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Chang Liu,1,2,&ast; Weixing Jiang,3,&ast; Juxian Sun,1,&ast; Jingwei Cui,4 Dandan He,1 Shuqun Cheng,1 Jie Shi1 1Department of Hepatic Surgery VI, Eastern Hepatobiliary Surgery Hospital, The Second Military Medical University, Shanghai, People’s Republic of China; 2Yangzhou Clinical Medical College, Xuzhou Medical University, Yangzhou, People’s Republic of China; 3Department of General Surgery, Nantong Haimen People’s Hospital, Nantong, People’s Republic of China; 4Department of General Surgery, Yancheng Clinical College of Xuzhou Medical University & The First People’s Hospital of Yancheng, Yancheng, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Shi; Shuqun Cheng, Eastern Hepatobiliary Surgery Hospital, Naval Medical University, 225 Changhai Road, Shanghai, 200433, People’s Republic of China, Tel +86 13816768296; +86 13901746139, Email docshijie@aliyun.com; chengshuqun@aliyun.comBackground: Hepatocellular carcinoma (HCC) with pulmonary metastasis (PM) significantly worsens prognosis, and current treatment options remain limited.Methods: A retrospective study was conducted on HCC patients treated with sintilimab combined with lenvatinib at three hospitals in China between 2020 and 2021. Progression-free survival (PFS), overall survival (OS), and tumor response based on RECIST 1.1 were compared. Treatment safety was assessed by analyzing treatment-related adverse events (TRAEs).Results: Among 144 patients, 105 received sintilimab combined with lenvatinib (S+L), while 39 were treated with radiotherapy combined with sintilimab and lenvatinib (RT+S+L). The RT+S+L group showed superior outcomes in OS (25 months vs 16 months, HR = 0.58, 95% CI = 0.35– 0.94, P=0.025) and PFS (14 months vs 6 months, HR = 0.61, 95% CI = 0.40– 0.94, P=0.022) compared to the S+L group. Similarly, the RT+S+L group exhibited significantly higher objective response rate (ORR) and disease control rate (DCR) compared to the S+L group (61.5% vs 27.6%, P< 0.001; 94.9% vs 76.2%, P=0.011). The most common grade 3/4 TRAEs in the RT+S+L group were hypertension, decreased platelet count, elevated total bilirubin, and proteinuria.Conclusion: Radiotherapy combined with sintilimab and lenvatinib is an effective strategy for treating HCC with pulmonary metastasis. These findings highlight the critical role of radiotherapy in the management of HCC.Keywords: hepatocellular carcinoma, pulmonary metastasis, radiotherapy, targeted therapy, immunotherapy

Jinbao Shi, Aliang Xu, Liuying Huang, Shaojie Liu, Binxuan Wu, Zuhong Zhang Department of Nephrology, Ningde Hospital of Traditional Chinese Medicine, Ningde, Fujian, People’s Republic of ChinaCorrespondence: Jinbao Shi, Department of Nephrology, Ningde Hospital of Traditional Chinese Medicine, No. 16 Donghu Road, Ningde, Fujian, People’s Republic of China, Email shijinbao00721@aliyun.comBackground: Chronic kidney disease (CKD) involves complex immune dysregulation and altered gene expression profiles. This study investigates immune cell infiltration, differential gene expression, and pathway enrichment in CKD patients to identify key diagnostic biomarkers through machine learning methods.Methods: We assessed immune cell infiltration and immune microenvironment scores using the xCell algorithm. Differentially expressed genes (DEGs) were identified using the limma package. Gene Set Enrichment Analysis (GSEA) and Gene Set Variation Analysis (GSVA) were performed to evaluate pathway enrichment. Machine learning techniques (LASSO and Random Forest) pinpointed diagnostic genes. A nomogram model was constructed and validated for diagnostic prediction. Spearman correlation explored associations between key genes and immune cell recruitment.Results: The CKD group exhibited significantly altered immune cell infiltration and increased immune microenvironment scores compared to the normal group. We identified 2335 DEGs, including 124 differentially expressed immune-related genes. GSEA highlighted significant enrichment of inflammatory and immune pathways in the high immune score (HIS) subgroup, while GSVA indicated upregulation of immune responses and metabolic processes in HIS. Machine learning identified four key diagnostic genes: RGS1, IL4I1, NR4A3, and SOCS3. Validation in an independent dataset (GSE96804) and clinical samples confirmed their diagnostic potential. The nomogram model integrating these genes demonstrated high predictive accuracy. Spearman correlation revealed positive associations between the key genes and various immune cells, indicating their roles in immune modulation and CKD pathogenesis.Conclusion: This study provides a comprehensive analysis of immune alterations and gene expression profiles in CKD. The identified diagnostic genes and the constructed nomogram model offer potent tools for CKD diagnosis. The immunomodulatory roles of RGS1, IL4I1, NR4A3, and SOCS3 warrant further investigation as potential therapeutic targets in CKD.Keywords: chronic kidney disease, diagnostic biomarkers, immune microenvironment, GSEA, GSVA, machine learning

Qijun Wo,1 Lei Shi,2 Jun Shi,3 Yeqing Mao,4 Liping Xie4 1Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2Cancer Center, Department of Radiation Oncology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Urology,The Second People’s Hospital of Fuyang, Hangzhou, Zhejiang, People’s Republic of China; 4Department of Urology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Liping Xie, Department of Urology, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310003, People’s Republic of China, Email xielp@zju.edu.cnPurpose: Prostate cancer (PCa) is seriously affecting men’s health and quality of life. Existing studies indicate that PCa stem cells are responsible for promoting the growth and contributing to the high recurrence rate of PCa.Methods: We retrieved and downloaded PCa-related datasets from both the GEO and TCGA database. These datasets were subsequently analyzed using single-cell analysis, difference analysis, WGCNA, and machine learning algorithms. WB was performed to detect the expression of Hedgehog interacting protein (HHIP), JAK1/STAT3 pathway-related protein, CD133 and CD44. Immunohistochemistry was conducted to assess the distribution of HHIP and Ki67. The levels of inflammatory factors were measured using ELISA. The tumor cell stemness was evaluated through spheroid formation assay and flow cytometry.Results: Through bioinformatics analysis, we identified eight genes (ARHGAP24, HHIP, MITF, CBX7, PPP1R12B, PLEKHA1, ADGRA2, and PGR). Among these genes, we selected HHIP for follow-up experiments and confirmed its low expression in PCa tumor tissues. Primary cancer-associated fibroblasts (CAFs) were extracted, and to further explore the mechanism of HHIP, we overexpressed or knocked down HHIP in CAFs. Overexpression of HHIP was found to inhibit the JAK1/STAT3 pathway and the secretion of inflammatory factors, thus suppressing both the proliferation and stemness of PCa cells. Treatment of CAFs with the JAK1/STAT3 pathway inhibitor AG490 led to a decrease in inflammatory factor secretion, along with inhibition of PCa cell proliferation and stemness. On this basis, knockdown of HHIP partially reversed the inhibitory effects of AG490 on PCa cells. Finally, we constructed a mouse subcutaneous tumor model and found that HHIP inhibited tumor proliferation and densification.Conclusion: In summary, HHIP in CAFs can regulate the JAK1/STAT3 pathway and affect the secretion of inflammatory factors, thus affecting the proliferation of PCa.Keywords: prostate cancer, single-cell analysis, Hedgehog interacting protein, JAK1/STAT3 pathway, cancer stemness

Zhen Cheng,&ast; Chunyu Hu,&ast; Yalan Zhang, Jie Zhou, Jiayang Shi, Li Sun, Zongtao Chen Health Management Centre, First Affiliated Hospital of Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zongtao Chen; Li Sun, Health Management Centre, First Affiliated Hospital of Army Medical University, No. 30, Gaotanyan Street, Shapingba District, Chongqing, People’s Republic of China, Tel +86 2368765191 ; +86 2368765228, Email zongtaochen@126.com; 51088031@qq.comPurpose: The aim of this study was to comprehensively compare the predictive effect of 10 body fat indexes on MAFLD in different sex, age and BMI subgroups.Patients and Methods: A total of 5403 physical examination data were included and divided into the MAFLD group (N=2632) and non-MAFLD group (N=2771). The differences and correlation of 10 promising indicators between the two groups were compared, including fatty liver index (FLI), hepatic steatosis index (HSI), lipid accumulation product (LAP), visceral fat index (VAI), cardiometabolic index (CMI), body adiposity index (BAI), and triglyceride-glucose index (TyG), waist circumference index (WC), body mass index (BMI), waist to height ratio (WHtR). Logistic regression was used to analyze the risk of MAFLD under different adjustment conditions. The operating characteristic curve of different genders, BMI levels and age subgroups was plotted.Results: Male gender, smoking, alcohol drinking, and higher age are risk factors for MAFLD. In addition to BAI, the other 9 indicators had a high correlation with MAFLD, the area under the curve (AUC) value was > 0.7, and the prediction effect was better in females, BMI< 24 kg/m2, age < 35 years subgroup, among which FLI (AUC: 0.912, 95% CI: 0.905– 0.920), LAP (AUC: 0.894, 95% CI: 0.8866– 0.903), and HSI (AUC: 0.881, 95% CI: 0.872– 0.890) have better prediction effects.Conclusion: Our study confirmed the accuracy of body fat-related indexes in predicting MAFLD in people of different sexes, ages, and BMI levels. Among them, FLI, LAP and HSI have high predictive value and can be utilized as simple and cost-effective tools for screening MAFLD in clinical settings.Keywords: metabolic dysfunction-associated fatty liver disease, body fat index, metabolic index, cross-sectional study

Xiwen Yin,1,&ast; Qiang Zhang,1,&ast; Yuting Wang,1 Bilin Tao,1 Xiaolong Zhang,2 Jinyan Shi,3 Xiaowei Deng,1 Jianming Wang1,4,5 1Department of Epidemiology, Key Laboratory of Public Health Safety and Emergency Prevention and Control Technology of Higher Education Institutions in Jiangsu Province, Center for Global Health, School of Public Health, Nanjing, 211166, People’s Republic of China; 2Department of Tuberculosis Control, Center for Disease Control and Prevention, Suzhou, 215000, People’s Republic of China; 3Department of Clinical Laboratory, The Fourth People’s Hospital of Lianyungang, Lianyungang, 222000, People’s Republic of China; 4Department of Tuberculosis, The Third People’s Hospital of Changzhou, Changzhou, 215000, People’s Republic of China; 5National Vaccine Innovation Platform, Nanjing Medical University, Nanjing, 211166, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianming Wang, Department of Epidemiology, Key Laboratory of Public Health Safety and Emergency Prevention and Control Technology of Higher Education Institutions in Jiangsu Province, Center for Global Health, School of Public Health, Nanjing, 211166, People’s Republic of China, Tel +86-25-86868414, Email jmwang@njmu.edu.cnPurpose: Understanding the mode of Mycobacterium tuberculosis (M. tuberculosis) transmission is crucial for disease prevention and control. Compared to traditional genotyping methods, whole genome sequencing (WGS) provides higher resolution and comprehensive genetic information, enabling the tracing of infection sources and determining of transmission routes to resolve extensive tuberculosis (TB) outbreaks. We conducted a ten-year study on the transmission of M. tuberculosis in a population in eastern China.Patients and Methods: We selected Lianyungang, an eastern city in China, as the study site. Patients diagnosed with active pulmonary TB from 2011 to 2020 were enrolled as the study subjects. We isolated and sequenced 2252 M. tuberculosis. Strains with pairwise genetic distances of less than 12 single nucleotide polymorphisms were defined as genomic clusters and which were considered recent transmissions. Kernel density estimation and K-function analysis were applied to explore the spatial distribution of recently transmitted strains.Results: After excluding non-tuberculous mycobacteria and duplicated samples, 2114 strains were included in the final analysis. These strains comprised lineage 2 (1593, 75.35%) and 4 (521, 24.65%). There were 672 clustered strains, with a recent transmission rate of 31.79%. The logistic regression model showed that the risk of recent transmission was high in students [adjusted odds ratio (aOR): 2.68, 95% confidence interval (CI): 1.63– 4.49, P< 0.001] and people infected with L2.2.1 strains (aOR: 1.59, 95% CI: 1.20– 2.12). Higher spatial aggregation of TB transmission has been concentrated in Haizhou, Donghai, and Guanyun for the past 10 years. Three outbreaks affecting 46 patients were spatially spaced, with 11 to 23 persons each. Different groups exhibited varying geographic distances between the initial and later cases.Conclusion: There are areas with a high risk of transmission for M. tuberculosis in the research site, and the risk varies among different populations. Accurate prevention strategies targeted at specific regions and key populations can help curb the prevalence of TB.Keywords: tuberculosis, transmission, cluster, whole genome sequencing, spatial analysis

Juan Qiao,1,2 Shiwan Tao,2 Yurong Sun,3,4 Jiabo Shi,2,5 Yu Chen,2,5 Shui Tian,3,4 Zhijian Yao,2,5 Qing Lu3,4 1Department of Psychology, Xuzhou East Hospital Affiliated to Xuzhou Medical University, Xuzhou, People’s Republic of China; 2Department of Psychiatry, Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China; 3School of Biological Sciences and Medical Engineering, Southeast University, Nanjing, People’s Republic of China; 4Key Laboratory of Child Development and Learning Science, Ministry of Education, Nanjing, People’s Republic of China; 5Nanjing Brain Hospital, School of Medicine, Nanjing University, Nanjing, People’s Republic of ChinaCorrespondence: Zhijian Yao, Department of Psychiatry, Brain Hospital Affiliated to Nanjing Medical University, Nanjing, 210029, People’s Republic of China, Email zjyao@njmu.edu.cn Qing Lu, Email luq@seu.edu.cnBackground: γ-aminobutyric acid (GABA) and its main receptor, the GABAA receptor, are implicated in major depressive disorder (MDD). Anxious depression (AD) is deemed to be a primary subtype of MDD. The amygdala and the dorsolateral prefrontal cortex (DLPFC) are key brain regions involved in emotional regulation. These regions contain the most GABAA receptors. Although the GABAergic deficit hypothesis of MDD is generally accepted, few studies have demonstrated how GABAA receptor gene polymorphisms affect the functions of specific brain regions, in particular, the amygdala and the DLPFC.Methods: The sample comprised 83 patients with AD, 70 patients with non-anxious depression (NAD), and 62 healthy controls (HC). All participants underwent genotyping for polymorphisms of GABAA receptor subunit genes, followed by a resting-state fMRI scan. The HAMD-17 was used to evaluate the severity of MDD. ANOVA was performed to obtain the difference in the imaging data, GABAA receptor multi-locus genetic profile scores (MGPS), and HAMD-17 scores among three groups, then the significant differences between AD and NAD groups were identified. Mediating effect analysis was used to explore the role of functional connectivity (FC) between the amygdala and DLPFC in the association between the GABAA receptor gene MGPS and AD clinical features.Results: Compared with the NAD group, the AD group had a higher GABAA receptor MGPS. AD patients exhibited a negative correlation between the MGPS and FC of the right centromedial (CM) subregion, and the right middle frontal gyrus (MFG). A negative correlation was also observed between the MGPS and anxiety/somatic symptoms. More importantly, the right CM and right MFG connectivity mediated the association between the GABAA receptor MGPS and anxiety/somatic symptoms in patients with AD.Conclusion: The decreased FC between the right MFG and right CM subregion mediates the association between GABAA receptor MGPS and AD.Keywords: anxious depression, GABAA receptor, multi-locus genetic profile scores, dorsolateral prefrontal cortex, amygdala subregion

