, and the strain homology was determined by pulsed field gel electrophoresis (PFGE).Results: From 2014 to 2018, 28 different strains of pathogenic bacteria were isolated from 657 samples of faeces and blood, including 23 strains of Salmonella, 3 strains of Vibrio parahaemolyticus and 2 strains of diarrheal Escherichia coli, with detection rates of 3.5%, 0.46% and 0.30% respectively. Among them, 22 strains of Salmonella exhibited significant drug resistance, with a drug resistance rate of 95.65%. A total of 11 different PFGE fingerprints of 23 Salmonella strains were also obtained, with a homology of 56.5– 100%.Conclusion: Among the various pathogens causing infective diarrhea in East Heilongjiang, China, Salmonella displayed multiple drug resistance and its distribution was found to be polymorphic.Keywords: diarrhea, pathogen, drug resistance, homology

Jian Qiu,1 Jiewei Xu,2 Guorong Yao,1 Fengjia Zhu,1 Yanyan Wang,3 Yunfeng Fu4 1Department of Obstetrics and Gynaecology, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, 313000, People’s Republic of China; 2Department of General Surgery, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, 313000, People’s Republic of China; 3Department of Pathology, Huzhou Central Hospital, Affiliated Central Hospital Huzhou University, Huzhou, 313000, People’s Republic of China; 4Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou, 310006, People’s Republic of ChinaCorrespondence: Yunfeng Fu, Department of Gynecologic Oncology, Women’s Hospital, School of Medicine, Zhejiang University, Xueshi Road #2, Hangzhou, 310006, People’s Republic of China, Tel +86-571-87061501, Fax +86-571-87061878, Email 5100008@zju.edu.cnAbstract: Large cell neuroendocrine carcinoma (LCNEC) is a rare histological subtype of ovarian cancer. A few cases have been reported in the literature with extreme invasiveness and a poor prognosis. However, there still have not been accepted criteria for diagnosis and treatment of LCNEC. Here we report an unmarried 37 year-old woman who was diagnosed with LCNEC associated with clear cell carcinoma and the tumor index was manifested with a specific increase of AFP. The case received six courses of etoposide and carboplatin chemotherapy as an adjuvant therapy after primary curative surgery. However, she relapsed within 6 months after surgery and metastasized rapidly to distant organs despite combined chemotherapy of paclitaxel, cisplatin, and bevacizumab, and died 18 months after primary surgery. This is the first reported case of LCNEC manifested with a specific increase of AFP and characteristically metastasized to the spine as recurrence. Reviewing our case as well as previously reported cases, LCNEC present with aggressive malignancy and vulnerable to distant metastasis through a hematogenous approach, we conjectured that adding Bevacizumab in primary chemotherapy may be beneficial to extend disease-free survival. But so far there is no recommendation of this regimen for treatment of LCNEC in current guidelines. Further research is needed to confirm this view so as to find the best treatment of LCNEC and improve the prognosis of these patients.Keywords: large cell neuroendocrine carcinoma, ovarian tumors

Wenzeng Xu, Yiqi Fu, Yake Yao, Jianying Zhou, Hua Zhou Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310003, People’s Republic of ChinaCorrespondence: Hua Zhou; Jianying Zhou, Email zhouhua1@zju.edu.cn; zjyhz@zju.edu.cnBackground: The effect of nosocomial infections (NIs) in adult patients undergoing ECMO has been rarely reported in China. Moreover, the effect of NIs on ECMO patients’ mortality is still unclear and inconclusive according to literature data. In this study, we examined the prevalence, risk factors, causative organisms, and effects on outcomes of NIs in ECMO patients.Methods: A total of 79 nonsurgical patients (mean age 53.3± 15.2 year (yr); 66% male) who underwent ECMO between January 2011 and September 2020 were enrolled in this retrospective study. Patients’ demographic and clinical data and ECMO parameters were collected from all patients.Results: Among 79 patients who underwent ECMO for a total of 1253 ECMO days (mean time 15.9± 14.1 d), 42 developed NIs. We observed 30 ventilator-associated pneumonia (VAP), 19 bloodstream infections (BSIs), and 4 urinary tract infections, corresponding to 23.9/1000 ECMO days, 15.2/1000 ECMO days, and 3.2/1000 ECMO days, respectively. ECMO duration (22.0± 16.5 VS 8.9± 5.3 d, P < 0.001), invasive mechanical ventilation (IMV) duration (27.4± 20.5 VS 11.4± 10.1 d, P < 0001), and ICU length of stay (35.9± 22.9 VS 15.7± 9.2 d, P < 0.001) were longer in patients with NIs. The independent risk factors for NIs were ECMO duration (Odds Ratio [OR], 1.414; 95% Confidence Interval [CI], (1.051– 1.238); P = 0.002) and viral pneumonia (OR, 5.788; 95% CI, (1.551– 21.596); P = 0.009). Gram-negative bacteria were the most common causative organisms of NIs; Acinetobacter baumannii (A. baumannii), Klebsiella pneumoniae (K. pneumoniae), and Pseudomonas aeruginosa (P. aeruginosa) were the most common bacteria. BSI (OR, 8.106; 95% CI, (1.384– 47.474); P = 0.02) was an independent predictor for mortality.Conclusion: NIs are common complications in patients during ECMO treatment, especially VAP, followed by BSI. Also, BSI can negatively affect the survival rate.Keywords: extracorporeal membrane oxygenation, healthcare-associated infections, bloodstream infections, risk factors, mortality

