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Since the first plasma realized in 2020, a series of key systems on HL-3 (known as HL-2M before) tokamak have been equipped/upgraded, including in-vessel components (the first wall, lower divertor, and toroidal cryogenic/water-cooling/baking/glow discharge systems, etc.), auxiliary heating system of 11 MW, and 28 diagnostic systems (to measure the plasma density electron temperature, radiation, magnetic field, etc.). Magnet field systems were commissioned firstly for divertor plasma discharges. During the 2nd experimental campaign of HL-3 tokamak, several great progresses have been achieved. Firstly, the successful operation with plasma current larger than 1 MA was achieved under a divertor configuration. Secondly, the advanced divertor concept with two distinct snowflake configurations was realized. It is found that the distribution of ion saturation current and heat flux on bottom plate becomes wide due to magnetic surface expansion, demonstrating the advantage of such configuration in the heat flux mitigation. In addition, using the combination of NBI, ECRH and LHCD, the standard sawtoothing high confinement mode of megampere plasma was firstly accessed on the HL-3. The successful commissioning of HL-3 is beneficial for the initial operation of ITER.

Dong-Xia Wu,1,&ast; Jing-Xian Hu,2,&ast; Jian-Hong Ma,1,&ast; Ke-Yi Chang,1,&ast; Yun Zhang,1 Xiao-Li Quan,1 Jia-Ning Han,1 Hai-Jing Long,1 Chen Chen,1 Wei Zhai,1 Huan-Huan Guo,1 Li-Li Zhang,2 Xiao-Lan Wang2 1Department of Infection and Immunology, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Department of Nursing, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-Li Zhang; Xiao-Lan Wang, Department of Nursing, Beijing Youan Hospital, Capital Medical University, No. 8 of Xitoutiao, Fengtai District, Beijing, 100069, People’s Republic of China, Tel/Fax +86 010 8399 7143, Email lillizhang3200z@163.comPurpose: To investigate and analyse the status quo of the self-management of patients living with HIV/AIDS (PLWHA) and its influencing factors and to provide the basis for formulating intervention strategies.Methods: In this cross-sectional study, 300 PLWHA who visited the Infection Center of Beijing Youan Hospital, Capital Medical University between September 2021 and December 2021 were enrolled using the convenience sampling method. Demographic characteristics and disease-related data were collected for each participant. The HIV/AIDS Self-Management Scale was used to evaluate the self-management ability of PLWHA.Results: A total of 251 male and 49 female PLWHA were included in this study, with an average age of 39.08 ± 12.09 years and an average disease duration of 9.61 ± 37.04 months. Univariate analysis showed that the PLWHA’s place of residence, educational level, physical condition, family relations, duration of HIV disease, receipt or not of antiviral therapy and knowledge of disease had an influence on the scores of the HIV Self-Management Scale (all p < 0.05). The results of the self-management scores indicated that the total score for self-management was 41.5 ± 6.4 points, with a scoring rate of 69.6%, which was at a medium level. Long-term self-management had the highest scoring rate (12.2 ± 2.5 points), followed by daily health management (22.3 ± 4.3 points), and social support for self-management had the lowest scoring (5.1 ± 0.9 points). Multivariable analysis showed that the self-management ability of PLWHA was related to educational level, duration of disease and family relations (R2 = 0.67, F = 121.7, p < 0.05).Conclusion: The self-management level of patients with AIDS, especially the social support of daily health management and self-management, needs to be further improved. Educational level, duration of disease and family relations are important factors influencing the self-management of PLWHA.Keywords: HIV/AIDS, AIDS, self-management

Yong Chen,1 Yan-Juan Chen,1 Jian-Feng Luo,2 Mang He,1 Si-Jin Zhao,3 Shi-Dan Tian,1 Yong-Qiao Zhang,3 Xiao-Long Chen,3 Chuan-Jie Yang,3 Yu-Zhuo Luo,3 Kutty Selva Nandakumar,4 Mei Tian1 1Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi, People’s Republic of China; 2Department of Biostatistics, School of Public Health, Fudan University, Shanghai, People’s Republic of China; 3The First School of Clinical Medicine, Zunyi Medical University, Zunyi, People’s Republic of China; 4Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, SwedenCorrespondence: Mei Tian, Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi City, Guizhou Province, 563000, People’s Republic of China, Email 348820517@qq.com Kutty Selva Nandakumar, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, 17177, Sweden, Email ksnandakumar@outlook.comPurpose: The quality of life (QoL) of elderly patients with rheumatoid arthritis (RA) in Zunyi China based on health parameters has not been previously analyzed. This study compares the 36-Item Short Form Health Survey (SF-36) scores and prevailing health complications between < 60y and ≥ 60y patients with RA. Data from 1166 patients with RA who visited the rheumatology department of Zunyi Medical University Hospital were followed up and retrospectively analyzed.Patients and Methods: Data from 1166 patients with RA who visited the rheumatology department of Zunyi Medical University Hospital (2021.1– 2022.8) were followed up and retrospectively analyzed.Results: Twenty cases passed away at 61.55 ± 8.11y, which was 6.75 years less than the local average age of death. Elderly patients with RA reported lower recovery levels, and their levels of inflammatory markers such as Immunoglobulin M-rheumatoid factor (IgM-RF), erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP) levels were significantly higher than those of younger patients during their past one-year observation period. The SF-36 results indicated that eight items of QoL in the elderly patients were all significantly inferior to < 60y patients, while the complications of interstitial lung disease (ILD), latent tuberculosis infection (LTBI) and, lung and herpes zoster infections were significantly higher.Conclusion: Elderly patients had a higher disease activity along with poor QoL, more health-related complications, and susceptibility to infections. Our study emphasizes the imperative need for optimization of RA treatment modalities in the elderly to alleviate their sufferings.Keywords: elderly rheumatoid arthritis, SF-36 scores, clinical characteristics, treatment outcomes

Xiao-ling Wu, Ya-nan Guo Intensive Care Unit, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Ya-nan Guo, Intensive Care Unit, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, 26 Shengli Street, Wuhan, 430014, People’s Republic of China, Tel +86-18186120762, Fax +86-27-82811446, Email guoyanan1104@sina.comIntroduction: Sepsis is the leading cause of death in critically ill patients; it results in multiorgan dysfunction, including acute respiratory distress syndrome (ARDS). Our study was conducted to determine the role of cellular senescence genes and immune infiltration in sepsis and sepsis-induced ARDS via bioinformatic analyses.Experimental Procedures: Datasets GSE66890 and GSE145227 were obtained from the Gene Expression Omnibus (GEO) database and utilized for bioinformatics analyses. Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses of the differentially expressed genes (DEGs) were performed to identify the key functional modules. Two machine learning algorithms, least absolute shrinkage and selection operator (LASSO) and support vector machine recursive feature elimination (SVM-RFE), were used to screen for characteristic genes in sepsis and sepsis-induced ARDS. ROC curves were generated to evaluate the predictive ability of gene hubs. Differences in immune infiltration levels between the disease and control groups were compared via ssGSEA. The diagnostic value of the hub genes was verified via quantitative PCR (qPCR) in hospitalized patients.Results: Four characteristic genes (ATM, CCNB1, CCNA1, and E2F2) were identified as biomarkers for the progression of sepsis-induced ARDS. E2F2 showed the highest predictive ability for the occurrence of ARDS in patients with sepsis. CD56bright and plasmacytoid dendritic cells exhibited high infiltration in the sepsis-induced ARDS group, whereas eosinophils, MDSCs, macrophages, and neutrophils exhibited low infiltration. In addition, ATM expression was lower in patients with sepsis than in those without sepsis (n = 6).Conclusion: Sepsis-induced ARDS is correlated with circulating immune responses, and the expression of ATM, CCNB1, CCNA1, and E2F2 may serve as potential diagnostic biomarkers and therapeutic targets in sepsis-induced ARDS.Keywords: sepsis, cellular senescence genes, immune infiltration, acute respiratory distress syndrome, bioinformatics analysis

Xiao Wang,1,&ast; Ying Cao,2,&ast; Jing Hu,3 Lian-Cheng Jia,4 Bo Li,3 Baoli Liu,5 Wei-Hai Yao,2 Xiao-Lu Pei,6 Wei Peng,2 Shuang Wang,2 Cun-Zhi Liu,1,7 Jian-Feng Tu,1,7 Zhi-Cheng Qu2 1School of Acupuncture-Moxibustion and Tuina, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Emergency Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 3Evidence Based Medicine Center, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 4Urinary Surgery, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 5Nephrology Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 6Nursing Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 7International Acupuncture and Moxibustion Innovation Institute, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhi-Cheng Qu, Emergency Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, 23 Meishuguanhou Street, Dongcheng District, Beijing, 100010, People’s Republic of China, Email qzhch0824@163.com Jian-Feng Tu, 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 tujianfeng1@126.comIntroduction: Analgesia is often delayed for suspected acute renal colic due to urinary calculi (ARCUC) even in emergency department. Acupuncture has a rapid onset and is effective for analgesia, however, evidence about early-acupuncture for suspected ARCUC is limited. This trial aims to evaluate the efficacy of early-intervention acupuncture compared with sham acupuncture on pain relief among emergency department suspected ARCUC patients.Methods and Analysis: A total of 84 eligible patients who are suspected diagnosed with ARCUC will be randomly allocated to the acupuncture group or the sham acupuncture group. Each patient will receive 1 session of acupuncture or sham acupuncture before diagnostic imaging. The primary outcome will be the response rate at 10 min after needle manipulation, defined as the proportion of patients whose Numeric Rating Scale (NRS) score decrease by at least 50% from baseline. Secondary outcomes will include pain intensity assessed by NRS, further analgesia requirement, revisit rate, surgical intervention rate, satisfaction evaluation, and adverse events. The final diagnosis rate determined by radiography will be recorded and reported. All patients who receive randomization will be included in the intention-to-treat analysis.Conclusion: This study’s findings are anticipated to evaluate the analgesic effect of early-intervention acupuncture for acute renal colic in emergency department, which could be useful for moving the timing of analgesia forward and aligning pain management for acute renal colic more with the guidelines.Trial Registration Number: ChiCTR2100049069 (https://www.chictr.org.cn/showproj.html?proj=125338).Keywords: acupuncture, complementary medicine, pain management, emergency medicine, renal colic

Ya-zhi Xi,1,2 Xue-lian Wei,1,2 Lei Xie,1,2 Xiao-yu Jia,2 Zhen-ping Li,2 Qing-he Zhou2 1Anesthesia Medicine, Zhejiang Chinese Medical University, Hangzhou City, Zhejiang Province, People’s Republic of China; 2Department of Anesthesiology and Pain Medicine, the Affiliated Hospital of Jiaxing University, Jiaxing City, Zhejiang Province, People’s Republic of ChinaCorrespondence: Qing-he Zhou, Department of Anesthesiology and Pain Medicine, the Affiliated Hospital of Jiaxing University, No. 1882, South of the Second Ring Road, Jiaxing City, Zhejiang Province, 314000, People’s Republic of China, Tel +8613732573379, Fax +86057389997760, Email zqh10980@zjxu.edu.cnBackground: The effects of intraoperative permissive hypercapnia (PaCO2 of 45– 55 mmHg) on the central nervous system remain unclear. Neurofilament light chain (NfL, a protein found in the axons and nerve fibers of neurons) has been associated with central nervous system disorders. This study investigated the effect of intraoperative permissive hypercapnia on plasma NfL concentration 1 day postoperatively, and in turn on the central nervous system, during laparoscopic surgery.Methods: This investigation was a prospective, single-blind randomized controlled trial. Eighty-four individuals aged above 60 years were randomly allocated to either the normocapnia group with an PaCO2 of 35– 45 mmHg (n=42) or the hypercapnia group with a PaCO2 of 45– 55 mmHg (n=42). The primary outcome was the 1-day postoperative plasma NfL concentration. Secondary outcomes included the area under the curve (AUC) values for PaCO2 and regional cerebral oxygen saturation (rSO2). The Mann–Whitney U-test was mainly used to analyze the outcomes.Results: The final analysis included 38 and 40 patients in the normocapnia and hypercapnia groups, respectively. There was no statistically significant difference observed between the groups regarding the preoperative and 1-day postoperative plasma NfL concentration (14.0 [11.1, 19.9] vs 16.3 [9.06, 19.9] pg/mL, P> 0.05; 23.4 [16.8, 32.3] vs 21.5 [15.6, 29.9] pg/mL, P> 0.05, respectively). However, in both groups, the postoperative plasma concentration of NfL showed a significant increase when compared with the preoperative levels (both P < 0.001). The AUCs of PaCO2 and rSO2 from the beginning to the end of the pneumoperitoneum were significantly higher in the hypercapnia group compared with the normocapnia group (both P

Xiong Lv, Chun Xiang, Yan Zheng, Wan-Xuan Zhou, Xu-Ling Lv Department of Plastic Surgery, The Quzhou Affiliated Hospital of Wenzhou Medical University, Quzhou People’s Hospital, Quzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Xiong Lv, Email 13157056997@163.comAbstract: Skin photoaging, resulting from prolonged exposure to ultraviolet (UV) radiation, is characterized by intricate biological changes involving oxidative damage and structural alterations. Despite an increasing demand for effective interventions, the current therapeutic options for treating skin photoaging are limited. We discovered through literature data search on PubMed that recent research has shifted its focus to the application of microneedle patches as an innovative approach to address this concern. Microneedle patches, serving as a novel transdermal delivery system, exhibit the potential to deliver bioactive substances such as cytokines, cellular vesicles, gene fragments and even alive algae to mitigate the effects of skin photoaging. This review aims to provide a comprehensive overview of recent advancements in research about utilizing microneedle patches for the treatment of skin photoaging and potential future directions in leveraging microneedle patches as clinical therapeutic agents for skin rejuvenation. Ultimately, we believe that microneedle patches have a broader application prospect in the fields of medical cosmetology and anti-photoaging. Keywords: skin photoaging, antioxidants, microneedle patch, transdermal delivery, skin rejuvenation

