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Hui Zeng,1,* Rong Liu,1,2,* Chuanli Cheng,2,* Nana Yang,2 Luwen Luo,1,2 Shengshuang Long,3 Renjia Zhou,4 Kai Yan,1 Huantao Huang1 1Nursing Department of the Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 2School of Nursing of Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 3Infection Department of the Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China; 4ICU of the Second Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, 563000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hui Zeng, Email zenghui.1221@163.comObjective: This study investigated the distribution and resistance patterns of pathogens in the intensive care unit of a newly established hospital in Guizhou Province to promote the rational use of antibiotics to reduce multidrug resistance.Methods: A retrospective analysis was conducted on the distribution of pathogens and changes in drug resistance in the ICU of a newly built hospital in Guizhou Province from March 2019 to December 2023. WHONET 5.6 was used to analyze the results.Results: A total of 2444 culture samples were received, predominantly sputum (34.66%) and blood (23.36%) samples, with a steady annual increase in specimen types. A total of 572 pathogenic strains were isolated, predominantly from respiratory specimens (54.02%), including 345 Gram-negative bacteria (60.31%), 135 Gram-positive cocci (23.60%), and 92 fungi (16.08%). The most frequent pathogens included Acinetobacter baumannii (30.77%), Candida albicans (11.71%), and Klebsiella pneumoniae (9.97%). Drug sensitivity tests indicated a fluctuating resistance rate of Acinetobacter baumannii over the past five years. Staphylococcus aureus displayed strong in vitro activity against vancomycin, tigecycline, and linezolid, with no resistant strains identified. The detection rates of carbapenem-resistant Acinetobacter baumannii (CR-AB), carbapenem-resistant Pseudomonas aeruginosa (CR-PA), methicillin-resistant Staphylococcus aureus (MRSA), and strains producing extended-spectrum beta-lactamases (ESBL) were 86.78%, 26.79%, 32.45%, 70.27%, and 23.54%, respectively.Conclusion: Compared with other countries in the world, China has increased its data on the prevalence of MDR pathogens and antibiotic resistance.The high resistance rate of Acinetobacter baumannii in the ICU underscores the need for effective infection control measures. Enhanced monitoring of CR-AB, ESBL-producing bacteria, and MRSA is essential, along with improved management of antibacterial drugs and the pursuit of new therapeutic options.Keywords: new-built hospital, intensive care unit, pathogens, multidrug-resistant bacteria, antimicrobial resistance

Renjiao Liu,1 Zhouhuiling Li,2 Yanju Zhang,2 Meiyang Du,2 Xincheng Wang,3 Shi Zhang,3 Chunjun Li1,3 1Graduate School, Tianjin Medical University, Tianjin, People’s Republic of China; 2Tianjin University of Traditional Chinese Medicine, Tianjin, People’s Republic of China; 3Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, Tianjin, People’s Republic of ChinaCorrespondence: Chunjun Li, Health Management Center, Tianjin Union Medical Center, Nankai University Affiliated Hospital, No. 190 of Jieyuan Road, Hongqiao District, Tianjin, 300121, People’s Republic of China, Tel +86-22-13752090635, Email li_chunjun@126.comBackground: Insulin resistance (IR) is a key feature of type 2 diabetes (T2D) and an independent risk factor for metabolic syndrome. Previous studies have linked elevated serum uric acid (SUA) to an increased risk of T2D.Aim: The purpose of this study was to investigate the relationship between SUA and IR. At the same time, the correlation between New model and SUA compared with other IR alternatives was compared, so as to provide a simple and effective new indicator for early detection and prediction of IR risk and early prevention of T2D.Methods: The first cohort was the Discovery Cohort, which included 318 obese patients. And the second cohort was the Verification Cohort, which included a total of 4333 subjects who underwent a routine health checkup at our hospital. Spearman correlation analysis and binary logistic regression analysis were used to discuss the correlation between SUA and IR.Results: Regardless of sex, fasting insulin (FINS) and IR replacement markers increased with SUA (P< 0.001). In both cohorts, SUA was associated with IR alternatives, especially with New model, and differed between men and women in all correlation analyses. After adjusting for confounding factors, SUA was still associated with IR (P< 0.001).Conclusion: The correlation between SUA and IR was significantly stronger in women than in men. And the correlation between SUA and New model is stronger than other IR replacement models. However, the causal relationship between SUA and IR has not been clearly established.Keywords: insulin resistance, serum uric acid, HDL-c, triglycerides

Hongyu Duan,1,&ast; Yifan Zhou,2,&ast; Baikai Ma,1,&ast; Rongjun Liu,3 Tingting Yang,4 Hongling Chu,5 Zejun Huo,6 Hong Qi1 1Department of Ophthalmology, Peking University Third Hospital, Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, Beijing, People’s Republic of China; 2Department of Ophthalmology, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 3Department of Ophthalmology, Peking University First Hospital, Beijing, People’s Republic of China; 4Department of Ophthalmology, Guangdong Provincial People’s Hospital, Southern Medical University, Guangzhou, People’s Republic of China; 5Research Center of Clinical Epidemiology, Peking University Third Hospital, Beijing, People’s Republic of China; 6Department of Traditional Chinese Medicine, Peking University Third Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Qi, Department of Ophthalmology, Peking University Third Hospital, Beijing Key Laboratory of Restoration of Damaged Ocular Nerve, 49 North Garden Road, Haidian District, Beijing, 100191, People’s Republic of China, Email doctorqihong@163.com Zejun Huo, Department of Traditional Chinese Medicine, Peking University Third Hospital, 49 North Garden Road, Haidian District, Beijing, 100191, People’s Republic of China, Email huozejun@163.comBackground: Ocular pain is a prevalent symptom of dry eye disease (DED), which often accompanies potential psychological issues. The study aimed to explore whether acupuncture could improve ocular pain, mental state, and dry eye parameters in patients with DED.Methods: The non-randomized pilot study included 48 patients divided into two groups: the acupuncture group (n=27) and the 0.3% sodium hyaluronate (SH) group (n=21). Participants in the acupuncture group underwent treatments on six bilateral acupuncture points (BL1, BL2, ST1, LI 20, SI1 and SI3) 3 times per week for 4 weeks. Patients in the SH group received 0.3% SH 4 times per day for 4 weeks. Ocular pain was assessed using the numerical rating scale (NRS), and mental state was evaluated through the self-rating anxiety scale (SAS) and self-rating depression scale (SDS). Ocular surface parameters, concentrations of inflammatory cytokines, and corneal nerve morphological indicators were measured at baseline, the first week, and the fourth week. Randomization procedures were not used in this study, and outcome assessors and statistical analysts were blinded.Results: Compared with baseline, both NRS scores (from 5.91 ± 1.52 to 1.94 ± 1.57) and ocular surface discomfort index (OSDI) scores (from 49.75 ± 14.92 to 29.64 ± 18.79) were decreased after 1 and 4 weeks of treatment in both groups (all p < 0.05). At 4 weeks, the acupuncture group showed significant improvements, including increased tear break-up time (TBUT) and corneal perception, decreased SAS and SDS scores, and reduced concentrations of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α concentration in tears (all p < 0.05). These changes were not observed in the SH group (all p > 0.05).Conclusion: Acupuncture treatment could improve ocular surface characteristics in patients with DED, and more importantly, it alleviates their ocular pain and depressive state. The anti-inflammatory effect of acupuncture may be involved in this process. Future research with larger, randomized controlled trials (RCTs) is necessary to confirm these findings and clarify the mechanisms involved.Keywords: acupuncture, dry eye disease, ocular pain, depression, inflammatory cytokines

Xiangan Gong,1,2 Qian Zhao,1,2 Huimin Zhang,1,2 Rui Liu,1,2 Jie Wu,1,2 Nanxin Zhang,3 Yuanxian Zou,1,2 Wen Zhao,1,2 Ran Huo,1,2,4 Rongtao Cui1– 4 1Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 3School of Clinical Medicine, Shandong Second Medical University, Weifang, People’s Republic of China; 4Department of Burn and Plastic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of ChinaCorrespondence: Rongtao Cui, Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Tel +86 18653170822, Email cuirt1986@outlook.comAbstract: Pathological scarring results from aberrant cutaneous wound healing due to the overactivation of biological behaviors of human skin fibroblasts, characterized by local inordinate inflammation, excessive extracellular matrix and collagen deposition. Yet, its underlying pathogenesis opinions vary, which could be caused by increased local mechanical tension, enhanced and continuous inflammation, gene mutation, as well as cellular metabolic disorder, etc. Metabolic reprogramming is the process by which the metabolic pattern of cells undergoes a systematic adjustment and transformation to adapt to the changes of the external environment and meet the needs of their growth and differentiation. Therefore, the abnormality of metabolic reprogramming in cells within wounds and scars attaches great importance to scar formation. Mesenchymal stem cells-derived exosomes (MSC-Exo) are the extracellular vesicles that play an important role in tissue repair, cancer treatment as well as immune and metabolic regulation. However, there is not a systematic work to detail the relevant studies. Herein, we gave a comprehensive summary of the existing research on three main metabolisms, including glycometabolism, lipid metabolism and amino acid metabolism, and MSC-Exo regulating metabolic reprogramming in wound healing and scar formation for further research reference.Keywords: mesenchymal stem cells-derived exosomes, metabolic reprogramming, scar, wound healing, fibroblast

Rong Liu,1,&ast; Tingfen Ji,1,2,&ast; Yixia Jiang,1 Hequan Li1 1Department of Respiratory Medicine, The First Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Lishui People’s Hospital, Lishui, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hequan Li, Email lihequan@zju.edu.cnPurpose: Recurrent inflammatory fevers with multisystem involvement occur clinically and may indicate an autoimmune disease.Case: We present a young male diagnosed with pulmonary embolism who experienced recurrent fever during hospitalization and was unresponsive to antibiotics and antipyretics. A follow-up history revealed chronic oral and genital ulcers, leading to a final diagnosis of Behçet’s disease.Conclusion: The patient’s temperature normalized rapidly after corticosteroid therapy, and infection markers returned to normal. Complete remission was achieved with immunosuppression and glucocorticoid therapy. Reporting characteristics, treatment experience, and outcomes of such cases are essential to inform future diagnosis and management strategies.Keywords: fever, Behçet’s disease, pulmonary embolism, atrial mass

Yujie Hao, Runmin Liu, Hao Wang, Tao Rui, Junfang Guo Division of Cardiology, Department of Medicine, the Affiliated People’s Hospital of Jiangsu University, Zhenjiang, Jiangsu, People’s Republic of ChinaCorrespondence: Junfang Guo, Email zjyyxngjf@163.comAbstract: Sepsis is a syndrome of organ dysfunction caused by a dysregulated immune response to infection, with high morbidity and mortality. At present, there have been many advances in the study of its pathogenesis, especially the cardiac dysfunction caused by sepsis, namely sepsis-induced myocardial dysfunction, SIMD, which has received widespread attention. The mechanisms of SIMD mainly include excessive release of inflammatory mediators, impaired mitochondrial function, autophagy, apoptosis and myocardial dysfunction. This article reviews the pathogenesis of SIMD and elaborates on the progress in its treatment, aiming to improve the prognosis of patients with SIMD and sepsis.Keywords: sepsis, sepsis-induced myocardial dysfunction, pathogenesis, treatment

Shuping Zhang,1,&ast; Yamei Ma,1,&ast; Xiu Zang,2 Hao Heng,2 Xuekui Liu,2 Gangshan Peng,3 Ran Liu,3 Jun Liang,1,2,&ast; Houfa Geng1,2,&ast; 1Graduate School, Bengbu Medical University, Bengbu, Anhui, People’s Republic of China; 2Department of Endocrinology, Xuzhou Central Hospital, Xuzhou, Jiangsu, People’s Republic of China; 3The Affiliated Xuzhou Clinical College, Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Houfa Geng; Jun Liang, Email genghoufa@xzhmu.edu.cn; liangjun@xzhmu.edu.cnAbstract: Maturity Onset Diabetes of the Young (MODY) is an autosomal dominant inherited disorder prevalent among adolescents. Typically, it manifests with hyperglycemia before the age of 25. MODY5 is attributed to a mutation in the Hepatocyte Nuclear Factor-1β (HNF-1β) gene. A complete absence of HNF-1β is observed in 50% of those with MODY5. The 17q12 microdeletion syndrome closely linked with MODY5. Its incidence in the general population is around 1 in 14,500 and is linked with facial deformities, diabetes, polycystic kidneys, pancreatic hypertrophy, liver anomalies, and neuropsychological impairments. The most primary clinical signs are predominantly associated with the HNF-1β gene deletion. We chronicle the case of a male of 19 years of age diagnosed with diabetes, who, alongside persistent liver damage and polycystic kidneys, was referred from a community hospital to the Xuzhou Central Hospital. His clinical presentation included diabetes, liver dysfunction, polycystic kidneys, lipid irregularities, insulin resistance, and fatty atrophy. Subsequent genetic screening unveiled a 17q12 chromosomal deletion and an absence of the Hepatocyte Nuclear Factor-1β (HNF-1β) gene. Hence, for adolescent patients lacking a familial diabetes history but exhibiting symptoms like polycystic kidneys, liver damage, lipid irregularities, and fatty atrophy, a thorough assessment for the 17q12 microdeletion syndrome becomes imperative.Keywords: 17q12 microdeletion syndrome, HNF-1β gene, special-type diabetes, MODY5, polycystic kidneys, liver damage