Yi Wang,1,2 Wenhui Zhang,1,3 Shourong Liu,1 Fei Wang,1 Qian Huang,1 Er Li,3 Mingli Zhu,4 Jianhua Yu,1,&ast; Jinchuan Shi1,&ast; 1Department of Infection, Affiliated Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, People’s Republic of China; 2Institute of Hepatology and Epidemiology, Affiliated Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, People’s Republic of China; 3Department of Nursing, Affiliated Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, People’s Republic of China; 4Medical Laboratory, Affiliated Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianhua Yu; Jinchuan Shi, Department of Infection, Affiliated Hangzhou Xixi Hospital, Zhejiang University of Traditional Chinese Medicine, Hangzhou, People’s Republic of China, Email yujhmc@126.com; shijinchuan2008@126.comObjective: Precise prediction of the occurrence of complicated perianal abscesses (PAs) in monkeypox (mpox)-infected patients is important for therapeutic optimization. This study sought to identify risk factors of complicated PA.Methods: A total of 48 patients with mpox infection (PA group, n = 10; non-PA (NPA) group, n = 38) were enrolled in our study, who were hospitalized in Hangzhou Xixi Hospital, China from 29 June to 3 September 2023. The data of demographic characteristics, and clinical symptoms, serum SAA, PCT, CRP, and IL-6 levels were collected by the Electronic Medical Record. The diagnostic values of these biomarkers were assessed using multivariate logistic regression and ROC curve analyses.Results: A decrease in serum IL-6, SAA, and CRP levels (all p-value < 0.05), but not PCT, was observed in all mpox-infected patients. A significant positive correlation was also noted between IL-6, SAA, CRP, and PCT levels (all p-value < 0.05). There was a significant increase in IL-6 and SAA levels and the SAA/CRP ratio in serum samples from patients in the PA group. Multivariate logistic regression and ROC curve analyses identified that the combined use of perianal symptoms and SAA was more sensitive than perianal symptoms or SAA alone as predictors of complicated PA. This combination had the highest predictive value for disease progression, with an AUC of 0.920 (p-value < 0.001).Conclusion: The combination of perianal symptoms and SAA levels was strongly linked to the occurrence of complicated PA in mpox-infected patients. These findings may inform the early diagnosis of this patient population.Keywords: serum amyloid A, perianal symptoms, perianal abscess, mpox-infected patients

Chengfeng Fu,1,&ast; Junwei Shi,2,&ast; Ying Hu,1 Jing Luo1 1Respiratory and Critical Care Medicine, the Second People’s Hospital of Banan District, Chongqing, 400054, People’s Republic of China; 2State Key Laboratory of Analytical Chemistry for Life Science, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing, Jiangsu, 210023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Luo, Respiratory and Critical Care Medicine, the Second People’s Hospital of Banan District, Chongqing, 400054, People’s Republic of China, Tel +86 15823143609, Email luojing99510@126.comBackground: Chronic obstructive pulmonary disease (COPD) is a widespread respiratory condition characterized by chronic inflammation. Selenium, an essential trace element, possesses anti-inflammatory and antioxidant properties. However, the diet is often complex, and the absence of one nutrient may indicate a concurrent deficiency in others. Therefore, inadequate dietary selenium intake may suggest deficiencies in other elements. Despite its potential benefits, there is a scarcity of evidence regarding the association between dietary selenium intake and COPD.Purpose: This study aims to investigate the potential association between dietary selenium intake and COPD among American adults.Patients and Methods: This cross-sectional study analyzed data from the National Health and Nutrition Examination Survey conducted in the United States from 1999 to 2018. Multivariate logistic regression, restricted cubic spline analyses, subgroup analysis, and sensitivity analysis were conducted to assess the correlation between dietary selenium intake and COPD.Results: A total of 39,654 participants were included in the study. The adjusted odds ratio (OR) for COPD in the highest selenium intake group (T3, > 122.0 μg/day) was 0.80 (95% CI: 0.71– 0.91, p < 0.001) compared to the lowest intake group (T1, < 81.6 μg/day). Dietary selenium intake exhibited a linear negative correlation with COPD. Among participants reporting selenium supplementation, a similar negative association persisted.Conclusion: This study observed a negative correlation between dietary selenium intake and COPD among American adults, indicating a possible association between higher selenium intake and a lower risk of COPD.Keywords: cross-sectional study, chronic obstructive pulmonary disease, COPD, dietary selenium intake, National Health and Nutrition Examination Survey, NHANES

Zhangnan Sun,1,&ast; Ji Shi,2,&ast; Chaolei Liu,1 Jingjing Zhang,1 Yue Liu,1 Yini Wu,3 Xin Han,3 Hong Dai,3 Jimin Wu,3 Lijun Bo,1 Faxing Wang3 1Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Anesthesiology, The First Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Anesthesiology, Lishui People’s Hospital, Lishui Hospital of Wenzhou Medical University, Lishui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Faxing Wang, Department of Anesthesiology, Lishui People’s Hospital, Lishui Hospital of Wenzhou Medical University, No. 15, Dazhong Street, Lishui, Zhejiang Province, 323000, People’s Republic of China, Email wfx2023@wmu.edu.cn Lijun Bo, Department of Anesthesiology, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China, Email 27901566@hebmu.edu.cnObjective: This study investigates the effect of low-dose dexmedetomidine infusion on perioperative neurocognitive function in elderly patients undergoing endoscopic retrograde cholangiopancreatography (ERCP).Patients and Methods: This double-blind trial enrolled 80 elderly ERCP patients randomized to receive dexmedetomidine (Group D) or placebo (Group S). Group D received dexmedetomidine at 0.4 μg·kg− 1·h− 1 starting 15 minutes before surgery until completion, along with propofol at 1.5 mg/kg for anesthesia. Group S received saline and propofol in a similar manner. Anesthesia was maintained with dexmedetomidine at 0.4 μg·kg− 1·h− 1 and propofol at 1– 2 mg/kg during surgery. Cognitive function was assessed using the Mini-Mental State Examination (MMSE) preoperatively and on postoperative days 1, 3, and 5. Primary outcome was perioperative neurocognitive disorder (PND) incidence on day 5; secondary outcomes included changes in perioperative IL-6, cortisol, S100-β, hemodynamics, anesthesia parameters, postoperative pain, agitation scores, and adverse events.Results: All 80 patients completed the trial. On postoperative day 5, the cumulative probability of PND incidence was significantly lower in Group D than in Group S (12.5% vs 35%, P=0.018). Group D also had lower levels of IL-6 (F=199.472, P< 0.001), S100-β (F=2681.964, P< 0.001), and cortisol (F=137.637, P< 0.001). Propofol doses were lower in Group D (706.1 ± 202.4 vs 1003.3 ± 203.7, P< 0.001), and bradycardia rates were higher (45% vs 15%, P=0.003), though atropine use did not significantly differ between groups. Group D showed greater stability in mean arterial pressure. Postoperative complications and adverse reactions were similar across groups.Conclusion: Perioperative low-dose dexmedetomidine infusion with propofol in elderly ERCP patients ensures safe and effective monitored anesthesia care (MAC), reducing PND incidence by mitigating peripheral inflammation and stress responses. Long-term follow-up is needed to fully evaluate PND incidence.Keywords: ERCP, PND, dexmedetomidine, elderly patients

Yunxiao Gu,&ast; Jiaming Feng,&ast; Jiayi Shi,&ast; Guanyi Xiao,&ast; Weiwei Zhang, Shuijin Shao, Baonian Liu, Haidong Guo Department of Anatomy, School of Chinese Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Baonian Liu; Haidong Guo, Department of Anatomy, School of Chinese Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China, Email bnliu15@fudan.edu.cn; hdguo8@hotmail.comBackground: Exosomes in cardiovascular diseases (CVDs) have attracted huge attention with substantial value and potential. Our bibliometrics is based on literature from the field of cardiovascular exosomes over the past 30 years, which has been visualized to display the development process, research hotspots, and cutting-edge trends of clinical practices, mechanisms, and management strategies related to psych cardiology.Methods: We selected articles and reviews on exosomes in CVDs from the core collection of Web of Science, and generated visual charts by using CiteSpace and VOSviewer software.Results: Our research included 1613 publications. The number of exosome articles in CVD fluctuates slightly, but overall shows an increasing trend. The main research institutions were Tongji University and Nanjing Medical University. The International Journal of Molecular Sciences has the highest publication volume, while the Journal of Cellular and Molecular Medicine has the highest citation count. Among all the authors, Eduardo Marban ranks first in terms of publication volume and H-index. The most common keywords are exosome, extracellular vesicles, and angiogenesis.Conclusion: This is a bibliometric study on the research hotspots and trends of exosomes in CVD. Exosome research in the field of cardiovascular medicine is on the rise. Some exosome treatment methods may become the focus of future research.Keywords: exosomes, cardiovascular diseases, bibliometric, citespace, VOSviewer

Junhai Zhen,1 Chuan Liu,2 Jixiang Zhang,2 Fei Liao,2 Huabing Xie,1 Cheng Tan,2 Ping An,2 Zhongchun Liu,3 Changqing Jiang,4 Jie Shi,5 Kaichun Wu,6 Weiguo Dong2 1Department of General Practice, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, 430060, People’s Republic of China; 2Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, 430060, People’s Republic of China; 3Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 4Department of Clinical Psychology, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, People’s Republic of China; 5Department of Medical Psychology, Chinese People’s Liberation Army Rocket Army Characteristic Medical Center, Beijing, 100032, People’s Republic of China; 6Department of Gastroenterology, Xijing Hospital, Air Force Medical University, Xi’an, 710032, People’s Republic of ChinaCorrespondence: Kaichun Wu, Department of Gastroenterology, Xijing Hospital, Air Force Medical University, Xi’an, 710032, People’s Republic of China, Tel/Fax +8629-84771600, Email kaicwu@fmmu.edu.cn Weiguo Dong, Department of Gastroenterology, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuhan, Hubei Province, 430060, People’s Republic of China, Tel/Fax +8627-88041911, Email dongweiguo@whu.edu.cnPurpose: Impaired quality of life (QOL) is common in patients with inflammatory bowel disease (IBD). A tool to more quickly identify IBD patients at high risk of impaired QOL improves opportunities for earlier intervention and improves long-term prognosis. The purpose of this study was to use a machine learning (ML) approach to develop risk stratification models for evaluating IBD-related QOL impairments.Patients and Methods: An online questionnaire was used to collect clinical data on 2478 IBD patients from 42 hospitals distributed across 22 provinces in China from September 2021 to May 2022. Eight ML models used to predict the risk of IBD-related QOL impairments were developed and validated. Model performance was evaluated using a set of indexes and the best ML model was explained using a Local Interpretable Model-Agnostic Explanations (LIME) algorithm.Results: The support vector machine (SVM) classifier algorithm-based model outperformed other ML models with an area under the receiver operating characteristic curve (AUC) and an accuracy of 0.80 and 0.71, respectively. The feature importance calculated by the SVM classifier algorithm revealed that glucocorticoid use, anxiety, abdominal pain, sleep disorders, and more severe disease contributed to a higher risk of impaired QOL, while longer disease course and the use of biological agents and immunosuppressants were associated with a lower risk.Conclusion: An ML approach for assessing IBD-related QOL impairments is feasible and effective. This mechanism is a promising tool for gastroenterologists to identify IBD patients at high risk of impaired QOL.Keywords: clinical research, artificial intelligence, model development, clinical decision support system

Jun Yan,1 Rongrong Zheng,1 Zhongdong Zhang,1 Jinchuan Shi,1 Tingbo Yan,2 Hong Liu,3 Feng Li1 1The Second Infectious Disease Department, Xixi Hospital of Hangzhou, Hangzhou, 310023, People’s Republic of China; 2Radiology Department, Xixi Hospital of Hangzhou, Hangzhou, 310023, People’s Republic of China; 3Pathology Department, Xixi Hospital of Hangzhou, Hangzhou, 310023, People’s Republic of ChinaCorrespondence: Feng Li, The Second Infectious Disease Department, Xixi Hospital of Hangzhou, No. 2 Hengbu Street, Liuxia Town, Xihu District, Hangzhou, 310023, People’s Republic of China, Email lfnice@foxmail.comBackground: Non-tuberculous mycobacteria (NTM) are a group of mycobacteria that are commonly found in the environment and can cause disease in humans. The symptoms of NTM infection can be similar to those of tuberculosis, making diagnosis challenging. The morbidity associated with NTM is increasing, and clinical management can be challenging.Case Description: This report details the case of a 32-year-old male who was found to have multiple enlarged and partially necrotic lymph nodes in the neck, axilla, mediastinum, and retroperitoneum. The causative agent was rapidly identified as Mycobacterium paracondontium through pathogen-targeted sequencing (tNGS). After two weeks of treatment with azithromycin, moxifloxacin, rifabutin, and amikacin, the patient’s uncomfortable symptoms had resolved, and he is currently undergoing further review.Conclusion: It is imperative that clinicians remain vigilant for the presence of NTM, particularly those that are rare, given their pervasiveness in the environment. Prompt diagnosis is of paramount importance, and molecular identification techniques represent a crucial tool in this regard. In vitro drug sensitivity testing should be conducted whenever feasible to guarantee the administration of an efficacious treatment regimen.Keywords: non-tuberculous mycobacteria, Mycobacterium paracondontium, lymph nodes, case report