Xiao-Yang Xu,&ast; Ze Wang,&ast; Chen-You Liu,&ast; Hao-Dong Wu, Ze-Xin Hu, Yu-Ying Lin, Shuai Zhang, Jian Shen, Bin-Yan Zhong, Xiao-Li Zhu Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Li Zhu, Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, No. 899 Pinghai Street, Suzhou, 215006, People’s Republic of China, Email zhuxiaoli90@163.comObjective: To explore changing trends in circulating immune indicators of hepatocellular carcinoma (HCC) undergoing TACE plus immune checkpoint inhibitors (ICIs) and anti-VEGF antibodies/TKIs and to elucidate the relationship between immune response and tumor prognosis.Materials: This single-center retrospective study included patients with unresectable HCC undergoing TACE plus ICIs and anti-VEGF antibodies/TKIs from March 11, 2019, to February 15, 2024. Peripheral blood samples were collected at baseline and every cycle, from which blood cell counts and immune indicators were analyzed. The primary outcome was the objective response rate (ORR) at the first evaluation. According to the first evaluation based on mRECIST, patients were classified into PD, SD, and OR groups for analysis. Further subgroup analysis was performed on the OR group based on whether experiencing progression after the first evaluation. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The neutrophil-to-lymphocyte ratio (NLR) was measured by the complete blood count. Simple linear regression was employed to examine the dynamic trends.Results: A total of 63 patients were enrolled, with an ORR of 55.6% and a disease control rate (DCR) of 87.3% at the first evaluation. The median overall survival (mOS) was 27.5 months (95% CI: 22.5– 32.5 months). In the OR group (n=35), more active immune responses, expressed in a decrease in CD3−CD19+ (p=0.004), CFB (p=0.027), NLR (p< 0.001) and an increase in Ig λ (p=0.010), Ig κ (p=0.037), Ig A (p=0.005), Ig G (p=0.006), were related to better prognosis, while similar patterns seen in the OR-nPD subgroup. Concurrently, no significant differences were noted in the PD group (n=8).Conclusion: The combination therapy may modify the tumor microenvironment of HCC. Changing trends in circulating immune indicators and NLR can serve as potential biomarkers for predicting tumor response and guiding clinical treatment.Keywords: immune indicator, TACE, immune checkpoint inhibitors, tyrosine kinase inhibitors, tumor microenvironment

Yang Deng,1,&ast; Rui Duan,2,&ast; Ye Hong,2,&ast; Qiang Peng,2 Zhong-Yuan Li,2 Xiang-Liang Chen,2 Ying-Dong Zhang1 1Department of Neurology, Nanjing First Hospital, China Pharmaceutical University, Nanjing, 210006, People’s Republic of China; 2Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, 210006, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang-Liang Chen, Department of Neurology, Nanjing First Hospital, Nanjing Medical University, No. 68, Changle Road, Nanjing, Jiangsu, 210006, People’s Republic of China, Email chenxl@njmu.edu.cn Ying-Dong Zhang, Department of Neurology, Nanjing First Hospital, China Pharmaceutical University, No.68, Changle Road, Nanjing, Jiangsu, 210006, People’s Republic of China, Email zhangyingdong@njmu.edu.cnPurpose: Vascular dementia (VaD) is the second most common dementia in the world. An increasing number of studies have demonstrated the important role of long non-coding RNAs (lncRNAs) in VaD. Our previous investigation demonstrated that Trimethylamine-N-oxide (TMAO) exacerbates cognitive impairment and neuropathological alterations in VaD rats. Thus, we hypothesized that TMAO could play an injury role in VaD by regulating lncRNAs.Materials and Methods: The rats using the bilateral common carotid artery (2VO) model were administered TMAO (120 mg/kg) for 8 consecutive weeks, 4 weeks preoperatively and 4 weeks postoperatively. High-throughput sequencing was conducted to investigate the effects of TMAO treatment on lncRNA expression in rat hippocampus and bioinformatics analysis was performed to identify potential downstream targets. Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the levels of lncRNA fetal-lethal noncoding developmental regulatory RNA (Fendrr), miR-145-5p, and paxillin (PXN). Learning and spatial memory capacities were measured, as well as inflammatory factors. Nissl staining was used to observe neuronal injury in the CA1 area of the hippocampus. Furthermore, we used the Fendrr loss-of-function assay, miR-145-5p gain-of-function assays and PXN loss-of-function assay to explore the mechanisms by which TMAO acts on VaD.Results: TMAO administration upregulated lncRNA Fendrr expression in the rat hippocampus, while the damaging effects of TMAO were counteracted after knockdown of Fendrr. Fendrr exhibits highly expressed in 2VO rats and sponged miR-145-5p, which targets PXN. Silencing of Fendrr or PXN, or promotion of miR-145-5p improved neurological function injury, reduced neuronal damage, as well as repressed inflammation response. Inhibition of miR-145-5p abrogated up Fendrr knockdown mediated influence on 2VO rats.Conclusion: The results of this study indicated that TMAO inhibits the miR-145-5p/PXN axis by increasing the Fendrr expression, thus exacerbating the development of VaD.Keywords: trimethylamine N-oxide, neuroinflammation, Fendrr, MiR-145-5p, PXN, vascular dementia

Xu-Lin Wang,1,&ast; Ling-Ling Dai,2,&ast; Yan-Na Li,1 Jian-Wen Zhang,1 Ming-Cui Qu,1 Yao-Yao Zhou,1 Na Xing1 1Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Respiration, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Na Xing, Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, No. 1 East Jianshe Road, Zhengzhou, People’s Republic of China, Tel +8613949095172, Email 16427485@qq.comPurpose: This study aimed to compare the efficacy of remimazolam and propofol regarding postoperative anesthesia satisfaction in patients undergoing outpatient gynecological surgery.Patients and Methods: This was a single-center, open-label, non-inferiority, randomized clinical trial. Patients aged ≥ 18 years who underwent outpatient gynecological surgery with sedation were enrolled. Participants were randomly assigned to be sedated with remimazolam or propofol. The primary endpoint was the immediate postoperative anesthesia satisfaction score, evaluated through the Iowa Satisfaction with Anesthesia Scale (ISAS).Results: 168 patients were randomly allocated to either the remimazolam group (n = 84) or the propofol group (n = 84). The mean (standard deviation) ISAS scores immediately after surgery were 1.7 (0.6) for the remimazolam group and 2.0 (0.7) for the propofol group (difference, – 0.2; 97.5% confidence interval [CI]: – 0.5 to – 0.0; p = 0.02), indicating non-inferiority. The length of post-anesthesia care unit (PACU) stay was longer in the remimazolam group than in the propofol group (27.6 [9.1] min vs 22.4 [7.0] min; difference, 5.2 [95% CI: 2.7 to 7.6] min; p < 0.001). High-intensity injection pain was less frequently observed in the remimazolam group than in the propofol group (3.6% vs 45.2%; difference, – 41.7% [95% CI: – 54.2% to – 29.1%]; p < 0.001). The nausea score was higher in the remimazolam group immediately after surgery than in the propofol group. Pain, nausea, sleep quality, anxiety, and depression scores were higher in the remimazolam group than in the propofol group on postoperative day 1. The incidence of adverse events and other secondary endpoints was comparable between the two groups.Conclusion: Remimazolam was non-inferior to propofol regarding postoperative anesthesia satisfaction in patients undergoing outpatient gynecological surgery. Therefore, it should be considered as a new sedation alternative in such procedures.Keywords: remimazolam, propofol, patient satisfaction, outpatient gynecological surgery, sedation

Xin Luo,1,&ast; Hai-Jun Hou,2,&ast; Pei-Shan Chen,1 Xin-Lu Chang,1 Yang Li,1 Li-Xin An,1 Fu-Kun Liu,1 Fu-Shan Xue1,3 1Department of Anesthesiology, Beijing Friendship Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Pain Medicine, Guanganmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 3Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fu-Shan Xue, Department of Anesthesiology, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou, Fujian Province, 350001, People’s Republic of China, Tel +86-13911177655, Fax +86-0591-88217841, Email xuefushan@aliyun.com; fushanxue@outlook.comObjective: Postoperative pain is a common yet often underestimated complication following esophageal endoscopic submucosal dissection (ESD), with limited strategies for effective management. This prospective, double-blind, randomized controlled trial assessed the effects of adding dexmedetomidine (DEX) to the anesthesia regimen on postoperative pain and early recovery in patients undergoing esophageal ESD.Methods: In total, 60 patients scheduled for elective esophageal ESD under general anesthesia were randomly assigned to the DEX or control group. The DEX group received an intravenous loading dose of DEX at 1 μg/kg for 10 min, followed by a continuous intravenous infusion of 0.6 μg/kg/h, which was stopped 30 min before the end of the procedure. The control group received normal saline as a placebo. The study’s primary outcome was the incidence of moderate-to-severe postoperative pain. Secondary outcomes included postoperative pain scores, hemodynamic parameters, the occurrence of postoperative nausea and vomiting (PONV), patient satisfaction, and lengths of stay in the post-anesthesia care unit (PACU) and hospital.Results: The incidence of moderate-to-severe postoperative pain in the DEX group was significantly lower than that in the control group (absolute difference: − 33.4%; OR: 0.250; 95% CI: 0.085– 0.731, P = 0.01). Pain scores at 1 h postoperatively (0.5[2.0] vs 3.0[1.3], P = 0.003) were significantly lower in the DEX group. Additionally, morphine dosage in the PACU (0[0] vs 1.0[2.0] P = 0.004) was significantly reduced in the DEX group compared with the control group. In the DEX group, the incidence and severity of PONV were significantly decreased and the length of PACU stay was shorter than in the control group (P

Li Chen,1,2 Xi-Le Peng,1,2 Zhi-Xuan Chen,1,2 Lu-Ming Qi,1,2 Ting-Ting Deng,2,3 Li-Na Xia1,2 1School of Health Preservation and Rehabilitation, Chengdu University of TCM, Chengdu, Sichuan, People’s Republic of China; 2Key Laboratory of Traditional Chinese Medicine Regimen and Health Industry Development, State Administration of TCM, Chengdu, Sichuan, People’s Republic of China; 3School of Nursing, Chengdu University of TCM, Chengdu, Sichuan, People’s Republic of ChinaCorrespondence: Li-Na Xia, School of Health Preservation and Rehabilitation, Chengdu University of TCM, Chengdu, Sichuan, People’s Republic of China, Email xialina@cdutcm.edu.cnBackground: Excessive salt consumption has been associated with detrimental health consequences, including hypertension, colitis, and autoimmune disorders. However, recent studies have proposed that high salt diet (HSD) can both stimulate the immune system, affecting the differentiation of immune cells, promoting or inhibiting cytokine secretion to fight cancer or elicit a more potent autoimmune response, and exerting an immunosuppressive effect to influence disease development, providing mechanistic insights into the direction of immune regulation in which HSD affects disease.Objective: This paper reviews the immunomodulatory effects of HSD on various innate immune and adaptive cells, especially macrophages, dendritic cells, and T cells, in relation to disease development.Methods: We identified papers by electronically searching the Web of Science (WOS) database from inception through March 2023.Results: A growing number of animal experiments and in vitro cell culture studies have shown that HSD can regulate the differentiation and activation of a variety of immune cells, and promote or inhibit different cytokines to mediate the development of a variety of diseases, including nephropathy, hypertension, cancer, inflammatory bowel disease, and a number of autoimmune diseases. These findings provide a new mechanism for pathological changes in the direction of immune regulation and suggest that HSD is a predisposing factor for a variety of diseases, providing new mechanistic insights into dietary health modification.Conclusion: HSD mediates the development of multiple diseases by regulating the differentiation and activation of a variety of immune cells, and the underlying mechanisms may be related to gut microbes and their metabolites.Keywords: HSD, immune dysregulation, disease pathogenesis, mechanistic insights, review