Yihui Fu, Lirong Liu, Haihong Wu Department of Respiratory and Critical Care Medicine, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), Haikou, 570311, People’s Republic of ChinaCorrespondence: Haihong Wu, Department of Respiratory and Critical Care Medicine, Hainan General Hospital (Hainan Affiliated Hospital of Hainan Medical University), #19, Xiuhua Road, Xiuying District, Haikou, 570311, People’s Republic of China, Tel/Fax +86 13976906068, Email y7y@163.comBackground: Chronic obstructive pulmonary disease (COPD) is the most common chronic inflammatory airway disease. Il-12r beta 2 (IL-12Rβ 2) is important for the production of pathogenic Th1 cells. We aimed to explore the association between IL-12Rβ 2 genetic variants and COPD risk among southern Chinese Han population.Methods: We recruited 996 participants to perform an association analysis through SNPStats online software. We used false-positive report probability analysis to detect whether the positive findings were noteworthy. Haploview 4.2 software and SNPStats were used to conduct the haplotype analysis and linkage disequilibrium. Finally, the interaction of SNP-SNP in COPD risk was evaluated by multi-factor dimensionality reduction.Results: The study found evidence that genetic loci in IL-12Rβ 2 (rs2201584, rs1874791, rs6679356, and rs3790567) were potentially associated with the COPD susceptibility. In particular, IL-12Rβ 2-rs2201584 and -rs1874791 showed close associations with COPD risk in both overall and several stratified analyses. Overall analysis or several stratified analyses indicated that allele A or homozygous genotype AA of IL-12Rβ 2-rs2201584 were risk factors for COPD (Allele A: OR (95% CI) = 1.23 (1.02– 1.48), p = 0.033; genotype AA: OR (95% CI) = 1.76 (1.15– 2.69), p = 0.009). The allele A or homozygous genotype AA of IL-12Rβ 2- rs1874791 were also risk factors for COPD (Allele A: OR (95% CI) = 1.36 (1.10– 1.68), p = 0.004; genotype AA: OR (95% CI) = 2.17 (1.18– 3.99), p = 0.013).Conclusion: Intronic variants in IL-12Rβ 2 (rs2201584, rs1874791, rs6679356, and rs3790567) were associated with the COPD susceptibility. In particular, there were sufficient evidences that IL-12Rβ 2-rs2201584 and -rs1874791 were associated with the increasing risk of COPD.Keywords: chronic obstructive pulmonary disease, IL-12Rβ 2, genetic variants, Chinese Han population