Jiangpei Shi,1,&ast; Rongguang Zhang,1,&ast; Yu Wang,1 Yingwei Sun,1 Xiaoyan Gu,1 Yu An,1 Xinyu Chai,1 Xiaoyu Wang,2 Zhi Wang,1 Yaqi Lyu,1 Teng Guo,1 Nianping Feng,1 Ying Liu1 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Experiment Center for Science and Technology, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nianping Feng; Ying Liu, Email npfeng@shutcm.edu.cn; debbyly@shutcm.edu.cnBackground: Metastasis is a complex process involving multiple factors and stages, in which tumor cells and the tumor microenvironment (TME) play significant roles. A combination of orally bioavailable therapeutic agents that target both tumor cells and TME is conducive to prevent or impede the progression of metastasis, especially when undetectable. However, sequentially overcoming intestinal barriers, ensuring biodistribution in tumors and metastatic tissues, and enhancing therapeutic effects required for efficient therapy remain challenging.Methods: Inspired by the unique chemical features of natural herbs, we propose an oral herb–nanoparticle hybrid system (HNS) formed through the self-binding of Platycodon grandiflorum–Curcuma zedoaria (HG), a herb pair/group used in clinical practice to treat breast cancer metastasis, to lipid–polymer nanoparticles (LPNs) loaded with silibinin. The molecular structure responsible for HG association with LPNs was assessed using surface-enhanced Raman spectroscopy for HNS surface chemistry characterization. Moreover, the molecular class of HG was identified using UPLC–Orbitrap–MS/MS to further confirm the surface binding. Mucus diffusion and in vivo biodistribution were evaluated using in vitro multiple-particle tracking and environment-responsive fluorescence probe in 4T1 tumor-bearing mice, respectively. The alleviation of breast cancer metastasis was assessed in 4T1 tumor-bearing mice, and the underlying mechanism was investigated.Results: The HNS reduced particle–mucus interactions by altering hydrophilicity and surface characteristics compared to LPNs. The epithelium transportation of HNS and absorption through Peyer’s patch in mice were improved, promoting their biodistribution in the lung and tumor tissues. Furthermore, the HNS alleviated lung metastasis by inducing cell apoptosis and regulating the expression of MMP-9 and TGF-β 1, which altered the TME in 4T1 tumor-bearing mice.Conclusion: HNS provides an appealing system with multi-component binding of herbal medicine to facilitate both oral nanoparticle delivery efficiency and the alleviation of lung metastasis. This strategy may potentially help improve treatment for patients with breast cancer.Keywords: herb–nanoparticle hybrid system, intestinal biological barrier, tumor microenvironment, breast cancer lung metastasis

Jia Song,1 Jiancheng Zhang,2 Jun Shi,2 Xuming Pan,2 Dayu Mo3 1Department of General Practice, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Emergency, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 3Department of Education, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Dayu Mo, Department of Education, The Second Affiliated Hospital of Zhejiang Chinese Medical University, No. 318 Chaowang Road, Hangzhou, Zhejiang, 310005, People’s Republic of China, Tel +86-13857197190, Email modayu@zcmu.edu.cnBackground: Breviscapine has been demonstrated to have beneficial effects in ameliorating acute lung injury (ALI), yet its potential therapeutic value and molecular mechanisms in sepsis-induced ALI remain unexplored.Methods: We utilized network pharmacology approach to identify the potential targets and mechanisms of breviscapine in treating sepsis-induced ALI. To construct a murine model of sepsis, we performed cecal ligation and puncture (CLP). Hematoxylin and eosin (HE) staining and enzyme-linked immunosorbent assay (ELISA) were employed to respectively determine the pathologic changes and levels of inflammatory factors. Neutrophil count and total protein level in bronchoalveolar lavage fluid (BALF) were detected by corresponding kit. Additionally, we utilized flow cytometry, immunofluorescence, Western blotting, and real-time reverse transcription PCR (qRT-PCR) to detect cell apoptosis, protein expression, and gene expression. Finally, we used ELISA kits to detect the activity of myeloperoxidase (MPO) and caspase-8 (CASP8).Results: Breviscapine was revealed to target 81 potential proteins in the treatment of sepsis-induced ALI, while CASP8 was the most important one as demonstrated by network analysis. In vivo experiments demonstrated that breviscapine effectively reduced the severity of sepsis-induced ALI and inflammation, and significantly suppressed neutrophil infiltration in the lung tissues of CLP mice and promoted neutrophil apoptosis in the peripheral blood. In vitro experiments revealed that lipopolysaccharide (LPS)-induced neutrophil apoptosis was inhibited, and the expression and activity of CASP8 were down-regulated. Breviscapine intervention markedly up-regulated the expression and activity of CASP8, consequently activating neutrophil apoptosis and inhibiting inflammatory response by activating the NF-κB signaling pathway.Conclusion: Breviscapine is remarkably effective in improving sepsis-induced ALI, and its mechanism of action may be to induce neutrophil apoptosis, inhibit inflammatory overreaction and reduce its infiltration in pulmonary tissues by up-regulating the expression and activity of CASP8.Keywords: Breviscapine, acute lung injury, sepsis, network pharmacology, neutrophil

Guojuan Pu,1,2 Zhen Liang,1,2 Jieran Shi,2 Yuan Tao,1,2 Ping Lu,1,2 Huiling Qing,1,2 Junjie Zhang1,2 1Henan Eye Hospital, Henan Eye Institute, Henan Provincial People’s Hospital, Zhengzhou, 450003, People’s Republic of China; 2People’s Hospital of Zhengzhou University, Zhengzhou, 450003, People’s Republic of ChinaCorrespondence: Junjie Zhang, Henan Eye Hospital, Henan Eye Institute, Henan Provincial People’s Hospital, and People’s Hospital of Zhengzhou University, Number 7 Weiwu Road, Zhengzhou, 450003, People’s Republic of China, Email zhangjunjie@zzu.edu.cnBackground: Corneal neovascularization (CNV) is a common eye disease that leads to blindness. New treatment strategies are urgently needed due to the limitations of current treatment methods.Methods: We report the synthesis of peptide Nap-FFEEPCAIWF (Comp.3) via chemical conjugation of Nap-FFEE (Comp.2) to antiangiogenic peptide PCAIWF (Comp.1). Comp.3 self-assembled into a hydrogel (gel of 3) composed of nanofibers, which enhanced the antiangiogenic function of the epitope.Results: We developed a novel peptide with an amphiphilic framework, Comp.3, which could self-assemble into a supramolecular hydrogel with a well-ordered nanofiber structure. The nanofibers exhibited good biocompatibility with corneal epithelial cells, presenting a promising strategy to enhance the efficacy of free peptide–based drugs in the treatment of ocular vascular diseases, such as CNV and other angiogenesis-related diseases.Conclusion: Nap-FFEEPCAIWF nanofibers provide an alternative approach to enhancing the therapeutic efficiency of free peptide–based drugs against ocular vascular diseases. Keywords: antiangiogenic peptide, self-assembled, hydrogel, nanofiber, corneal neovascularization

Yi Shao,&ast; Yunfu Chen,&ast; Xin Lan, Jun Lu, Guangling Tang, Sijie Tang, Ruixue Zhai, Chao Chen, Xinglong Xiong, Jing Shi Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, 550001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Shi, Department of Anesthesiology, The Affiliated Hospital of Guizhou Medical University, No. 28 Beijing Road, Guiyi Street, Yunyan District, Guiyang, Guizhou, 550001, People’s Republic of China, Tel +86-18685034016, Email shijing81@gmc.edu.cnBackground: Morin can alleviate vincristine-induced neuropathic pain via inhibiting neuroinflammation. Microglial cells play an important role in initiating and maintenance of pain and neuroinflammation. It remains unclear whether morin exerts antinociceptive properties through the regulation of microglial cells. This study aimed to elucidate the mechanisms of morin against neuropathic pain focusing on microglial cells.Methods: The thermal withdrawal latency and mechanical withdrawal threshold were used as measures of pain behaviours. Histological abnormalities of the sciatic nerve were observed with transmission electron microscopy. The sciatic functional index and the sciatic nerve conduction velocity were used as measures of the functional deficits of the sciatic nerve. Inflammatory factors were detected using ELISA. The expression of M1/M2 polarization markers of microglia and nuclear factor κB (NF-κB) p65 were measured by immunofluorescence, real-time quantitative PCR and Western blotting.Results: Morin alleviated vincristine-induced abnormal pain, sciatic nerve injury, and neuroinflammatory response in rats. Furthermore, morin decreased the expression of NF-κB P65 and M1 activation markers, increased the expression of M2 activation markers. Additionally, phorbol 12-myristate 13-acetate reversed the effects of morin on microglial polarization, the production of inflammatory factors and neuropathic pain, while ammonium pyrrolidine dithiocarbamate showed the opposite effects.Conclusion: Our results demonstrate that morin inhibits neuroinflammation to alleviate vincristine-induced neuropathic pain via inhibiting the NF-κB signalling pathway to regulate M1/M2 microglial polarization.Keywords: neuropathic pain, morin, microglia, NF-κB, neuroinflammation

Peijun Li,1,&ast; Yingqi Wang,1,&ast; Yuanyuan Cao,2 Jiacheng Shi,1 Meiling Jiang,2 Xiaoyu Han,2 Linhong Jiang,1 Yidie Bao,1 Weibing Wu,2 Xiaodan Liu1,3,4 1School of Rehabilitation Science, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Sports Rehabilitation, Shanghai University of Sport, Shanghai, 200438, People’s Republic of China; 3Institute of Rehabilitation Medicine, Shanghai Academy of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 4Engineering Research Center of Traditional Chinese Medicine Intelligent Rehabilitation, Ministry of Education, Shanghai, 201203, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaodan Liu; Weibing Wu, Email hzhp403@126.com; wwb75@126.comBackground: Exercise is an indispensable component of pulmonary rehabilitation with strong anti-inflammatory effects. However, the mechanisms by which exercise prevents diaphragmatic atrophy in COPD (chronic obstructive pulmonary disease) remain unclear.Methods: Forty male C57BL/6 mice were assigned to the control (n=16) and smoke (n=24) groups. Mice in the smoke group were exposed to the cigarette smoke (CS) for six months. They were then divided into model and exercise training groups for 2 months. Histological changes were observed in lung and diaphragms. Subsequently, agonist U46639 and antagonist Y27632 of RhoA/ROCK were subjected to mechanical stretching in LPS-treated C2C12 myoblasts. The expression levels of Atrogin-1, MuRF-1, MyoD, Myf5, IL-1β, TNF-α, and RhoA/ROCK were determined by Western blotting.Results: Diaphragmatic atrophy and increased RhoA/ROCK expression were observed in COPD mice. Exercise training attenuated diaphragmatic atrophy, decreased the expression of MuRF-1, and increased MyoD expression in COPD diaphragms. Exercise also affects the upregulation of RhoA/ROCK and inflammation-related proteins. In in vitro experiments with C2C12 myoblasts, LPS remarkably increased the level of inflammation and protein degradation, whereas Y27632 or combined with mechanical stretching prevented this phenomenon considerably.Conclusion: RhoA/ROCK plays an important role in the prevention of diaphragmatic atrophy in COPD.Keywords: chronic obstructive pulmonary disease, diaphragmatic atrophy, exercise training, inflammation, RhoA/ROCK signaling

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

Jia Shi,1,2,&ast; Meng-Jiao Shao,3,&ast; Miao Yu,1,2 Bao-Peng Tang1,2 1Cardiac Pacing and Physiological Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Xinjiang Key Laboratory of Cardiac Electrophysiology and Cardiac Remodeling, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 3Department of Cardiology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bao-Peng Tang, Cardiac Pacing and Physiological Department, The First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China, Email tangbaopeng1111@163.comBackground: Inflammation and cardiac fibrosis are important pathogenic drivers of heart failure. The fibrosis-4 index (FIB-4) is associated with a higher degree of fibrosis. The systemic immune inflammation index (SII) is associated with a higher degree of systemic inflammation status. Previous studies have shown that they are associated with a poor prognosis for cardiovascular disease. We sought to investigate the value of FIB-4 combined with the SII as a novel inflammation-fibrosis combined index (IFCI) in predicting left ventricular reverse remodeling (LVRR) and prognosis among reduced ejection fraction heart failure (HFrEF) patients.Methods: A total of 895 patients with HFrEF were continuously recruited. Receiver operating characteristic curves were drawn to assess the abilities of inflammation-fibrosis indicators to predict LVRR. Multivariable Cox regression analysis was used to examine independent predictors of composite cardiac events and all-cause death.Results: After six months of follow-up, 344 (38.4%) patients experienced LVRR. The IFCI had the largest area under the curve (0.835, P < 0.001). In multivariate-adjusted logistic regression analyses, FIB-4, SII, and IFCI were predictive of LVRR (P value < 0.05). The IFCI was associated with a 3.686-fold higher risk of non-LVRR (odds ratio [OR] = 3.686, P < 0.001). Moreover, an increased IFCI predicted a poor prognosis in HFrEF patients. The highest risk of composite cardiac events (hazard ratio [HR] = 2.716, P < 0.001) was observed in the top IFCI-tertile group, and similar results were found regarding independent risk indicators of all-cause death.Conclusion: In summary, this study indicated that increased IFCI at admission offers good predictability regarding non-LVRR and predicts the risk of all-cause mortality or composite cardiovascular events due to HFrEF patients and could be used as a novel marker.Keywords: heart failure, left ventricular reverse remodeling, inflammation-fibrosis combined index, fibrosis-4 index, systemic immune inflammation index, prognosis