Lin Zhu,1 Qian Zhang,1 Ke Ni,2 Xue-Jun Yang,1 Kai Jin,3 Wei Wei,4– 6 David A Preece,7,8 Bao-Ming Li,1,9 Xin-Lu Cai1,9 1Institute of Brain Science and Jing Hengyi School of Education, Hangzhou Normal University, Hangzhou, People’s Republic of China; 2Qiqihar Mental Health Center, Qiqihar, People’s Republic of China; 3The Fifth People’s Hospital of Lin’an District, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Neurobiology, Affiliated Mental Health Center & Hangzhou Seventh People’s Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Liangzhu Laboratory, MOE Frontier Science Center for Brain Science and Brain-Machine Integration, State Key Laboratory of Brain-Machine Intelligence, Zhejiang University, Hangzhou, People’s Republic of China; 6NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou, People’s Republic of China; 7School of Population Health and Curtin enAble Institute, Curtin University, Perth, WA, Australia; 8School of Psychological Science, The University of Western Australia, Perth, WA, Australia; 9Zhejiang Philosophy and Social Science Laboratory for Research in Early Development and Childcare, Hangzhou Normal University, Hangzhou, People’s Republic of ChinaCorrespondence: Xin-Lu Cai, Institute of Brain Science and Jing Hengyi School of Education, Hangzhou Normal University, Hangzhou, 311121, People’s Republic of China, Tel +86 571-28864320, Email caixinlu@hznu.edu.cnBackground: Abnormalities of regulating positive and negative emotion have been documented in patients with mental disorders. Valid and reliable psychological instruments for measuring emotion regulation across different valences are needed. The Perth Emotion Regulation Competency Inventory (PERCI) is a 32-item self-report measure recently developed to compressively assess emotion regulation ability across both positive and negative valences.Purpose: This study aimed to validate the Chinese PERCI in a large non-clinical sample and examine the clinical utility in patients with major depressive disorder (MDD).Methods: The Chinese PERCI was administered to 1090 Chinese participants (mean age = 20.64 years, 773 females). The factor structure, internal consistency, test-retest reliability, convergent validity, concurrent validity, and predictive validity were examined. Moreover, a MDD group (n = 50) and a matched healthy control group (n = 50) were recruited. Group comparisons and the linear discriminant analysis were conducted to assess the clinical relevance of the PERCI.Results: Confirmatory factor analysis supported the intended eight-factor structure of the PERCI in the Chinese population. The PERCI showed high internal consistency, test-retest reliability, as well as good convergent and concurrent validity. The MDD group had significantly higher PERCI scores than the healthy control group. Linear discriminant function comprised of the eight factors successfully distinguish patients with MDD from their matched controls.Conclusion: The Chinese version of the PERCI is a valid and reliable instrument to compressively measure emotion regulation across positive and negative valences in the general Chinese population and patients with depression.Plain Language Summary: The Perth Emotion Regulation Competency Inventory was designed to comprehensively assess emotion regulation ability across both positive and negative valences. This study provided the first translation and psychometric evaluation of the PERCI in the Chinese context. The findings support that the Chinese version of the PERCI is a reliable and valid measurement for assessing emotion regulation across positive and negative valences in research and clinical practice.Keywords: emotion regulation, reliability, validity, factor structure, depression

Congenital diarrheal disorders (CDD) are a group of rare inherited intestinal disorders, among which CDD7 was recently identified to be associated with only 24 mutations in gene coding for diacylglycerol-acyltransferase 1 (DGAT1).

Kai Hong,1,&ast; Yan Liu,1,&ast; Hao Yin,2 Ke Huang,2 Xiao-Li Pu,1 Zhuan-Xu Zhu1 1Department of Gynaecology, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China; 2Department of Obstetrics, Taihe Hospital, Hubei University of Medicine, Shiyan, Hubei, 442000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuan-Xu Zhu, Email 13636196733@163.comBackground: Ovarian cancer (OC) remains the deadliest gynecologic malignancy worldwide due to delayed diagnosis, recurrence, and drug resistance. This study aimed to identify key factors affecting delayed diagnosis in OC patients.Methods: A retrospective analysis was conducted on OC patients treated at Taihe Hospital, Hubei University of Medicine from June 2023 to September 2023. Patients were categorized based on a three-months cut-off point for delayed diagnosis. Collected data included demographics, tumor incidence, and disease cognition. The analysis of variance and the chi-squared test was used for comparison between groups.Results: The significant differences were found in age, residence, education level, family income, family history of tumor, histology, FIGO stage, and tumor location between groups (P< 0.05). Multifactorial logistic regression analysis identified education level [odds ratio (OR) = 0.606; 95% confidence interval (CI): 0.440, 0.833; P = 0.002], family history of tumor (OR = 0.462; 95% CI: 0.214, 0.997; P = 0.049), emotional barriers (OR = 1.332; 95% CI: 1.081, 1.642; P = 0.007), and practical barriers (OR = 2.964; 95% CI: 2.195, 4.004; P < 0.001) as risk factors for delayed diagnosis of OC.Conclusion: Patient cognition is crucial in OC diagnosis delay. Enhancing public awareness and understanding of OC is essential to eliminate fear and improve early diagnosis.Keywords: ovarian cancer, delayed diagnosis, disease awareness, emotional barriers

Ying-Chao Ma,1 Ya-Qing Sun,2 Xia Wu,1 Yong-Jing Wang,1 Xiu-Ling Yang,1 Jian-Jun Gu3 1Department of Pharmacy, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050000, People’s Republic of China; 2College of Pharmacy, Hebei Medical University, Shijiazhuang, Hebei Province, 050000, People’s Republic of China; 3Department of Cardiac Surgery, Second Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 050000, People’s Republic of ChinaCorrespondence: Jian-Jun Gu, Department of Cardiac Surgery, Second Hospital of Hebei Medical University, No. 215 of Heping West Road, Xinhua District, Shijiazhuang, 050000, Hebei Province, People’s Republic of China, Tel +8631166002991, Email jianjungu62@126.com Xiu-Ling Yang, Department of Pharmacy, Second Hospital of Hebei Medical University, No. 215 of Heping West Road, Xinhua District, Shijiazhuang, Hebei Province, 050000, People’s Republic of China, Tel +8631166002712, Email yangxuilingyxl0d@126.comObjective: To assess the efficacy and safety of colistin sulfate in treating infections caused by carbapenem-resistant organisms (CRO) and to analyze potential factors impacting its effectiveness.Methods: In this retrospective study, medical records of CRO-infected patients from June 2020 to June 2023 were analyzed, divided into effective and ineffective treatment groups, and compared for clinical outcomes and adverse reactions. Multifactorial logistic regression and ROC curve analysis were used to identify influencing factors.Results: The study included 226 patients, with 124 in the effective treatment group and 102 in the ineffective group. A total of 293 CRO strains were cultured. The clinical efficacy rate of colistin sulfate was 54.87%, the microbiological efficacy rate 46.46%, and the hospital mortality rate 20.80%, with nephrotoxicity observed in 11.50% of patients. Multifactorial analysis identified APACHE II scores and vasoactive drug use as independent predictors of ineffective treatment, while treatment duration and albumin levels predicted effective treatment. ROC analysis indicated that albumin levels > 34 g/L, APACHE II scores < 13, and treatment duration > 10 days correlated with better clinical efficacy.Conclusion: Colistin sulfate is both safe and effective in clinical settings. Factors such as treatment duration, albumin levels, APACHE II scores, and vasoactive drug use independently affect its clinical efficacy, providing valuable guidance for its informed clinical application.Keywords: colistin sulphate, carbapenem-resistant organism, clinical efficacy, influencing factors, safety evaluation

Studying tropical hydroclimate and productivity change in the past is critical for understanding global climate dynamics. Northwest Australia is an ideal location for investigating Australian monsoon dynamics, the variability of the Indonesian Throughflow (ITF), and their impact on past productivity and Pacific warm pool evolution, which remain poorly understood during the 40 kyr world in the mid-early Pleistocene. In this study, we present multi-proxy records from International Ocean Discovery Program (IODP) Site U1483 in the Timor Sea spanning the last 2,000 ka, including orbitally-resolved records from the 40 kyr world between 2,000 and 1,300 ka. Our results suggest that northwest Australia underwent a step of increased aridification and that productivity in the Timor Sea declined during the transition from ∼1,700 to ∼1,400 ka. We attribute this aridification to the reduced moisture supply to this region caused by the ITF restriction and warm pool contraction. We ascribe the declined productivity to a decrease in the nutrient supply of the Pacific source water associated with global nutrient redistribution. At orbital timescale, multiple mechanisms, including sea level changes, monsoon, and the Intertropical Convergence Zone (ITCZ) dynamics, and variations in the ITF and Walker circulation could have controlled variations of productivity and terrigenous input in the Timor Sea during the 40 kyr world. Our bulk nitrogen and benthic carbon isotope records suggest a strong coupling to biogeochemical changes in the Pacific during this period. This research contributes to a better understanding of tropical hydroclimate and productivity changes during the 40 kyr world.

Rose Aniza Rusli,1,2 Mohd Makmor Bakry,1 Noraida Mohamed Shah,1 Xin Ling Loo,3 Stefanie Kar Yan Hung4 1Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Kuala Lumpur, Malaysia; 2Pharmacy Department, Hospital Shah Alam, Shah Alam, Selangor, Malaysia; 3Pharmacy Department, Hospital Tengku Ampuan Rahimah, Klang, Selangor, Malaysia; 4Neuromedical Unit, Hospital Tengku Ampuan Rahimah, Klang, Selangor, MalaysiaCorrespondence: Mohd Makmor Bakry, Faculty of Pharmacy, Universiti Kebangsaan Malaysia, Jalan Raja Muda Abdul Aziz, Kuala Lumpur, 50300, Malaysia, Tel +603 9289 7199, Fax +603 2698 3271, Email mohdclinpharm@ukm.edu.myAim: Identifying a patient’s risk for poor outcomes after starting antiseizure medication (ASM) therapy is crucial in managing epilepsy pharmacologically. To date, there is a lack of designated tools to assess such risks.Purpose: To develop and validate a risk assessment tool for the therapeutic outcomes of ASM therapy.Patients and Methods: A cross-sectional study was carried out in a hospital-based specialist clinic from September 2022 to August 2023. Data was analyzed from patients’ medical records and face-to-face assessments. The seizure control domain was determined from the patients’ medical records while seizure severity (SS) and adverse effects (AE) of ASM were assessed using the Seizure Severity Questionnaire and the Liverpool Adverse Event Profile respectively. The developed tool was devised from prediction models using logistic and linear regressions. Concurrent validity and interrater reliability methods were employed for validity assessments.Results: A total of 397 patients were included in the analysis. For seizure control, the identified predictors include ≥ 10 years’ epilepsy duration (OR:1.87,95% CI:1.10– 3.17), generalized onset (OR:7.42,95% CI:2.95– 18.66), focal onset seizure (OR:8.24,95% CI:2.98– 22.77), non-adherence (OR:3.55,95% CI:1.52– 8.27) and having ≥ 3 ASM (OR:3.29,95% CI:1.32– 8.24). Younger age at epilepsy onset (≤ 40) (OR:3.29,95% CI:1.32– 8.24) and neurological deficit (OR:3.55,95% CI:1.52– 8.27) were significant predictors for SS. For AE, the positive predictors were age > 35 (OR:0.12,95% CI:0.03– 0.20), < 13 years epilepsy duration (OR:2.89,95% CI:0.50– 5.29) and changes in ASM regimen (OR:2.93,95% CI: 0.24– 5.62). The seizure control domain showed a good discriminatory ability with a c-index of 0.711. From the Bonferroni (ANOVA) analysis, only SS predicted scores generated a linear plot against the mean of the actual scores. The AE domain was omitted from the final tool because it did not meet the requirements for validity assessment.Conclusion: This newly developed tool (RAS-TO) is a promising tool that could help healthcare providers in determining optimal treatment strategies for adults with epilepsy.Keywords: antiseizure medication, seizure control, risk assessment, therapeutic outcomes

Kehua Jiang,1 Qing Wang,1 Xiao-Long Chen,1 Xiaodong Wang,1 Xiaoya Gu,1 Shuangshuang Feng,1 Jian Wu,2 Haojie Shang,2 Xiaozhuo Ba,2 Yanlong Zhang,1 Kun Tang2 1Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China; 2Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaCorrespondence: Yanlong Zhang, Department of Urology, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China, Email ylzhang3030@163.com Kun Tang, Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, No. 1095, Jiefang Avenue, Qiaokou District, Wuhan, 430030, People’s Republic of China, Email tangsk1990@163.comAbstract: Tryptophan (Trp) metabolism plays a vital role in cancer immunity. Indoleamine 2.3-dioxygenase 1 (IDO1), is a crucial enzyme in the metabolic pathway by which Trp is degraded to kynurenine (Kyn). IDO1-mediated Trp metabolites can inhibit tumor immunity and facilitate immune evasion by cancer cells; thus, targeting IDO1 is a potential tumor immunotherapy strategy. Recently, numerous IDO1 inhibitors have been introduced into clinical trials as immunotherapeutic agents for cancer treatment. However, drawbacks such as low oral bioavailability, slow onset of action, and high toxicity are associated with these drugs. With the continuous development of nanotechnology, medicine is gradually entering an era of precision healthcare. Nanodrugs carried by inorganic, lipid, and polymer nanoparticles (NPs) have shown great potential for tumor therapy, providing new ways to overcome tumor diversity and improve therapeutic efficacy. Compared to traditional drugs, nanomedicines offer numerous significant advantages, including a prolonged half-life, low toxicity, targeted delivery, and responsive release. Moreover, based on the physicochemical properties of these nanomaterials (eg, photothermal, ultrasonic response, and chemocatalytic properties), various combination therapeutic strategies have been developed to synergize the effects of IDO1 inhibitors and enhance their anticancer efficacy. This review is an overview of the mechanism by which the Trp-IDO1-Kyn pathway acts in tumor immune escape. The classification of IDO1 inhibitors, their clinical applications, and barriers for translational development are discussed, the use of IDO1 inhibitor-based nanodrug delivery systems as combination therapy strategies is summarized, and the issues faced in their clinical application are elucidated. We expect that this review will provide guidance for the development of IDO1 inhibitor-based nanoparticle nanomedicines that can overcome the limitations of current treatments, improve the efficacy of cancer immunotherapy, and lead to new breakthroughs in the field of cancer immunotherapy.Keywords: indoleamine 2, 3-dioxygenase 1, IDO1, IDO1 inhibitors, nanodrugs, nanodelivery, cancer immunotherapy, combination therapy