Qiqi Cheng,1 Xiaolin Zhou,1 Peng Wang,2 Rong Liu,3 Qiang Liu1 1Department of Infectious Disease, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of China; 2Department of Clinical Laboratory, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of China; 3Department of Ultrasound, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of ChinaCorrespondence: Qiang Liu, Department of Infectious Disease, Yichang Central People’s Hospital, The First College of Clinical Medical Science, China Three Gorges University, Yichang, Hubei, 443000, People’s Republic of China, Tel +86 13720181669, Email liuqiang@ctgu.edu.cnAbstract: We report a rare case of mechanical aortic valve infective endocarditis caused by Neisseria sicca. A 44-year-old man, with a history of aortic valve replacement, presented to the hospital with a 10-day history of fever. Investigations revealed that the blood cultures grew Neisseria sicca. Although the transthoracic echocardiogram (TTE) was negative, a transesophageal echocardiogram showed a 0.5 cm × 0.3 cm piece of vegetation attached to the aortic valve. After eight weeks of therapy, according to the antibiotic susceptibility test, the patient’s blood cultures were negative, and repeat TTE showed no vegetation. This report can offer valuable insights for clinical diagnosis and treatment of Neisseria sicca endocarditis, particularly when selecting sensitive antibiotics.Keywords: infective endocarditis, Neisseria sicca, aortic valve, bacteremia

Bingjie Ma,1 Pengyi Hou,2 Ran Liu,3 Aijun Cang,1 Limei Zhao4 1Department of Pharmacy, People’s Hospital of Liaoning Province, Shenyang, 110010, People’s Republic of China; 2SCIEX Analytical Instrument Trading Co, Shanghai, 200000, People’s Republic of China; 3School of Food and Drug, Shenzhen Polytechnic, Shenzhen, 518000, People’s Republic of China; 4Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, 110010, People’s Republic of ChinaCorrespondence: Limei Zhao, Department of Pharmacy, Shengjing Hospital of China Medical University, Shenyang, 110010, People’s Republic of China, Email lmzhao19@163.comBackground: Chemotherapy-induced myelosuppression (CIM) is a common adverse reaction with a high incidence rate that seriously affects human health. Shengyu Decoction (SYD) is often used to treat CIM. However, its pharmacodynamic basis and therapeutic mechanisms remain unclear.Purpose: This study aimed to clarify the active components and mechanisms of SYD in CIM.Methods: LC-QTOF/MS was used to identify the absorbable components of SYD. A series of network pharmacology methods have been applied to explore hub targets and potential mechanisms. Molecular docking was used to identify the binding ability of potential active ingredients and hub targets. Finally, in vitro experiments were performed to validate these findings.Results: In this study, 33 absorbable prototype components were identified using LC-QTOF/MS. A total of 62 possible targets of SYD in myelosuppression were identified. KEGG pathway enrichment analyses showed that some signaling pathways such as PI3K-Akt and HIF-1 may be the mechanisms by which it functions. Among them, we verified the PI3K-Akt pathway. 6 Hub proteins were screened by Protein–protein interaction (PPI) network analysis. Molecular docking results showed that four absorbable components in SYD showed good binding with six Hub targets. The effectiveness of the four predicted compounds and the mechanism were verified in vitro. It has also been shown that the active component could promote the proliferation of bone marrow stromal cells (BMSCs) and block apoptosis of BMSCs, which may be related to the PI3K-Akt pathway. This result is consistent with the network pharmacology approach and molecular docking predictions.Conclusion: Our results provided not only the candidate active component of SYD, but also a new insights into mechanism of SYD in the treatment of CIM. Keywords: Shengyu decoction, SYD, myelosuppression, network pharmacology, molecular docking, active components, mechanism

Xue Bai,1,2,&ast; LiTing Yang,1,2,&ast; Ruxin Liu,1,2 YuJiao Tang,1,2 Long Yang,1,2 Lingna Ma,1,2 MengFei Chen,2 Ling Zhang2 1Department of Emergency, The Third Clinical Medical College of Ningxia Medical University, Yinchuan, People’s Republic of China; 2Department of Emergency, People’s Hospital of Ningxia Hui Autonomous Region, Yinchuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: MengFei Chen; Ling Zhang, Tel +86 13389513801 ; +86 13895318660, Email prayer_821@sina.com; zhangling_7015@sina.comObjective: Cellular pyroptosis is a pro-inflammatory mode of programmed cell death that has been identified in recent years, and studies have shown that the LncRNA SOX2OT regulates myocardial injury during sepsis, but the exact regulatory mechanism is unclear. The aim of this study was to assess the role of SOX2OT in regulating cardiomyocyte injury during sepsis cardiomyopathy.Methods: Rat cardiomyocytes, C57BL/6 mice, and transgenic mice were divided into four groups: control, LPS, LPS+ knockout LncRNA SOX2OT, and LPS+ overexpression LncRNA SOX2OT. Inflammatory factor levels were detected by qPCR. Associated proteins and gene expression were detected by Western blotting and qPCR. Dual luciferase was used to detect the target genes of SOX2OT. Nrf2 and EZH2 knockdown and overexpression cell lines were established, and the expression of related genes was detected by qPCR.Results: Results In this study, we found that SOX2OT knockdown exacerbated LPS-induced levels of inflammatory factors and procalcitoninogen (PCT), and increased the expression of pyroptosis-related proteins and LDH. The results of dual luciferase reporter gene assay showed that EZH2 is the target gene of SOX2OT, and overexpression of SOX2OT decreased the expression of EZH2; we also found that knockdown of EZH2 in H9c2 cells decreased the expression of Nrf2, which was positively correlated with the expression level of NLRP3. Further in vivo results showed that overexpression of SOX2OT attenuated SIMD (sepsis-induced myocardial dysfunction), as evidenced by improved myocardial structural integrity and reduced inflammatory cell infiltration. The expression of pyroptosis-related proteins and LDH was significantly increased in the mice in the LPS group; this effect was reversed by overexpression of SOX2OT, and potentiated by knockdown of SOX2OT.Conclusion: Our data reveal a novel mechanism by which SOX2OT inhibits cardiomyocyte sepsis through the EZH2/Nrf-2/NLRP3 pathway, thereby attenuating septic myocardial injury, which may contribute to the development of new therapeutic strategies.Keywords: SOX2OT, EZH2, Nrf2, sepsis, pyroptosis

Ling Zhang,1,2 Ronghua Liu,1,2 Shuangmei Ye,1,2 Mingfu Wu,1,2 Rong Liu1,2 1Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of China; 2National Clinical Research Center for Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, People’s Republic of ChinaCorrespondence: Mingfu Wu; Rong Liu, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Anv, Wuhan, Hubei, 430030, People’s Republic of China, Email wu_mingfu@tjh.tjmu.edu.cn; liurongdoctor@tjh.tjmu.edu.cnPurpose: To recommend the classification of unilateral genital tract obstruction with ipsilateral renal anomaly (UGTOIRA) syndrome into five types based on the site of obstruction, and to analyze the clinical manifestations and precise diagnosis of the syndrome.Methods: The data, including demographic characteristics, symptoms, and precise diagnoses from 59 patients over the last decade, were retrospectively analyzed. Data analysis was conducted using the statistical software package SPSS 26.0.Results: All 59 patients diagnosed with UGTOIRA syndrome were classified into five types based on the site of obstruction: Type I (vaginal obstruction) (45, 76.3%), Type II (cervicovaginal obstruction) (7, 11.9%), Type III (cervical obstruction) (3, 5.1%), Type IV (unilateral partial cervical aplasia) (3, 5.1%), and Type V (Unilateral isthmus atresia) (1, 1.7%). Of these cases, there were 34 cases (57.6%) with communication and 25 cases (42.4%) without communication between the left and right genital tracts. The chief complaints included dysmenorrhea alone in 28 cases (47.5%), dysmenorrhea accompanied by blood dripping after menstruation in 12 cases (20.3%), blood dripping after menstruation alone in 14 cases (23.7%), purulent vaginal secretions in one case (1.7%), vaginal pain in one case (1.7%), irregular menstruation in one case (l.7%), and infertility in two cases (3.4%). The precise diagnostic criteria include the affected side, abnormalities in the kidney and ureter, the site of obstruction, the location of blood accumulation, the size of the ipsilateral genital tract, whether there is communication and its site, the type based on the site of obstruction, and the presence and type of complications.Conclusion: This classification of UGTOIRA syndrome encompasses the anatomical features of all cases reported in our study. Only by fully understanding the anatomical characteristics of this syndrome and identifying its clinical manifestations can clinicians make precise diagnoses as early as possible and provide individualized management.Keywords: uterine malformation, cervical malformation, vaginal malformation, classification, clinical manifestation, diagnosis

Liuping Cui,1,2 Ran Liu,1 Fubo Zhou,1 Yumei Liu,1 Bing Tian,1 Ying Chen,2,&ast; Yingqi Xing1,3,4,&ast; 1Department of Vascular Ultrasound, Xuanwu Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurology, The First Hospital of Jilin University, Changchun, People’s Republic of China; 3Beijing Diagnostic Center of Vascular Ultrasound, Beijing, People’s Republic of China; 4Center of Vascular Ultrasound, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yingqi Xing, Department of Vascular Ultrasonography, Xuanwu Hospital, Capital Medical University, 45 Changchun Road, Beijing, Xicheng District, 100053, People’s Republic of China, Tel +86-18610047846, Email xingyq2009@sina.comPurpose: Intraplaque neovascularization, assessed using contrast-enhanced ultrasound (CEUS), is associated with ischemic stroke. It remains unclear whether detection of intraplaque neovascularization combined with color Doppler ultrasound (CDUS) provides additional value compared with CDUS alone in assessing ischemic stroke risk. Therefore, we investigated the clinical value of combined CEUS, CDUS, and clinical features for ischemic stroke risk stratification.Patients and Methods: We recruited 360 patients with ≥ 50% carotid stenosis between January 2019 and September 2022. Patients were examined using CDUS and CEUS. Covariates associated with ischemic stroke were identified using multivariate logistic regression analysis. The discrimination and calibration were verified using the C-statistic and Hosmer–Lemeshow test. The incremental value of intraplaque neovascularization in the assessment of ischemic stroke was analyzed using the Delong test.Results: We analyzed the data of 162 symptomatic and 159 asymptomatic patients who satisfied the inclusion and exclusion criteria, respectively. Based on multivariate logistic regression analysis, we constructed a nomogram using intraplaque neovascularization, degree of carotid stenosis, plaque hypoechoicity, and smoking status, with a C-statistic of 0.719 (95% confidence interval [CI]: 0.666– 0.768) and a Hosmer–Lemeshow test p value of 0.261. The net reclassification index of the nomogram was 0.249 (95% CI: 0.138– 0.359), and the integrated discrimination improvement was 0.053 (95% CI: 0.029– 0.079). Adding intraplaque neovascularization to the combination of CDUS and clinical features (0.672; 95% CI: 0.617– 0.723) increased the C-statistics (p=0.028).Conclusion: Further assessment of intraplaque neovascularization after CDUS may help more accurately identify patients at risk of ischemic stroke. Combining multiparametric carotid ultrasound and clinical features may help improve the risk stratification of patients with ischemic stroke with ≥ 50% carotid stenosis.Plain Language Summary: We studied whether using contrast-enhanced ultrasound (CEUS) to detect intraplaque neovascularization could help better determine the risk of ischemic stroke. We compared the combined use of color Doppler ultrasound (CDUS) and CEUS with CDUS alone in patients with more than 50% carotid narrowing. Our findings showed that combining clinical details, CDUS, and CEUS was more effective (0.719 vs 0.672). This means that CEUS provides extra insight when gauging ischemic stroke risk compared with CDUS alone. This could help in accurately identifying patients at high risk of stroke. However, more extensive studies are needed to fully understand the role of these tests in the evaluation of stroke risk. Keywords: atherosclerosis, contrast-enhanced ultrasound, vulnerable plaque, carotid ultrasound

Yudong Miao,1 Ruizhe Ren,1 Zhanlei Shen,1 Yi Li,1 Wanliang Zhang,1 Junwen Bai,1 Dongfang Zhu,1 Jingbao Zhang,1 Dan Guo,1,2 Clifford Silver Tarimo,3 Rongmei Liu,4 Qiuping Zhao,4 Jianping Hu,5 Xue Zhou,6 Wenyong Dong7 1College of Public Health, Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Neurology, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of China; 3Department of Science and Laboratory Technology, Dar es Salaam Institute of Technology, Dar es Salaam, Tanzania; 4Henan Key Laboratory for Health Management of Chronic Diseases, Central China Fuwai Hospital, Zhengzhou, People’s Republic of China; 5Henan Medical Communication and Project Forward Center, Zhengzhou, People’s Republic of China; 6College of Health Management, Mudanjiang Medical University, Mudanjiang, People’s Republic of China; 7Department of Hypertension, Henan Provincial People’s Hospital, Zhengzhou, People’s Republic of ChinaCorrespondence: Rongmei Liu, Assistant research fellow. Fuwai Central China Cardiovascular Hospital, Zhengzhou University Affiliated Central China Fuwai Hospital, &num;1, Fuwai Avenue, Zhengdong New District, Zhengzhou, 450014, People’s Republic of China, Tel +8615038204525, Email liuyongmei0203@163.comObjective: To evaluate the prevalence and influencing factors of long COVID, and measure the difference in health status between long COVID and non-long COVID cases.Methods: A cross-sectional survey was conducted from February 1 to 8, 2023, using a stratified random sampling method in four regions (eastern [Changzhou], central [Zhengzhou], western [Xining] and northeastern [Mudanjiang]) of China. The survey collected COVID-19 patients’ socio-demographic characteristics and lifestyles information. The scores of lifestyles and health status range from 5 to 21 and 0 to 100 points, respectively. The criteria of “persistent health problems after 4 weeks of COVID-19 infection” issued by the US Centers for Disease Control and Prevention was used to assess long COVID. Multiple linear regression was used to analyze the influencing factors of the health. The bootstrap method was used to analyze the lifestyles’ mediating effect. Propensity score matching (PSM) was used to evaluate the net difference in health scores between long COVID and non-long COVID cases.Results: The study included 3165 COVID-19 patients, with 308 (9.73%) long COVID cases. The health score of the long COVID cases (74.79) was lower than that of the non-long COVID cases (81.06). After adjusting for potential confounding variables, we found that never focused on mental decompression was a common risk factor for the health of both groups. Lifestyles was the mediating factor on individuals’ health. After PSM, the non-long COVID cases’ health scores remained higher than that of long COVID cases.Conclusion: The proportion of long COVID cases was low, but they were worse off in health. Given the positive moderating effect of healthy lifestyles on improving the health of long COVID cases, healthy lifestyles including mental decompression should be considered as the core strategy of primary prevention when the epidemic of COVID-19 is still at a low level.Keywords: long COVID, lifestyles, self-reported health status, propensity score matching, effect of mediation