Chenyu Zhang,1 Yi Dai,1 Junji Zhang,1 Xiaoyan Li,1 Shuangzheng Jia,2 Jinghua Shi,1,&ast; Jinhua Leng1,&ast; 1Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, National Clinical Research Center for Obstetric & Gynecologic Diseases, Beijing, People’s Republic of China; 2Department of Gynecologic Oncology, National Cancer Center / National Clinical Research Center for Cancer / Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinghua Shi; Jinhua Leng, Tel +86 151-0101-6294 ; +86 137-0129-8616, Email elisa_1984@163.com; lengjenny@vip.sina.comObjective: This study aimed to explore the distribution of nerve fibers in abdominal wall endometriosis (AWE) and discern their association with pain.Methods: A retrospective case–control study was conducted. The cases comprised 30 patients diagnosed with AWE, while the control group consisted of 17 patients who had undergone laparotomy without any history of endometriosis. We analyzed clinical characteristics and examined the innervation patterns in samples using stains for S-100, neuron-specific enolase (NSE), protein gene product 9.5 (PGP9.5), neurofilament (NF), and substance P (SP) antibodies.Results: There was a notable increase in the density of S-100, NSE and PGP9.5 immunoreactive nerve fibers and a higher proportion of SP positivity in AWE lesions compared to standard abdominal wall scars (p < 0.05). However, there were no significant differences in the density or proportion of NF-immunoreactive nerve fibers between the cases and the controls. Moreover, no statistically significant correlation was observed between the density of S-100, NSE, PGP9.5, NF, or SP-positive nerve fibers and pain scores.Conclusion: This study demonstrated an increased immunoreactive nerve fiber density located in AWE lesions compared to normal abdominal wall scars. Further high-quality studies are needed to investigate the mechanisms responsible for pain in women with endometriosis.Keywords: abdominal wall endometriosis, pain, nerve fibers, immunohistochemistry

Jingyun Shi,1,&ast; Fangping Zhao,1,&ast; Wanyin Yang,2 Yuru Zhu,1 Min Wang,1 Bin Yi1 1Department of NICU, Gansu Provincial Maternal and Child Care Hospital (Gansu Provincial Central Hospital), Lanzhou City, Gansu, 730050, People’s Republic of China; 2Department of NICU, Gansu University of Chinese Medicine, Lanzhou City, Gansu, 730050, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Wang; Bin Yi, Department of NICU, Gansu Provincial Maternal and Child care Hospital (Gansu Provincial Central Hospital), No. 143 of Qilihe North Street, Qilihe District, Lanzhou, 730050, People’s Republic of China, Tel +86 13919819662, Email wangmin_wm23@126.com; yibin_bin001@tom.comObjective: To explore the status and influencing factors of COVID-19 vaccination for 3– 7-year-old children born prematurely.Methods: A questionnaire was administered to parents of preterm infants born between 1 January 2016 and 31 December 2019 in Gansu Maternal and Child Health Hospital using convenience sampling.Results: It was found that 96.81% of 282 parents had known about COVID-19 vaccines and acquired COVID-19- and vaccine-related knowledge primarily through WeChat (104/282, 36.88%) and TikTok (91/282, 32.27%). Most parents of the group whose children were vaccinated with a COVID-19 vaccine believed that this approach was effective in preventing COVID-19 (49.75%), whereas most parents of the group whose children were not vaccinated were worried about the adverse reaction and safety of the vaccine (45.88%). According to the regression analysis, the risk factors of children born prematurely receiving a COVID-19 vaccine were no vaccination against COVID-19 in the mothers (odds ratio [OR]=48.489, 95% CI: 6.524– 360.406) and in younger children (OR=12.157, 95% CI: 6.388– 23.139). Previous history of referral (OR=0.229, 95% CI: 0.057– 0.920), history of diseases (OR=0.130, 95% CI: 0.034– 0.503) and high educational level of guardians (OR=0.142, 95% CI: 0.112– 0.557) were protective factors for children born prematurely to receive COVID-19 vaccination.Conclusion: There is a relatively high proportion of children born prematurely receiving COVID-19 vaccination, but some people still have concerns. Publicity in the later stage can be conducted through WeChat, TikTok and other social media platforms, with special attention paid to the populations with lower education levels.Keywords: COVID-19 vaccine, vaccination willingness, children born prematurely, influencing factors

Yuye Chen,1 Yue Liu,2 Hong Lv,1 Qian Li,1 Jingjia Shen,1 Weiyun Chen,2 Jia Shi,1 Chenghui Zhou3 1Department of Anesthesiology, Fuwai Hospital, Chinese Academy of Medical Sciences&Peking Union Medical College/National Center for Cardiovascular Diseases, Beijing, 100037, People’s Republic of China; 2Department of Anesthesiology, Peking Union Medical College Hospital, Beijing, 100730, People’s Republic of China; 3Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, 100029, People’s Republic of ChinaCorrespondence: Chenghui Zhou, Center for Anesthesiology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86-137-1889-4919, Email chenghuizhou@vip.163.com Jia Shi, Department of Anesthesiology, Fuwai Hospital, Chinese Academy of Medical Sciences&Peking Union Medical College/National Center for Cardiovascular Diseases, No. 167 North Lishi Road, Xicheng District, Beijing, 100037, People’s Republic of China, Email shijia@fuwai.comBackground: The potential myocardial protective effect of nicorandil (NICD) in patients undergoing percutaneous coronary intervention has been established. However, its efficacy in the context of cardiac surgery remains controversial. The present study aimed to evaluate the myocardial protective effect of perioperative NICD use in patients undergoing cardiac surgery with cardiopulmonary bypass (CPB).Methods: We retrospectively gathered data from patients undergoing cardiac bypass surgery between 12/2018 and 04/2021 in Fuwai Hospital. Subsequently, the patients were divided into two groups, NICD group and non-nicorandil (non-NICD) group. A 1, 3 propensity score matching (PSM) was conducted. The primary outcome was the incidence of myocardial injury. The secondary outcomes included the mechanical ventilation (MV) duration, intensive care unit (ICU) length of stay (LOS), hospital LOS, duration of chest drainage, the drainage volume, the total cost, the incidence of acute kidney injury (AKI), and the incidence of acute liver injury (ALI). Subsequently, we divided the entire population into two distinct subgroups based on their administration of NICD, and performed a comprehensive subgroup analysis.Results: A total of 2406 patients were ultimately included in the study. After PSM, 250 patients in NICD group and 750 patients in non-NICD group were included in the analysis. Perioperative NICD reduced the incidence of myocardial injury (47.2% versus 38.8%, P=0.025). Our subgroup analysis revealed that preoperative NICD administration not only provided myocardial protection benefits (45.7% vs 35.8%, OR 0.66, 95% CI [0.45– 0.97], P=0.041), but also demonstrated statistically significant reduction in ALI, the ICU and hospital LOS, and the duration of chest drainage (all P< 0.05).Conclusion: The perioperative NICD administration may confer myocardial protection in patients undergoing cardiac surgery with CPB. Furthermore, the preoperative utilization of NICD has the potential to mitigate the incidence of postoperative ALI, a reduction in the ICU and hospital LOS, and the duration of chest drainage.Keywords: nicorandil, cardiopulmonary bypass, perioperative myocardial injury, acute kidney injury, acute liver injury

Jinpeng Shi,1,&ast; Jiayu Li,1,&ast; Haowei Wang,1,&ast; Xuefei Li,2 Qi Wang,1 Chao Zhao,2 Lei Cheng,2 Ruoshuang Han,1 Peixin Chen,1 Haoyue Guo,1 Zhuoran Tang,1 Caicun Zhou,1 Zhemin Zhang,1 Fengying Wu1 1Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, School of Medicine, Tongji University, Shanghai, People’s Republic of China; 2Department of Lung Cancer and Immunology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Fengying Wu; Zhemin Zhang, Department of Medical Oncology, Shanghai Pulmonary Hospital & Thoracic Cancer Institute, School of Medicine, Tongji University, No. 507, Zheng Min Road, Shanghai, 200433, People’s Republic of China, Tel +86 21 6511 5006, Email fywu@163.com; zhemindoc@163.comPurpose: Neutrophils act as a non-negligible regulator in the initiation and progression of malignancies, playing bifacial roles in the process. Thus, to understand the heterogeneity of tumor-associated neutrophils (TANs) comprehensively in advanced non-small cell lung cancer (NSCLC) at single-cell resolution is necessary and urgent.Materials and Methods: We applied single-cell RNA-sequencing (scRNA-seq) to portray the subtype-specific transcriptome landscape of TANs in advanced NSCLC using nine freshly obtained specimens. The scRNA-seq data were further processed for pseudo-time analysis to depict the developmental trajectory of TANs. Meanwhile, the interplay between TANs and other cell types within tumor microenvironment (TME) was revealed by intercellular interaction analysis.Results: Seven distinct TAN subtypes were defined, of which, the N3 cluster was considered inflammatory phenotype expressing genes encoding multiple chemotactic cytokines, and correlated with inferior overall survival, indicating that N3 might be a pro-tumorigenic TAN subtype. N1 and N5 clusters were considered to be well differentiated and mature neutrophils based on CXCR2 expression and pseudo-time patterns, and both accounted for relatively high proportions in lung adenocarcinoma. In addition, genes related to neutrophil differentiation were discovered. We also found that TAN subtypes interacted most closely with macrophages through chemokine signaling pathways within TME.Conclusion: Our study refined TAN subtypes and mapped the transcriptome landscape of TANs at single-cell resolution in advanced NSCLC, collectively indicating the heterogeneity of TANs in NSCLC. Neutrophil differentiation- and maturation-related genes were also discovered, which shed light on different functions of TAN subclones in tumor immune escape, and may further provide novel targets for immunotherapy. Keywords: tumor-associated neutrophil, single-cell RNA-sequencing, non-small cell lung cancer, tumor microenvironment, heterogeneity

Shukun Chai, Chuan Wang, Yi Liu, Jingrong Xia, Xiaolin Wang, Jinying Shi Department of Respiratory Medicine, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of ChinaCorrespondence: Jinying Shi, Department of Respiratory Medicine, Shijiazhuang People’s Hospital, Shijiazhuang, Hebei, 050051, People’s Republic of China, Email 15176988001@163.comPurpose: Lower Respiratory Tract Infection (LRTI) is a leading cause of morbidity and mortality worldwide. In this study, the distribution patterns of causative pathogens in LRTI were evaluated within a city-level hospital by combining conventional microbiological tests (CMT) with metagenomic next-generation sequencing (mNGS).Patients and Methods: This retrospective cohort study involved 160 patients suspected of having LRTI in a single center. Specimens, including bronchoalveolar lavage fluid (BALF), blood, tissue, sputum, and pus were utilized to identify pathogens. The seasonal prevalence of pathogens and co-pathogens involved in multiple infections was analyzed.Results: A total of 137 patients with 156 samples were included in this study. Pseudomonas aeruginosa, Corynebacterium striatum, Klebsiella pneumoniae, Candida, and human herpesvirus were the top prevalent pathogens. We observed seasonal dynamic variation in the top prevalent bacteria (Pseudomonas aeruginosa and Klebsiella pneumoniae) and herpesvirus (Epstein-Barr virus and Human herpesvirus-7). The majority of patients had single bacterial infections, followed by instances of bacterial-viral co-infections, as well as mixed infections involving bacteria, fungi, and viruses. Notably, the spectrum of co-infecting pathogens was broader among the elderly population, and positive Spearman correlations were observed among these co-infecting pathogens.Conclusion: Co-infections were prevalent among patients with LRTI, and the pathogens displayed distinct seasonal distribution patterns. The findings underscored the significance of comprehending pathogen distribution and epidemic patterns, which can serve as a basis for early etiological identification.Keywords: metagenomic next-generation sequencing, low respiratory tract infection, co-pathogens, seasonal prevalence

Qian Wu,1 Jing Shi,2 Juan Huang,3 Delu Gan,1 Lijun Zhang,1 Pu Li1 1Department of Laboratory Medicine, The Second Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Clinical Laboratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 3Department of Information Center, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Pu Li, Department of Clinical Laboratory, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of China, Fax +86-23-63693195, Email lipu@hospital.cqmu.edu.cnBackground: Escherichia coli (E. coli) is a common pathogen in bloodstream infections (BSI), and the production of extended-spectrum beta-lactamases (ESBLs) is its main mechanism of resistance. However, the impact of different ESBL genotypes of E. coli on the resistance to Cefepime (FEP) remains unclear.Methods: A total of 2356 cases of BSI patients were collected. The experimental group included 188 ESBL-positive E. coli strains that were resistant to FEP but sensitive to ceftazidime (CAZ). Antibiotic usage and resistance rates were evaluated through antimicrobial susceptibility testing and antibiotic usage records. The ESBL genotypes were identified, and the minimum inhibitory concentration (MIC) and mutant prevention concentration (MPC) of FEP were determined.Results: In ESBL-positive E. coli, three ESBL genotypes were identified: 188 strains of CTX-M, 130 strains of TEM-1, and 26 strains of OXA-10. Among them, 124 strains carried both CTX-M-9 and TEM-1 genotypes, 22 strains carried two CTX-M genotypes (CTX-M-1 and CTX-M-2), 20 strains carried both CTX-M-9 and OXA-10, and 6 strains carried three genotypes (CTX-M-9, CTX-TEM-1, and OXA-10). The MIC50, MIC90, MPC50, and MPC90 of the 188 ESBL-positive E. coli were 64, 256, 128, and 528, respectively. The MIC values ranged from 32 to 256, while the MPC values ranged from 64 to 528. The MIC50, MIC90, MPC50, and MPC90 of the 40 ESBL-negative E. coli were 0.5, 1, 64, and 128, respectively; the MIC values ranged from 0.25 to 4, while the MPC values ranged from 32 to 256, respectively.Conclusion: ESBL-positive E. coli induces an increase in the MIC value of FEP, leading to an increase in FEP resistance. The inoculation effect also causes a significant increase in the MPC value of FEP, especially the increase in selection index value, indicating selective enrichment and amplification of drug-resistant mutants, resulting in clinical treatment failure.Keywords: Escherichia coli, cefepime, ESBLs, mutant prevention concentration