Yong Chen,1 Mang He,1 Si-Jin Zhao,2 Yan-Juan Chen,1 Yong-Qiao Zhang,2 Xiao-Long Chen,2 Chuan-Jie Yang,2 Yu-Zhuo Luo,2 Kutty Selva Nandakumar,3 Zhou-Xiong Xing,4 Mei Tian1 1Department of Rheumatology and Immunology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China; 2Undergraduate Students of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of China; 3Docent, Department of Medical Biochemistry and Biophysics, Karolinska Institute, Stockholm, Sweden; 4Department of Critical Care Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of ChinaCorrespondence: Mei Tian; Zhou-Xiong Xing, Affiliated Hospital of Zunyi Medical University, 149 Dalian Road, Huichuan District, Zunyi City, Guizhou Province, People’s Republic of China, Email 348820517@qq.com; xingzhouxiong111@126.comPurpose: To investigate the clinical value of adding Jin-gu-lian (JGL) capsules into rheumatoid arthritis (RA) treatment by examining its impact on disease activity and quality of life (QoL) through a real-world study (RWS).Patients and methods: RWS was conducted to compare the inflammatory markers, including IgM-RF, ESR, and CRP, between RA patients treated with only Western medicine (reference group) and Western medicine plus JGL (study group) during one-year follow-up. The clinical data was acquired from the hospital information system (HIS). Telephone call-based follow-up on QoL (SF-36) and accompanying symptoms, including gastrointestinal complaints, attacks of pneumonia, herpes zoster, URTIs, UTIs, and LTBIs. Finally, the anti-rheumatic drugs given to both groups were also compared. RWS was further validated for its feasibility by performing studies with hydroxychloroquine (HCQ) treatment, which is a commonly used anti-rheumatic drug for RA with mild effect.Results: The study group failed to show a significant effect on inflammatory markers, especially on the CRP levels, indicating no additional clinical value of supplementing with JGL. Similarly, at the endpoint, no significant differences between the two groups on QoL and related symptoms were observed. Our study suggests that the patients in the study group might need more anti-rheumatic drugs to fill the treatment insufficiency, and the application ratio of NSAIDs would be significantly higher than the reference group. By conducting this study on HCQ treatment, the positive aspects of controlling disease activity and reducing NSAIDs application were found, which demonstrates the utility of performing the RWS to evaluate the effect of JGL.Conclusion: Adding JGL did not significantly improve the clinical efficacy of RA treatment by this RWS. Folk herbal prescriptions such as JGL are suggested to underwent strict clinical trials before application.Keywords: real-world study, rheumatoid arthritis, traditional Chinese medicine, disease activity, hydroxychloroquine

Hao-Huan Tang,1,&ast; Lin-Feng Zhou,2,3,&ast; Chun-Xin Wang,4,&ast; Yang Zha,4 Chen Fan,1 Bin-Yan Zhong,2 Xiao-Li Zhu,2 Wei-Dong Wang1 1Department of Interventional Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People’s Republic of China; 2Department of Interventional Radiology, The First Affiliated Hospital of Soochow University, Suzhou, 215006, People’s Republic of China; 3Department of Radiology, Hubei Cancer Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430079, People’s Republic of China; 4Department of Radiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Li Zhu, The First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Suzhou, 215006, People’s Republic of China, Tel/Fax +86 512 67780375, Email zhuxiaoli90@163.com Wei-Dong Wang, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing, No. 299, Qingyang Road, Medical University, Wuxi, 214023, People’s Republic of China, Tel/Fax +86 510 85350121, Email wdoc@sina.comBackground and Aims: The objective of this study was to investigate the effect of neutrophil-to-lymphocyte ratio (NLR) on the survival of cirrhotic patients with esophagogastric variceal bleeding (EGVB) treated with transjugular intrahepatic portosystemic shunt (TIPS).Methods: A total of 293 patients treated with TIPS were included. The receiver operator characteristic curve (ROC) was used to calculate the optimal cut-off values of parameters such as NLR. The Kaplan-Meier curve and Cox proportional risk model were used to evaluate the effects of NLR and other variables on 2-year all-cause mortality.Results: The area under the ROC for NLR was 0.634, with an optimal cutoff value of 4.9. Two-year mortality rates for patients with high (≥ 4.9) and low (< 4.9) NLR were 22.1% and 9.3%, respectively (Log rank test: P = 0.002). After correcting for confounders, multivariate analysis demonstrated that NLR ≥ 4.9 (HR = 2.741, 95% CI 1.467– 5.121, P = 0.002), age ≥ 63 (HR = 3.403, 95% CI 1.835– 6.310, P < 0.001), and gender (male) (HR = 2.842, 95% CI 1.366– 5.912, P = 0.001) were independent risk factors for the mortality outcome. Considering the stratification of early and selective TIPS treatment, high NLR still significantly increased the risk of mortality for patients (Log rank test: P = 0.007, HR = 2.317, 95% CI 1.232– 4.356).Conclusion: NLR can help to predict survival in EGVB patients after TIPS, and the type of TIPS should also be considered in practical applications.Keywords: neutrophil-to-lymphocyte ratio, transjugular intrahepatic portosystemic shunt, esophagogastric variceal bleeding, prognostic factor

Qian Wu,1,&ast; Qing-Qing Dong,1,&ast; Si-Hui Wang,1 Yi Lu,1 Yi Shi,1 Xiao-Ling Xu,2 Wei Chen1 1ICU, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Shulan International Medical College, Zhejiang Shuren University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Chen, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, 725 South WanPing Road, Shanghai, 200032, People’s Republic of China, Tel +86-21-64385700-3522, Email cwdoctor@shutcm.edu.cn Xiao-Ling Xu, Shulan International Medical College, Zhejiang Shuren University, 8 Shuren Street, Hangzhou, 310015, People’s Republic of China, Email ziyao1988@zju.edu.cnBackground: Sepsis continues to exert a significant impact on morbidity and mortality in clinical settings, with immunosuppression, multi-organ failure, and disruptions in gut microbiota being key features. Although rheinic acid and tanshinone IIA show promise in mitigating macrophage apoptosis in sepsis treatment, their precise targeting of macrophages remains limited. Additionally, the evaluation of intestinal flora changes following treatment, which plays a significant role in subsequent cytokine storms, has been overlooked. Leveraging the innate inflammation chemotaxis of tumor cell-derived exosomes allows for their rapid recognition and uptake by activated macrophages, facilitating phenotypic changes and harnessing anti-inflammatory effects.Methods: We extracted exosomes from H1299 cells using a precipitation method. Then we developed a tumor cell-derived exosomal hybrid nanosystem loaded with rhubarbic acid and tanshinone IIA (R+T/Lipo/EXO) for sepsis treatment. In vitro studies, we verify the anti-inflammatory effect and the mechanism of inhibiting cell apoptosis of nano drug delivery system. The anti-inflammatory effects, safety, and modulation of intestinal microbiota by the nanoformulations were further validated in the in vivo study.Results: Nanoformulation demonstrated enhanced macrophage internalization, reduced TNF-α expression, inhibited apoptosis, modulated intestinal flora, and alleviated immunosuppression.Conclusion: R+T/Lipo/EXO presents a promising approach using exosomal hybrid nanosystems for treating sepsis. Keywords: sepsis, rheinic acid, tanshinone IIA, exosome, hybrid nanosystem

Xiao-Ling Shen,1,&ast; Zhuo-Yi Li,1,&ast; Qing Li,1 Kai Wang2 1Department of Women Health Care, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, 361005, People’s Republic of China; 2Department of Aristogenesis, Women and Children’s Hospital, School of Medicine, Xiamen University, Xiamen, Fujian, 361005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Wang; Qing Li, Email wangkai111909@163.com; lq5090@126.comPurpose: To verify whether there is lower incidence of adverse pregnancy outcomes after high-intensity focused ultrasound (HIFU) treatment than loop electrosurgical excision procedure (LEEP) in young women of childbearing age.Patients and Methods: This retrospective cohort study enrolled 46 patients treated with HIFU and 46 patients treated with LEEP. To compare the differences between the two groups, Fisher’s exact test or the Kruskal–Wallis (K-W/H) test was used in the univariate analysis, while the logistic regression method was applied for further verification.Results: Basic characteristics showed no differences between the two groups (P > 0.05) except for parity (P < 0.001). Preterm birth rates were 6.52% and 0.00% in patients with cervical high-grade squamous intraepithelial lesions (HSIL) treated with LEEP and HIFU, respectively. The incidence rates of premature rupture of membranes (PROM) were respectively 15.22% and 21.74% in the two groups. There was no significant difference in pregnancy outcomes between the two groups (P > 0.05).Conclusion: This study is the first to compare the pregnancy outcomes of patients with cervical HSIL who treated with LEEP and HIFU procedures. Both HIFU treatment and LEEP are available options for patients of reproductive age with cervical HSIL. Therefore, it is necessary to conduct prospective single-center or multicenter randomized controlled studies.Keywords: cervical high-grade squamous intraepithelial lesions, high-intensity focused ultrasound, loop electrosurgical excision procedure, pregnancy outcome

Xian-Lin Wu,1,2,&ast; Hong-Yan Liu,1,&ast; Qiu-Hong Xiang,1 Zhuan Yin,3 Rong Zhou,1 Ye-Juan Wang,1 Bi-Yu Zhou,1 Fang Wang,1 Min Zhao,1 Mei Chen1 1Department of Obstetrics, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, 410007, People’s Republic of China; 2Department of Nursing, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, 410007, People’s Republic of China; 3Department of Neonatology, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, Changsha, 410007, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiu-Hong Xiang, Department of obstetrics, Changsha Hospital for Maternal & Child Health Care Affiliated to Hunan Normal University, No. 416 of Chengnan Dong Lu, Yuhua District, Changsha, 410007, People’s Republic of China, Tel +18684888525, Email xqhong1313@163.comObjective: Labor induction during the late trimester of pregnancy is a common option of terminating pregnancy by inducing uterine contractions through medication or cervical mechanical dilation. However, there are few researches on the factors influencing the effectiveness of cervical ripening balloon combined with oxytocin in inducing labor. To explore factors affecting the efficacy of cervical ripening double balloon combined with oxytocin in labor induction.Methods: Using a convenient sampling method, this study retrospectively collected the clinical data of 230 pregnant women who underwent cervical ripening double balloon combined with oxytocin for labor induction in our hospital from September 2021 to August 2022. The included subjects were divided into a vaginal delivery group (n = 180) and a cesarean section group (n = 50) based on the delivery mode for comparing relevant indicators between the two groups.Results: The presence of acute chorioamnionitis (OR = 1.456, 95% CI: 1.257– 2.112), fetal distress (OR = 1.371, 95% CI: 1.331– 2.633), and the placement of cervical ripening balloon catheter for > 12h (OR = 1.563, 95% CI: 1.231– 3.263) were risk factors for successful application of cervical ripening double balloon combined with oxytocin for labor induction in pregnant women; while multi-gravidity (OR = 0.736, 95% CI: 0.455– 0.875) was a protective factor. In addition, evaluation of the predictive value revealed that acute chorioamnionitis, fetal distress, the placement of cervical ripening balloon catheter for > 12h, and gravidity all had certain predictive value for the failure of cervical ripening double balloon combined with oxytocin for labor induction, with the highest predictive value found through joint predictive (AUC: 0.931, 95% CI: 0.714– 0.811).Conclusion: Cervical ripening double balloon combined with oxytocin for labor induction may have a high success rate in multigravida. Acute chorioamnionitis, fetal distress, and prolonged placement of the balloon may have a negative impact on the success rate of cervical ripening double balloon combined with oxytocin for labor induction.Keywords: cervical ripening balloon, cervical ripening double balloon, labor induction, oxytocin

YiLin Luo, Xin Yue Bai, Lei Zhang, Qian Qian Hu, Ning Zhang, Jun Zhi Cheng, Ming Zheng Hou, Xiao Long Liu Yan ‘an Small Molecule Innovative Drug R&D Engineering Research Center, School of Medicine, Yan’an University, Yan’an, People’s Republic of ChinaCorrespondence: Xiao Long Liu, Email liuxiaolong@yau.edu.cnAbstract: Ferroptosis, a unique form of programmed cell death, is initiated by an excess of iron accumulation and lipid peroxidation-induced damage. There is a growing body of evidence indicating that ferroptosis plays a critical role in the advancement of tumors. The increased metabolic activity and higher iron levels in tumor cells make them particularly vulnerable to ferroptosis. As a result, the targeted induction of ferroptosis is becoming an increasingly promising approach for cancer treatment. This review offers an overview of the regulatory mechanisms of ferroptosis, delves into the mechanism of action of traditional small molecule ferroptosis inducers and their effects on various tumors. In addition, the latest progress in inducing ferroptosis using new means such as proteolysis-targeting chimeras (PROTACs), photodynamic therapy (PDT), sonodynamic therapy (SDT) and nanomaterials is summarized. Finally, this review discusses the challenges and opportunities in the development of ferroptosis-inducing agents, focusing on discovering new targets, improving selectivity, and reducing toxic and side effects.Keywords: ferroptosis inducers, small molecules, PROTACs, PDT, SDT, nanomaterials