Jingsong Luo,1,2 Yuxin Chen,2 Yanmin Tao,1 Yaxin Xu,3 Kexin Yu,2 Ranran Liu,2 Yuchen Jiang,2 Cichong Cai,2 Yiyang Mao,2 Jingyi Li,2 Ziyi Yang,2 Tingting Deng1 1School of Nursing, The Chengdu University of Traditional Chinese Medicine, Sichuan, 610000, People’s Republic of China; 2Jockey Club School of Public Health and Primary Care, The Chinese University of Hong Kong, Hong Kong SAR, People’s Republic of China; 3School of Nursing, Tongji University, Shanghai, 200000, People’s Republic of ChinaCorrespondence: Tingting Deng, School of Nursing, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, People’s Republic of China, Email dengtingting999@163.comBackground: There is substantial evidence from previous studies that abnormalities in sleep parameters associated with depression are demonstrated in almost all stages of sleep architecture. Patients with symptoms of sleep-wake disorders have a much higher risk of developing major depressive disorders (MDD) compared to those without.Objective: The aim of the present study is to establish and compare the performance of different machine learning models based on sleep-wake disorder symptoms data and to select the optimal model to interpret the importance of sleep-wake disorder symptoms to predict MDD occurrence in adolescents.Methods: We derived data for this work from 2020 to 2021 Assessing Nocturnal Sleep/Wake Effects on Risk of Suicide Phase I Study from National Sleep Research Resource. Using demographic and sleep-wake disorder symptoms data as predictors and the occurrence of MDD measured base on the center for epidemiologic studies depression scale as an outcome, the following six machine learning predictive models were developed: eXtreme Gradient Boosting model (XGBoost), Light Gradient Boosting mode, AdaBoost, Gaussian Naïve Bayes, Complement Naïve Bayes, and multilayer perceptron. The models’ performance was assessed using the AUC and other metrics, and the final model’s predictor importance ranking was explained.Results: XGBoost is the optimal predictive model in comprehensive performance with the AUC of 0.804 in the test set. All sleep-wake disorder symptoms were significantly positively correlated with the occurrence of adolescent MDD. The insomnia severity was the most important predictor compared with the other predictors in this study.Conclusion: This machine learning predictive model based on sleep-wake disorder symptoms can help to raise the awareness of risk of symptoms between sleep-wake disorders and MDD in adolescents and improve primary care and prevention.Keywords: adolescent major depressive disorder, sleep-wake disorders symptom, insomnia, obstruct sleep apnea, machine learning prediction model, xgboost

Xiaokang Zheng,1,2,&ast; Yu Li,2,&ast; Xuejun Shang,3 Ranlu Liu1 1Department of Urology, Tianjin Medical University General Hospital, Tianjin Medical University, Tianjin, 300052, People’s Republic of China; 2Department of Andrology, Henan Provincial People’s Hospital; Zhengzhou University People’s Hospital; Henan University People’s Hospital, Zhengzhou, Henan, 450003, People’s Republic of China; 3Department of Urology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ranlu Liu, Department of Urology, Tianjin Medical University General Hospital, Tianjin Medical University, No.154, Anshan Road, Tianjin, 300052, People’s Republic of China, Email ranluliu@126.com Yu Li, Department of Andrology, Henan Provincial People’s Hospital; Zhengzhou University People’s Hospital; Henan University People’s Hospital, No.7 Weiwu Road, Zhengzhou, Henan, 450003, People’s Republic of China, Email liyu7715@126.comPurpose: The systemic infection and inflammation can result in testes injury, whereas the exact mechanism is unknown. The lipid metabolism has a dual impact on controlling metabolism and inflammation, which is a potential pathway. The objective of this study was to determine if changes in plasma lipids during lipopolysaccharide (LPS)-induced systemic inflammation affect the dysregulation of testes lipid metabolism.Materials and Methods: LPS (5 mg/kg) was used to induce systemic inflammation in rats after a single intraperitoneal injection. After 4 weeks, the rats were sacrificed, and the serum and testes were used for laboratory measurements and histology examination. Plasma and testis were used for lipidomics analysis based the liquid chromatography-mass spectrometry. Spearman rank correlation analysis was used to compare the correlation of differential lipids in phospholipids, glycerolipids, and sphingolipids between testis and plasma.Results: LPS raised the levels of cytokines in serum and testis, decreased the activities of antioxidant enzymes, increased the levels of lipid peroxidation products, and damaged testis tissue. In testis and plasma, 146 and 401 differential lipids, mostly phosphatidylcholine, phosphatidylethanolamine an so on, were found in comparison to the control group. Correlation analysis produced a total of 2528 correlation coefficients, 1150 of which were P< 0.05 and accounted for 45.49%.Conclusion: The changes of lipid composition and content in the testis are related to cytokine overload and oxidative stress. Testis lipid metabolism disorders caused by LPS-induced systemic inflammation are lack of a correlation with plasma lipid changes, and are likely owing to interference with the testis itself.Keywords: systemic inflammation, infertility, lipidomics, oxidative stress, correlation analysis

Ruijia Liu,1,2,&ast; Xudong Yu,1,&ast; Xu Cao,1,2 Xuyun Wang,3 Yijun Liang,2 Wenying Qi,1,2 Yong’an Ye,1,2 Xiaobin Zao1,2,4 1Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, People’s Republic of China; 2Institute of Liver Diseases, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, People’s Republic of China; 3Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 4Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, 100700, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaobin Zao, Assistant Researcher, Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, 5 Haiyuncang Road, Dongcheng District, Beijing, 100700, People’s Republic of China, Tel +86-10-8401-3194, Email A3417@bucm.edu.cnPurpose: ST6 Beta-Galactoside Alpha-2,6-Sialyltransferase 2 (ST6GAL2), a member of the sialic acid transferase family, is differentially expressed in diverse cancers. However, it remains poorly understood in tumorigenesis and impacts on immune cell infiltration (ICI) in hepatocellular carcinoma (HCC).Patients and Methods: Herein, the expression, diagnosis, prognosis, functional enrichment, genetic alterations, immune characteristics, and targeted drugs of ST6GAL2 in HCC were researched by conducting bioinformatics analysis, in vivo, and in vitro experiments.Results: ST6GAL2 was remarkably decreased in HCC compared to non-tumor tissues, portending a poor prognosis associated with high DNA methylation levels. Functional enrichment and GSVA analyses revealed that ST6GAL2 might function through the extracellular matrix, PI3K-Akt signaling pathways, and tumor inflammation signature. We found that ST6GAL2 expression was proportional to ICI, immunostimulator, and immune subtypes. ST6GAL2 expression first increased and then decreased during the progression of liver inflammation to HCC. The dysfunctional experiment indicated that ST6GAL2 might exert immunosuppressive effects during HCC progression through regulating ICI. Several broad-spectrum anticancer drugs were obtained by drug sensitivity prediction analysis of ST6GAL2.Conclusion: In conclusion, ST6GAL2 was a reliable prognostic biomarker strongly associated with ICI, and could be a potential immunotherapeutic target for HCC.Keywords: hepatocellular carcinoma, ST6GAL2, prognosis, immune cell infiltration, biomarker

Can Chen,1 Fan Yang,1 Mantao Chen,2 Ying Xu,1 Yaping Xie,1 Ruishan Liu,3 Pengfei Shi,1 Shenxian Qian1 1Department of Hematology, Affiliated Hangzhou First People’s Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, 310006, People’s Republic of China; 2Department of Neurosurgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of ChinaCorrespondence: Shenxian Qian; Pengfei Shi, Email sxqian1028@zju.edu.cn; sypfshi@163.comBackground: The emergence of the ST11-CRKP (ST11-CRKP) strain is expected to become a serious public health problem in China. As one of the most serious complications in patients with acute myeloid lymphoma, infections can cause systemic infection and life-threatening sepsis, seriously affecting the morbidity, mortality, and quality of life of patients. Thus, ST11-CRKP infections in patients with acute myeloid lymphoma are worthy of our attention.Aim: To investigate the occurrence and genetic characteristics of the ST11-CRKP from a patient with acute myeloid lymphoma.Methods: Species identification was determined by MALDI-TOF MS. Antimicrobial susceptibility testing (AST) was conducted by VITEK 2 system with AST-N335 panel. Whole-genome sequencing was performed on the Illumina NovaSeq 6000 platform. Phylogenetic analyses were performed using Snippy based on the core-genome SNPs.Findings: S1 nuclease pulsed-field gel electrophoresis (S1-PFGE), Southern blot and Whole-genome analysis indicated blaKPC-2 genes were located on plasmids with a conserved genetic environment. Moreover, the eight ST11-CRKP strains carry a variety of antimicrobial resistance genes (ARGs) and virulence factors. The ability of biofilm formation of eight strains was verified by a crystal violet assay. Core genome single-nucleotide polymorphism (cgSNP) analysis suggesting a possible bacterial translocation event.Conclusion: We performed a comprehensive analysis of ST11-CRKP strains from a patient with acute myelocytic leukemia. Our study emphasized the need for continuous surveillance of ST11-CRKP in the clinic especially in the immunocompromised population.Keywords: KPC-2, acute myelocytic leukemia, whole-genome sequencing, multiple site infections

Peiying Fu,&ast; Ling Zhang,&ast; Ting Zhou, Shixuan Wang, Ronghua Liu Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ronghua Liu, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Anv., Wuhan, Hubei, 430030, People’s Republic of China, Tel/Fax +86-27-83663078, Email Liuzhu38@126.comObjective: Cesarean scar pregnancy (CSP) is an uncommon form of ectopic pregnancy that carries the risk of severe bleeding. To date, there has not been a universally accepted classification and treatment strategy. We performed this study to establish a risk scoring system and new CSP classification system for CSP and evaluate its efficacy.Methods: A total of five groups were generated based on different methods of treatment, and the factors that increase the risk of intraoperative bleeding were examined in our center from 2013 to 2018. The construction of a risk scoring system in this study was based on the use of the chi-square test and multivariate logistic regression analysis. To determine the appropriate cutoff scores, receiver operating characteristic (ROC) curves and the area under the curve (AUC) were generated.Results: We identified the main high-risk factors for excessive intraoperative hemorrhage during CSP surgery through univariate and multivariate analyses. Within this investigation, the risk factors included gestational sac location and gestational sac diameter. Through analysis, an optimal cutoff score of 3 was determined, and the area under the ROC curve was calculated to be 0.8113 (95% CI=0.7696– 0.8531). A score ranging from 0– 3 was classified as low risk, while a score ranging from 5– 7 was classified as high risk. Additionally, a new classification system for CSP has been established based on sonographic parameters. We also established a diagnostic and treatment process for CSP patients according to the risk scoring method and new CSP classification.Conclusion: We identified the high-risk factors associated with bleeding during CSP surgery and developed a scoring system incorporating these factors. The utilization of this novel CSP typing method, in conjunction with the risk scoring system, can effectively inform doctors in their decision-making process concerning treatment strategies for patients with CSP.Keywords: cesarean scar pregnancy, scoring system, risk, classification, treatment

Liping Lei,1,2,&ast; Jingjing Yang,1,&ast; Hao Peng,1 Ruiyan Huang,1 Lichun Liang,1 Ruifang Liu,1 Jiangfa Li1 1Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, People’s Republic of China; 2Department of Geriatric Medicine, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiangfa Li, Department of Hepatobiliary and Pancreatic Surgery, The Affiliated Hospital of Guilin Medical University, Guilin, 541001, People’s Republic of China, Tel +86-7732824373, Email 247546160@qq.comBackground: Abnormal expression of genes causes tumorigenesis, tumor progression, and poor prognosis in hepatocellular carcinoma (HCC). Therefore, the aims of this study were to explore the transcription enhancer domain factor 4 (TEAD4) in patients with liver cancer and its relationship with prognosis.Methods: HTSeq-FPKM data and corresponding clinical data of HCC patients were obtained from The Cancer Genome Atlas (TCGA). Difference in TEAD4 expression between normal and tumor and the correlation with clinical characteristics were analyzed by the chi-squared test based on UALCAN. HepG2 cell lines were used to study the effect of TEAD4 on HCC cell lines. The expression and clinical significance of TEAD4 in HCC were detected in clinical cases.Results: The transcription and post-transcription levels of TEAD4 were higher in HCC tumors than normal illustrated different expressed transcription of TEAD4 in gender, nodal metastasis status, tumor grades, and individual cancer stages. The high TEAD4 expression was significantly associated with tumor grades. The high expression of TEAD4 was significantly correlated to shorter 2– 5 years overall survival. Inhibition of TEAD4 expression in HepG2 cells resulted in significantly decreased cell proliferation and invasion.Conclusion: TEAD4 was identified as an independent prognostic factor, and inhibition of TEAD4 expression in HepG2 cells resulted in significantly decreased cell proliferation and invasion.Keywords: TCGA, TEAD4, hepatocellular carcinoma