Jia Wei,1 Xiaofeng Lu,2 Qin Liu,1 Yao Fu,3 Song Liu,4 Lin Li,3 Fangcen Liu,3 Xiangshan Fan,3 Ju Yang,1 Yang Yang,1 Yang Zhao,5 Wenxian Guan,2 Baorui Liu1 1The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, 210008, People’s Republic of China; 2Department of General Surgery, Drum Tower Hospital, Nanjing, 210008, People’s Republic of China; 3Department of Pathology, Drum Tower Hospital, Nanjing, 210008, People’s Republic of China; 4Department of Radiology, Drum Tower Hospital, Nanjing, 210008, People’s Republic of China; 5Department of Biostatistics, Nanjing Medical University, Nanjing, 210029, People’s Republic of ChinaCorrespondence: Baorui Liu, The Comprehensive Cancer Centre of Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, 210008, People’s Republic of China, Tel +86 2583107081, Email baoruiliu@nju.edu.cnPurpose: Concurrent chemoradiotherapy (cCRT) is the mainstay therapy of locally advanced gastric (G) and gastroesophageal junction (GEJ) cancers with a poor prognosis. Programmed cell death receptor-1 (PD-1) inhibitor has been approved and recommended to treat ≥ 3 line G/GEJ patients. A significant clinical benefit of PD-1 inhibitors in addition to cCRT has been observed in locally advanced lung cancer. Sintilimab, a humanized IgG4 monoclonal antibody with high affinity and specificity for PD-1, has shown promising efficacy with an overall response rate of 85% in combination with chemotherapy in gastric cancer in a phase Ib study (NCT02937116).Patients and Methods: SHARED is a prospective, multicentre, single-arm Phase II trial in China, exploring the efficacy of sintilimab in combination with cCRT in locally advanced G/GEJ adenocarcinoma. According to a Simon optimal two-stage clinical design, 34 patients will be enrolled. All the eligible patients will receive one cycle of induction chemotherapy (S-1 plus nab-PTX) combined with sintilimab, followed by cCRT (radiotherapy plus nab-PTX) combined with sintilimab. Prior to the surgery, patients will receive another cycle of chemotherapy (S-1 plus nab-PTX) combined with sintilimab. In the adjuvant setting, all participants will be treated with 3 cycles of chemotherapy (S-1 plus nab-PTX) combined with sintilimab. The primary endpoint is the rate of pathological complete response (pCR). The secondary endpoints include disease-free survival (DFS), major pathological response (MPR), R0 resection rate, surgical AEs, overall survival (OS), event-free survival (EFS), and safety profile. Moreover, the prognostic value of tumor biomarkers and immune biomarkers will be explored.Conclusion: SHARED is designed to primally evaluate the efficacy and safety of sintilimab in combination with cCRT in locally advanced G/GEJ cancers and to prospectively validate the prognostic value of tumor biomarkers and immune biomarkers.Keywords: anti-PD-1, induction chemotherapy, chemoradiotherapy, immunotherapy

Zhongfang Yang,1– 3,&ast; Xiaoning Liu,4,5,&ast; Zheng Zhu,1,3,6 Lin Zhang,7 Shuyu Han,8 Yanfen Fu,9 Hongzhou Lu4 1School of Nursing, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Institute of Infectious Disease and Biosecurity, Fudan University, Shanghai, People’s Republic of China; 3Fudan University Centre for Evidence-Based Nursing: A Joanna Briggs Institute Centre of Excellence, Shanghai, People’s Republic of China; 4Department of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen, People’s Republic of China; 5National Heart & Lung Institute, Faculty of Medicine, Imperial College London, London, UK; 6NYU Rory Meyers College of Nursing, New York University, New York, NY, USA; 7Shanghai Public Health Clinical Center, Shanghai, People’s Republic of China; 8School of Nursing, Peking University, Beijing, People’s Republic of China; 9School of Nursing, Dali University, Dali, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zheng Zhu, School of Nursing, Fudan University, 305 Fenglin Road, Xuhui District, Shanghai, 200032, People’s Republic of China, Tel +86 21-6443 0093, Email zhengzhu@fudan.edu.cn Hongzhou Lu, Department of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Shenzhen Third People’s Hospital, Shenzhen, 518112, Guangdong Province, People’s Republic of China, Email luhongzhou@szsy.sustech.edu.cnAbstract: With Western Pacific Region reporting more imported cases, the World Health Organization (WHO) declared monkeypox a public health emergency of international concern in July. Currently, we are now at the beginning of forming stigmatization toward monkeypox. Based on the experience of combating HIV stigmatization for over 30 years, in this comment, we proposed measures based on the three stages of the stigma formation process. We believe the paper may be of particular interest to the readers of your journal as it offered implications for both healthcare professionals and researchers in Western Pacific Region.Keywords: infectious disease, stigmatization, global public health, measures