Xiao-Bei Si,1,2 Ling-Yun Zhang,2 Shuo Yang,3 Xiao-Lu Chen,2 Yan-Yan Shi,4 Yu Lan,2 Shi-Gang Ding1 1Department of Gastroenterology, Peking University Third Hospital, Beijing, People’s Republic of China; 2Department of Gastroenterology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Pharmacy, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, People’s Republic of ChinaCorrespondence: Shi-Gang Ding, Department of Gastroenterology, Peking University Third Hospital, Beijing, People’s Republic of China, Email dingshigang222@163.com Yu Lan, Department of Gastroenterology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China, Email lany_2022@163.comBackground: Minocycline, a derivative of tetracycline, has anti-Helicobacter pylori (H. pylori) properties and can be used to treat H. pylori infection. However, only a few randomized controlled trials (RCTs) have investigated the efficacy of minocycline-containing quadruple therapy (MCQT) in treating H. pylori infection. This study aimed to determine the efficacy and safety of MCQT and investigate the factors influencing both aspects.Methods: This was a retrospective cohort study. Patients diagnosed with H. pylori infection between January 1, 2022, and July 31, 2023 at. The primary outcome was the eradication rate of H. pylori, and the secondary outcome was the number and type of adverse events.Results: A total of 828 patients were included in this study. The overall H. pylori eradication rate among the included patients at 95% confidence interval (CI) (Range 0.864 to 0.907) was 88.53%. The H. pylori eradication rate for patients who received MCQT regimen as the primary therapy was 92.28% (95% CI: 0.901– 0.945), significantly higher than that of patients who received MCQT as rescue therapy (80.81%; 95% CI: 0.761– 0.855, P= 0.003). Adverse events, including dizziness, abdominal distension, diarrhea, nausea, abdominal discomfort, constipation, headache, rash, sleep disorder, palpitation, backache, and anorexia, occurred in 185 (22.34%) patients, with dizziness being the most common (75/828, 9.06%). Compliance with MCQT therapy was an independent factor influencing H. pylori eradication in patients receiving MCQT as a primary therapy. Compliance and presence or absence of H. pylori infection symptoms at the time of screening were independent factors influencing H. Pylori eradication in patients receiving MCQT as rescue therapy. Factors that influenced the occurrence of adverse events included reasons for H. pylori infection screening, residence, treatment compliance, and the use of acid-suppressant regimens.Conclusion: MCQT regimens were effective in H. pylori infection eradication, and the treatment resulted only in fewer adverse events when used as primary or rescue therapies for H. pylori infection treatment. Future prospective studies with larger sample sizes and more comprehensive data are needed to validate our findings.Keywords: Helicobacter pylori, minocycline, cohort study

Chun-Yan Zhang, Yu-Shen Yang, Meng-Qin Pei, Xin-Li Chen, Wei-can Chen, He-Fan He Department of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, People’s Republic of ChinaCorrespondence: He-Fan He, Department of Anesthesiology, The Second Affiliated Hospital of Fujian Medical University, Quanzhou, Fujian Province, People’s Republic of China, Tel +86 15860905262, Email 15860905262@163.comAbstract: Postoperative cognitive dysfunction (POCD) is a neurological complication associated with surgery and anesthesia that is commonly observed in older patients, and it can significantly affect patient prognosis and survival. Therefore, predicting and preventing POCD is important. Regional cerebral oxygen saturation (rSO2) reflects cerebral perfusion and oxygenation, and decreased intraoperative cerebral oxygen saturation has been reported to increase the risk of POCD. In this review, we elucidated the important relationship between the decline in rSO2 and risk of POCD in older patients. We also emphasized the importance of monitoring rSO2 during surgery to predict and prevent adverse perioperative cognitive outcomes. The findings reveal that incorporating intraoperative rSO2 monitoring into clinical practice has potential benefits, such as protecting cognitive function, reducing perioperative adverse outcomes, and ultimately improving the overall quality of life of older adults.Keywords: anesthesia, surgery, prognosis, perioperative adverse outcome, cognitive function

Miao-Miao Hua,1 Jia Li,2 Jie Zheng,2 Jing-Jing Wang,2 Chang Liu,2 Yan Zhang,2 Zhi-Feng Zhang,2 Xiao-Li Cao,1,2 Han Shen1,2 1Department of Laboratory Medicine, Nanjing Drum Tower Hospital Clinical College of Jiangsu University, Nanjing, People’s Republic of China; 2Department of Laboratory Medicine, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital, Nanjing, People’s Republic of ChinaCorrespondence: Xiao-Li Cao; Han Shen, Email cao-xiao-li@163.com; shenhan10366@sina.comObjective: To investigate the clinical and molecular characteristics of Salmonella spp. causing bloodstream infections (BSIs) in our hospital.Methods: We studied 22 clinical Salmonella isolates from BSIs and 16 from non-BSIs, performing antimicrobial susceptibility testing (AST) and whole genome sequencing (WGS). The analysis included serovars, antibiotic resistance genes (ARGs), virulence factors (VFs), sequence types (STs), plasmid replicons, and genetic relationships. We also assessed pathogenicity of the isolates causing BSIs through growth, biofilm formation, and anti-serum killing assays.Results: WGS analysis identified 13 Salmonella serovars, with four responsible for BSIs. S. Enteritidis was the most prevalent serovar, involved in 19 (50.0%) cases. BSIs were caused by 17S. Enteritidis, two S. Typhimurium, two S. Munster and one S. Diguel. Of the 38 isolates, 27 (71.1%) exhibited high resistance to ampicillin, and 24 (63.2%) to ampicillin/sulbactam. Thirty-six types of ARGs were identified, with blaTEM-1B (n = 25, 65.8%) being the most frequent. Ten plasmid replicons were found; the combination of IncFIB(S)-IncFII(S)-IncX1 was the most common in S. Enteritidis (94.7%). Fifteen STs were identified, among which ST11 was the most prevalent and clonally disseminated, primarily responsible for BSIs. A total of 333 different VFs were detected, 177 of which were common across all strains. No significant differences were observed between the BSI and non-BSI isolates in terms of resistance rates, ARGs, plasmid replicons, and VFs, except for seven VFs. No strong pathogenicity was observed in the BSI-causing isolates.Conclusion: BSIs were predominantly caused by clonally disseminated S. Enteritidis ST11, the majority of which carried multiple ARGs, VFs and plasmid replicons. This study provides the first data on clonally disseminated S. Enteritidis ST11 causing BSIs, highlighting the urgent need for enhanced infection control measures.Keywords: Salmonella enteritidis, bloodstream infections, serovars, antibiotic-resistance genes, virulence factors, sequence type

Yue Song,1,&ast; Qing-Qing Dong,2,&ast; Yi-Ke Ni,3 Xiao-Ling Xu,3 Chao-Xiang Chen,3 Wei Chen2 1Stomatology Hospital, School of Stomatology, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, 310003, People’s Republic of China; 2ICU, Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 200032, People’s Republic of China; 3Shulan International Medical College, Zhejiang Shuren University, Hangzhou, Zhejiang Province, 310015, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiao-Ling Xu; Chao-Xiang Chen, Shulan International Medical College, Zhejiang Shuren University, 8 Shuren Street, Hangzhou, 310015, People’s Republic of China, Email ziyao1988@zju.edu.cn; ccx@zjsru.edu.cnAbstract: Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules that have the capability to induce specific protein degradation. While playing a revolutionary role in effectively degrading the protein of interest (POI), PROTACs encounter certain limitations that impede their clinical translation. These limitations encompass off-target effects, inadequate cell membrane permeability, and the hook effect. The advent of nanotechnology presents a promising avenue to surmount the challenges associated with conventional PROTACs. The utilization of nano-proteolysis targeting chimeras (nano-PROTACs) holds the potential to enhance specific tissue accumulation, augment membrane permeability, and enable controlled release. Consequently, this approach has the capacity to significantly enhance the controllable degradation of target proteins. Additionally, they enable a synergistic effect by combining with other therapeutic strategies. This review comprehensively summarizes the structural basis, advantages, and limitations of PROTACs. Furthermore, it highlights the latest advancements in nanosystems engineered for delivering PROTACs, as well as the development of nano-sized PROTACs employing nanocarriers as linkers. Moreover, it delves into the underlying principles of nanotechnology tailored specifically for PROTACs, alongside the current prospects of clinical research. In conclusion, the integration of nanotechnology into PROTACs harbors vast potential in enhancing the anti-tumor treatment response and expediting clinical translation. Keywords: Proteolysis-targeting chimeras, nanotechnology, delivery, linker, designing principles

Shi-Yuan Fan,1,&ast; Zi-Chi Zhao,1,&ast; Xing-Lv Liu,1 Ying-Gang Peng,1 Hui-Min Zhu,1 Shi-Fan Yan,2 Yan-Juan Liu,2 Qin Xie,2 Yu Jiang,2 Sai-Zhen Zeng1 1The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People’s Hospital), Changsha, Hunan, 410005, People’s Republic of China; 2Department of Emergency, Institute of Emergency Medicine, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), Changsha, Hunan, 410005, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sai-Zhen Zeng, The First Affiliated Hospital of Hunan Normal University (Hunan Provincial People’s Hospital), 61 Jie-Fang West Road, Fu-Rong District, Changsha, Hunan, 410005, People’s Republic of China, Email 55445321@qq.com Yu Jiang, Department of Emergency, Institute of Emergency Medicine, Hunan Provincial People’s Hospital (The First Affiliated Hospital of Hunan Normal University), 61 Jie-Fang West Road, Fu-Rong District, Changsha, 410005, People’s Republic of China, Email jiangyu@hunnu.edu.cnBackground: Globally, the subsequent complications that accompany sepsis result in remarkable morbidity and mortality rates. The lung is among the vulnerable organs that incur the sepsis-linked inflammatory storm and frequently culminates into ARDS/ALI. The metformin-prescribed anti-diabetic drug has been revealed with anti-inflammatory effects in sepsis, but the underlying mechanisms remain unclear. This study aimed to ascertain metformin’s effects and functions in a young mouse model of sepsis-induced ALI.Methods: Mice were randomly divided into 4 groups: sham, sham+ Met, CLP, and CLP+ Met. CLP was established as the sepsis-induced ALI model accompanied by intraperitoneal metformin treatment. At day 7, the survival state of mice was noted, including survival rate, weight, and M-CASS. Lung histological pathology and injury scores were determined by hematoxylin–eosin staining. The pulmonary coefficient was used to evaluate pulmonary edema. Furthermore, IL-1β, CCL3, CXCL11, S100A8, S100A9 and NLRP3 expression in tissues collected from lungs were determined by qPCR, IL-1β, IL-18, TNF-α by ELISA, caspase-1, ASC, NLRP3, P65, p-P65, GSDMD-F, GSDMD-N, IL-1β and S100A8/A9 by Western blot.Results: The data affirmed that metformin enhanced the survival rate, lessened lung tissue injury, and diminished the expression of inflammatory factors in young mice with sepsis induced by CLP. In contrast to sham mice, the CLP mice were affirmed to manifest ALI-linked pathologies following CLP-induced sepsis. The expressions of pro-inflammatory factors, for instance, IL-1β, IL-18, TNF-α, CXCL11, S100A8, and S100A9 are markedly enhanced by CLP, while metformin abolished this adverse effect. Western blot analyses indicated that metformin inhibited the sepsis-induced activation of GSDMD and the upregulation of S100A8/A9, NLRP3, and ASC.Conclusion: Metformin could improve the survival rate, lessen lung tissue injury, and minimize the expression of inflammatory factors in young mice with sepsis induced by CLP. Metformin reduced sepsis-induced ALI via inhibiting the NF-κB signaling pathway and inhibiting pyroptosis by the S100A8/A9-NLRP3-IL-1β pathway.Keywords: sepsis, pediatric, inflammation, pyroptosis, ALI

Li-Chao Ma,1,2 Shi-Ning Lou,3 Xiao-Li Zhu,3 Ruo-Lan Zhang,1 Lin Wu,1 Jiang-Yuan Xu,1 Xiao-Juan Ding,1 Juan Liu,4 Yan Wang1 1School of Nursing, Hebei University, Baoding, Hebei, 071000, People’s Republic of China; 2Operating Room, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China; 3Department of Traditional Chinese Medicine, Work’s Hospital of China Lucky Group Corporation, Baoding, Hebei, 07100, People’s Republic of China; 4Department of Rehabilitation Medicine, Affiliated Hospital of Hebei University, Baoding, Hebei, 071000, People’s Republic of ChinaCorrespondence: Juan Liu, Department of Rehabilitation Medicine, Affiliated Hospital of Hebei University, No. 212 of Yuhua East Road, Lianchi District, Baoding City, Hebei Province, 071000, People’s Republic of China, Tel +86 13582292161, Email juanliulj07@126.com Yan Wang, School of Nursing, Hebei University, No. 342 of Yuhua East Road, Lianchi District, Baoding City, Hebei Province, 071000, People’s Republic of China, Tel +86 13833258628, Email ywang_dr06@163.comObjective: This study aimed to explore the needs and constraints to cardiac rehabilitation (CR) among patients diagnosed with coronary heart disease (CHD) in a community-based setting, and thereby facilitating the implementation of effective CR programs for this population.Methods: Focus group interviews were used as the primary research methodology. A total of 11 community-dwelling individuals diagnosed with CHD were selected from a community hospital to participate in in-depth interviews, aiming to discern and analyze their requirements and constraints experienced concerning medical resources and healthcare agency. The textual data underwent examination using Colaizzi’s method of descriptive data analysis.Results: Deficits existed in the perceptions of patients with CHD within a community-based setting about their condition and CR, and in the social support for this disease. Patients expressed expectations for professional guidance during CR, gained an understanding about the beneficial effects of emotional stability on cognitive function. Patients expressed their thoughts and feelings regarding the diversity of physical exercise options. Two main themes and seven sub-themes were identified: (a) “Insufficient CR resources for patients”: Lack of awareness about CHD; inadequate knowledge about secondary prevention/CR; insufficient support from family and friends. (b) “Patient CR initiative”: Patient self-adjustment; expectation of professional rehabilitation guidance; stable emotions improving cognition; diverse attitudes and awareness of exercise.Conclusion: For more effective CR, community-based medical teams should provide more comprehensive and individualized rehabilitation programs. They should focus on individual variations and preferences of patients, as well as enhance the autonomy of patients and improve their self-care ability through effective empowerment measures.Keywords: coronary heart disease, cardiac rehabilitation, community sanitation service, self-care, patient needs