Huimin Zhang,1,&ast; Chengyu Zang,1,2,&ast; Wen Zhao,1 Linfeng Zhang,1 Rui Liu,1 Zhang Feng,1 Jie Wu,1 Rongtao Cui1– 3 1Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Department of Burn and Plastic Surgery, Shandong Provincial Hospital, Shandong University, Jinan, People’s Republic of China; 3Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongtao Cui, Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Tel +86 18653170822, Email cuirt1986@outlook.comBackground: Mesenchymal stem cell-derived exosomes (MSC-exo) have been shown to have significant potential in wound healing and scar relief processes. According to reports, TNFSF13 and HSPG2 are associated with various fibrotic diseases. The aim of this study is to investigate how TNFSF13 and HSPG2 affect the formation of hypertrophic scar (HS) and the mechanism by which exosomes regulate HS.Methods: Immunohistochemistry, qRT-PCR, Western blot, and immunofluorescence were performed to measure TNFSF13 expression in HS skin tissues and hypertrophic scar fibroblast (HSF). HSF were treated with recombinant TNFSF13 protein and TNFSF13 siRNAs to probe the effect of TNFSF13 on the activity of HSF. The CCK-8, EdU, Transwell, and Western blot were used to investigate the role of TNFSF13 in viability, proliferation and inflammation. The influence of MSC-exo on the proliferation and function of HSF was determined by scratch and Western blot.Results: TNFSF13 was dramatically up-regulated in HS skin tissues and HSF. Recombinant TNFSF13 protein increased cell viability, proliferation, migration, fibrosis, inflammation, and the binding between TNFSF13 and HSPG2 of HSF. The opposite results were obtained in TNFSF13 siRNAs transferred HSF. Furthermore, TNFSF13 activated the nuclear factor-κB (NF-κB) signaling pathway. Silencing of HSPG2 and inhibition of NF-κB remarkably eliminated the promoting effects of TNFSF13 on cell viability, proliferation, migration, fibrosis and inflammation of HSF. MSC-exo reduced α-SMA and COL1A1 inhibited the proliferation and migration of HSF by inhibiting TNFSF13 and HSPG2.Conclusion: TNFSF13 activates NF-κB signaling pathway by interacting with HSPG2, which regulates the proliferation, migration, fibrosis and inflammatory response of HSF. Through the above mechanisms, knocking out TNFSF13 can inhibit the proliferation, migration, fibrosis and inflammatory response of HSF, whereas MSC-exo could reverse this process. These results suggest that MSC-exo alleviates HS by inhibiting the fibroblasts via TNFSF-13/HSPG2 signaling pathway.Keywords: TNFSF13, HSPG2, hypertrophic scar(HS), MSC-exo, fibroblasts

Jiali Yao, Kun Chen, Hongjie Tong, Ruixin Liu Department of Critical Care Medicine, Jinhua Hospital Affiliated to Zhejiang University, Zhejiang, People’s Republic of ChinaCorrespondence: Kun Chen; Hongjie Tong, Department of Critical Care Medicine, Jinhua Hospital Affiliated to Zhejiang University, 365 Renmin East Road, Wucheng District, Zhejiang, 321000, People’s Republic of China, Email 13957970707@sina.com; 444370182@qq.comPurpose: Sepsis patients with persistent inflammation, immunosuppression, and catabolism syndrome (PICS) have a poor prognosis, and early detection of biomarkers to predict its prognosis is particularly important. The purpose of this study is to investigate the predictive value of glycemic variability (GV) and high density lipid-cholesterol (HDL-C) for secondary PICS in patients with sepsis.Patients and Methods: One hundred and sixty-five patients with sepsis were enrolled in the retrospective study and divided into sepsis secondary PICS and non-PICS group. The daily blood glucose levels from 1 to 7 days after the diagnosis of sepsis were recorded, and GV was calculated. Logistic regression was used to analyze the risk factors of sepsis with PICS, receiver operating characteristic (ROC) curve was drawn to evaluate the predictive value of GV, and HDL-C for the prognosis of sepsis with PICS.Results: In a study of 165 patients, PICS group tended to have higher GV and lower HDL-C levels than those in the non-PICS group. Logistic regression analysis identified GV and HDL-C as independent risk factors for the secondary PICS of sepsis. The results of ROC curve showed that GV and HDL-C had a certain predictive value for the secondary PICS of sepsis, the sensitivity of GV was 77.5%, specificity of 81.8%, the sensitivity of HDL-C was 76.6%, and specificity of 74.8%.Conclusion: GV and HDL are risk factors for PICS secondary to sepsis and have predictive value for patients’ prognosis.Keywords: glycemic variability, high density lipid-cholesterol, sepsis, persistent inflammatory immunosuppressed catabolic syndrome

Xingxing Li,1 Rongpeng Liu,1 Wei Liu,1 Xin Liu,2 Zongjing Fan,1 Jie Cui,1 Yang Wu,1 Huijun Yin,3 Quan Lin1 1Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, 100078, People’s Republic of China; 2The Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, 100029, People’s Republic of China; 3Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, 100091, People’s Republic of ChinaCorrespondence: Quan Lin, Dongfang Hospital, Beijing University of Chinese Medicine, No. 6, Fangxingyuan District 1, Fengtai District, Beijing, 100078, People’s Republic of China, Tel +86-10-67689757, Email linquanys@163.comBackground: Combination of Panax quinquefolium L and Salvia miltiorrhiza Bunge. (PS) has been widely used in the clinical treatment of ischemic heart disease. The purpose of this study was to explore the therapeutic effect and mechanism of PS on angiogenesis in rats after acute myocardial infarction (AMI).Methods: A rat model of AMI was established by ligating the left anterior descending (LAD) artery. The grouping and administration scheme were as follows: sham group, model group, PS low-dose (PS-L) group, PS high-dose (PS-H) group, PX-478 group and angiotensin converting enzyme inhibitor (ACEI) group. After 28 days of treatment, echocardiography, myocardial infarct size, some angiogenesis markers and the miR-155-5p/HIF-1α/VEGF axis were measured.Results: PS improved cardiac structure and function, reduced infarct size, and alleviated myocardial fibrosis and inflammatory cell infiltration in AMI rats. Mechanistically, PS enhanced the expression of HGF and bFGF in serum, increased the levels of MVD and CD31 in myocardial tissues, and inhibited the activation of the miR-155-5p/HIF-1α/VEGF pathway, which ultimately promoted angiogenesis. In addition, the regulatory effect of PS on angiogenesis was partly abolished by PX-478.Conclusion: PS increased the expression of MVD and CD31 in the myocardium and stimulated angiogenesis. The above effects of PS may be associated with the inhibition of the miR-155-5p/HIF-1α/VEGF axis. Keywords: Panax quinquefolium L, Salvia miltiorrhiza Bunge, angiogenesis, acute myocardial infarction, miR-155-5p/HIF-1α/VEGF

Yi-Kun Zhao,1 Xiang-Dong Zhu,2 Rong Liu,1 Xia Yang,1 Yong-Lin Liang,1 Yan Wang2 1Department of Basic Medical College, Gansu University of Chinese Medicine, Lanzhou City, People’s Republic of China; 2Department of Traditional Chinese Medicine College, Ningxia Medical University, Yinchuan city, People’s Republic of ChinaCorrespondence: Yong-Lin Liang, Gansu University of Chinese Medicine, No. 35, Dingxi East Road, Chengguan District, Lanzhou City, Gansu, 730030, People’s Republic of China, Email andong5011@163.com Yan Wang, Ningxia Medical University, No. 1160 Shengli Street, Xingqing District, Yinchuan City, Ningxia Hui Autonomous Region, 750004, People’s Republic of China, Tel +86-18153952736, Email wyan1232004@163.comAbstract: Over the past decade, there has been a significant increase in studies investigating the relationship between the polymorphisms of the Peroxisome Proliferator-Activated Receptor gamma (PPARγ) gene and Type 2 Diabetes (T2D). PPARγ, a critical transcription factor, plays a central role in lipid metabolism, insulin resistance, and inflammatory response. Concurrently, the influence of gut microbiota on the development of T2D has gained increasing attention, especially their role in affecting host metabolism, such as lipid metabolism and the PPARγ signaling pathway. This review provides a comprehensive analysis of recent studies on PPARγ gene polymorphisms and their association with T2D, with a specific emphasis on the implications of gut microbiota and their interaction with PPARγ pathways. We also discuss the potential of manipulating gut microbiota and targeting PPARγ gene polymorphisms in T2D management. By deepening our understanding of these relationships, we aim to pave the way for novel preventative and therapeutic strategies for T2D.Keywords: PPARγ, T2D, lipid metabolism, insulin resistance, gut microbiota

Yu Zhou,1,&ast; Huoying Cai,1,&ast; Lin Huang,1,&ast; Mingshan Wang,1 Ruiming Liu,2 Siwen Wang,1 Yuansen Qin,1 Chen Yao,1 Zuojun Hu1 1Division of Vascular Surgery, National-Guangdong Joint Engineering Laboratory for Diagnosis and Treatment of Vascular Disease, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 2Laboratory of Department of Surgery, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zuojun Hu; Chen Yao, Email huzuojun@mail.sysu.edu.cn; yaochen@mail.sysu.edu.cnBackground: Arteriosclerosis obliterans (ASO) is the leading cause of nontraumatic lower-extremity amputations. Multiple researches have suggested that circular RNAs (circRNAs) played vital regulatory functions in cancer and cardiovascular disease. Nevertheless, the underlying effect and pathological mechanism of circRNAs in the formation and progression of ASO are still indistinct.Methods and Results: This study used microarray analysis to investigate the expression portrait of circRNAs in normal lower extremity arteries and ASO arteries. Bioinformatics analysis was conducted using the KEGG database to study the enrichment of differentially expressed circRNAs (DE circRNAs) and predict their functions. The accuracy of microarray assay was verified by evaluating expression of the top 5 upregulated and 5 downregulated circRNAs (raw density of normal group ≥ 200) using RT-qPCR. A circRNA-miRNA-mRNA interaction network was further predicted using software. Compared to the normal lower extremity group, the ASO arteries with HE and EVG staining presented hyperplastic fibrous membrane and luminal stenosis. A total of 12,735 circRNAs were identified, including 1196 DE circRNAs with 276 upregulated and 920 downregulated in ASO group based on |log2(FC)| > 1 and padj < 0.05. Among selected 10 circRNAs, RT-qPCR confirmed that hsa_circ_0003266, hsa_circ_0118936 and hsa_circ_0067161 were upregulated while hsa_circ_0091934 and hsa_circ_0092022 were downregulated in ASO group (p < 0.05). GO analysis presented that the DE circRNAs were primarily enriched in protein binding, intracellular part and organelle organization. KEGG pathway analysis indicated that MAPK signaling pathway, human T-cell leukemia virus 1 infection, proteoglycans in cancer were associated with the DE circRNAs. The circRNA-miRNA-mRNA interactive network revealed that both mRNAs and miRNAs linked to circRNAs played an indispensable role in ASO.Conclusion: This study described the expression portrait of circRNAs in human ASO arteries, and revealed the molecular background for further investigations of the circRNA regulatory mechanism in the formation and progression of ASO.Keywords: arteriosclerosis obliterans, circular RNA, gene ontology analysis, pathway analysis, circRNA-miRNA-mRNA interaction network

Rong Liu,1,&ast; Min Zhu,2,&ast; Jiaojiao Chen,3 Junwei Gai,2 Jing Huang,2 Yingqun Zhou,1 Yakun Wan,2 Chuantao Tu4 1Department of Gastroenterology, Shanghai Tenth People’s Hospital, Tongji University School of Medicine, Shanghai, 200072, People’s Republic of China; 2Shanghai Novamab Biopharmaceuticals Co., Ltd, Shanghai, 201318, People’s Republic of China; 3Department of Gastroenterology, Shanghai Fourth People’s Hospital, Tongji University School of Medicine, Shanghai, 200434, People’s Republic of China; 4Department of Gastroenterology, Shanghai Public Health Clinical Center, Fudan University, Shanghai, 201508, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chuantao Tu; Yakun Wan, Email tuchuantao@hotmail.com; ykwan@novamab.comBackground: No agents are currently available for the treatment or reversal of liver fibrosis. Novel antifibrotic therapies for chronic liver diseases are thus urgently needed. Connective tissue growth factor (CTGF) has been shown to contributes profoundly to liver fibrogenesis, which makes CTGF as a promising target for developing antifibrotic agents.Methods: In this study, we identified a novel nanobody (Nb) against human CTGF (anti-CTGF Nb) by phage display using an immunized camel, which showed high affinity and specificity in vitro. LX-2 cells, the immortalized human hepatic stellate cells, were induced by transforming growth factor beta1 (TGFβ 1) as an in vitro model of liver fibrosis to verify the antifibrotic activity of the anti-CTGF Nb.Results: Our data demonstrated that anti-CTGF Nb effectively alleviated TGFβ 1-induced LX-2 cell proliferation, activation, and migration, and promoted the apoptosis of activated LX-2 cells in response to TGFβ 1. Moreover, the anti-CTGF Nb remarkably reduced the levels of TGFβ 1, Smad2, and Smad3 expression in LX-2 stellate cells stimulated by TGFβ 1.Conclusion: Taken together, we successfully identified a novel Nb against human CTGF, which exhibited antifibrotic effects in vitro by regulating the biological functions of human stellate cells LX-2.Graphical Abstract: Keywords: nanobody, connective tissue growth factor, liver fibrosis, hepatic stellate cells