Jinchuan Shi, Gaoxiang Ying, Zhongdong Zhang The Second Infectious Disease Department, Xixi Hospital of Hangzhou, Hangzhou, 310023, People’s Republic of ChinaCorrespondence: Zhongdong Zhang, The Second Infectious Disease Department, Xixi Hospital of Hangzhou, No. 2 Hengbu Street, Liuxia Town, Xihu District, Hangzhou, 310023, People’s Republic of China, Email ttvz@sina.comBackground: As a malignant tumor derived from vascular endothelial cells, Kaposi’s sarcoma (KS) is quite common in AIDS patients. Nonspecific clinical symptoms often lead to timely diagnosis or wrong treatment, leading to recurrent disease and poor prognosis. Anti-retroviral therapy (ART) could significantly reduce its morbidity and aggressiveness. As one of the ARTs, liposome anthracyclines are the preferred chemotherapy regimen for disseminated KS with multiple organs or tissue invasion. The curative effect is highly related to the degree of immunosuppression. This is the first case of AIDS with Kaposi’s sarcoma, who was cured after ART and two consecutive chemotherapy with doxorubicin liposome without recurrence. This case may provide new ideas and methods for the clinical management of AIDS with Kaposi’s sarcoma.Case Description: The patient, a male aged 60 years, was hospitalized on 21/11/2018 following having a cough, expectoration, and difficulty breathing. He was infected with HIV eight years ago and presented symptoms of blood-stained sputum. The patient complained that he had not received ART before. After admission, he was diagnosed as KS with disseminated AIDS after multiple biopsies and histopathological examinations. The patient was treated with ten months of ART (lamivudine+tenofovir+dolutegravir) and 14 times of chemotherapy with doxorubicin liposome (20 mg/m2, three times per week, seven times per course of treatment). The patient’s disease was finally alleviated, and there was no recurrence during the follow-up.Conclusion: The reconstitution of immune function and consecutive chemotherapy with doxorubicin liposome play a vital role in treating KS. In addition, for the early general symptoms of AIDS patients, such as thrombocytopenia and hemorrhagic purple papules, it is necessary to increase vigilance and obtain the results of histopathological verification as soon as possible to diagnose KS patients at an earlier stage and realize clinical intervention in time.Keywords: AIDS, Kaposi’s sarcoma, human herpesvirus 8, doxorubicin liposome

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

Xuchen Huang,1,2 Sainan Li,1,2 Wei Gao,1,2 Jiajie Shi,1,2 Meng Cheng,1,2 Yunzhe Mi,1,2 Yueping Liu,3 Meixiang Sang,4 Ziyi Li,4 Cuizhi Geng1,2 1Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 2Key Laboratory in Hebei Province for Molecular Medicine of Breast Cancer, Shijiazhuang, Hebei, People’s Republic of China; 3Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 4Research Center and Tumor Research Institute, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of ChinaCorrespondence: Cuizhi Geng, Department of Breast Center, The Fourth Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050000, People’s Republic of China, Tel/Fax +86-311-66696313, Email gengcuizhisci@163.comPurpose: Our aim was to verify whether KIF20A has the potential to serve as a prognostic marker for female patients with estrogen receptor (ER)-positive breast cancer (BC) and treated with tamoxifen (TAM).Patients and Methods: Online tools were used to investigate the potential correlation between KIF20A gene expression and survival of patients with ER-positive BC and TAM treatment. Furthermore, immunohistochemistry (IHC) was conducted to assess the expression levels of KIF20A in patients included from our center. The prognostic value of KIF20A for disease-free survival (DFS) and overall survival (OS) was further evaluated using Cox regression analysis.Results: According to the results obtained from online tools, it was found that patients with low KIF20A expression exhibited significantly better survival outcomes in terms of relapse-free survival (RFS), distant metastasis-free survival (DMFS), and OS compared to those with high KIF20A expression (P < 0.001, P < 0.001, and P = 0.008, respectively). Additionally, significantly lower gene expression of KIF20A was found in patients who responded to TAM than in those who did not respond to TAM (P < 0.001). We further included 203 patients with adjuvant TAM therapy, and IHC for KIF20A was performed on sections from paraffin-embedded blocks. Patients with low KIF20A expression had significantly better DFS and OS (P = 0.001 and 0.002, respectively, log rank test), and the expression of KIF20A was identified as an independent factor for predicting both DFS and OS (P = 0.001 and 0.008, respectively).Conclusion: KIF20A expression is an independent prognostic factor for survival in patients with ER-positive BC who received adjuvant TAM therapy. In clinical practice, IHC evaluation of KIF20A expression in surgical samples before administering tamoxifen may assist in predicting the treatment outcomes of these patients.Keywords: KIF20A, breast carcinoma, biomarker, tamoxifen, survival, prognosis

Shanshan Li,1,&ast; Cheng Yang,1,&ast; Junqiang Li,1,&ast; Chao Zhang,1 Liaoliao Zhu,1 Yang Song,1 Yongdong Guo,1 Ronglin Wang,1 Dongxue Gan,1 Jingjie Shi,1 Peixiang Ma,1 Fei Gao,2 Haichuan Su1 1Department of Oncology, The Second Affiliated Hospital, Air Force Medical University, Xi’an City, People’s Republic of China; 2Center for Peptide Functional Materials and Innovative Drugs, Institute of Translational Medicine, Shanghai University, ShangHai City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haichuan Su, Department of Oncology, The Second Affiliated Hospital, Air Force Medical University, No. 569 Xinsi Road, Baqiao District, Xi’an City, People’s Republic of China, Email suhc@fmmu.edu.cn Fei Gao, Center for Peptide Functional Materials and Innovative Drugs, Institute of Translational Medicine, Shanghai University, No. 99 ShangDa Road, BaoShan District, ShangHai City, People’s Republic of China, Email flyhightly@shu.edu.cnAbstract: Pluronic F127 hydrogel biomaterial has garnered considerable attention in wound healing and repair due to its remarkable properties including temperature sensitivity, injectability, biodegradability, and maintain a moist wound environment. This comprehensive review provides an in-depth exploration of the recent advancements in Pluronic F127-derived hydrogels, such as F127-CHO, F127-NH2, and F127-DA, focusing on their applications in the treatment of various types of wounds, ranging from burns and acute wounds to infected wounds, diabetic wounds, cutaneous tumor wounds, and uterine scars. Furthermore, the review meticulously examines the intricate interaction mechanisms employed by these hydrogels within the wound microenvironment. By elucidating the underlying mechanisms, discussing the strengths and weaknesses of Pluronic F127, analyzing the current state of wound healing development, and expanding on the trend of targeting mitochondria and cells with F127 as a nanomaterial. The review enhances our understanding of the therapeutic effects of these hydrogels aims to foster the development of effective and safe wound-healing modalities. The valuable insights provided this review have the potential to inspire novel ideas for clinical treatment and facilitate the advancement of innovative wound management approaches.Keywords: Pluronic F127, F127-CHO, F127-NH2, F127-DA, wound healing and repair

Wenhui Zhang,1,2,&ast; Yi Wang,2,3,&ast; Er Li,1 Dingyan Yan,1,2 Jianhua Yu,2 Mingli Zhu,4 Jinchuan Shi,2,&ast; Liping Zheng1,&ast; 1Department of Nursing, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Department of Infection, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 3Institute of Hepatology and Epidemiology, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 4Medical Laboratory, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinchuan Shi, Department of Infection, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, No. 2 Hengbu Street, Liuxia Town, Xihu District, Hangzhou, Zhejiang, People’s Republic of China, Email shijinchuan2008@126.com Liping Zheng, Department of Nursing, Affiliated Hangzhou Xixi Hospital, Zhejiang University School of Medicine, No. 2 Hengbu Street, Liuxia Town, Xihu District, Hangzhou, Zhejiang, People’s Republic of China, Email zhengliping512@126.comPurpose: Neuropsychiatric adverse events (NPAEs) occur frequently in people living with human immunodeficiency virus (PLWH) receiving antiretroviral therapy (ART). This study aimed to assess the dynamic trends and risk factors of NPAEs among PLWH in Hangzhou taking efavirenz (EFV)- or dolutegravir (DTG)- or elvitegravir (EVG)-based regimens.Patients and Methods: A total of 287 ART-naive PLWH were included in this study, EFV (400mg)- (n = 122), EFV (600mg)- (n = 37), DTG- (n = 73), EVG-based (n = 47) and other ART regimens (n = 8) as the initial ART regimen were administered for 12 months. All data were collected at five time points within a 12-month follow-up. The Pittsburgh Sleep Quality Index and Hospital Anxiety and Depression Scale were used to evaluate sleep disorders and anxiety and depression symptoms, respectively. The dynamic trends and potential risk factors of NPAEs were investigated using a generalized linear mixed model.Results: Mean age was 29.4 (SD: 7.5) years with 97.2% males. After 12 months of ART, the prevalence of sleep disorders and anxiety decreased significantly, although only a slight improvement was observed for depression. In addition, there was a significant positive correlation between sleep disorders, anxiety, and depression. The risk factors for NPAEs differed slightly depending on the choice of ART regimen, but the seven factors most commonly associated with NPAEs were age, sex, marital status, education level, smoking status, body mass index, and WHO clinical stage. Treatment-induced changes in CD4-positive T-cell count and virological suppression did not depend on the particular choice of ART regimen.Conclusion: The prevalence of sleep disorders and anxiety changed significantly over time on ART and the risks of these disorders were associated with seven common clinical and demographic factors.Keywords: sleep disorders, anxiety, depression, antiretroviral therapy, people living with HIV

Jipeng Shi,1 Zhen-Qi Lu,1 Qing-Mei Lin,2 Wang Zeng,1 Ping-Jiao Gu,1 Qing Yu,3 Jing Long,1 Da-Gui Huang,1 Yi-Heng Dai1 1Department of Neonatal, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University (Foshan Maternity & Child Healthcare Hospital), Foshan, Guangdong, 528000, People’s Republic of China; 2Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University (Foshan Maternity & Child Healthcare Hospital), Foshan, Guangdong, 528000, People’s Republic of China; 3Department of Clinical Laboratory, Affiliated Foshan Maternity & Child Healthcare Hospital, Southern Medical University (Foshan Maternity & Child Healthcare Hospital), Foshan, Guangdong, 528000, People’s Republic of ChinaCorrespondence: Yi-Heng Dai, Email daiyiheng@163.comBackground: There are many difficulties and uncertainties in the early diagnosis of neonatal sepsis. The aim of this study was to determine whether albumin (ALB) is useful for the early diagnosis of neonatal sepsis using ALB, C-reactive protein (CRP) and procalcitonin (PCT) together.Methods: ALB, CRP, PCT and white blood cell (WBC) data from 732 patients with neonatal sepsis and 1317 neonatal infection patients hospitalized in Foshan Maternal and Child Health Hospital from 2011 to 2022 were collected. Receiver operating characteristic (ROC) and logistic regression analyses were performed to assess the diagnostic value of ALB, CRP, PCT and the WBC count for neonatal sepsis. The roles of ALB, CRP, PCT and the WBC count in the diagnosis of neonatal sepsis were analysed by using subject working characteristics (ROC) and areas under the curve (AUCs), and the variables were combined to determine which combination had the best diagnostic efficacy.Results: In the sepsis group, the ALB, CRP, and PCT levels and the WBC count were significantly higher than those in the infection group (P< 0.001). In all infants, the sensitivities and specificities of ALB, CRP, PCT, and WBC count were 0.411, 0.596, 0.483 and 0.411, respectively, and 0.833, 0.846, 0.901 and 0.796, respectively. With a sensitivity of 0.646, a specificity of 0.929, and an AUC of 0.834, the best combination was that of ALB, CRP, and PCT, which was better than that of CRP + PCT, CRP + ALB and PCT + ALB.Conclusion: In neonatal sepsis, in the absence of blood culture results, the combination of ALB, CRP, and PCT is more reliable than CRP, PCT, or CRP+PCT alone. These results suggest that ALB is a useful inflammatory biomarker for the early diagnosis of neonatal sepsis, and can improve the diagnostic efficiency.Keywords: albumin, C-reactive protein, procalcitonin, diagnosis, neonatal sepsis

Jichan Shi,1,&ast; Gexin Gao,2,&ast; Jing Pan,3 Lian-Peng Wu,4 Hongye Ning,1 Zhengxin Wu,1 Xinchun Ye,1 Xiangao Jiang1 1Department of Infectious Disease, The Theorem Clinical College of Wenzhou Medical University, Wenzhou Central Hospital, Wenzhou, People’s Republic of China; 2Department of Nursing, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of Geriatric Medicine, The Theorem Clinical College of Wenzhou Medical University, Wenzhou Central Hospital, Wenzhou, People’s Republic of China; 4Department of Laboratory, The Dingli Clinical Institute of Wenzhou Medical University, Wenzhou Central Hospital, Wenzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangao Jiang, Department of Infectious Disease, The Theorem Clinical College of Wenzhou Medical University, Wenzhou Central Hospital, 252 BaiLiDong Road, Wenzhou, Zhejiang, 325000, People’s Republic of China, Tel +86 13676788085, Email xiangaojiang09@163.comObjective: To evaluate the clinical value of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in detecting Nontuberculous mycobacteria (NTM).Methods: The clinical data of 172 patients with suspected NTM lung disease were collected from our hospital from January 1, 2018, to December 30, 2021. The results were compared with those of BACTEC MGIT 960 in liquid culture and gene chip. This study also utilised MALDI-TOF MS to detect macrolide (MA) and amikacin (Am) mutations.Results: One hundred thirty-seven cases of NTM pulmonary disease were confirmed by identifying the NTM gene chip in bronchoalveolar lavage fluid and/or MALDI-TOF MS detection. The positive predictive value and negative predictive value were 100% (131/131) and 85.37% (35/41), respectively, and the consistency of the two methods was high (kappa=0.899). For the drug resistance detection of MAs, the consistency rate between MALDI-TOF MS detection and drug sensitivity detection was 97.71% (128/131), the sensitivity was 81.25% (13/16) and the specificity was 100% (115/115). The positive and negative predictive values were 100% (13/13) and 93.75% (115/118), respectively. There was no coincidental consistency between the two methods, and the consistency was high (P< 0.001, kappa=0.884). For the drug resistance test of Am, the consistency rate between the MALDI-TOF MS test and the drug sensitivity test was 93.13% (122/131), the sensitivity was 93.52% (101/108), the specificity was 90.91% (21/23) and the positive predictive value and negative predictive value were 98.06% (101/103) and 75.00% (21/28), respectively. The two methods had high consistency, and the consistency was not coincidental (P< 0.001, kappa=0.781).Conclusion: Utilising MALDI-TOF MS has a good consistency with the drug resistance gene chip method and can be a rapid and effective method to identify strains and drug resistance of NTM. Therefore, it has certain clinical application value in patients with suspected NTM lung disease.Keywords: Nontuberculosis mycobacteria, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, strain identification, resistance