Xiao-Li Wan,1 Xu Wang,1 Zhi-Ping Feng,1 Xiao-Ling Zhou,1 Zhen-Wen Han,1 Jia-Mei Wu,1 Hong-Mei Xu,1 Ting Hu2 1Department of Gynaecology and Obstetrics, People’s Hospital of Leshan, Leshan, Sichuan, 614000, People’s Republic of China; 2Department of Gynaecological Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, Chengdu, Sichuan, 610041, People’s Republic of ChinaCorrespondence: Ting Hu, Department of Gynaecological Oncology, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, Affiliated Cancer Hospital of University of Electronic Science and Technology of China, 55 Section 4, Renmin South Road, Chengdu, Sichuan, 610041, People’s Republic of China, Tel +86 18615786531, Email hu5ting@126.com Hong-Mei Xu, Department of Gynaecology and Obstetrics, People’s Hospital of Leshan, No. 238 of BaiTa Street, Shizhong District, Leshan, Sichuan, 614000, People’s Republic of China, Tel +86 18981392030, Email hongmeixuu@126.comObjective: The objective of this study was to investigate the risk factors associated with cesarean scar pregnancy (CSP) and to develop a model for predicting intraoperative bleeding risk.Methods: We retrospectively analyzed the clinical data of 208 patients with CSP who were admitted to the People’s Hospital of Leshan between January 2018 and December 2022. Based on whether intraoperative bleeding was ≥ 200 mL, we categorized them into two groups for comparative analysis: the excessive bleeding group (n = 27) and the control group (n = 181). Identifying relevant factors, we constructed a prediction model and created a nomogram.Results: We observed that there were significant differences between the two groups in several parameters. These included the time of menstrual cessation (P = 0.002), maximum diameter of the gestational sac (P < 0.001), thickness of the myometrium at the uterine scar (P = 0.001), pre-treatment blood HCG levels (P = 0.016), and the grade of blood flow signals (P < 0.001). We consolidated the above data and constructed a clinical prediction model. The model exhibited favorable results in terms of predictive efficacy, discriminative ability (C-index = 0.894, specificity = 0.834, sensitivity = 0.852), calibration precision (mean absolute error = 0.018), and clinical decision-making utility, indicating its effectiveness.Conclusion: The clinical prediction model related to the risk of hemorrhage that we developed in this experiment can assist in the development of appropriate interventions and effectively improve patient prognosis.Keywords: cesarean section, prediction modeling, risk factors, uterine scar pregnancy

Reactor neutrino experiments play a crucial role in advancing our knowledge of neutrinos. In this Letter, the evolution of the flux and spectrum as a function of the reactor isotopic content is reported in terms of the inverse-beta-decay yield at Daya Bay with 1958 days of data and improved systematic uncertainties. These measurements are compared with two signature model predictions: the Huber-Mueller model based on the conversion method and the SM2018 model based on the summation method. The measured average flux and spectrum, as well as the flux evolution with the ^{239}Pu isotopic fraction, are inconsistent with the predictions of the Huber-Mueller model. In contrast, the SM2018 model is shown to agree with the average flux and its evolution but fails to describe the energy spectrum. Altering the predicted inverse-beta-decay spectrum from ^{239}Pu fission does not improve the agreement with the measurement for either model. The models can be brought into better agreement with the measurements if either the predicted spectrum due to ^{235}U fission is changed or the predicted ^{235}U, ^{238}U, ^{239}Pu, and ^{241}Pu spectra are changed in equal measure.

We present a new determination of the smallest neutrino mixing angle θ_{13} and the mass-squared difference Δm_{32}^{2} using a final sample of 5.55×10^{6} inverse beta-decay (IBD) candidates with the final-state neutron captured on gadolinium. This sample is selected from the complete dataset obtained by the Daya Bay reactor neutrino experiment in 3158 days of operation. Compared to the previous Daya Bay results, selection of IBD candidates has been optimized, energy calibration refined, and treatment of backgrounds further improved. The resulting oscillation parameters are sin^{2}2θ_{13}=0.0851±0.0024, Δm_{32}^{2}=(2.466±0.060)×10^{-3}  eV^{2} for the normal mass ordering or Δm_{32}^{2}=-(2.571±0.060)×10^{-3}  eV^{2} for the inverted mass ordering.

Xiaoqing Wei,1,&ast; Junying Zhang,2,&ast; Youwen Mei,3 Eqiong Li,4 Qianling Dai,1 Xiaoli Yang,1 Dan Luo,5 Biao Li,6 Ping Hua,7 Jian Cai,7 Hua Lai,8 Dongfeng Qi,9 Sha Lai,10 Mi Qin,11 Yonghong Lin4 1Department of Cervical Disease and Cervical Cancer Prevention and Treatment, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 2Clinical Laboratory Department, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 3Department of Reproduction and Infertility, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 4Department of Gynecology, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 5Department of Obstetrics, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 6Department of Neonatal Intensive Care Unit, Chengdu Women’ and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 7Department of Pathology, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 8Department of Radiation and Interventional Therapy, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 9Department of Ultrasonics, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 10Dermatology Department, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China; 11Department of Pediatric Surgery, Chengdu Women’s and Children’s Central Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, 611731, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yonghong Lin; Xiaoqing Wei, Email linyhcd2011@163.com; xqcherry@163.comObjective: We report a case of Carmi Syndrome in a neonate.Aim: To share our lessons in diagnosis of the case of Carmi Syndrome.Case Report: Carmi Syndrome is an extremely rare autosomal recessive genetic disorder characterized the coexistence of pyloric atresia and junctional epidermolysis bullosa, and with aplasia cutis congenita in approximately 28% patients. In this case, a full-term male neonate was born to a G4P2+1L1 multipara through cesarean section delivery in hospital in a non-consanguineous marriage with 4000mL of II°meconium-stained amniotic fluid. He was found extensive skin loss over lower legs and other parts, with scattered blisters and bilateral microtia. Plain abdominal X-ray revealed a large gastric air bubble with no gas distally. The mother had an intrauterine fetal loss previously for reasons unknown. The dermatologist diagnosed the newborn with Bart Syndrome, while the pediatric surgeon diagnosed congenital pyloric atresia(CPA). The parents refused further treatment and the neonate passed away about 30 hours after birth.Outcome: The neonate passed away about 30 hours after birth.Conclusion: Lessons from this case:①.Rule out Carmi Syndrome in patients with PA, and differentiate Bart syndrome and Carmi Syndrome in patients with abnormal skin manifestations. ②. For rare and/or severe diseases, multidisciplinary teams(MDTs) should be establish. ③. Genetic counseling and prenatal diagnosis are necessary prior to subsequent childbearings. ④.Termination of pregnancy might be contemplated if certain indicators are revealed.Keywords: Carmi syndrome, bart syndrome, epidermolysis bullosa, EB, junctional epidermolysis bullosa, JEB, congenital pyloric atresia, CPA, aplasia cutis congenita, ACC, congenital localized absence of skin, CLAS, pyloric atresia, PA, epidermolysis bullosa with pyloric atresia, EB-PA, multidisciplinary teams, MDT

Xiu-Li Xiao,1,&ast; Qian-Xue Yang,2,&ast; Hui-Zhong Niu,1 Li-Jing Li,1 Jian-Lei Geng,1 Dan Zhao,1 Hui Ren,1 Pan-Pan Yang1 1Department of General Surgery I, Hebei Children’s Hospital, Shijiazhaung, 050000, People’s Republic of China; 2Department of Operating Room, Hebei Children’s Hospital, Shijiazhaung, 050000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiu-Li Xiao, Department of General Surgery I, Hebei Children’s Hospital, No. 133 Jianhuanan Street, Shijiazhuang, Yuhua District, 050000, People’s Republic of China, Tel +86 0311 8591 1321, Email xxlwwvt7@email.cnPurpose: This study aimed to investigate the maintenance effect of two puncture methods using non-coring needles in children with totally implantable venous access device (TIVAD).Methods: The 110 children who received TIVAD implantation for short bowel syndrome and solid tumors in our department from 2021.12 to 2022.12 were selected as the study subjects. Blinded method was used and divided into experimental group and control group according to random number table The experimental group underwent painless surround puncture method to place the needles and compound lidocaine ointment for topical anesthesia, while the control group underwent traditional puncture method to complete this operation. The effects of the two puncture methods on pain, catheter seal fluid volume, and catheter occlusion rate were evaluated using the Facial Pain Scale Revised, Behavioral Assessment Scale, and in vitro digital subtraction angiography test.Results: In the control group, the degree of puncture pain was mild in 5 patients, moderate in 19 patients, and severe in 28 patients; the amount of catheter sealing solution was 9.32 ± 1.32 mL, and the catheter occlusion rate was 25.00%. In the experimental group, the degree of puncture pain was mild in 16 patients, moderate in 22 patients, and severe in 16 patients; the amount of sealing solution was 7.66 ± 1.08 mL, and the blocking rate was 9.26%. The total pain score in the experimental group was lower than that in the control group (5.23± 6.17 VS 7.89± 2.38). The difference between the two groups had statistical significance (P < 0.05).Conclusion: The use of the painless surround puncture method can effectively reduce the pain experienced by children during puncture, decrease the volume of catheter sealing fluid, reduce the rate of catheter blockage, provide a valuable basis for enhancing the maintenance effect of TIVAD in clinical practice for children.Keywords: catheter blockage rate, catheter sealing fluid volume, pain, puncture method, totally implantable venous access device

Zi-Guo Sun,1,2 Shi-Cheng Xu,2 Qin Yang,3 Yun Yao,2 Qi-Long Mao,2 Cheng-Feng He,2 Chang-Jiang Guan,2 Yan Du,2 Li Ma,2 Xie-Shan Huang,2 Xiao-Long Hou,2 Hong-Mei Yang,2 Xia Peng,2 Jun-Jie Jian4 1Department of Intensive Care and Emergency Center, Bazhong Hospital of Integrated Chinese and Western Medicine, Bazhong, Sichuan, 636600, People’s Republic of China; 2Department of Critical Care Medicine, Bazhong Central Hospital, Bazhong, Sichuan, 636600, People’s Republic of China; 3School of Clinical Medicine, Chengdu Medical College, Chengdu, Sichuan, 610000, People’s Republic of China; 4Department of Health Management, Bazhong Center for Health Education and Health Management, Bazhong, Sichuan, 636600, People’s Republic of ChinaCorrespondence: Xia Peng; Jun-Jie Jian, Email bzyszkzx@126.com; 2906194909@qq.comBackground: Fat overload syndrome is a rare and severe adverse reaction triggered by the infusion of a single source of lipid emulsion, resulting in elevated blood triacylglycerol (TG) levels. The majority of literature reports focus on cases of fat overload syndrome in patients with mild symptoms. This case is significant because it demonstrates the diagnostic and therapeutic experience and provide valuable insights for the management for severe fat overload syndrome.Case Presentation: We present a case report of a female patient who developed fat overload syndrome following prolonged and excessive infusion of lipid emulsion after colon resection surgery. In the setting of compromised immune function and malnutrition, the patient’s pulmonary infection and respiratory distress symptoms have further exacerbated. Hence, in addition to severe pancreatitis, the patient has also contracted severe pneumonia. Upon admission, tracheal intubation, plasma exchange and blood perfusion were performed. Subsequently, comprehensive treatment was provided, including anti-infection, antispasmodic, acid suppression, enzyme inhibition, as well as targeted supportive measures to stabilize electrolytes and nutritional status. After treatment, there was a progressive reduction in blood lipid levels. After assessing the relevant risks, it was deemed necessary to perform an emergency computed tomography (CT)-guided percutaneous drainage tube placement procedure targeting the necrotic area of the pancreas while the patient was still intubated. Finally, the patient was discharged from the hospital.Conclusion: The case highlights the association between fat overload syndrome and pancreatitis as well as the use of lipid emulsions and suggests the treatment strategies for severe fat overload syndrome.Keywords: lipid overload syndrome, plasma exchange, blood perfusion, pancreatitis, pneumonia