Xiaojiao Xu,1,2 Yuheng Shan,3 Yuying Cen,2,4 Jiahua Zhao,2,4 Xiaosa Yang,2,4 Rui Liu,1,2 Qingche Tan,2 Yubao Ma,2 Mianwang He,2 Jiatang Zhang,1,2,4 Fei Yang,2 Shengyuan Yu2 1School of Medicine, Nankai University, Tianjin, 300071, People’s Republic of China; 2Department of Neurology, The First Medical Centre, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 3Department of Neurology, Characteristic Medical Centre of People’s Armed Police Force, Tianjin, 300162, People’s Republic of China; 4Medical School of Chinese PLA, Beijing, 100853, People’s Republic of ChinaCorrespondence: Jiatang Zhang; Fei Yang, Department of Neurology, The First Medical Centre, Chinese PLA General Hospital, No. 28, Fuxing Road, Beijing, 100853, People’s Republic of China, Tel +86 13601380322 ; Tel +86 13910973120, Email zjt1128@aliyun.com; yangfeiyanbian@163.comPurpose: Listeria monocytogenes infections are rare in the central nervous system (CNS) and frequently difficult-to-diagnose. Our goal is to assess CNS listeriosis patients’ clinical characteristics, diagnosis, treatment, and prognosis.Patients and Methods: Patients with CNS listeriosis admitted to the Department of neurology, the first medical center of the Chinese PLA general hospital, were enrolled in this study from March 2018 to August 2022.Results: This study analyzed eight adults, including five males and three females. The average age of onset was (50.25 ± 11.52) years. The clinical manifestations included fever, headache, altered mental status, vomiting, seizures, neck rigidity, hemiplegia and cranial nerve palsies. Cerebrospinal fluid (CSF) tests revealed intracranial hypertension, elevated cell count and protein concentration, and decreased glucose levels. The positive rates of blood and CSF culture were 40% and 28.57%, respectively. All patients underwent CSF metagenomic next-generation sequencing (mNGS), with a 100% positive rate and the specific read number 12– 20394. Magnetic resonance imaging (MRI) exhibited leptomeningitis, meningoencephalitis, and brain abscess, and no specific changes were discovered in two patients. All patients received antibiotic treatment, seven were cured, and one died.Conclusion: Monitoring the proportion of monocytes in blood and mNGS results of CSF can play a crucial role in diagnosing pathogens. Early and sufficient application of two to three sensitive antibiotics with a BBB permeability of 20– 30% for at least 2– 3 months can significantly improve CNS listeriosis prognosis.Keywords: Listeria monocytogenes, central nervous system, CNS, clinical characteristics, treatment, metagenomic next-generation sequencing, mNGS

Shaoxing Zhang,1 Yuxin Zhang,1 Ruijie Liu,1 Shuying Yuan,2 Yanwen Chen,1 Wenjie Li,1 Xinrong Lu,3 Yongliang Tong,3 Linlin Hou,4 Li Chen,3 Guiqin Sun1 1School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Clinical Laboratory Department, Jiaxing Maternity and Child Health Care Hospital, Jiaxing, Zhejiang, People’s Republic of China; 3Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, Shanghai, People’s Republic of China; 4College of Veterinary Medicine, Qingdao Agricultural University, Qingdao, Shandong, People’s Republic of ChinaCorrespondence: Guiqin Sun, School of Medical Technology and Information Engineering, Zhejiang Chinese Medical University, 548 Binwen Road, Binjiang District, Hangzhou, Zhejiang, People’s Republic of China, Tel +86 13868118601, Fax +86 571-86633307, Email sunguiqin2001@163.com Li Chen, Key Laboratory of Medical Molecular Virology (MOE/NHC/CAMS), School of Basic Medical Sciences, Fudan University, 131 Dongan Road, Xuhui District, Shanghai, People’s Republic of China, Tel +86 15821138980, Fax +86 21-54237381, Email lichen_bk@fudan.edu.cnPurpose: Elizabethkingia meningoseptica (EM) is a multi-drug-resistant bacterium of global concern for its role in nosocomial infection and is generally resistant to aminoglycoside antibiotics. In the whole genome of an EM strain (FMS-007), an aminoglycoside-6-adenyl transferase gene (ant(6)FMS-007) was predicted. This study aimed to characterize the biochemical function of ANT(6)FMS-007 and analyze the relationship between genotype and phenotype of ant(6) in clinical EM isolates, so as to provide evidence for clinical precision drug use. This study could establish a method for the verification of known or unknown functionally resistant genes.Methods: A total of 42 EM clinical isolates were collected from clinical departments during 2015– 2023. The phenotype of aminoglycoside antibiotics was analyzed by broth microdilution (BMD) and Kirby-Bauer (K-B) methods. The whole-length ant(6) from EM clinical isolates was analyzed by polymerase chain reaction (PCR) and sequencing. The biochemical function of predictive ANT(6)FMS-007 from the FMS-007 whole genome was identified by 3D plate experiment and mass spectrometry analysis. Candidate active sites were predicted by multi-species sequence alignment and molecular docking, and other important sites were identified in the comparison of ant(6) genotypes and phenotypes of EM clinical isolates. Drug susceptibility test was used to verify the function of these sites.Results: The predictive ANT(6)FMS-007 protein could inactivate STR by modifying STR with ATP to form STR-AMP. Four active sites (Asp-38, Asp-42, Lys-95, and Lys-213) of ANT(6)FMS-007 were identified. Thirty-one EM clinical isolates (74%) carried the ant(6) gene. Eight EM clinical isolates containing the ant(6) gene had MIC values (

Hang Qian,1 Xu Wang,1 Pengbo Wang,1 Guangyang Zhang,1 Jun Liu,1 Xiaoqian Dang,1 Jianbin Guo,2 Ruiyu Liu1 1Department of Orthopedics, The Second Affiliated Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 2Department of Orthopedics, Honghui Hospital, Xi’an Jiaotong University, Xi’an, People’s Republic of ChinaCorrespondence: Ruiyu Liu, Department of Orthopaedics, The Second Affiliated Hospital, Xi’an Jiaotong University, No. 157, Xiwu Road, Xi’an, Shaanxi, 710004, People’s Republic of China, Email liuryu@126.comObjective: Hip ankylosis is a prevalent condition in patients with Ankylosing spondylitis (AS) that can significantly impact their psychological well-being. This study aimed to investigate the impact of Total Hip Arthroplasty (THA) on anxiety and depression among AS patients.Methods: 62 AS patients undergoing primary THA were recruited and separated into two groups based on preoperative hip motion. The 40 patients with hip mobility of 0° were assigned to group A, and others were assigned to group NA. Self-rating Anxiety Scale (SAS), Self-rating Depression scale (SDS), Harris hip scores (HHS) and 36-Item Short Form Survey (SF-36) were obtained one week before and there, six and twelve months after THA.Results: The study found that AS patients in group A had significantly higher levels of anxiety and depression (SAS score = 75.05± 2.79, SDS index score = 0.74± 0.02) compared to group B (SAS score = 54.58± 3.35, SDS index score= 0.64± 0.03, P=0.01). However, both groups showed significant improvements in anxiety and depression scores from there to twelve months after THA (P< 0.001). Correlation analyses revealed that the improvement in group NA was associated with hip pain relief (p< 0.001), while the improvement in group A was related to joint function, disease duration, age at THA and spine imaging lesions (p< 0.001).Conclusion: Some degree of anxiety and depression was present in both groups of AS patients. Levels of depression and anxiety were higher in patients with combined hip ankylosis. And their improvement was associated with improved hip function and quality of life after THA. Hip pain relief played a significant role in patients without hip joint ankylosis. The impact of the degree of lesion on spinal imaging on psychological status needs to be considered in both groups.Keywords: ankylosing spondylitis, depression and anxiety, hip pain, hip joint range of motion, hip ankylosing

Xue Zhao,&ast; Junde Zhu, Shan Chen,&ast; Ruojing Liu, Tingting Long Department of Human Anatomy, School of Basic Medicine, Guizhou Medical University, Guiyang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junde Zhu, Department of Human Anatomy, School of Basic Medicine, Guizhou Medical University, Guian New Area, Guiyang, 550025, People’s Republic of China, Tel +86-851-88416251, Email jdzhu73@126.comPurpose: To investigate the effect of neural stem cell-derived exosomes (NSC-Exos) on neural function after rat cerebral ischemia-reperfusion injury by regulating microglia-mediated inflammatory response.Methods: SD rats were randomly divided into Sham group, IRI group, PBS group and NSC-Exos group. Each group was divided into 1d, 3d, 7d and 14d subgroups. In the Sham group, only cervical vessels were isolated without blockage. MCAO model was constructed in the other three groups by blocking middle cerebral artery with thread embolism. PBS group and NSC-Exos group were, respectively, injected into the lateral ventricle of PBS and Exos. Neurobehavioral deficit scores were performed for each subgroup at relative time points, then brains were taken for TTC staining, parietal cortex histopathology and microglia-mediated inflammatory response-related factors were detected.Results: Compared with Sham group, neurological defect score and infarction volume in both the IRI and PBS groups were significantly increased. The exploration target quadrant time and escape latency time of maze test were increased. The number of CD86+/Iba1+ double-positive cells increased, while CD206+/Iba1+ double-positive cells decreased. The expressions of IL-6 and CD86 in parietal cortex were increased, while the expressions of Arg1 and CD206 were decreased. Compared with the IRI group and PBS group, neurological defect score and infarction volume in NSC-Exos group were decreased. The exploration target quadrant time and escape latency time of water maze test were decreased. The number of CD206+/Iba1+ double-positive cells increased, while CD86+/Iba1+ double-positive cells decreased. The expressions of Arg1 and CD206 in parietal cortex were increased, while the expressions of IL-6 and CD86 were decreased.Conclusion: NSC-Exos can promote the polarization of microglia, that is, inhibit the polarization of M1 and promote polarization of M2, reduce microglia-mediated neuroinflammation, suggesting that NSC-Exos may be a strategy for the treatment of microglia-mediated neuroinflammation after ischemic brain injury.Graphical Abstract: Keywords: cerebral ischemia, neural stem cell, exosome, microglia, neuroinflammation

Zhen-Yun Wu,1,&ast; Xiang-Min Lu,2,&ast; Rui Liu,1,&ast; Yan-Xia Han,3 Hong-Ying Qian,1 Qian Zhao,1 Mei’e Niu3 1Department of Pulmonary and Critical Care Medicine, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China; 2School of Nursing, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 3Department of Nursing, The First Affiliated Hospital of Soochow University, Suzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mei’e Niu, Department of Nursing, the First Affiliated Hospital of Soochow University, No. 899, Pinghai Road, Suzhou, Jiangsu, 215006, People’s Republic of China, Email meniu_123@163.com Qian Zhao, Department of Pulmonary and Critical Care Medicine, the First Affiliated Hospital of Soochow University, No. 188, Shizi Street, Suzhou, Jiangsu, 215006, People’s Republic of China, Email xujiali1983_01@163.comPurpose: This study was designed to investigate the differences in skeletal-muscle atrophy between patients with stable chronic obstructive pulmonary disease (COPD) and healthy controls; associated factors were also considered. The study comprised selected residents of communities near the First Affiliated Hospital of Soochow University in Suzhou City, East China.Patients and Methods: Included in this study were 123 COPD patients and 60 controls. All patients completed spirometry as well as examinations to determine their functional exercise capacity, body composition, and handgrip strength (HGS).Results: COPD patients had less fat-free mass (FFM), a lower FFM index (FFMI), and a lower 6-min walking distance (6MWD) compared with controls (P = 0.007, P = 0.020, and P < 0.001, respectively) (FFMI: 17.59 ± 1.83 vs 18.34 ± 1.64). The HGS of these patients was also lower compared with that of controls (32.88 ± 7.84 vs 35.48 ± 7.42), and HGS tended toward statistical significance (P = 0.064, respectively). In multivariate analysis, age (β = − 0.107, P < 0.001), gender (β = 0.212, P < 0.001), body mass index (BMI) (β = 0.462, P < 0.001), FEV1% (β = 0.108, P = 0.009), and calf circumference (CC) (β = 0.457, P < 0.001) were significantly associated with FFMI.Conclusion: Impaired skeletal muscle mass was more common in COPD patients than in controls. Multiple regression analysis showed that CC may be used to detect the degree of impairment, particularly by health-care providers working outside of the hospital.Keywords: airflow obstruction, calf circumference, chronic obstructive pulmonary disease, fat-free mass index, skeletal muscle atrophy, skeletal muscle mass

Songsong Shi,&ast; Rong Liu,&ast; Haiying Yu,&ast; Long Xiang, Hua Lu Department of Pediatric Intensive Care Unit, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hua Lu, Department of Pediatric Intensive Care Unit, Shanghai Children’s Medical Center, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200127, People’s Republic of China, Tel +86 18930830609, Email luhua@scmc.com.cnBackground: The omicron pandemic in Shanghai has created unprecedented challenges for pediatric medical institutions, and the work of pediatric nurses has changed rapidly due to the introduction of parent-child treatment. This study aimed to explore the experiences of pediatric nurses in the parent-child isolation unit of COVID-19-designated hospitals and provide a basis for developing feasible interventions as the next step.Methods: Using phenomenological research methods, 12 nurses working in the parent-child isolation unit of Shanghai Children’s Medical Center affiliated with Shanghai Jiao Tong University School of Medicine from April 1, 2022, to June 15, 2022, were selected by purposive sampling. Semi-structured interviews and data analysis were conducted using Colaizzi’s 7-step analysis.Results: Data analysis revealed three major themes and 11 subthemes. The main themes were “risk factors”, “protection factors”, and “resilience strategies”. The sub-themes were “challenge of caring for both adults and children simultaneously”, “lack of adult expertise leads to inadequate coping skills”, “change in the care population increased communication difficulties”, “physical and psychological distress”, “social support”, “social recognition”, “awareness of responsibilities and roles”, “team coming together”, “hunger for knowledge”, “health promotion”, and “psychological adjustment strategies”.Conclusion: Hospital managers should optimize hospital management strategies, pay attention to multi-departmental and multidisciplinary team cooperation, reduce the burden on pediatric nurses, improve the work and rest environment, mobilize the hospital support system, and maintain nurse’s physical and mental health, establish a warm parent-child isolation unit encourages nurses to listen to the patients’ voices and adopt diversified communication methods, and strengthen the publicity of the nursing profession, improve social support and recognition, and enhance the sense of self-worth and mission.Keywords: pediatric nurse, COVID-19, parent-child unit, qualitative study

