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Xuebing Zhang,1 Lianjie Wang,1 Ge Wang,1 Jiayue Li,1 Yiming Mu,2 Shidong Wang,1 Xiaoran Li1 1Department of Endocrinology, Dongzhimen Hospital Beijing University of Chinese Medicine, Beijing 100700, People’s Republic of China; 2Department of Endocrinology, First Medical Centre of Chinese PLA General Hospital, Beijing 100853, People’s Republic of ChinaCorrespondence: Shidong Wang; Xiaoran Li, Email A2082@bucm.edu.cn; 466187309@qq.comBackground: Nonalcoholic fatty liver disease (NAFLD) has become a major global health burden, which increases the risk of extra-hepatic complications such as type 2 diabetes mellitus (T2DM), dyslipidemia, metabolic syndrome (MetS), and cardiovascular disease (CVD). However, NAFLD remains underappreciated and underdiagnosed. Our study aimed to explore the prevalence of NAFLD and the association between NAFLD and CVD events among adults aged 40 and older in Northern China.Methods: This study was conducted in the Shijingshan district of Beijing, China from November 2011 to August 2012. A total of 18891 subjects were recruited in the study. The information including demographical information, lifestyle, previous history of diabetes, hypertension, dyslipidemia, CVD, and liver disease were gathered. Data on physical examination, blood lipid profile, fasting blood glucose, and 2-hour blood glucose were recorded. Determination of MetS was according to T2DM guideline of Chinese Diabetes Society (2020 edition). The association between CVD and NAFLD was evaluated by multivariate logistic regression.Results: The prevalence of NAFLD was 15.2%. After adjustment for age, smoking status, alcohol intake, WC, hypertension, dyslipidemia and hyperglycemia, the odds ratios (ORs) of CVD in men were 1.622 (95%CI: 1.345– 1.957) and 1.990 (95%CI: 1.709– 2.316) in women with NAFLD, compared with the subjects without NAFLD.Conclusions: NAFLD is independently associated with increased risk of CVD development.Keywords: nonalcoholic fatty liver disease, metabolic syndrome, cardiovascular disease, middle-aged and elderly, Chinese

Wei Sun,1,* Yun Liu,2,* Li Wang3 1Department of Oncology, Beijing Ditan Hospital, Capital Medical University, Beijing, 100015, People’s Republic of China; 2Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100021, People’s Republic of China; 3Department of Oncology, Beijing Luhe Hospital, Capital Medical University, Beijing, 101149, People’s Republic of China*These authors contributed equally to this workCorrespondence: Li Wang, Department of Oncology, Beijing Luhe Hospital, Capital Medical University, No. 82, Xinhua South Road, Tongzhou District, Beijing, 101149, People’s Republic of China, Tel +86 18010279916, Email lhyywl@163.comObjective: This study aimed to investigate the feasibility of the efficacy and safety of TACE combined with Lenvatinib and PD-1 blockade in HCC with portal vein tumor thrombus (PVTT).Methods: Patients with HCC and PVTT who underwent TACE combined with Lenvatinib and PD-1 blockade as first-line therapy in clinical practice were retrospectively included. All subjects were followed-up regularly to obtain prognostic outcomes. The safety profile observed during the combination therapy was collected and documented. The Log rank test was used for exploratory analysis of prognosis and baseline characteristics and Cox regression analysis was used for multivariate analysis.Results: A total of 67 HCC patients with PVTT who received TACE combined with Lenvatinib and PD-1 blockade were included in this study. The best therapeutic response during treatment suggested that 4 patients achieved complete response, 30 patients showed partial response, 25 patients were stable disease, 5 patients had disease progression and 3 patients were not available. Objective response rate of this regimen was 50.7% [95% confidence interval (CI): 38.2– 63.2%] and disease control rate was 88.1% (95% CI: 77.8– 94.7%). The median progression-free survival of 67 HCC patients with PVTT who received TACE combined with Lenvatinib and PD-1 blockades was 9.3 months (95% CI: 5.85– 12.75), and the median overall survival was 24.4 months (95% CI: 19.11– 29.69). The safety profile highlighted that 65 patients experienced adverse reactions regardless of grade during treatment (97.0%), among whom 34 patients were deemed as grade ≥ 3 adverse reactions (50.7%). The most common adverse reactions were hypertension, fatigue, abnormal liver function, nausea, vomiting, and diarrhea. Overall adverse reactions were acceptable and controllable.Conclusion: TACE combined with Lenvatinib and PD-1 blockades as first-line therapy for HCC with PVTT demonstrated potential feasibility and encouraging clinical outcomes, providing long-term survival benefits for HCC patients. This conclusion should be confirmed in prospective large-scale clinical trials.Keywords: hepatocellular carcinoma, portal vein tumor thrombus, TACE, Lenvatinib, PD-1 blockades, efficacy, safety