Xuan Wang,1,&ast; Jing-Xian Hu,2,&ast; Ying Wang,1 Fang Wang,1 Xuan Wu,1 Fei Wang,1 Yan-Chao Zhao,1 Xiao-Lan Wang,2 Li-Li Zhang2 1Second Department of Hepatology Center for Liver Diseases, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China; 2Department of Nursing, Beijing Youan Hospital, Capital Medical University, Beijing, 100069, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li-Li Zhang; Jing-Xian Hu, Department of Nursing, Beijing Youan Hospital, Capital Medical University, No. 8 of Xitoutiao, Youanmen wai, FengtaiDistrict, Beijing, 100069, People’s Republic of China, Email zhanglyliy@163.com; 819211326@mail.ccmu.edu.cnObjective: This study explores the correlation between coping style, quality of life, and illness uncertainty in the family caregivers of patients with liver cancer.Methods: Employing convenience sampling, 210 family caregivers of patients with liver cancer who met the admission criteria were selected from a grade A infectious disease hospital in Beijing between January and December 2022. A cross-sectional survey was conducted using the Simplified Coping Style Questionnaire, Caregiver Quality of Life, and the Mishel Uncertainty in Illness Scale for Family Members. This study analysed the correlations between coping styles, quality of life, and illness uncertainty in these caregivers.Results: The study found that family caregivers of patients with liver cancer had average scores for illness uncertainty (83.44 ± 11.86), coping style (33.19 ± 9.79; both positive [23.02 ± 6.81] and negative [10.17 ± 5.05]), and quality of life (169.53 ± 32.46). A negative association was observed between illness uncertainty in these caregivers and positive coping style (r = − 0.207, p = 0.003), physical status (r = − 0.182, p = 0.008), psychological status (r = − 0.200, p = 0.004), and social adaptation (r = − 0.229, p = 0.001).Conclusion: The study concludes that illness uncertainty in family caregivers of patients with liver cancer is at a moderate level. Furthermore, there is a notable correlation between illness uncertainty, coping style, and quality of life in these caregivers.Keywords: liver cancer, family caregivers, uncertainty in illness, coping style, quality of life

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

Ming-Zhu Chen,1,&ast; Xiao-Lei Chen,2,&ast; Qin Xu,3 Xiao-Dong Cao,2 Meng-Yu Wang,1 Rong Cao1 1Department of Endocrinology, The Affiliated Wuxi People’s Hospital to Nanjing Medical University, Wuxi, 214001, People’s Republic of China; 2Nursing Department, The Affiliated Wuxi People’s Hospital to Nanjing Medical University, Wuxi, 214001, People’s Republic of China; 3School of Nursing, Nanjing Medical University, Nanjing, 211166, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qin Xu, School of Nursing, Nanjing Medical University, No. 101 of Longmian Road, Jiangning District, Nanijing, 211166, People’s Republic of China, Tel +86 25-86869553, Fax +86 25-86869555, Email qinxu@njmu.edu.cn Xiao-Dong Cao, Email dongdonger99@163.comObjective: To explore the mediating effects of perceived social support between frailty and self-perceived burden (SPB) in elderly patients with diabetes and to provide a theoretical basis for reducing that burden.Methods: A total of 169 elderly patients with diabetes who were hospitalised in the endocrinology department of a third-class hospital in Wuxi between May 2020 and July 2022 were included in this study using the convenience sampling method. Patients were assessed by the general information questionnaire, the Chinese version of the Tilburg frailty inventory (TFI), the Self-Perceived Burden Scale (SPBS) and the Perceived Social Support Scale (PSSS). The SPSS 22.0 software was used for Pearson’s correlation analysis and multiple linear regression analysis. Model four of the SPSS PROCESS was used for mediating the effect analysis.Results: The SPBS of elderly patients with diabetes was positively correlated with the TFI (P < 0.01) and negatively correlated with the PSSS (P < 0.01). The results of the Bootstrap test showed that the mediating effect of the PSSS on the relationship between the TFI and the SPBS in elderly patients with diabetes was 0.296 (95% CI: 0.007, 0.066), and the mesomeric effect accounted for 17.3% of the total effect.Conclusion: The debilitation of elderly patients with diabetes can be reduced by decreasing their SPB through perceived social support. This can be achieved through comprehensive interventions by nurses.Keywords: elderly patients with diabetes, frailty, self-perceived burden, mediating effects

Qin Ma,1 Yao-Bang Liu,2 Tong She,3 Xin-Lan Liu4 1Department of Radiation Oncology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 2Department of Surgical Oncology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of China; 3Hospital of Zhongwei, Zhongwei, People’s Republic of China; 4Department of Medical Oncology, General Hospital of Ningxia Medical University, Yinchuan, Ningxia, 750004, People’s Republic of ChinaCorrespondence: Xin-Lan Liu, Tel +8613709577339, Email nxliuxinlan@126.comObjective: This study determined the cut-off value of Ki-67 expression and discussed the interaction between Ki-67 and histological grade, further explored the prognostic role of Ki-67 in hormone receptor-positive and human epidermal growth factor receptor 2 negative (HR+/HER2-) breast cancer;.Materials and Methods: We assessed the Ki-67 expression of 956 patients with HR+/HER2 breast cancer diagnosed in the General Hospital of Ningxia Medical University from 2015 to 2019 by immunohistochemistry (IHC), The disease-free survival (DFS) was defined as the time from postoperative to the first local recurrence, distant metastasis or death of the disease. The follow-up by means of inpatient or outpatient medical records and telephone.Results: 22.5% was used as the cut-off for low/high Ki-67 expression in HR+/HER2- breast cancer. Compared with the value of 14%, which is commonly used in clinic at present, the consistency of the two values is moderate (Kappa = 0.484, P< 0.001). The expression of Ki-67 was increased with the grade. (Median: G1:10%; G2:20%; G3:40%. Mean: G1:13%; G2:23%; G3:39%, P < 0.001). Survival analysis was based on all patients for a median of 51 months (24– 89 months), 63 cases had recurrence or metastasis during the follow-up, which 21 cases had low expression of Ki-67 and 42 cases had high expression. The patients with Ki-67 ≥ 22.5% had a 2.969 higher risk of early recurrence and metastasis than the patients with Ki-67 < 22.5%. There were 4 cases of local recurrence, 7 cases of regional lymph node metastasis, and 52 cases of distant metastasis in all patients, the common distant metastases were bone, liver, and lung, and rare metastases were adrenal gland, bone marrow, and pericardium.Conclusion: In HR+/HER2- breast cancer, patients with Ki-67 > 22.5% have a worse prognosis and are more likely to have early recurrence and metastasis.Keywords: Ki-67, breast cancer, cut-off value, histological grade, recurrence and metastasis

Yan-Hua Chen,1 Xue-Luo Zhang,1 Zhong-Yun Li,2 Xian-Ping Wang,1 Jun Wang,3 Zhi-Ping Zhang,1 Peng-Fei Zhu,1 Xue-Qing Wu1 1Reproductive Medicine Center, Shanxi Maternal and Child Health Care Hospital, Taiyuan, People’s Republic of China; 2Rectum Branch, Shanxi Provincial Hospital of Traditional Chinese Medicine, Taiyuan, People’s Republic of China; 3The Sixth Hospital of Shanxi Medical University (General Hospital of Tisco), Taiyuan, People’s Republic of ChinaCorrespondence: Xue-Qing Wu, Reproductive Medicine Center, Shanxi Maternal and Child Health Care Hospital, No. 13, Xinmin Middle Street, Xinghualing District, Taiyuan, Shanxi Province, 030013, People’s Republic of China, Tel +86 351-3360725, Email xueqingwu18@outlook.comObjective: This study aimed to evaluate the therapeutic efficacy and safety of Dan’e Fukang soft extracts in moderate ovarian hyperstimulation syndrome (OHSS) for the simultaneous treatment of blood and fluid, guided by the traditional Chinese medicine principle of “triple prevention”.Methods: This study conducted a retrospective analysis of clinical data from outpatients who underwent in vitro fertilization (IVF)/intracytoplasmic sperm injection embryo transfer (ICSI-ET). A total of 2245 cases were included and divided into a treatment group (1002 cases) and a control group (1243 cases). Patients in the treatment group were administered Dan’e Fukang soft extracts orally in addition to conventional Western medicine. Comparative assessments were made between the two groups on pelvic ascites volume, maximum ovary diameter, dysmenorrhea incidence post-oocyte retrieval, and safety indicators.Results: There were no statistically significant differences between the treatment group and the control group in terms of general characteristics or the levels of follicle-stimulating hormone (FSH), luteotropic hormone (LH), estradiol (E2), or progesterone (P) at the time of gonadotropin (Gn) initiation. The groups did not differ significantly when we compared the levels of LH, E2, or P on the day of human chorionic gonadotropin (hCG) injection and during ovarian hyperstimulation protocols (P > 0.05 for all indicators). The differences in the volume of pelvic ascites, the maximum ovarian diameter, and the incidence of dysmenorrhea after oocyte retrieval were statistically significant between the treatment group and the control group (P < 0.05 in both). There were no instances of adverse reactions in either group.Conclusion: Based on the traditional Chinese medicine principle of “triple prevention”, the use of Dan’e Fukang soft extracts for the simultaneous treatment of blood and fluid in moderate OHSS significantly improved the absorption of pelvic ascites, promoted ovarian recovery, and reduced the incidence of dysmenorrhea after oocyte retrieval.Keywords: Dan’e Fukang soft extracts, guiding principle of triple prevention, in vitro fertilization embryo transfer/intracytoplasmic sperm injection embryo transfer, ovarian hyperstimulation syndrome, simultaneous treatment of blood and fluid

Hai-Yan Yu,1,&ast; Yun-Peng Bai,2,&ast; Xu-Chen Song,1 Fang Miao,1 Xiao-Ling Guo,1 Xing Wang,3 Wen-Ling Su1 1Department of Endocrinology, Tianjin Chest Hospital, Tianjin, 300070, People’s Republic of China; 2Department of Cardiac Surgery, Tianjin Chest Hospital, Tianjin, 300070, People’s Republic of China; 3Department of Imaging, Tianjin Chest Hospital, Tianjin, 300070, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wen-Ling Su, Department of Endocrinology, Tianjin Chest Hospital, No. 261 of Taierzhuang South Road, Jinnan District, Tianjin, 300070, People’s Republic of China, Tel +86-18702263436, Email wenlingsuswl@126.comPurpose: This study aims to explore the factors linked to the occurrence of acute pulmonary thromboembolism (PE) within a cohort of patients exhibiting hypoxic saturation (oxygen saturation levels falling below 93%), subsequent to undergoing off-pump coronary artery bypass grafting (OPCABG).Methods: A retrospective case-control study was conducted. A total of 296 patients met the inclusion and exclusion criteria, divided into PE group (100 cases) and non-PE group (196 cases) according to whether they had PE or not. The preoperative and postoperative information of patients were collected and statistically analyzed.Results: The results from a multivariate logistic regression analysis indicated the following factors were independently linked to PE following OPCABG: history of smoking (OR = 3.019, 95% CI, 1.437– 6.634, P = 0.004), preoperative arterial oxygen partial pressure ≤ 78.9 mmHg (OR = 3.686, 95% CI, 1.708– 8.220, P = 0.001), presence of postoperative lower extremity deep venous thrombosis (OR = 4.125, 95% CI, 1.886– 9.310, P < 0.001), elevated postoperative D-dimer levels > 6.76 mg/l (OR = 8.078, 95% CI, 3.749– 18.217, P< 0.001), postoperative NT-BNP levels (OR = 1.001, 95% CI: 1.000– 1.001, P = 0.011), and elevated postoperative pulmonary arterial pressure > 33.0 mmHg (OR = 10.743, 95% CI: 3.422– 37.203, P < 0.001). The developed nomogram exhibited a high predictive accuracy with an area under the curve of 0.913 (95% CI: 0.878– 0.948).Conclusion: When patients have a history of preoperative smoking, decreased preoperative arterial oxygen pressure, postoperative lower limb DVT, increased postoperative pulmonary artery pressure, and elevated postoperative D-Dimer and NT pro-BNP levels, it is recommended to take perioperative preventive measures, timely diagnostic evaluation, and if necessary, anticoagulant treatment. In addition, the results of this study may improve the diagnostic sensitivity of medical staff for postoperative PE in OPCABG, thereby increasing the detection rate and potentially reducing the need for excessive medical imaging procedures.Keywords: case-control study, off-pump coronary artery bypass grafting, prediction model, pulmonary embolism, risk factor

Nan Tang,1,&ast; Xiao-Ting Liu,2,&ast; Xiao-Li Lin,2 Wen-Xiu Yang,2 Qi-Lin Li,3 Guo-En Wang,2 Yan-Hua Wu1 1Departments of Traditional Chinese Medicine, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, 510220, People’s Republic of China; 2School of Chinese Materia Medica, Guangdong Pharmaceutical University, Guangzhou, Guangdong, 510006, People’s Republic of China; 3Departments of Dermatology, Guangzhou Red Cross Hospital, Jinan University, Guangzhou, Guangdong, 510220, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan-Hua Wu, No. 396 Tongfu Zhong Road, Guangzhou, Guangdong Province, 510220, People’s Republic of China, Email wuyanhua368@163.com Guo-En Wang, No. 280, Waihuan East Road, University Town, Guangzhou, Guangdong Province, 510006, People’s Republic of China, Email wangge07@126.comPurpose: Vitiligo is an autoimmune disease that results in the loss of epidermal melanocytes. The treatments for patients with vitiligo remain lacking. Erzhiwan (EZW), a traditional Chinese Medicine composed of Ligustri Lucidi Fructus and Ecliptae Herba, was used to ameliorate depigmentation since ancient China. This study aims to investigate the effect of EZW on vitiligo-related depigmentation.Methods: A vitiligo-related depigmentation mouse model was induced by monobenzone and restraint stress. The experimental depigmentation mice were treated with EZW. Histological observation of skin was conducted. Cutaneous oxidative damage and inflammation were determined. A network pharmacology analysis was carried out.Results: EZW reduced depigmentation score (p< 0.01), cutaneous inflammatory infiltration (p< 0.01), and CD8α-positive expression (p< 0.01), and increased cutaneous melanin content in experimental depigmentation mice. EZW reduced stress reaction in experimental depigmentation mice (p< 0.01). EZW inhibited 8-hydroxy-2-deoxyguanosine (8-OHdG)-related DNA oxidative damage in the skin (p< 0.05, p< 0.01). In addition, EZW reduced cutaneous macrophage migration inhibitory factor (MIF)-CD74-NF-κB signaling (p< 0.01). The network pharmacology analysis demonstrated that EZW regulated necroptosis, apoptosis, and FoxO signaling pathways in vitiligo. An in vitro experiment showed that the main ingredient of EZW, specnuezhenide, protected against monobenzone and MIF-induced cell death in HaCaT cells (p< 0.01).Conclusion: EZW ameliorates restraint stress- and monobenzone-induced depigmentation via the inhibition of MIF and 8-OHdG signaling. The findings provide a data basis of an utilization of EZW in vitiligo.Keywords: vitiligo, 8-hydroxy-2-deoxyguanosine, Ligustri Lucidi Fructus, Ecliptae Herba, specnuezhenide