Wen Zhao,1,2,&ast; Huimin Zhang,1,2,&ast; Rui Liu,1,2 Rongtao Cui1– 3 1Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China; 2Medical Science and Technology Innovation Center, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 3Department of Burn and Plastic Surgery, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Rongtao Cui, Department of Burn and Plastic Surgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, People’s Republic of China, Tel +86 18653170822, Email cuirt1986@outlook.comAbstract: Pathological scars are the result of over-repair and excessive tissue proliferation of the skin injury. It may cause serious dysfunction, resulting in psychological and physiological burdens on the patients. Currently, mesenchymal stem cells-derived exosomes (MSC-Exo) displayed a promising therapeutic effect on wound repair and scar attenuation. But the regulatory mechanisms are opinions vary. In view of inflammation has long been proven as the initial factor of wound healing and scarring, and the unique immunomodulation mechanism of MSC-Exo, the utilization of MSC-Exo may be promising therapeutic for pathological scars. However, different immune cells function differently during wound repair and scar formation. The immunoregulatory mechanism of MSC-Exo would differ among different immune cells and molecules. Herein, this review gave a comprehensive summary of MSC-Exo immunomodulating different immune cells in wound healing and scar formation to provide basic theoretical references and therapeutic exploration of inflammatory wound healing and pathological scars.Keywords: exosomes, inflammation, immune cells, immunoregulation, scars

Yuhong Tang,1,&ast; Jun Cao,1,&ast; Rui Peng,1 Xingkang Mao,1 Bingbing Su,1 Hao Tang,1 Daoyuan Tu,1 Jie Zhou,1 Guoqing Jiang,1 Shengjie Jin,1 Qian Wang,1 Chen Zhang,2 Renjie Liu,1 Chi Zhang,1,3 Dousheng Bai1,3 1Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, Yangzhou, People’s Republic of China; 2The Second Affiliated Hospital of Xuzhou Medical University, Xuzhou, People’s Republic of China; 3General Surgery Institute of Yangzhou, Yangzhou University, Yangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dousheng Bai; Chi Zhang, Department of Hepatobiliary Surgery, Clinical Medical College, Yangzhou University, 98 West Nantong Road, Yangzhou, 225000, People’s Republic of China, Email drbaidousheng@yzu.edu.cn; zc17212850@163.comIntroduction: Immune checkpoint therapy (ICIs) effectively improves the prognosis of advanced (stage III/IV) hepatocellular carcinoma (HCC) patients. However, its objective response rate (ORR) is below 20%, significantly limiting ICI use in advanced HCC patients. The level of tumour immune infiltration influences ICI response rate. Recent studies have found ubiquitinase to be an important factor that regulates tumour immune infiltration. Therefore, the aim of this study is to explore the key ubiquitination genes that regulate immune infiltration in advanced HCC and further validate them.Methods: A biotechnological process was performed as a means of classifying 90 advanced HCC patients into three immune subtypes and identifying associations with immune infiltration in the co-expressed modules. Ubiquitination-related genes were then screened with WGCNA. Gene enrichment analysis was performed for the target module and 30 hub genes were screened out by protein–protein interaction network (PPI). ssGSEA, single-gene sequencing and the MCP counter were used for exploring immune infiltration. TIDE score was applied for predicting drug efficacy and GSEA was used for exploring potential pathways. Finally, GRB2 expression in HCC tissue was validated by in vitro experiments.Results: GRB2 expression was found to have a significant correlation with the pathological stage and prognosis of HCC patients and a positive correlation with immune infiltration and tumour mutation burden (TMB). In addition, significant correlations with the efficacy of ICIs, sorafenib and transarterial chemoembolization (TACE) were identified. GRB2 was found to be most significantly associated with the JAK-STAT signalling pathway and cytosolic DNA sensing pathway. Finally, it was found that GRB2 expression is closely related to the prognosis, tumour size and TMN stage.Conclusion: A significant association was observed between the ubiquitinated gene GRB2 and the prognosis and immune infiltration of advanced HCC patients and it may potentially be used for predicting therapy efficacy in advanced HCC patients in the future.Keywords: ubiquitination, growth factor receptor-binding protein 2, liver cancer, tumour-infiltrating immune cells

Yuqi Zhou,1,&ast; Yuanmeng Yang,2,&ast; Rongpu Liu,1,&ast; Qin Zhou,3 Haixia Lu,2 Wenjie Zhang1 1Department of Prosthodontics, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Department of Preventive Dentistry, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Oral Surgery, Ninth People’s Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjie Zhang, Department of Prosthodontics, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, People’s Republic of China, Email zhangwenjie586@126.com Haixia Lu, Department of Preventive Dentistry, Ninth People’s Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, People’s Republic of China, Email ritalu0225@hotmail.comAbstract: Oral diseases represent one of the most prevalent diseases globally and are associated with serious health and economic burdens, greatly altering the quality of life of affected individuals. Various biomaterials play important roles in the treatment of oral diseases. To some extent, the development of biomaterials has promoted progress in clinically available oral medicines. Hydrogels have unique tunable advantages that make them useful in the next generation of regenerative strategies and have been widely applied in both oral soft and hard tissues repair. However, most hydrogels lack self-adhesive properties, which may result in low repair efficacy. Polydopamine (PDA), the primary adhesive component, has attracted increasing attention in recent years. PDA-modified hydrogels exhibit reliable and suitable adherence to tissues and easily integrate into tissues to promote repair efficiency. This paper reviews the latest research progress on PDA hydrogels and elaborates on the mechanism of the reaction between PDA functional groups and hydrogels, and summarizes the biological properties and the applications of PDA hydrogels in the prevention and treatment of the field of oral diseases. It is also proposed that in future research we should simulate the complex microenvironment of the oral cavity as much as possible, coordinate and plan various biological events rationally, and realize the translation from scientific research to clinical practice.Graphical Abstract: Keywords: polydopamine, hydrogel, catechol groups, adhesive properties, prevention and treatment, oral diseases

Rui Liu, Dandan Shi, Lu Guo, Shan Xiao, Mengmeng Shang, Xiao Sun, Dong Meng, Yading Zhao, Xiaoxuan Wang, Jie Li Department of Ultrasound, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of ChinaCorrespondence: Jie Li, Department of Ultrasound, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China, Email jieli@email.sdu.edu.cnIntroduction: Triple-negative breast cancer (TNBC) is known to be the most aggressive form of breast cancer. Due to its high recurrence and mortality rates, the treatment of TNBC is a significant challenge for the medical community. Besides, ferroptosis is an emerging regulatory cell death that may provide new insights into the treatment of TNBC. As a central inhibitor of the ferroptosis process, the selenoenzyme glutathione peroxidase 4 (GPX4) is its classical therapeutic target. However, inhibition of GPX4 expression is quite detrimental to normal tissues. Ultrasound contrast agents, as an emerging visualization precision treatment, may provide a solution to the existing problem.Methods: In this study, nanodroplets (NDs) carrying simvastatin (SIM) were constructed using the homogeneous/emulsification method. Then, the characterization of SIM-NDs was systematically evaluated. Meanwhile, in this study, the ability of SIM-NDs combined with ultrasound-targeted microbubble disruption (UTMD) to initiate ferroptosis and its respective mechanisms of ferroptosis induction were verified. Finally, the antitumor activity of SIM-NDs was investigated in vitro and in vivo using MDA-MB-231 cells and TNBC animal models.Results: SIM-NDs exhibited excellent pH- and ultrasound-responsive drug release and noticeable ultrasonographic imaging ability, also showing good biocompatibility and biosafety. UTMD could promote increased intracellular reactive oxygen species and consume intracellular glutathione. However, SIM-NDs were efficiently internalized into cells under ultrasound irradiation, followed by the rapid release of SIM, which inhibited intracellular mevalonate production, and synergistically downregulated GPX4 expression, thereby promoting ferroptosis. Moreover, this combined treatment demonstrated strong antitumor ability in vitro and in vivo.Conclusion: The combination of UTMD and SIM-NDs presents a promising avenue for harnessing ferroptosis in the treatment of malignant tumors.Graphical Abstract: Keywords: ultrasound-targeted microbubble disruption, nanodroplets, ferroptosis, glutathione peroxidase 4, theranostics, lipid peroxidation

Mengdi Xie,1,&ast; Kang Yuan,2,&ast; Xinyi Zhu,2,&ast; Jingjing Chen,3 Xiaohao Zhang,4 Yi Xie,2 Min Wu,1 Zhaojun Wang,2 Rui Liu,2 Xinfeng Liu1,2,5 1Department of Neurology, Jinling Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Neurology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing, People’s Republic of China; 3Department of Neurology, Changhai Hospital, Navy Medical University, Shanghai, People’s Republic of China; 4Department of Neurology, Nanjing First Hospital, Nanjing Medical University, Nanjing, People’s Republic of China; 5Stroke Center & Department of Neurology, Division of Life Sciences and Medicine, The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinfeng Liu, Department of Neurology, Jinling Hospital, Nanjing Medical University, No. 305 East Zhongshan Road, Nanjing, Jiangsu Province, 210000, People’s Republic of China, Tel +86 2584801861, Fax +86 2584805169, Email xfliu2@vip.163.com Rui Liu, Department of Neurology, Affiliated Jinling Hospital, Medical School of Nanjing University, No. 305 East Zhongshan Road, Nanjing, 210000, Jiangsu Province, People’s Republic of China, Tel +86 2584801861, Fax +86 2584805169, Email liurui8616@163.comBackground: Systemic immune inflammation has been investigated as a prognostic marker of different diseases. This study is designed to assess the association of systemic immune-inflammation index (SII) with long-term mortality of stroke-associated pneumonia (SAP) patients.Methods: Patients aged ≥ 18 years with SAP were selected from the Nanjing Stroke Registry Program in China. We retrospectively evaluated systemic immune-inflammation response with SII and pneumonia severity with the pneumonia severity index and the confusion, uremia, elevated respiratory rate, hypotension, and aged 65 years or older score. To explore the correlation between SII and mortality in SAP patients, multivariable Cox regressions and competing risk regressions were conducted. Mediation analysis was also performed to assess the role of pneumonia severity.Results: Among 611 patients in the SAP population, death occurred in 164 patients (26.8%) during the median follow-up of 3.0 (1.2– 4.6) years. In multivariate analysis, higher SII scores could predict increased mortality in patients with SAP (adjusted hazard ratio 2.061; 95% confidence interval, 1.256– 3.383; P = 0.004), and the association was mediated by pneumonia severity. Moreover, adding SII to traditional models improved their predictive ability for mortality.Conclusion: Our study displayed that SII was characterized in SAP patients with different prognoses. Elevated SII scores increased the risk of mortality. Further research is required for the clinical practice of the index among SAP patients.Keywords: systemic immune-inflammation index, stroke-associated pneumonia, mortality, China

Nan Yu,&ast; Ting Zhou,&ast; Haiying Sun, Peiying Fu, Ronghua Liu Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ronghua Liu, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Anv., Wuhan, Hubei, 430030, People’s Republic of China, Tel +86-27-63639807, Fax +86 (27) 83663078, Email liuzhu38@126.comAbstract: Port site metastasis (PSM) is considered an uncommon and rare complication in gynecologic malignancies with unclear treatment recommendations or guidelines. Thus, we report the treatment strategies and outcomes of two cases of PSMs following gynecologic malignancies and a review of the literature to provide much information about the most frequent sites of PSMs and the incidence of PSMs in different gynecological tumors. A 57-year-old woman underwent laparoscopic radical surgery for right ovarian serous carcinoma in June 2016 followed by postoperative chemotherapy. Because PSMs were present near the port site of the bilateral iliac fossa, the tumors were completely removed on August 4, 2020, and the patient received chemotherapy. She has shown no signs of relapse. During the same period, a 39-year-old woman underwent laparoscopic type II radical hysterectomy for endometrial adenocarcinoma involving the endometrium and cervix on May 4, 2014, without adjuvant treatment. In July 2020, a subcutaneous mass under her abdominal incision was removed, and chemotherapy plus radiotherapy was administered. Metastasis was found in the left lung in September 2022, but there was no abnormality in the abdominal incision. We showed the two cases of PSMs, reviewed articles to provide some new insights about the incidences of PSMs in the gynecologic tumors, and discussed the proper preventive strategies.Keywords: ovarian cancer, endometrial cancer, port site, metastasis