Dongyuan Qin,1 Lin Wang,2 Yahui Ni,1 Zhangtao Shan,1 Lifang Yang1 1Department of Gastroenterology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of China; 2Department of Pathology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, People’s Republic of ChinaCorrespondence: Lin Wang, Department of Pathology, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Third Hospital of Shanxi Medical University, Taiyuan, 030032, People’s Republic of China, Email 13613411069@139.comBackground: Chronic gastritis affects more than half of the global population to varying extents.Objectives: This study aimed to investigate the knowledge, attitude, and practice (KAP) of patients admitted to the gastroenterology department in the Shanxi region concerning chronic gastritis.Methods: This study was conducted in Shanxi between April and July 2023. The participants were enrolled when they consulted at the clinic. Demographic characteristics and KAP scores were collected through a self-administered questionnaire. KAP scores > 60% were considered good. Structural equation modeling (SEM) was utilized to examine the relationships among the dimensions of knowledge, attitude, and practice.Results: A total of 416 valid questionnaires were collected. The median knowledge score was 28 (0– 60) (with possible values of 0– 60), the median attitude score was 60 (28– 77) (with possible values of 16– 80), and the median practice score was 45 (12– 60) (with possible values of 12– 60). Hence, 133, 379, and 343 participants had knowledge, attitude, and practice scores, respectively, above the 60% threshold. Significant positive correlations were found between knowledge and attitude (r=0.300, P< 0.001), knowledge and practice (r = 0.297, P< 0.001), and attitude and practice (r=0.353, P=0.004) through correlation analysis. Structural Equation Modeling (SEM) revealed that knowledge directly and significantly influenced attitude (β=0.643, P< 0.001), as well as practice (β=0.095, P=0.034), and attitude had a direct effect on practice (β=0.094, P=0.009).Conclusion: Insufficient knowledge, positive attitudes, and proactive practices concerning chronic gastritis were observed in patients in the gastroenterology department. Prioritizing patient education and addressing patient attitudes during clinical consultations can enhance healthcare practices and improve the management of chronic gastritis.Keywords: knowledge, attitude, practice, Helicobacter pylori, chronic gastritis, cross-sectional study

Chen Kong,1,&ast; Meifeng Yang,2,&ast; Ningning Yue,3,&ast; Yuan Zhang,4 Chengmei Tian,5 Daoru Wei,6 Ruiyue Shi,1 Jun Yao,1 Lisheng Wang,1 Defeng Li1 1The Second Clinical Medical College, Jinan University; Shenzhen, Guangdong, People’s Republic of China; 2Department of Hematology, Yantian District People’s Hospital, Shenzhen, Guangdong, People’s Republic of China; 3Department of Gastroenterology, Shenzhen People’s Hospital (the Second Clinical Medical College, Jinan University), Shenzhen, Guangdong, People’s Republic of China; 4Department of Medical Administration, Huizhou Institute of Occupational Diseases Control and Prevention, Huizhou, Guangdong, People’s Republic of China; 5Department of Emergency, Shenzhen People’s Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China; 6Department of Rehabilitation, Shenzhen People’s Hospital (the Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lisheng Wang; Defeng Li, Department of Gastroenterology, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University; the First Affiliated Hospital, Southern University of Science and Technology), No. 1017, Dongmen North Road, Luohu District, Shenzhen, 518020, People’s Republic of China, Tel +86 755 25533018, Email wanglsszrmyy@163.com; ldf830712@163.comAbstract: The intestinal barrier maintained by various types of columnar epithelial cells, plays a crucial role in regulating the interactions between the intestinal contents (such as the intestinal microbiota), the immune system, and other components. Dysfunction of the intestinal mucosa is a significant pathophysiological mechanism and clinical manifestation of inflammatory bowel disease (IBD). However, current therapies for IBD primarily focus on suppressing inflammation, and no disease-modifying treatments specifically target the epithelial barrier. Given the side effects associated with chronic immunotherapy, effective alternative therapies that promote mucosal healing are highly attractive. In this review, we examined the function of intestinal epithelial barrier function and the mechanisms of behind its disruption in IBD. We illustrated the complex process of intestinal mucosal healing and proposed therapeutic approaches to promote mucosal healing strategies in IBD. These included the application of stem cell transplantation and organ-like tissue engineering approaches to generate new intestinal tissue. Finally, we discussed potential strategies to restore the function of the intestinal barrier as a treatment for IBD.Keywords: inflammatory bowel disease, intestinal barrier, pathophysiology, treatment