Yujun Xiong,1,&ast; Haoqi Yan,2,&ast; Lang Qu,3 Shuqi Wang,4 Xiangda Meng,5 Xingyun Zhu,6 Pan Zhang,1 Su Yuan,2 Jihua Shi1 1Department of Gastroenterology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Anesthesiology, Fuwai Hospital, National Center of Cardiovascular Diseases, Chinese Academy of Medical Sciences; Peking Union Medical College, Beijing, 100037, People’s Republic of China; 3Department of Anesthesiology, Shanghai General Hospital, Shanghai, People’s Republic of China; 4Department of Otolaryngology, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 5Department of Neurosurgery, Beijing Chaoyang Hospital, Capital Medical University, Beijing, People’s Republic of China; 6Department of Endocrinology, Beijing Jishuitan Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Su Yuan, Department of Anesthesiology, Fuwai Hospital, Chinese Academy of Medical Sciences; Peking Union Medical College, Xicheng District, Beijing, People’s Republic of China, Email fuwaiys@126.com Jihua Shi, Department of Gastroenterology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, 100370, People’s Republic of China, Email shijihua1981@sina.comBackground: Gastrointestinal (GI) endoscopy becomes more and more common now in order to diagnose and treat GI diseases, and anesthesia/sedation plays an important role. We aim to discuss the developmental trends and evaluate the research hotspots using bibliometric methods for GI endoscopy anesthesia/sedation in the past two decades.Methods: The original and review articles published from 2001 to December 2022 related to GI endoscopy anesthesia/sedation were extracted from the Web of Science database. Four different softwares (CiteSpace, VOSviewer, and Bibliometrix, Online Analysis Platform of Literature Metrology (Bibliometric)) were used for this comprehensive analysis.Results: According to our retrieval strategy, we found a total of 3154 related literatures. Original research articles were 2855, and reviews were 299. There has been a substantial increase in the research on GI endoscopy anesthesia/sedation in recent 22 years. These publications have been cited 66,418 times, with a mean of 21.04 citations per publication. The US maintained a leading position in global research, with the largest number of publications (29.94%), and China ranked second (19.92%). Keyword burst and concurrence showed that conscious sedation, colonoscopy and midazolam were the most frequently occurring keywords.Conclusion: Our research found that GI endoscopy anesthesia/sedation was in a period of rapid development and demonstrated the improvement of medical instruments and surgical options that had significantly contributed to the field of GI endoscopy anesthesia/sedation. The US dominates this field, and the selection and dosage of sedative regimens have always been the foci of disease research to improve comfort and safety, while adverse events and risks arouse attention gradually. In the past 20 years, hotspots mainly focus on upper gastrointestinal endoscopy, gastroscopy, and esophagogastroduodenoscopy. These data would provide future directions for clinicians and researchers regarding GI endoscopy anesthesia/sedation.Keywords: gastrointestinal endoscopy anesthesia, sedation, bibliometric analysis, CiteSpace, VOSviewer

Meng Tao,1,2 Jing Han,3 Juanyi Shi,1,2 Hao Liao,1,2 Kai Wen,1,2 Weidong Wang,1,2 Sintim Mui,1,2 Huoming Li,1,2 Yongcong Yan,1,2 Zhiyu Xiao1,2 1Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, 510120, People’s Republic of China; 3Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, People’s Republic of ChinaCorrespondence: Yongcong Yan; Zhiyu Xiao, Department of Hepatobiliary Surgery, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Yanjiang West Road &num;107, Guangzhou, 510120, People’s Republic of China, Tel +86-15800039176 ; +86-13682283695, Fax +86 20 34071073, Email yanyc3@mail.sysu.edu.cn; xiaozhiy@mail.sysu.edu.cnAbstract: Lenvatinib, a multitargeted tyrosine kinase inhibitor (TKI), is one of the preferred targeted drugs for the treatment of advanced hepatocellular carcinoma (aHCC). Since the REFLECT study showed that lenvatinib was noninferior to sorafenib in overall survival (OS), lenvatinib monotherapy has been widely used for aHCC. Moreover, lenvatinib combination therapy, especially lenvatinib combined with immune checkpoint inhibitors (ICIs), has shown more encouraging clinical results. However, drug development and comprehensive treatment have not significantly improved the prognosis, and lenvatinib resistance is often encountered in treatment. The underlying molecular mechanism of lenvatinib resistance is still unclear, and studies to solve drug resistance are ongoing. The molecular mechanisms of lenvatinib resistance in patients with aHCC include the regulation of signaling pathways, the regulation of noncoding RNAs, the impact of the immune microenvironment, tumor stem cell activation and other mechanisms. This review aims to (1) summarize the progress of lenvatinib in treating aHCC, (2) delineate the known lenvatinib resistance mechanisms of current therapy, and (3) describe the development of therapeutic methods intended to overcome these resistance mechanisms.Keywords: lenvatinib, application, drug resistance, hepatocellular carcinoma

Min Zhu,1 Yuyu Sun,1 Huawei Xue,1 Gang Wu,1 Zhen Wang,1 Junfeng Shi,1 Jiye Ma,1 Baorong Gu,1 Xiaoling Yan2 1Department of Spine Surgery, Nantong Third People’s Hospital, Affiliated Nantong Hospital 3 of Nantong University, Nantong, People’s Republic of China; 2Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong, People’s Republic of ChinaCorrespondence: Xiaoling Yan, Department of Chemotherapy, Affiliated Hospital of Nantong University, Nantong, 226001, People’s Republic of China, Email 5200007@ntu.edu.cnBackground: Osteosarcoma is a malignant tumor originating from the skeletal system. There is no effective treatment other than surgery and chemotherapy, which seriously endangers the health of children and adolescents. NEK6 is a novel discovered Serine/Threonine protein kinase that can regulate cell cycle and activate several oncogenic pathways.Methods: NEK6 expression in pan-cancer including sarcoma was evaluated using analysis tools of TIMER, UALCNA and GEPIA with TCGA database, and its association with overall survival in patients with sarcoma was also analyzed. TargetScan, tarbase, microT-CDS and Starbase online software were used to predict NEK6-targeted miRNAs, including miR-26a-5p. Tumor tissues from patients with osteosarcoma were collected for NEK6 and miRNA detection using RT-qPCR. NEK6 down-regulated by siRNAs or miR-26a-5p in osteosarcoma cells was detected by RT-qPCR, Western blot and Immunofluorescence staining assays. Effects of NEK6 knockdown on proliferation, migration, invasion and apoptosis of osteosarcoma cells were detected by CCK-8, wound healing, transwell and flow cytometry, respectively. The expressions of STAT3, metastasis and apoptosis-related genes were detected by Western blot.Results: High expression of NEK6 and low expression of miR-26a-5p were lowly expressed in osteosarcoma and they were negative correlation. NEK6 has been confirmed as a direct target for miR-26a-5p. In addition, NEK6 down-regulated by siRNAs or miR-26a-5p led to inhibition of cell proliferation, migration and invasion while promoting cell apoptosis. The levels of phosphorylated STAT3 and metastasis genes (MMP-2, MMP-9) were inhibited, while apoptotic gene Bax was promoted and Bcl2 was inhibited by miR-26a-5p upregulation.Conclusion: NEK6 can promote osteosarcoma progression via activating STAT3 signaling pathway, which is inhibited by miR-26a-5p, suggesting that NEK6 is a potential oncogene and miR-26a-5p is a suppressor of osteosarcoma. The strategy of inhibiting of NEK6 by miR-26a-5p may be an effective approach for osteosarcoma therapy.Keywords: osteosarcoma, NEK6, miR-26a-5p, STAT3 signaling pathway

Haoyuan Liu,1 Rurong Wang,1 Liang Zhang,1 Jingming Shi,1 Jiaxi Yao2 1Department of Intervention, Hexi University Affiliated Zhangye People’s Hospital, Zhangye City, Gansu Province, 734000, People’s Republic of China; 2Institute of Urology, Hexi University, Zhangye City, Gansu Province, 734000, People’s Republic of ChinaCorrespondence: Jingming Shi, Department of Intervention, Hexi University Affiliated Zhangye People’s Hospital, 67 Xihuan Road, Zhangye, Gansu, 734000, People’s Republic of China, Email 947043582@qq.com Jiaxi Yao, Institute of Urology, Hexi University Affiliated Zhangye People’s Hospital, 67 Xihuan Road, Zhangye, Gansu, 734000, People’s Republic of China, Email 16111210057@fudan.edu.cnPurpose: Observe uninterrupted thrombolytic therapy via indwelling catheter for lower limb deep vein thrombosis.Methods: We retrospectively studied data from 32 patients with lower extremity deep vein thrombosis who received comprehensive treatment, consisting of general treatment, inferior vena cava filter implantation, interventional thrombolysis, angioplasty, stenting, and post-operative monitoring.Results: The efficacy and safety of the comprehensive treatment were observed for a follow-up period of 6– 12 months. The treatment was 100% effective; patient results indicated no serious bleeding, acute pulmonary embolism, or death after surgery.Conclusion: The combination of intravenous and healthy side femoral vein puncture and directed thrombolysis to treat acute lower limb deep vein thrombosis is safe, effective, and minimally invasive while still achieving a good therapeutic effect.Keywords: deep vein thrombosis, uninterrupted thrombolytic, interventional, stent implantation

Yuhan Wang,1 Zhenyu Yin,1 Lei Gao,1 Bin Ma,1 Jianming Shi,1 Hao Chen2 1Lanzhou University Second Hospital, Lanzhou, 730030, People’s Republic of China; 2Department of Surgical Oncology, Key Laboratory of the Digestive System Tumors of Gansu Province, Lanzhou University Second Hospital, Lanzhou, 730030, Gansu Province, People’s Republic of ChinaCorrespondence: Hao Chen, Tel +8615009467790, Fax +8609315109551, Email ery_chenh@lzu.edu.cnAbstract: Metastasis to the liver, as one of the most frequent metastatic patterns, was associated with poor prognosis. Major drawbacks of conventional therapies in liver metastasis were the lack of metastatic-targeting ability, predominant systemic toxicities and incapability of tumor microenvironment modulations. Lipid nanoparticles-based strategies like galactosylated, lyso-thermosensitive or active-targeting chemotherapeutics liposomes have been explored in liver metastasis management. This review aimed to summarize the state-of-art lipid nanoparticles-based therapies in liver metastasis management. Clinical and translational studies on the lipid nanoparticles in treating liver metastasis were searched up to April, 2023 from online databases. This review focused not only on the updates in drug-encapsulated lipid nanoparticles directly targeting metastatic cancer cells in treating liver metastasis, but more importantly on research frontiers in drug-loading lipid nanoparticles targeting nonparenchymal liver tumor microenvironment components in treating liver metastasis, which showed promise for future clinical oncological practice.Keywords: liver neoplasms, neoplasm metastasis, liposomes, tumor microenvironment

Xinyu Fan,1,2,&ast; Jiachen Shi,1,&ast; Ye Liu,3 Mengqiu Zhang,1 Min Lu,1,2 Ding Qu1,2 1Affiliated Hospital of Integrated Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China; 2Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing, People’s Republic of China; 3The Second Affiliated Hospital of Nanjing University of Chinese Medicine, Nanjing University of Chinese Medicine, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Min Lu, Jiangsu Province Academy of Traditional Chinese Medicine, 100 Shizi Street, Hongshan Road Nanjing 210028, People’s Republic of China, Email lmxlsr6666@163.com Ding Qu, Jiangsu Province Academy of Traditional Chinese Medicine, 100 Shizi Street, Hongshan Road, Nanjing, 210028, People’s Republic of China, Email quding1985@hotmail.comBackground: Berberine (BR) shows promise as a candidate for treating irritable bowel syndrome with diarrhea (IBS-D). However, the undesired physicochemical properties and poor oral absorption limit its clinical translation. A ketogenic diet (KD) can induce intestinal overexpression of cannabidiol (CB) receptors, which may offer a potential target for IBS-D-specific delivery of BR.Methods: The microemulsions loaded with BR and decorated with cannabidiol (CBD/BR-MEs) were developed through a one-step emulsion method. The pharmaceutical behaviors of the CBD/BR-MEs were measured using dynamic light scattering and high-performance liquid chromatography. The efficacy of the anti-IBS-D therapy was evaluated by assessing fecal water content, Bristol score, and AWR score. The intestinal permeability were assessed through immunofluorescent staining of CB1 and ZO-1, respectively. The signaling of CREB/BDNF/c-Fos was also studied along with immunofluorescent and immunohistochemical examination of brain sections.Results: The CBD/BR-MEs, which had a particle size of approximately 30 nm and a surface density of 2% (wt%) CBD, achieved greater than 80% (wt%) encapsulation efficiency of BR. The pharmacokinetics performance of CBD/BR-MEs was significantly improved in the KD-fed IBS-D rats than the standard diet-fed ones, which is highly related to intestinal expression of CB1 receptors. The treatment with CBD/BR-MEs and KD exhibited evident comprehensive advantages over the other groups in terms of anti-IBS-D efficacy. CBD/BR-MEs and KD synergistically decreased intestinal permeability. Moreover, the treatment with CBD/BR-MEs and KD not only blocked the CREB/BDNF/c-Fos signaling in the brain but also decreased the levels of neurotrophic factors, neurotransmitters, and inflammatory cytokines in the serum of IBS-D model rats.Conclusion: Such a design represents the first attempt at IBS-D-targeted drug delivery for improved oral absorption and efficacy through KD-induced target exposure, which holds promising potential for the treatment of IBS-D.Keywords: irritable bowel syndrome-diarrhea, berberine, microemulsion, ketogenic diet, CB1 receptors