Sheng Ye,1 Huichun Xiao,1 Jian Chen,1 Di Zhang,1 Li Qi,1 Ting Peng,2 Yanyang Gao,2 Qianbing Zhang,3 Jinqing Qu,2 Lei Wang,4 Ruiyuan Liu1 1Guangdong Provincial Key Laboratory of Medical Image Processing, School of Biomedical Engineering, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2School of Chemistry and Chemical Engineering, South China University of Technology, Guangzhou, Guangdong, People’s Republic of China; 3Cancer Research Institute, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 4College of Materials and Chemical Engineering, Key Laboratory of Inorganic Nonmetallic Crystalline and Energy Conversion Materials, China Three Gorges University, Yichang, People’s Republic of ChinaCorrespondence: Jinqing Qu; Ruiyuan Liu, Email cejqqu@scut.edu.cn; ruiyliu@smu.edu.cnIntroduction: The high concentration of glutathione (GSH) and hydrogen peroxide (H2O2) levels within the tumor microenvironment (TME) are the major obstacle to induce the unsatisfactory anticancer treatment efficiency. The synergistic cancer therapy strategies of the combination the GSH depletion enhanced chemodynamic therapy (CDT) with photothermal therapy (PTT) have been proved to be the promising method to significantly improve the therapeutic efficacy.Methods: The copperphosphotungstate was incorporated into polyanilines to design copperphosphotungstate doped polyaniline nanorods (CuPW@PANI Nanorods) via chemical oxidant polymerization of aniline. The low long-term toxicity and biocompatibility were evaluated. Both in vitro and in vivo experiments were carried out to confirm the GSH depletion enhanced CDT/NIR-II PTT synergistic therapy.Results: CuPW@PANI Nanorods feature biosafety and biocompatibility, strong NIR-II absorbance, and high photothermal-conversion efficiency (45.14%) in NIR-II bio-window, making them highly applicable for photoacoustic imaging and NIR-II PTT. Moreover, CuPW@PANI Nanorods could consume endogenous GSH to disrupt redox homeostasis and perform a Fenton-like reaction with H2O2 to produce cytotoxic •OH for the enhanced CDT. Furthermore, NIR-II photothermal-induced local hyperthermia accelerates •OH generation to enhance CDT, which realizes high therapeutic efficacy in vivo.Conclusion: This study provides a proof of concept of GSH-depletion augmented chemodynamic/NIR-II photothermal therapy.Keywords: copperphosphotungstate, NIR-II absorption nanorods, NIR-II photothermal therapy, GSH depletion, chemodynamic therapy, synergistic therapy

Haoyu Ge,1,2,&ast; Jie Qiao,1,2,&ast; Hao Xu,2 Ruishan Liu,2 Junhui Zhao,3 Ruyan Chen,1 Chenyu Li,1 Mantao Chen,4 Xiaobing Guo1 1Department of Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China; 2Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 3School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 4Department of Neurosurgery, the First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaobing Guo, Department of Laboratory Medicine, The First Affiliated Hospital of Zhengzhou University, Jianshe East Road, Zhengzhou, Henan Province, 450000, People’s Republic of China, Tel +86 371 6627 8237, Fax +86 371 6691 3569, Email gxbing928@zzu.edu.cnPurpose: The frequent and inappropriate use of antibiotics has caused a dramatic rise in the number, species, and degree of multi-drug resistant bacteria, making them more prevalent and difficult to treat. In this context, the aim of the present study was to characterize the OXA-484-producing strains isolated from a perianal swab of a patient by using whole-genome analysis.Patients and Methods: In this study, carbapenemase-producing Klebsiella variicola was identified by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), average nucleotide identity (ANI) and PCR. S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting were utilized to characterize the plasmid profiles of K. variicola 4717. In particular, WGS was performed to obtain genomic information on this clinical isolate, and assemble all the plasmids of the blaOXA-484-harboring strain.Results: The antimicrobial susceptibility pattern of K. variicola 4717 revealed that it was resistant to a range of antibiotics, including aztreonam, imipenem, meropenem, ceftriaxone, cefotaxime, ceftazidime, levofloxacin, ciprofloxacin, piperacillin-tazobactam, methylene-sulfamer oxazole, amoxicillin-clavulanic acid, cefepime, and tigecycline. Its susceptibility to chloromycin was intermediate, while it was still susceptible to amikacin, gentamicin, fosfomycin, and polymyxin B. The presence of two companion plasmids, p4717_1 and p4717_2, together with a plasmid carrying the blaOXA-484 gene was observed. An in-depth investigation of p4717-OXA-484 uncovered that it is an IncX3-type plasmid and shares a similar segment encoded by IS26. Given the similar genetic background, it was conceivable that blaOXA-484 could have developed from blaOXA-181 through a series of mutations.Conclusion: Herein, we described the first genome sequence of K. variicola strain harbouring the class D β-actamase blaOXA-484 in an Inc-X3-type plasmid. Our work also uncovered the genetic characterization of K. variicola 4717 and the importance of initiating antimicrobial detection promptly.Keywords: Klebsiella variicola, OXA-484, IncX3, mutation

Zuoya Sun,1 Zhiyuan Chen,1 Ruihong Liu,1 Gang Lu,1 Zhuo Li,1 Yi Sun2 1Department of Family Medicine, the University of Hong Kong-Shenzhen Hospital, Shenzhen, People’s Republic of China; 2Department of Nephrology, Beijing Huairou Hospital, Beijing, People’s Republic of ChinaCorrespondence: Yi Sun, Department of Nephrology, Beijing Huairou Hospital, No. 9 Yongtai North Street, Huairou District, Beijing, 101400, People’s Republic of China, Tel +86-010-69644822, Fax +86-010-69622761, Email Sunyihuairou@163.comAbstract: The mineralocorticoid receptor antagonist spironolactone has been shown to improve cardiac function and reverse left ventricular hypertrophy in heart failure patients, but there are no consistent findings on the efficacy and safety in hemodialysis patients. Abnormal aldosterone secretion plays a critical role in the formation of left ventricular hypertrophy. Because of the existence of “aldosterone escape”, the routine use of angiotensin-converting enzyme inhibitors/angiotensin receptor blockers does not completely inhibit aldosterone secretion. Low-dose spironolactone (25 mg/d) has been found in small-sample clinical studies to have a significant positive impact with respect to decreasing left ventricular mass index, increasing left ventricular ejection fraction, reversing left ventricular hypertrophy, and improving cardiovascular function while still being safe. More prospective multicenter clinical trials with large sample sizes are needed, however, to provide convincing evidence.Keywords: spironolactone, hemodialysis, left ventricular hypertrophy, LVH, mineralocorticoid receptor antagonists, MRA, hyperkalemia

Chen Tian,1,&ast; XiaoLei Xue,2,&ast; Ye Chen,3,&ast; Ruiyuan Liu,4 Yutong Wang,5 Sheng Ye,4 Zeyu Fu,5 Yingrui Luo,5 Shengmiao Wang,5 Xiaofeng He,1 Huajin Pang1 1Division of Vascular and Interventional Radiology, Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 2Department Pathology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 3Laboratory of Interventional Radiology, Department of Minimally Invasive Interventional Radiology and Department of Radiology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong Province, 510260, People’s Republic of China; 4Guangdong Provincial Key Laboratory of Medical Image Processing, School of BioMedical Engineering, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 5Cancer Research Institute, Experimental Education/Administration Center, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaofeng He; Huajin Pang, Tel +86 13760661610, Email ozonetherapy@126.com; nfyyphj@163.comIntroduction: Second near-infrared photothermal therapy (NIR-II PTT) has become a promising strategy for treating cancer in terms of safety and potency. However, the application of NIR-II PTT was limited in the treatment of deep-buried solid tumors due to the low dose of NIR-II absorption nanomaterials and the inadequate laser energy in the deep tumor.Methods: Herein, the authors report the engineering of NIR-II absorbing polyaniline nanorods, termed HPW@PANI Nanorods, for in situ NIR-II PTT based on optical fibers transmission of laser power and transarterial infusion for the treatment of orthotopic hepatocellular carcinoma in the rabbit. HPW@PANI Nanorods were prepared via chemical oxidant polymerization of aniline under phosphotungstic acid, which exhibited effective NIR-II absorption for hyperthermia ablation cells.Results: HPW@PANI Nanorods were fast and efficiently deposited into primary orthotopic transplantation VX2 tumor in rabbits via transarterial infusion. Furthermore, an optical fiber was interventionally inserted into the primary VX2 tumor to transmit 1064nm laser energy for in situ NIR-II PTT, which could ablate primary tumor, inhibit distant tumor, and suppress peritoneal metastasis.Conclusion: This study provides new insights into the application of in situ NIR-II PTT based on optical fibers transmission of laser power and transarterial injection of NIR-II absorption nanomaterials to treat deep-buried tumors.Graphical Abstract: Keywords: NIR-II absorption nanomaterials, orthotopic animal model, transarterial infusion, optical fiber transmission of laser power, deep-buried tumors

Chunlei Chen,1,&ast; Qingmiao Shi,1,&ast; Xinjun Hu,2 Xiaojing Liu,1,3 Yi Liu,1 Ruishan Liu1 1Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 2Department of Infectious Diseases, The First Affiliated Hospital, College of Clinical Medicine, Henan University of Science and Technology, Luoyang, People’s Republic of China; 3Department of Structure and Morphology, Jinan Microecological Biomedicine Shandong Laboratory, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruishan Liu, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou, Zhejiang, 310000, People’s Republic of China, Tel +86 571 872 364 23, Fax +86 571 872 364 21, Email 924172261@qq.comPurpose: Beta-lactamase-producing Klebsiella pneumoniae is common in the clinic, but research associated with the co-existence of KPC-2, LAP-2, and CTX-M-65 in K. pneumoniae is still rare. In this study, the phenotypic and genetic characteristics of a multidrug-resistant K. pneumoniae strain SJ25 co-harboring blaKPC-2, blaLAP-2, and blaCTX-M-65 with rare ST1469 were investigated.Methods and Results: Antimicrobial susceptibility testing revealed that strain SJ25 was resistant to various common antibiotics, except ciprofloxacin, fosfomycin, colistin, and tigecycline. Whole-genome analysis revealed that strain SJ25 carries a variety of antimicrobial resistance genes and virulence determinants. Plasmid analysis confirmed that the blaKPC-2 and blaCTX-M-65 genes were located on an ~136 kb transferrable IncFII/IncR plasmid and that blaLAP-2 was located on an untypeable plasmid.Conclusion: Our findings emphasized the need for continuous surveillance of β-lactamase-bearing K. pneumoniae in the clinic to control potential dissemination and outbreak.Keywords: Klebsiella pneumoniae, multidrug-resistant, blaKPC-2, blaLAP-2, blaCTX-M-65

Yunfeng Qu, Ruiyang Liu School of Law, Hainan University, Haikou, People’s Republic of ChinaCorrespondence: Ruiyang Liu, School of Law, Hainan University, No. 58 Renmin Road, Meilan District, Haikou, 570228, People’s Republic of China, Email lawliuruiyang@163.comAbstract: With the advent of 5G network technology and the maturity of medical applications associated with 5G, the Internet medical service industry is gradually developing. Given the COVID-19 pandemic crisis occasionally happened in China, hospitals were taken up most of the medical resources, the Internet medical care is seen as the alternative way for patients to access medical care and treatment. With the aid of 5G, patients nowadays can seek remote medical care, diagnosis, and surgery. However, this is not without any problems. The current legal supervision system in the Internet medical service industry is still incomplete, and ought to be augmented. This essay serves to identify and evaluate the loopholes existing in the legal supervision system in the Internet medical service industry, in the hope to improve the current system and ensure the safety of patients who are seeking Internet medical services.Keywords: internet medical care, legal supervision, 5G technology, remote surgery

Ruijia Liu,1,2,&ast; Xu Cao,1,2,&ast; Yijun Liang,1,2 Xiaobin Li,1 Qian Jin,1 Ying Li,3 Hongbo Du,1,2 Xiaobin Zao,1,4 Yong’an Ye1,2 1Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Institute of Liver Diseases, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Third Affiliated Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Key Laboratory of Chinese Internal Medicine of Ministry of Education and Beijing, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yong’an Ye; Xiaobin Zao, Email yeyongan@vip.163.com; A3417@bucm.edu.cnBackground: Hepatocellular carcinoma (HCC) is one of the most malignant tumors worldwide. The ST6 β-galactoside α-2, 6-sialyltransferase 1 (ST6GAL1) has been found aberrantly expressed in a variety of cancers including HCC, but its function and mechanism in regulating liver inflammation remain to be investigated. This study aimed to explore the role of ST6GAL1 in HCC. The data of ST6GAL1 expression, prognosis, and clinical parameters were collected and further analyzed from the public databases including The Cancer Genome Atlas (TCGA), Human Protein Atlas (HPA), and Gene Expression Omnibus (GEO). The HCC rat model was constructed by intraperitoneal injection of diethylnitrosamine. The mRNA and protein expression levels of ST6GAL1 in rat liver tissues were detected by real-time quantitative polymerase chain reaction, capillary electrophoresis, and Western blot.Results: The ST6GAL1 mRNA and protein expression levels were both lower in HCC tissues compared with normal liver tissues in the public databases and HCC rat model. The survival analysis showed that upregulation of ST6GAL1 was an independent prognostic factor for good prognosis in HCC patients. The ST6GAL1 mRNA expression showed a negative correlation with ST6GAL1 methylation levels. Enrichment analysis showed that ST6GAL1 expression was most associated with metabolic, cancer, estrogen, axon guidance, cAMP, and PI3K-AKT signaling pathways. The ST6GAL1 mRNA expression negatively correlated with liver inflammation status and proportion of NK CD56bright, NK CD56dim, pDC, and CD8+ T cells in liver.Conclusion: Compared with normal tissues, ST6GAL1 was lower expressed in HCC tumor tissues, and the downregulation of ST6GAL1 was associated with a poor prognosis in HCC patients. ST6GAL1 could further affect the infiltration of immune cells to exert anti-inflammation function in liver. Our study indicated that ST6GAL1 could be a potential biomarker and therapeutic target to assess the prognosis and regulate the immune cells infiltration level of HCC.Keywords: hepatocellular carcinoma, ST6GAL1, prognosis, immune infiltration, biomarker