Qi Kong,1 Ling-ling Qian,1 Lei Zhang,1 Huan-huan Liu,1,2 Fan Yang,1 Xiao-lu Zhang,1 Chao Wang,1 Xiao-xi Zhao,1 Ku-lin Li,1 Ru-xing Wang1,2 1Department of Cardiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People’s Republic of China; 2Wuxi School of Medicine, Jiangnan University, Wuxi, 214122, People’s Republic of ChinaCorrespondence: Ru-xing Wang; Ku-lin Li, Department of Cardiology, The Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi People’s Hospital, Wuxi Medical Center, Nanjing Medical University, Wuxi, 214023, People’s Republic of China, Email ruxingw@aliyun.com; liyantong2002@126.comPurpose: The aim of this study was to investigate the effects and mechanisms of SGLT2 inhibitor empagliflozin on diabetic coronary function.Methods: A rat diabetic model was established by injection of streptozotocin. Rats in the treated group were administered empagliflozin by gavage and rat coronary vascular tensions were measured after eight weeks. Large conductance calcium activated K+ channel currents were recorded using a patch clamp technique, while human coronary artery smooth muscle cells were used to explore the underlying mechanisms.Results: After incubation with empagliflozin (10, 30, 100, 300, 1000 μmol/L), the Δ relaxation % of rat coronary arteries were 2.459 ± 1.304, 3.251 ± 1.119, 6.946 ± 3.407, 28.36 ± 11.47, 86.90 ± 3.868, respectively. Without and with empagliflozin in the bath solution, BK channel opening probabilities at a membrane potential of +60 mV were 0.0458 ± 0.0517 and 0.3413 ± 0.2047, respectively (p < 0.05, n = 4 cells). After incubation with iberiotoxin, the Δ tensions of rat coronary arteries in the control (Ctrl), untreated (DM), low empagliflozin (10 mg/kg/d)-treated (DM+L-EMPA) and high empagliflozin (30mg/kg/d)-treated (DM+H-EMPA) group were 103.20 ± 5.85, 40.37 ± 22.12, 99.47 ± 28.51, 78.06 ± 40.98, respectively (p < 0.01 vs Ctrl, n = 3– 7; p < 0.001 vs DM+L-EMPA, n = 5– 7). Empagliflozin restored high glucose-induced downregulation of Sirt1, Nrf2, and BK-β 1, while the effect of empagliflozin disappeared in the presence of EX-527, a Sirt1 selective inhibitor.Conclusion: Empagliflozin has a vasodilation effect on the coronary arteries in a concentration-dependent manner and can activate BK channels via the Sirt1-Nrf2 mechanism.Keywords: diabetes, SGLT2 inhibitor, vasodilatation, large conductance calcium activated potassium channel

Min Zhao,1 Fei-xiang Liu,1,&ast; Xiao-lin Wang,2,&ast; Ya-hui Gao,2 Xiang Li3,4 1The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of China; 2The First Clinical Medical School, Henan University of Chinese Medicine, Zhengzhou, Henan Province, People’s Republic of China; 3State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Research Units of Infectious Disease and Microecology, Chinese Academy of Medical Sciences, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fei-xiang Liu, No. 19 Renmin Road, Zhengzhou, 450008, People’s Republic of China, Email spiritofwestlfx@126.comPurpose: The Coronavirus disease 2019 (COVID-19) remains a global public health concern. Many people have been forced to change their lifestyles, which has led to psychological and sleep problem. This study aims to investigate the psychological health problems and factors among patients in the Fangcang Shelter Hospital (FSH) during the COVID-19 pandemic.Patients and Methods: A Cross-Sectional survey was conducted to investigate the sleep, anxiety, depression and stress disorders of 2628 asymptomatic and mild patients treated in FSH of Zhengzhou, Henan Province, from 30 October to 6 December 2022, by scanning a WeChat two-dimensional code. Sociodemographic data and influencing factors in FSH were collected, Insomnia Severity Index (ISI), 9-item Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder-7 (GAD-7), and Impact of Event Scale-Revised (IES-R) were administered. Descriptive statistics, t-tests or analysis of variance, Spearman or Pearson correlation analysis, and multivariate regression analysis were used to explore the relationships between different variables and their impact on psychological health indicators.Results: The proportions of patients with insomnia, depressive disorder, anxiety, and stress disorders were 33.49%, 35.80%, 31.74%, and 43.57%, respectively. Spearman correlation analysis demonstrated that factors such as gender, higher education level, positive nucleic acid test results, longer illness duration, underlying diseases, and extended electronic device use were associated with elevated psychological distress scores. Notably, within FSH, extended exposure to light, a noisy environment, and sleep schedule management significantly impacted the prevalence of insomnia, depression, anxiety, and stress disorders (p< 0.01). Multivariable binary logistic regression analysis identified higher education level, light exposure, noisy environment, sleep management, and electronic device usage as the primary risk factors for psychological distress.Conclusion: Patients in FSH face psychological distress influenced by sociodemographic factors, environment, and lifestyle, highlighting the need for integrated psychological support in healthcare, particularly in temporary medical facilities during crises.Keywords: anxiety, COVID-19, depressive disorder, insomnia, stress disorders

Xuan Zhao,1,&ast; Yang Niu,1,&ast; Xue-Lin Zhao,1,&ast; Hui-Juan Ruan,1 Yi Xiang,1 Ling-Yu Wang,1 Yi Feng,1,2 Qing-Ya Tang1,2 1Department of Clinical Nutrition, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Pediatric Digestion and Nutrition, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qing-Ya Tang; Yi Feng, Email tangqingya@xinhuamed.com.cn; fengyi@xinhuamed.com.cnPurpose: To explore the relationships between serum tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high-sensitivity C-reactive protein (hs-CRP) levels and glucolipid metabolism disorders (GLMD) in obese children and adolescents.Patients and Methods: In this cross-sectional study, 105 obese children and adolescents were selected for the detection of TNF-α, IL-6, hs-CRP, and glycolipid metabolism indicators. All participants were divided into elevated TNF-α group (≥ 8.1 pg/mL; n=49) and normal TNF-α group (< 8.1 pg/mL; n=56), elevated IL-6 group (≥ 5.9 pg/mL; n=13) and normal IL-6 group (< 5.9 pg/mL; n=92), elevated hs-CRP group (≥ 3.0 mg/L; n=44) and normal hs-CRP group (< 3.0 mg/L; n=61), respectively.Results: Low-density lipoprotein cholesterol (LDL-C) in the elevated TNF-α group was higher than that in the normal TNF-α group (P=0.010). TNF-α was positively correlated with LDL-C (P=0.005). Fasting insulin (FINS) and homeostasis model assessment of insulin resistance (HOMA-IR) in the elevated IL-6 group were higher than those in the normal IL-6 group (all for P < 0.05), while high-density lipoprotein cholesterol (HDL-C) in the elevated IL-6 group was lower than that in the normal IL-6 group (P< 0.001). IL-6 was positively correlated with FINS, 2-hour postprandial insulin, HOMA-IR and triglyceride (all for P < 0.01), while was negatively correlated with HDL-C (P=0.006). Moreover, hs-CRP was positively correlated with FINS and HOMA-IR (all for P < 0.05).Conclusion: There may be correlations between serum TNF-α, IL-6, hs-CRP levels and GLMD in obese children and adolescents. Attention should be paid to monitoring serum inflammatory factors and preventing their elevation in obese children and adolescents, thus reducing the occurrence of GLMD.Keywords: tumor necrosis factor-alpha, interleukin-6, high-sensitivity C-reactive protein, glucolipid metabolism disorders, obesity, children and adolescents

Bang Liu,1,2,&ast; Jia Liu,3,&ast; Xuan Mei,1,&ast; Zhi-Qiang Zhang,1,2 Jian Fang,4 Li-Li Zhou,2 Jiao-Long Zheng,2 Hai-Yan Lin,2 Xiu-Ling Zhu,2 Dong-Liang Li1,2 1Fuzong Clinical Medical College of Fujian Medical University, Fuzhou, 350025, People’s Republic of China; 2Department of Hepatobiliary Disease, 900TH Hospital of Joint Logistics Support Force, Fuzhou, 350025, People’s Republic of China; 3Department of Hepatobiliary Surgery, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, 100039, People’s Republic of China; 4Department of Hepatobiliary Medicine, The Third Affiliated People’s Hospital of Fujian University of Traditional Chinese Medicine, Fuzhou, 350108, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong-Liang Li, Department of Hepatobiliary Disease, Fuzong Clinical Medical College of Fujian Medical University & 900TH Hospital of Joint Logistics Support Force, Fuzhou, 350025, People’s Republic of China, Email ldliang900@163.comBackground: PVTT is a hallmark of advanced hepatocellular carcinoma (HCC). We aim to explore the influence of non-invasive biomarkers on the occurrence of PVTT and develop and validate models for predicting prognosis in HBV-related HCC patients without PVTT.Methods: A total of 1026 HBV-related HCC patients without PVTT were enrolled, with 515 in the training cohort, 216 in the internal validation cohort, and 295 in the external validation cohort. We conducted Cox regression analyses to discern the independent risk factors associated with PVTT events, PFS, and OS, then constructed and validated predictive models. The predictive and discriminatory capabilities of models were assessed using the calibration, time-dependent ROC, and DCA curves.Results: In our study, 136 patients (13.3%) experienced PVTT events during the follow-up period. The Cox regression analysis unveiled that male gender, AAPR ≤ 0.49, APRI > 0.48, extrahepatic metastasis, and multiple tumors were independent risk factors for PVTT. In the training cohort, non-invasive biomarkers (AAR and APRI), AFP, ascites, and tumor-related characteristics (extrahepatic metastasis, tumor diameter, tumor number, and PVTT event) were independent risk factors for both OS and PFS, whereas age and ALBI grade independently correlated with OS. The C-indexes of OS and PFS nomogram models were 0.795 and 0.733 in the training cohort, 0.765 and 0.716 in the internal validation cohort, and 0.780 and 0.722 in the external validation cohort, respectively. Our models demonstrated strong predictive and discriminative abilities in all cohorts and yielded a greater net benefit compared to three traditional staging systems.Conclusion: Non-invasive biomarkers are expected to be reliable predictors for assessing PVTT risk and predicting prognosis among HBV-related HCC patients without PVTT.Keywords: non-invasive biomarker, portal vein tumor thrombosis, HBV-related HCC, nomogram, prognosis

Yi-Can Yang,1 Qiong Tang,1 Li-Juan Yan,1 Shi-Bin Zhang,2 Xiao-Min Ye,1 Dai Gong,1 Li Zou,1 Xiang-Lan Wen1 1Department of Children Health Care Center, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, Zhuzhou City, Hunan Province, 412007, People’s Republic of China; 2Department of Pediatrics, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, Zhuzhou City, Hunan Province, 412007, People’s Republic of ChinaCorrespondence: Xiang-Lan Wen, Department of Children Health Care Center, Zhuzhou Hospital Affiliated to Xiangya Medical College, Central South University, No. 116 of Changjiang South Road, Tianyuan District, Zhuzhou City, Hunan Province, 412007, People’s Republic of China, Tel/Fax +8673128561905, Email wenxianglianwxl@126.comBackground: Floating-Harbor syndrome (FHS) is a rare autosomal dominant inherited disease characterized primarily by short stature, delayed language development, and typical facial features. There are currently few case reports, diagnoses and treatments for these syndromes at home and abroad.Case Description: This study reports a case of a boy with “growth and language development delay” as the predominant clinical manifestation. FHS was clinically diagnosed based on his growth hormone (GH) deficiency, significant bone age delay, left testicular hydrocele, and the whole exon gene in peripheral blood, which indicated heterozygous mutation of SRCAP gene. Following the treatment with recombinant human GH (rhGH), the child exhibited height increase benefits, and his articulation improved after language therapy.Conclusion: Genetic testing facilitates early detection, diagnosis, and treatment of the FHS. Additionally, treatment with rhGH effectively increases the height of these children, and language rehabilitation is especially important for their language development.Keywords: Floating-Harbor syndrome, language development, growth and development, rhGH, language rehabilitation