Rong Yu,1,&ast; Chuan Liu,1,&ast; Jixiang Zhang,1,&ast; Jiao Li,1,&ast; Shan Tian,2 Fugui Ding,1 Zhengru Liu,3 Ting Wang,4 Zhongchun Liu,5 Changqing Jiang,6 Jie Shi,7 Kaichun Wu,8 Weiguo Dong1 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 2Department of Infectious Diseases, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, People’s Republic of China; 3Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of China; 4Department of Gastroenterology, First Affiliated Hospital of Hainan Medical College, Haikou, 570102, People’s Republic of China; 5Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 6Department of Clinical Psychology, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, People’s Republic of China; 7Department of Medical Psychology, Chinese People’s Liberation Army Rocket Army Characteristic Medical Center, Beijing, 100088, People’s Republic of China; 8Department of Gastroenterology, Xijing Hospital, Air Force Medical University, Xi’an, 710032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiguo Dong, Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuhan, Hubei Province, 430060, People’s Republic of China, Tel +86 027-88041911, Email dongweiguo@whu.edu.cn Kaichun Wu, Department of Gastroenterology, Xijing Hospital, Air Force Medical University, No. 127 West Changle Road, Xi’an, Shaanxi Province, 710032, People’s Republic of China, Tel +86 029-84771600, Email kaicwu@fmmu.edu.cnObjective: To explore the correlation between disease activity and anxiety, depression, sleep quality, and quality of life in patients with inflammatory bowel disease (IBD).Methods: The disease activity of IBD patients was evaluated by 66 gastroenterologists from 42 hospitals in 22 provinces in China from September 2021 to May 2022. Anxiety, depression, sleep quality and quality of life of IBD patients were investigated and statistically analyzed by different scales, including Generalized Anxiety Disorder 7-item Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Quality-of-Life Questionnaire (IBD-Q).Results: A total of 2478 IBD patients were included, of which 1532 (61.8%) were in active stage and 946 (38.2%) were in remission. The proportions of active IBD with anxiety, depression, sleep disturbance, and poor quality of life were 29.5%, 29.7%, 71.1%, and 50.1%, respectively, while the proportions of remission IBD with anxiety, depression, sleep disturbance, and poor quality of life were 19.1%, 24.4%, 69.3%, and 17.4%, respectively. IBD patients who also had anxiety, depression, sleep disturbances and poor quality of life had 80 cases (8.46%) in remission and 114 cases (7.44%) in active stage, with 54 cases (9.18%) in mild activity, 51 cases (6.95%) in moderate activity and 9 cases (4.49%) in severe activity. IBD patients with different disease activity levels differed in GAD-7 scores, PHQ-9 scores, PSQI scores, and IBD-Q scores (all P< 0.001). In IBD patients, anxiety, depression, and sleep disturbance, which interact with each other, can further aggravate their disease activity (all P< 0.001).Conclusion: Anxiety, depression, sleep disturbances, and quality of life are strongly correlated with disease activity in IBD patients, and IBD patients with psychological disturbances are most often in the active stage and have a poor quality of life.Keywords: inflammatory bowel disease, disease activity, anxiety, depression, sleep quality, quality of life, survey

Jun Huang,&ast; Peizhuang Zhao,&ast; Jialing Shi, Jiajia Ning, Zhen Wang, Yihua Luo, Jingqian Qin, Xue Huang Department of Geriatrics and Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xue Huang, Department of Geriatrics and Gastroenterology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530000, People’s Republic of China, Email hb960305@163.comPurpose: Prolyl 4-hydroxylase subunit alpha 3 (P4HA3) has been proven to participate in the occurrence and development of multiple cancers. However, the functional role of P4HA3 in the tumor immune microenvironment (TIME) of colon adenocarcinoma (COAD) and the prognosis of COAD patients has not been clarified. This study aimed to elucidate the immunological role and prognostic value of P4HA3 in COAD.Methods: P4HA3 expression in COAD tissues was analyzed via experiments and a bioinformatics algorithm. Based on the COAD patients in The Cancer Genome Atlas database, we comprehensively evaluated whether the expression levels of P4HA3 affected clinical prognosis, TIME, and immunotherapy of COAD using the R platforms and several public databases, including GEPIA, TIMER, TISIDB, and TCIA.Results: The results of the pan-cancer analysis indicated that P4HA3 expression was significantly different in most tumor tissues compared with normal tissues. P4HA3 was overexpressed in COAD tissues, and overexpression of P4HA3 was associated with a worse overall survival and a shorted progression-free interval in COAD patients. The expression of P4HA3 was positively correlated with pathological stage, T stage, N stage, perineural infiltration, and lymphatic infiltration. There were significant correlations of P4HA3 expression levels with immune cell infiltration and their makers, as well as immunomodulators, chemokines, and microsatellite status. Moreover, overexpression of P4HA3 was associated with a lower response rate to immunotherapy in the IMvigor210 cohort.Conclusion: Overexpression of P4HA3 is closely related to the poor prognosis of COAD patients, and P4HA3 is a potential target for immunotherapy in COAD patients.Keywords: P4HA3, colon adenocarcinoma, prognosis, immunotherapy, tumor immune microenvironment

Jin Zhang,1 Luxin Li,1 Jing Yu,2 Fan Zhang,1 Jiayi Shi,1 Meiyun LI,1 Jianyong Liu,3 Haitao Li,3 Jie Gao,4 Yan Wu1 1College of Life Science, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 2Department of Endocrinology, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, 157011, People’s Republic of China; 3Department of Vascular Surgery, Wuhan Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of ChinaCorrespondence: Yan Wu, College of Life Science, Mudanjiang Medical University, Mudanjiang, Heilongjiang, 157001, People’s Republic of China, Tel/Fax +86-453-6984647, Email wuyan@mdjmu.edu.cn; Jie Gao, Changhai Clinical Research Unit, Shanghai Changhai Hospital, Naval Medical University, Shanghai, 200433, People’s Republic of China, Tel/Fax +86 21-31166666, Email jmsx2021@shu.edu.cnAbstract: Autophagy, a self-renewal mechanism, can help to maintain the stability of the intracellular environment of organisms. Autophagy can also regulate several cellular functions and is strongly related to the onset and progression of several diseases. Wound healing is a biological process that is coregulated by different types of cells. However, it is troublesome owing to prolonged treatment duration and poor recovery. In recent years, biomaterials have been reported to influence the skin wound healing process by finely regulating autophagy. Biomaterials that regulate autophagy in various cells involved in skin wound healing to regulate the differentiation, proliferation and migration of cells, inflammatory responses, oxidative stress and formation of the extracellular matrix (ECM) have emerged as a key method for improving the tissue regeneration ability of biomaterials. During the inflammatory phase, autophagy enhances the clearance of pathogens from the wound site and leads to macrophage polarization from the M1 to the M2 phenotype, thus preventing enhanced inflammation that can lead to further tissue damage. Autophagy plays important roles in facilitating the formation of extracellular matrix (ECM) during the proliferative phase, removing excess intracellular ROS, and promoting the proliferation and differentiation of endothelial cells, fibroblasts, and keratinocytes. This review summarizes the close association between autophagy and skin wound healing and discusses the role of biomaterial-based autophagy in tissue regeneration. The applications of recent biomaterials designed to target autophagy are highlighted, including polymeric materials, cellular materials, metal nanomaterials, and carbon-based materials. A better understanding of biomaterial-regulated autophagy and skin regeneration and the underlying molecular mechanisms may open new possibilities for promoting skin regeneration. Moreover, this can lay the foundation for the development of more effective therapeutic approaches and novel biomaterials for clinical applications.Keywords: wound healing, autophagy, biomaterial, antibacterial effects, inflammatory response, oxidative stress

Lijun Zuo,1 YanHong Dong,2 Yang Hu,1 Xianglong Xiang,3 Tao Liu,4 Jianxin Zhou,5 Jiong Shi,1 Yongjun Wang1 1Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Alice Lee Centre for Nursing Studies, Yong Loo Lin School of Medicine, National University of Singapore, 117597 Singapore; 3China National Clinical Research Center for Neurological Diseases, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of China; 4Beijing Advanced Innovation Center for Biomedical Engineering, School of Biological Science and Medical Engineering, Beihang University, Beijing, People’s Republic of China; 5Department of Critical Care Medicine, Beijing Tiantan Hospital, Capital Medical University, Beijing, People’s Republic of ChinaCorrespondence: Yongjun Wang, Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, No. 119, South Fourth Ring West Road, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +86-010-59978350, Fax +86-010-59973383, Email yongjunwang@ncrcnd.org.cnIntroduction: Stroke has been considered to raise the risk of dementia in several studies, but the relationship between brain structural changes and poststroke cognitive impairment (PSCI) is unclear.Methods: In this study, 23 PSCI patients with basal ganglia infarcts after 2 weeks and 29 age-matched controls underwent magnetic resonance imaging measuring cortical thickness and volume changes, as well as neuropsychological tests. CI was derived from a performance score < 1.5 standard deviations for normally distributed scores. We compared Z scores in different cognitive domains and cortical thickness and volumes in two groups. Multiple linear regressions were used to investigate the relationship between cortical thickness and volumes and neuropsychological tests.Results: A majority of PSCI patients were in their 50s (55.19± 8.52 years). PSCI patients exhibited significantly decreased Z scores in multiple domains, such as memory, language, visuomotor speed, and attention/executive function. The volumes of the middle posterior corpus callosum, middle anterior corpus callosum, and hippocampus in PSCI patients were markedly lower than controls. The thickness of the right inferior temporal cortex and insula were significantly smaller than controls. It found that the reduced right hippocampus was related to executive dysfunction. Hippocampus dysfunction may be involved in language impairment (p< 0.05) in PSCI patients with basal ganglia infarcts.Conclusion: These findings demonstrated that brain structure changed after ischemic stroke, and different gray-matter structural changes could lead to specific cognitive decline in PSCI patients with basal ganglia infarcts. Atrophy of the right hippocampus potentially serves as an imaging marker of early executive function of PSCI.Keywords: hippocampus volume, poststroke cognitive impairment, structural changes

Jiaheng Xie,&ast; Wei Yan,&ast; Zhechen Zhu,&ast; Ming Wang, Jingping Shi Department of Burn and Plastic Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jingping Shi; Ming Wang, Department of Burn and Plastic Surgery, The First Hospital Affiliated to Nanjing Medical University, Nanjing, Jiangsu, 210029, People’s Republic of China, Tel +8613082555422, Email drshi_njmu@163.com; wangming@jsph.org.cnAbstract: Breast reconstruction can be divided into prepectoral breast reconstruction (PPBR) and subpectoral breast reconstruction (SPBR) according to the implant plane. The original prepectoral breast reconstruction was abandoned for a long time due to the frequent and severe complications. Now, advances in materials technology and improved methods of mastectomy have made safe prepectoral breast reconstruction possible. Moreover, a number of studies have gradually demonstrated the advantages of prepectoral breast reconstruction. As prepectoral breast reconstruction becomes more and more attractive, it is time to review the current advances in prepectoral breast reconstruction.Keywords: breast reconstruction, breast cancer, complications, patient report outcome, prepectoral, subpectoral

Miao Wang,1,&ast; Jin Shi,2,&ast; Kepei Zhang,1,&ast; Jie Hong,2,&ast; Xinwei Peng,2 Yu Tian,1 Wei Lu,3 Ke Li,2 Zengliang Wang,4 Feng Li,1 Zhijie Zhang,2 Guojiang Mei1 1Department of Internal Medicine of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Epidemiology and Health Statistics, Fudan University, Shanghai, People’s Republic of China; 3Department of Nursing, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 4Department of Epidemiology, School of Public Health, Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhijie Zhang, Department of Epidemiology and Health Statistics, School of Public Health, Fudan University, Xuhui District, School of Medicine Road, 130, Shanghai, People’s Republic of China, Tel +86-21-54237410, Email epistat@gmail.com; Guojiang Mei, Department of Internal Medicine of Traditional Chinese Medicine, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, 725 South Wanping Road, Shanghai, 200032, People’s Republic of China, Tel + 86-21-64385700, Email mgj_761014@sina.comPurpose: This study aimed to evaluate the clinical efficacy of Longyizhengqi granule, a traditional Chinese medicine, in patients with mild COVID-19.Patients and Methods: We conducted a prospective study including mild COVID-19 participants conducted at Mobile Cabin Hospital in Shanghai, China. Participants were assigned to receive Longyizhengqi granule or conventional treatment. The primary outcome was the time for nucleic acid to turn negative and the secondary outcomes are hospital stay and changes in cycle threshold (Ct) values for N gene and Orf gene. Multilevel random-intercept model was performed to analyze the effects of treatment.Results: A total of 3243 patients were included in this study (Longyizhengqi granule 667 patients; conventional treatment 2576 patients). Age (43.5 vs 42.1, p< 0.01) and vaccination doses (not vaccinated: 15.8% vs 21.7%, 1 dose: 3.5% vs 2.9%, 2 doses: 27.9% vs 25.6%, 3 doses: 52.8% vs 49.8%. p< 0.01) show statistical difference between Conventional treatment group and LYZQ granules group. The use of Longyizhengqi granule could significantly reduce the time for nucleic acid to turn negative (14.2 days vs 10.7 days, p< 0.01), shorten hospital stay (12.5 days vs 9.9 days, p< 0.01), and increase the changes in Ct value for N gene (8.44 vs 10.33, p< 0.01) and Orf gene (7.31 vs 8.44, p< 0.01) to approximately 1.5. Moreover, the difference in the changes of Ct values on the 4th, 6th, 8th, and 10th days seem to increase between two groups. No serious adverse events were reported.Conclusion: Longyizhengqi granule might be a promising drug for the treatment of mild COVID-19, and it might be beneficial to effectively shorten the negative transition time of nucleic acid, the total days of hospitalization, and increase the changes of Ct values. Long-term randomized controlled trials with follow-up evaluations are required to confirm its long-term efficacy.Keywords: COVID-19, Omicron variant, traditional Chinese medicine, prospective study