Chuangang Shen,1 Rui Liu,1 Jing Yang,2 Sanman Hu,1 Peixu He1 1Business School, Huaqiao University, Quanzhou City, Fujian Province, 362021, People’s Republic of China; 2College of Tourism, Huaqiao University, Quanzhou City, Fujian Province, 362021, People’s Republic of ChinaCorrespondence: Jing Yang, College of Tourism, Huaqiao University, Quanzhou, 362021, People’s Republic of China, Tel +86 186-4995-3896, Email jingpsy@hqu.edu.cn Rui Liu, Business School, Huaqiao University, Quanzhou, 362021, People’s Republic of China, Tel +86 175-5418-6578, Email lrecho@foxmail.comPurpose: From the perspective of the work-home resource model, the present research aims to investigate the effect mechanism of family supportive supervisor behaviors (FSSB) on work-family enrichment.Sample and Method: Based on 316 Chinese employees’ samples, this study takes the multiple linear regression technique to test our hypothesis model.Results: Our study reveals that FSSB is positively related to work-family enrichment. In addition, thriving at work can mediate the positive relationship between family-supportive supervisor behaviors and work-family enrichment. Furthermore, the moderating role of intrinsic motivation is also found in this study. Specifically, intrinsic motivation strengthens the positive relationship between FSSB and thriving at work. Facing FSSB, individuals who score high in intrinsic motivation are prone to experience stronger thriving at work, while individuals who score low will hardly experience thriving at work.Conclusion: The current study comprehensively explores how informal organizational support (in our case, family supportive supervisor behaviors) leads to a better family outcome, thus contributing to the work-family interface literature. At the same time, our study also has some guiding significance for practitioners to build a family-friendly environment.Keywords: family supportive supervisor behaviors, thriving at work, work-family enrichment, work-home resource model

Kai Bao,1,&ast; Jijun Chen,2,&ast; Ruifang Liu,1,3 Yuanyuan Xiang,1 Wenlong Gao1 1Institution of Epidemiology and Health Statistics, School of Public Health, Lanzhou University, Lanzhou, Gansu, People’s Republic of China; 2STD and AIDS Prevention and Control Institute, Lanzhou Municipal Center for Disease Control and Prevention, Lanzhou, Gansu, People’s Republic of China; 3Department of Science and Education, Xi’an No. 5 Hospital, Xi’an, Shanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenlong Gao, Lanzhou University, No. 222 South Tianshui Road, Lanzhou, Gansu, People’s Republic of China, Tel +8613919026975, Email gaowl2019@sina.comObjective: To investigate the prevalence of hepatitis C virus (HCV) infection among hemodialysis (HD) patients in Lanzhou of Northwestern China, we interviewed 565 patients from five randomly sampled HD centers in Lanzhou with a structured questionnaire including sociodemographic characteristics, past medical history and HD-related factors.Methods: The testing results of anti-HCV and HCV-RNA in a recent HD from clinical information system were collected. A generalized estimated equation (GEE) logistic regression model was used to identify the determinants of HCV infection among HD patients.Results: The prevalence of anti-HCV or HCV-RNA infection among HD patients was 1.77% or 1.42% respectively. GEE model showed that history of kidney transplantation (HCV-RNA: OR=19.79, 95%CI: 12.69– 30.85) could dramatically increase the risk of current HCV infection in dialysis patients. Compared with never using of blood products, using of blood products (anti-HCV: OR=2.38, 95%CI: 1.22– 4.64; HCV-RNA: OR=15.23, 95%CI: 1.79– 129.49) could increase the risk of HCV infection in dialysis patients. Moreover, with the increase of HD duration, the risk increased one time or so (anti-HCV: OR=1.83, 95%CI: 1.22– 2.72; HCV-RNA: OR=2.00, 95%CI: 1.11– 3.61). Furthermore, dialysis in multiple hospitals possessed more than three times risk of HCV infection (anti-HCV: OR=3.56, 95%CI: 3.11– 4.08; HCV-RNA: OR=3.35, 95%CI: 1.88– 5.96). Besides, HD patients having the history of acupuncture (HCV-RNA: OR=5.56; 95%CI: 1.16– 26.67) or surgery (HCV-RNA: OR=6.39; 95%CI: 2.86– 14.29) caused an about-six-times risk of current infections.Conclusion: It could be concluded that the prevalence of HCV infection was mild and using of blood products or kidney transplantation, long dialysis duration, dialysis in multiple hospitals, surgery or acupuncture treatment were some risk factors of HCV infection among HD patients in Lanzhou of Northwestern China.Keywords: hemodialysis, hepatitis C virus, generalized estimating equation introduction

Wenxia Ruan,1 Rui Liu,2 Huimin Yang,1 Jiajia Ren,2 Yonglin Liu2 1Clinical Laboratory, Shenmu Hospital, The Affiliated Shenmu Hospital of Northwest University, Shenmu, Shaanxi, 719300, People’s Republic of China; 2Department of Science and Education, Shenmu Hospital, The Affiliated Shenmu Hospital of Northwest University, Shenmu, Shaanxi, 719300, People’s Republic of ChinaCorrespondence: Yonglin Liu, Department of Science and Education, Shenmu Hospital, The Affiliated Shenmu Hospital of Northwest University, Middle Section of Guangming Road, Shenmu, Shaanxi, 719300, People’s Republic of China, Tel/Fax +86-13389120319, Email lylsmsyy@126.comBackground: Allergic rhinitis (AR) is a common allergic disease in otolaryngology. Its pathogenesis is still unclear. PLC1 plays a key role in calcium homeostasis and immune response, which is potentially related to AR. We aimed to explore the association between PLCL1 genetic loci and susceptibility to AR.Methods: We recruited 1975 volunteers to perform an association analysis through SNPStats online software. False-positive report probability (FPRP) analysis was used to detect whether the positive findings were worth noting. Linkage disequilibrium and haplotype analysis were completed through Haploview and SNPStats. The influence of SNP-SNP interaction on AR susceptibility was evaluated through multifactor dimensionality reduction (MDR).Results: The results showed that four genetic loci in PLCL1 (rs2139049, rs212164068, rs2228135, and rs6738825) are associated with AR susceptibility under multiple genetic models. Allele “A” of PLCL1-rs2139049 (OR = 0.85, p = 0.031) or of -rs212164068 (OR = 0.85, p = 0.030), and allele “G” of PLCL1-rs6738825 (OR = 0.84, p = 0.022) are significantly associated with reduced AR risk. PLCL1-rs2228135 is associated with an increased risk of AR in males or participants older than 43 years of age. FPRP analysis showed that most of positive results are noteworthy findings. Three loci model composed of rs2139049, rs2164068, and rs2228135 is the best model for predicting AR risk (p = 0.0022). In addition, the haplotype “Grs2139049Ars6738825Ars2164068Ars2228135” (OR = 0.50, p = 0.033) can reduce the AR risk.Conclusion: Allele “A” of PLCL1-rs2139049, allele “A” of -rs212164068, and allele “G” of PLCL1-rs6738825 are protective factors of AR in Han population from northern Shaanxi, China.Keywords: allergic rhinitis, PLCL1, genetic loci, association analysis

Peiying Fu, Ting Zhou, Pengfei Cui, Wenwen Wang, Shixuan Wang, Ronghua Liu Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of ChinaCorrespondence: Ronghua Liu, Department of Obstetrics and Gynecology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Anv, Wuhan, Hubei, 430030, People’s Republic of China, Tel/Fax +86 27 83663078, Email Liuzhu38@126.comObjective: Cesarean scar pregnancy (CSP) can have catastrophic consequences, but a standardized diagnosis and treatment for CSP are lacking. At least 10 different treatments are currently available, further confusing treatment selection. The aim of this study was to compare the outcomes of using laparotomy or laparoscopy to treat CSP.Methods: We reviewed data from 935 patients with suspected CSP from 1 January 2013 to 31 December 2018. A total of 278 patients were included in the study, of whom 121 were treated with laparoscopy and 157 were treated with laparotomy. We compared and analyzed the characteristics of laparoscopic and open surgeries for treating CSP cases and the advantages and disadvantages of different vascular pretreatments.Results: Intraoperative bleeding, the transfusion rate, total days of hospitalization and postoperative hospital length of stay were lower with laparoscopy than laparotomy (P < 0.05). There was no difference in the factors (beta human chorionic gonadotropin [β-HCG] decrease, reoperation rate and tissue residues) closely related to the success of the surgery in the two groups. Furthermore, we used different blood vessel pretreatments among patients. The rates of tissue residue, reoperation and intraoperative blood transfusion were lower in patients with temporary vascular occlusion than in patients with permanent vascular occlusion.Conclusion: This study revealed that laparoscopic surgery is superior to laparotomic surgery for treating CSP. Patients in both groups benefited from temporary arterial occlusion. Thus, temporary arterial occlusion with laparoscopic surgery may be the best treatment for CSP.Keywords: cesarean scar pregnancy, hysterotomy, laparoscopy, laparotomy, arterial occlusion

Zhenjie Teng,1,2 Jing Feng,3 Ronghui Liu,4 Yanhong Dong,2 Huifang Chen,2 Jing Xu,2 Xin Jiang,2 Rui Li,2 Peiyuan Lv1,2 1Department of Neurology, Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of China; 2Department of Neurology, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of China; 3Department of Endocrinology, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of China; 4Department of Radiology, Hebei General Hospital, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: Peiyuan Lv, Department of Neurology, Hebei General Hospital, 348 Heping West Road, Shijiazhuang, Hebei Province, 050051, People’s Republic of China, Tel/Fax +86 31185988906, Email peiyuanlu2@163.comObjective: Type 2 diabetes mellitus (T2DM) is associated with cognitive impairment, but the underlying cerebral small vessel disease (CSVD)-related structural brain correlates are unclear. The aim of this study was to investigate the relationship between various imaging markers of CSVD and mild cognitive impairment (MCI) in patients with T2DM.Methods: A total of 228 eligible participants with T2DM who were divided into MCI group and normal cognitive group based on neuropsychological assessment were enrolled in this retrospective study. White matter hyperintensity (WMH), lacunes, cerebral microbleeds (CMBs) and enlarged perivascular spaces (EPVS) were evaluated based on brain magnetic resonance imaging (MRI). The total CSVD burden score was calculated by combining the above four markers of CSVD. Binary logistic regression analysis was used to evaluate the relationship between different imaging markers of CSVD and MCI in patients with T2DM. Kruskal–Wallis test and Jonckheere–Terpstra test were used to compare mean MoCA scores among individuals with varying CSVD markers.Results: In the multivariate binary logistic regression analyses, moderate or severe total CSVD burden (OR: 3.29, 95% CI: 1.63– 7.38, P=0.004; OR: 10.97, 95% CI: 4.94– 24.34, P< 0.001, respectively), moderate dWMH (OR: 3.26, 95% CI: 1.43– 7.41, P=0.005), extensive lacunes (OR: 4.97, 95% CI: 1.79– 13.81, P=0.002), and moderate BG-EPVS (OR: 3.84, 95% CI: 1.81– 8.13, P< 0.001) were associated with MCI in patients with T2DM related to MCI after adjusting for potential confounders. There was a trend for significant decrease in MoCA scores with increase severity of dWMH, pWMH, lacunes, BG-EPVS, deep CMBs, or total CSVD burden (P for trend < 0.05).Conclusion: Different imaging markers of CSVD, particularly total CSVD burden, were associated with an increased risk of MCI and decline in MoCA scores in patients with T2DM. These findings may provide clues for future studies to explore early diagnostic imaging markers of cognitive impairment in relation to T2DM.Keywords: type 2 diabetes mellitus, mild cognitive impairment, cerebral small vessel disease

Keli Wang,1 Meijiao Li,1 Rui Liu,1 Yang Ji,2 Jin Yan1,3 1Department of Clinical Medicine, Southwest Medical University, Luzhou, People’s Republic of China; 2Department of Clinical Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 3Department of Gastrointestinal Surgery, Sichuan Cancer Hospital & Institute, Affiliated Cancer Hospital, School of Medicine, University of Electronic Science and Technology, Chengdu, People’s Republic of ChinaCorrespondence: Jin Yan, Email yanjin_1111@163.comObjective: To explore the risk factors of anastomotic leakage (AL) after laparoscopic anterior resection (AR) of rectal cancer and establish a nomogram prediction model.Methods: Clinical and surgical data of patients who underwent AR of rectal cancer at Sichuan Cancer Hospital from January 2017 to December 2020 were retrospectively collected. Univariate and multivariate logistic regression analyses were used to screen the independent risk factors of AL after AR. A nomogram risk prediction model was established based on the selected independent risk factors and the predictive performance of nomogram was evaluated.Results: A 1013 patients undergoing laparoscopic AR were included, of which 67 had AL, with an incidence of 6.6%. Univariate and multivariate logistic regression analyses showed that male gender, tumors distance from the anus verge of ≤ 5cm, tumors distance from the anus verge of 5– 10cm, circumferential tumor growth, operation time ≥ 240min, and no diverting stoma were independent risk factors for AL after AR. A nomogram prediction model was established based on these results. The calibration curve showed that the predicted occurrence probability of the nomogram model was in good agreement with the actual occurrence probability. The area under the receiver operating characteristic (ROC) curve was 0.749.Conclusion: The nomogram prediction model based on the independent risk factors of patients undergoing AL after AR can effectively predict the probability of AL.Keywords: rectal cancer, laparoscopic anterior resection, anastomotic leakage, risk factor, nomogram prediction model