Junyi Jiang,1– 5,&ast; WeiJun Zhong,1– 4,&ast; WeiHua Huang,1– 4 Yongchao Gao,1– 4 Yijing He,1– 4 Xi Li,1– 4 Zhaoqian Liu,1– 4 Honghao Zhou,1– 4 Yacheng Fu,1,6 Rong Liu,1– 4 Wei Zhang1– 4 1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, People’s Republic of China; 3Engineering Research Center of Applied Technology of Pharmacogenomics, Ministry of Education, Changsha, People’s Republic of China; 4National Clinical Research Center for Geriatric Disorders, Changsha, Hunan, People’s Republic of China; 5Aier Eye Institute, Changsha, Hunan, People’s Republic of China; 6Cofoe Medical Technology Co., Ltd, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Zhang; Rong Liu, Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Changsha, 410008, People’s Republic of China, Tel +86 731 84805380, Fax +86 731 82354476, Email csuzhangwei@csu.edu.cn; csuliurong@csu.edu.cnPurpose: To identify more objectively predictive factors of severe outcome among patients hospitalized for coronavirus disease 2019 (COVID-19).Patients and Methods: A retrospective cohort of 479 hospitalized patients diagnosed with COVID-19 in Hunan Province was selected. The prognostic effects of factors such as age and laboratory indicators were analyzed using the Kaplan–Meier method and Cox proportional hazards model. A prognostic nomogram model was established to predict the progression of patients with COVID-19.Results: A total of 524 patients in Hunan province with COVID-19 from December 2019 to October 2020 were retrospectively recruited. Among them, 479 eligible patients were randomly assigned into the training cohort (n = 383) and validation cohort (n = 96), at a ratio of 8:2. Sixty-eight (17.8%) and 15 (15.6%) patients developed severe COVID-19 after admission in the training cohort and validation cohort, respectively. The differences in baseline characteristics were not statistically significant between the two cohorts with regard to age, sex, and comorbidities (P > 0.05). Multivariable analyses included age, C-reactive protein, fibrinogen, lactic dehydrogenase, neutrophil-to-lymphocyte ratio, urea, albumin-to-globulin ratio, and eosinophil count as predictive factors for patients with progression to severe COVID-19. A nomogram was constructed with sufficient discriminatory power (C index = 0.81), and proper consistency between the prediction and observation, with an area under the ROC curve of 0.81 and 0.86 in the training and validation cohort, respectively.Conclusion: We proposed a simple nomogram for early detection of patients with non-severe COVID-19 but at high risk of progression to severe COVID-19, which could help optimize clinical care and personalized decision-making therapies.Keywords: nomogram, COVID-19, SARS-CoV-2, C-reactive protein, predictive model

Hongxin Shen,1– 3 Yuzhi Fu,1– 3 Ying Chen,1– 3 Wenxing Xia,1– 3 Zhi-Jun Jia,1– 4 Qin Yu,3,5 Lingli Zhang,1– 3 Lu Han1– 3 1Department of Pharmacy, West China Second University Hospital of Sichuan University, Chengdu, People’s Republic of China; 2Evidence-Based Pharmacy Center, West China Second University Hospital of Sichuan University, Chengdu, People’s Republic of China; 3Key Laboratory of Birth Defects and Related Diseases of Women and Children (Sichuan University), Ministry of Education, Chengdu, People’s Republic of China; 4West China School of Pharmacy, Sichuan University, Chengdu, People’s Republic of China; 5Institute of Drug Clinical Trial GCP, West China Second University Hospital, Sichuan University, Chengdu, People’s Republic of ChinaCorrespondence: Lu Han, West China Second University Hospital, Sichuan University, No. 20, Third Section, Renmin South Road, Chengdu, Sichuan, 610041, People’s Republic of China, Email luhan830301@sina.comObjective: Pediatric electrolyte supplements injection is mainly used to supplement heat and body fluid, and commonly used in pediatrics. Its compatibility and stability with common clinical drugs such as antibiotics was rarely reported to ensure the children’s safety and the rational use of drugs. The aim of the present study was to investigate physical and chemical stability of pediatric electrolyte supplements injection mixed with ten commonly used clinical drugs.Methods: According to clinical drug concentration, we mix the pediatric electrolyte supplements injection mixed with ten drugs. The compatible solutions were withdrawn at certain time intervals (0, 0.5, 1, 2, 4, 6 hours) after mixing and tested by description, insoluble particles detection, pH determination and high performance liquid chromatography (HPLC) assay of active ingredient as measures of physicochemical compatibility.Results: No obvious appearance changes were observed when mixing. Furthermore, over the 6 hours post-preparation period the pH values were within the requirements of each drug quality standard and the number of insoluble particles (≥ 10 and ≥ 25μm) met requirements of Chinese Pharmacopeia (Edition 2020) except for mezlocillin sodium for injection. The percentages of the initial concentrations maintained at a minimum of 97% in the mixtures within 6 hours.Conclusions: Nine commonly used clinical drugs remained stable in the pediatric electrolyte supplements injection for 6 hours at 25°C and avoiding from light. Mezlocillin sodium for injection was not recommended to be combined with electrolyte supplement injection for children because its insoluble particles exceed the standard.Keywords: compatibility, stability, pediatric electrolyte supplements injection