Zhaolin Li,1,&ast; Qiaojun Zeng,1,&ast; Shuwan Xu,2,&ast; Yuewei Li,1 Tiantian Tang,1 Jianting Shi,1 Xueming Song,1 Wenman He,1 Liang Chen,1 Guirong Liu,1 Boying Gao,3 Jianming Zheng,4 Linjie Huang,1 Ming Chen,1 Shanping Jiang1 1Department of Pulmonary and Critical Care Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Department of Cardiology, the Eighth Affiliated Hospital, Sun Yat-sen University, Shenzhen, People’s Republic of China; 3Breast Tumor Center, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 4Cardiovascular Medicine Department, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shanping Jiang; Ming Chen, Department of Pulmonary and Critical Care Medicine, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Yan-jiang Xi Road 107, Guangzhou, 510120, People’s Republic of China, Tel +86-20-81332441, Email jiangshp@mail.sysu.edu.cn; chenm69@mail.sysu.edu.cnBackground: Although tigecycline is an effective drug against drug-resistant bacteria, it demonstrated a higher all-cause mortality than comparator antibiotics and a high incidence of coagulation disorders which can be accompanied by severe bleeding. At present, a predictive model for tigecycline-related coagulopathy is not readily available, and the prognostic value of coagulopathy in tigecycline-administered patients has not been elucidated. In this paper, we investigate the association between tigecycline-related coagulopathy and in-hospital mortality to develop a nomogram for the prediction of tigecycline-related coagulopathy.Methods: This retrospective cohort study includes 311 adults prescribed with tigecycline from 2018 to 2020. The primary cohort and validation cohort were constructed by dividing the participants in a ratio of 7:3. The endpoint is tigecycline-related coagulopathy, defined as a condition with no abnormality in coagulation prior to tigecycline application but developed the following symptoms upon prescription: activated partial thromboplastin time (APTT) extended by > 10 s than the upper limit of normal (ULN), prothrombin time (PT) prolonged for > 3 s than the ULN or reduced serum level of fibrinogen to < 2.0 g/L. A predictive nomogram based on logistic regression was subsequently constructed.Results: Tigecycline intake for over 7 days, combined other antibiotics, initial PT, initial fibrinogen and estimated glomerular filtration rate (eGFR), are independent prognostic factors of tigecycline-related coagulopathy. The primary and validation cohort each has an area under the receiver operating characteristic curve (AUC) of 0.792 (0.732– 0.851) and 0.730 (0.629– 0.832) for nomogram, respectively. Furthermore, the fitted calibration curve illustrated adequate fit of the model, while the decision curve analysis demonstrated good clinical value. Survival curves showed a high mortality rate among patients with tigecycline-related coagulopathy.Conclusion: This nomogram exhibited helpful clinical value in predicting tigecycline-related coagulopathy that could reduce the high mortality rate of patients prescribed with tigecycline.Keywords: tigecycline, drug-resistant bacteria, coagulopathy, nomogram

Hongli Yang,1,&ast; Fajuan Rui,2,&ast; Rui Li,3,&ast; Shengxia Yin,4 Qi Xue,1 Xinyu Hu,5 Yayun Xu,5 Chao Wu,4 Junping Shi,6 Jie Li2,4 1Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Ji’nan, People’s Republic of China; 2Department of Infectious Diseases, Nanjing Drum Tower Hospital Clinical College of Traditional Chinese and Western Medicine, Nanjing, People’s Republic of China; 3Department of Gastroenterology, Binzhou Medical University Hospital, Binzhou, People’s Republic of China; 4Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 5Department of Gastroenterology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Ji’nan, People’s Republic of China; 6Department of Infectious Disease, The Affiliated Hospital of Hangzhou Normal University, Wenzhou Road, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jie Li, Department of Infectious Diseases, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, Jiangsu, People’s Republic of China, Email lijier@sina.com Junping Shi, Department of Infectious Disease, The Affiliated Hospital of Hangzhou Normal University, Wenzhou Road, Hangzhou, Zhejiang, People’s Republic of China, Email 20131004@hznu.edu.cnAbstract: Background and Aims: Changes in living standards and diet structure, non-alcoholic fatty liver disease (NAFLD) is prevalent globally, including in Asia, where chronic hepatitis B (CHB) is endemic. As such, cooccurrence of NAFLD with CHB is common in Asia. However, the pathogenesis underlying the onset of fatty liver in CHB prognosis has not been fully elucidated. Therefore, we aimed to investigate the effects and mechanisms of lipotoxicity on hepatitis B virus (HBV) DNA replication.Methods: The expression of adenosine deaminase acting on RNA-1 (ADAR1) and miR-122 was evaluated in liver tissues from patients with CHB concurrent NAFLD. Palmitic acid-treated HepG2.2.15 cells were used as the cell model. The effect of lipotoxicity on HBV DNA replication was evaluated in vitro by transfecting the ADAR1 overexpression or knockdown lentiviral vector into HepG2.2.15 cells, respectively. qRT-PCR, western blotting and immunofluorescence were performed to determine ADAR1 expression.Results: The expression of ADAR1 in the liver tissues of CHB patients with concurrent NAFLD was significantly down-regulated compared with that in CHB patients. Enforced expression of ADAR1 inhibited the HBV DNA replication, whereas ADAR1 knockdown resulted in increased HBV DNA expression in palmitic acid - treated HepG2.2.15 cells. Additionally, ADAR1 inhibited the HBV DNA replication by upregulating miR-122, which is most abundant in the liver and mainly inhibits HBV DNA replication.Conclusions: ADAR1 may act as a suppressor of HBV replication in palmitic acid -treated HepG2.2.15 cells by increasing miR-122 levels. Thus, ADAR1 may serve as a potential biomarker and therapeutic target for CHB with concurrent NAFLD.Graphical Abstract: Keywords: chronic hepatitis B, non-alcoholic fatty liver disease, ADAR1, miR-122, HBV DNA

Yanfang Zhang, Lirong Gong, Yuan Zhang, Shuan Dong, Jia Shi, Xiangyun Li, Yan Guo, Simeng He, Xiaoyang Wu, Shasha Liu, Huayang Liu, Lantian Zhang, Jianbo Yu Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, Tianjin Medical University, Tianjin, People’s Republic of ChinaCorrespondence: Jianbo Yu, Department of Anesthesiology and Critical Care Medicine, Tianjin Nankai Hospital, 6 Changjiang Road, Tianjin, 300100, People’s Republic of China, Tel +86-22-23475289, Email 30717008@nankai.edu.cnPurpose: To investigate the effect of transcutaneous electrical acupoint stimulation (TEAS) on urinary retention after laparoscopic cholecystectomy in elderly patients, and to explore the relationship between TEAS and urinary ATP.Patients and Methods: The TEAS group was administered active TEAS at specific acupuncture points prior to induction of anesthesia and continued for 45 mins after surgery. In the control group, participants received sham stimulus at the same acupoints and no output current was delivered by disconnecting the device’s output line. Urine samples were collected and evaluated in the first spontaneous voiding after surgery. In this study, postoperative urinary retention (POUR) was the primary outcome, which was diagnosed based on clinical symptoms, ultrasound assessments, and the need for bladder catheterization. Secondary outcomes include urinary ATP, postoperative spontaneous urination, urination symptoms, catheter-related bladder discomfort (CRBD), delirium, duration and hospitalization costs.Results: The study involved 598 patients recruited and randomized between August 2018 and June 2020. Among these patients, 547 (91.5%) completed the study and were analyzed. There were 64 cases of POUR, including 23 (8.4%, 95% confidence interval [CI]: 6.4– 9.9%) in the TEAS group and 41 (15.0%, 95% CI: 9.3– 13.4%) in the control group (p = 0.017). A significant difference was observed between the TEAS and control groups for urinary ATP concentration in the first spontaneous urine postoperatively (344 nmol/L versus 233 nmol/L, p=0.001). There was a shorter spontaneous voiding recovery time, smaller voiding threshold, less postoperative catheterization, less CRBD, and lower hospitalization costs in TEAS group compared with control group.Conclusion: TEAS reduces the incidence of POUR in elderly patients undergoing laparoscopic cholecystectomy, which may be related to an increase in bladder ATP release.Keywords: transcutaneous electrical acupoint stimulation, urinary retention, ATP, catheterization, laparoscopic surgery, catheter-related bladder discomfort

Weihao Chen,1– 4 Yanmin Zhao,1– 4 Yi Luo,1– 4 Jian Yu,1– 4 Huarui Fu,1– 4 Xiaoyu Lai,1– 4 Lizhen Liu,1– 4 Yishan Ye,1– 4 Jingsong He,1– 4 Jie Sun,1– 4 Weiyan Zheng,1– 4 Yi Zhao,1– 4 Guoqing Wei,1– 4 Zhen Cai,1– 4 He Huang,1– 4 Jimin Shi1– 4 1Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Liangzhu Laboratory, Zhejiang University Medical Center, Hangzhou, 311121, People’s Republic of China; 3Institute of Hematology, Zhejiang University, Hangzhou, People’s Republic of China; 4Zhejiang Province Engineering Laboratory for Stem Cell and Immunity Therapy, Hangzhou, People’s Republic of ChinaCorrespondence: Jimin Shi; He Huang, Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, People’s Republic of China, Tel/Fax +86-0571-87236706, Email shijimin@zju.edu.cn; huanghe@zju.edu.cnBackground: Bloodstream infection (BSI) is a common and serious complication that may lead to high mortality during the different phases after hematopoietic stem cell transplant (HSCT). We investigated BSI in patients undergoing HSCT to provide an appropriate clinical anti-infection experience and improve the prognosis of recipients with BSI after HSCT.Methods: A total of 105 patients with BSI after HSCT at our center from January 2015 to June 2020 were included in this retrospective study. We analyzed the clinical and microbiological data, and the risk factors for mortality at 3 months after BSI.Results: Of the 1141 HSCT recipients, 105 (9.2%) patients presented with 122 episodes of BSI, of which we isolated 85 (65.9%) gram-negative bacteria, 32 (24.8%) gram-positive bacteria and 12 (9.3%) fungi. Multidrug-resistant bacteria (MDR) were more than 70% of all pathogens and carbapenem-resistant organisms (CRO) were 25.6%. There were 55 episodes of BSI in the pre-engraftment phase and 67 episodes in the post-engraftment phase. The mortality of post-engraftment BSI was significantly higher than that of pre-engraftment (56.7% vs 32.7%, p = 0.005). Through multivariate analysis, the independent risk factors for all-cause mortality at 3 months after BSI were higher levels of procalcitonin (PCT), failure to cover appropriate antibiotics timely, and CRO BSI in pre-engraftment period or multidrug-resistant gram-negative bacteria (MDRGNB) BSI in post-engraftment period.Conclusion: Although the incidence of BSI was lower after HSCT, MDR-dominated BSI had a high mortality rate. Rapid identification of infection or pathogens’ classification with various testing methods and the more sensible and timely antibiotic cover are critical to the outcome of BSI after HSCT.Keywords: bloodstream infection, hematopoietic stem cell transplantation, multidrug-resistant bacteria, all-cause mortality

Chao Wang,1 Zhiqiong Wang,2 Fankai Meng,2 Li Luo,2 Xian Liu,2 Jiayu Shi,1,3 Lifang Huang2 1Department of Hepatic Surgery, Institute of Hepato-Pancreato-Biliary Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 3Department of Hepatobiliary Surgery, Tongji Tianyou Hospital, Wuhan University of Science and Technology, Wuhan, 430064, People’s Republic of ChinaCorrespondence: Lifang Huang, Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, #1095 Jiefang Ave, Wuhan, 430030, People’s Republic of China, Tel +86-027-83665507, Email huanglifang627@163.comIntroduction: Chronic myelomonocytic leukemia (CMML) is a rare hematological malignancy bearing of both myelodysplastic syndrome and myeloproliferative neoplasm characteristics. Despite the low incidence, the clinical diagnosis of CMML was difficult and the survival was poor. The optimal first-line therapy for CMML still remains a matter of debate.Methods: We retrospectively analyzed the clinical characteristics of 66 CMML patients in a single center during the past 10 years and studied the survival status of CMML patients in the real world and the influence of treatment methods on the prognosis of patients.Results: For the 66 CMML patients, the median age was 60 years old (IQR 47.0– 67.0), and an approximately 1.6:1.0 male-to-female ratio was found. CMML-0, CMML-1 and CMML-2 accounted for 13.7% (9/66), 43.9% (29/66) and 42.4% (28/66), respectively. The chromosome abnormality rate was 27.2% (18/66). Gene mutation was detected in 60 patients by sequenced in first-generation with 51.1% (22/43) gene mutations and in NGS with 82.3% (14/17) gene mutations. The top three mutation genes were ASXL1MT (11/60, 18.3%), TET2MT (10/60, 16.7%), and SRSF2 MT (9/60, 15.0%). There were 27 patients in supportive therapy group, and 39 patients in chemotherapy group including patients undergoing HSCT. Patients in chemotherapy group showed better OS than those in the supportive group before and after PSM analysis with p < 0.05. Patients with blast cell in bone marrow ≥ 10% or WHO CMML-2 benefited more from chemotherapy treatment achieving better OS. Multivariate analysis showed that supportive therapy and intermediate-2/high in CPSS were independent risk factors for OS after PSM.Discussion: Chemotherapy including hypomethylating agents prolonged overall survival of CMML patients, especially in patients with blast cell ≥ 10% in bone marrow or WHO CMML-2 comparing with supportive therapy. Sequencing may provide direct insight into the molecular mechanism by detection of gene mutation, enabling personalized treatment in the future.Keywords: chronic myelomonocytic leukemia, hypomethylating agents, therapy, survival, prognosis

Hai Feng,1,&ast; Yunhui Zhuo,2,&ast; Xuemei Zhang,2 Yuyao Li,1 Yue Li,1 Xiangjuan Duan,2 Jia Shi,1 Chengbin Xu,3 Yueqiu Gao,1,2 Zhuo Yu2 1Institute of Infectious Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Department of Informatics, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yueqiu Gao, Institute of Infectious Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Tel +86 21 20256507, Fax +86 21 20256699, Email gaoyueqiu@shutcm.edu.cn Zhuo Yu, Department of Liver Disease, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China, Tel +86 21 20256507, Fax +86 21 20256699, Email zhuoyu@shutcm.edu.cnAbstract: Hepatocellular carcinoma (HCC) remains a serious medical therapeutic challenge as conventional curative avenues such as surgery and chemotherapy only benefit for few patients with limited tumor burden. Immunotherapy achieves clinical progress in the treatment of this prevalent malignant disease by virtue of the development of tumor immunology; however, most patients have experienced minimal or no clinical benefit in terms of overall survival. The complexity and diversity of tumor microenvironment (TME) built by immune and stromal cell subsets has been considered to be responsible for the insufficiency of immunotherapy. The advance of bioanalytical technology boosts the exploration of the composition and differentiation of these infiltrated cells, which reflect the immune state of the TME and impact the efficacy of the antitumor immune response. Targeting these cells to remodel the TME is one of the important immunotherapeutic approaches to improve HCC treatment. In this review, we focused on the role of these non-cancerous cells in the tumor progression, and elaborated their function on cancer immunotherapy when manipulating them as potential targets.Keywords: immune cells, stromal cells, tumor microenvironment, hepatocellular carcinoma, immunotherapy