Liying Zhan,1,&ast; Zhihua Lv,2,&ast; Yunjing Zhang,3,&ast; Jingdi Chen,4 Lu Wang,1 Raojuan Huang,5 Yaqi Sun,5 Wei Wu1 1Department of Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Clinical Laboratory, Institute of Translational medicine, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Department of Ultrasound, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 4Department of Orthopedics, the Airborne Military Hospital, Wuhan, Hubei, People’s Republic of China; 5First Clinical College of Wuhan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Wu, Email weiwu2012@whu.edu.cnPurpose: Application of metagenomic next-generation sequencing (mNGS) in identifying nosocomial central nervous system (CNS) infections in critical care units remains understudied.Methods: We conducted a retrospective analysis of microbiological results through both mNGS and routine examination of cerebrospinal fluid (CSF) samples from patients with nosocomial CNS infections. The aim of this study was to assess the clinical diagnostic effect of nosocomial mNGS in this population.Results: The study included 26 cases of nosocomial CNS infections in total. A total of 69.2% (18/26) of the samples tested positive for mNGS, which is substantially greater than the 7.7% (2/26; p< 0.05) detected through conventional techniques. Administration of antibiotics before culture is most likely the cause of the low CSF culture rate. Twenty-five pathogenic strains that were missed by standard testing. Three pathogens that were consistent with the mNGS results were positive by routine tests. Eight cases were negative by mNGS due to low pathogen CSF titres. Compared to traditional testing, mNGS demonstrated 100% sensitivity and 33.3% specificity in diagnosing CNS infections. The thirty-day mortality rate was 26.9% (7/26).Conclusion: Routine microbiologic testing frequently falls short of detecting all neuroinvasive pathogens. Our research suggests that mNGS offers an alternative means of detecting nosocomial CNS infections. By applying mNGS to CSF samples from patients with meningitis or encephalitis, we were able to improve the ability to diagnose nosocomial neurologic infections.Keywords: metagenomic next-generation sequencing, cerebrospinal fluid, central nervous system infections, diagnosis

Haotian Chen, Juan Zhi, Lei Wang, Zibin Jin, Jin Xu, Fei Xing, Chao Wen, Qianyu Wang, Chunmei Chen, Weiou Li, Ermeng Xu, Jie An, Lingxin Wei Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of ChinaCorrespondence: Lingxin Wei, Department of Anesthesiology, Plastic Surgery Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, 33 Badachu Road, Shijingshan District, Beijing, 100144, People’s Republic of China, Tel +86 010 85557917, Email weilx3934@sina.comPurpose: Esketamine have anesthetic and analgesic properties. This study aimed to observe the enhancing effect of subanesthetic doses of esketamine (0.15– 0.3 mg/kg/h) with dexmedetomidine and remifentanil during anesthesia for liposuction surgery.Patients and Methods: A total of 155 subjects were randomized with a 1:1 ratio to Group E (esketamine-dexmedetomidine/remifentanil, n=78) or Group C (saline-dexmedetomidine/remifentanil group, n=77). The primary outcome was satisfaction of patient and surgical team with the procedure. The secondary outcomes were the postoperative Athens Insomnia Scale (AIS) and Hospital Anxiety and Depression Scale (HADS) scores, hemodynamic and respiratory changes, drug consumption, adverse event rates, and predictors associated with patient satisfaction.Results: Patient and surgical team satisfaction with the procedure was significantly higher in Group E than in Group C (4.7 ± 0.6 vs 4.2 ± 0.7, P < 0.001; 4.7 ± 0.5 vs 4.4 ± 0.7, P = 0.005). The postoperative AIS (4 [1, 6] vs 5 [2, 9], P = 0.012) and HADS-A (1 [0, 3] vs 2 [0, 6], P = 0.012) scores were significantly lower in Group E than in Group C. Hemodynamic and respiratory parameters were more stable in Group E than in Group C, with the lower opioids consumption of sufentanil (0 [0, 4] vs 5 [2.5, 7.7], P < 0.001) and remifentanil (700 [480, 900] vs 800 [500, 1200], P = 0.023) in Group E compared to Group C. On ordinal logistics regression, postoperative sleep quality (OR, 0.70; 95% CI, 0.62– 0.79), anxiety level (OR, 0.77; 95% CI, 0.62– 0.95) and recovery time in post-anesthesia care unit (PACU) (OR, 0.69; 95% CI, 0.56– 0.98) were identified as significant predictors associated with patient satisfaction.Conclusion: A subanesthetic dose of esketamine (0.15– 0.3 mg/kg/h) as an adjuvant can improves the sedative and analgesic effects of dexmedetomidine and remifentanil during anesthesia for liposuction surgery.Clinical Trial Registration: ChiCTR2400080363.Keywords: esketamine, sedation, analgesia, satisfaction, liposuction

Xianjun Xiao,1,&ast; Peiwen Xue,1,&ast; Xiangyun Yan,2,&ast; Yanqiu Li,2,&ast; Yunzhou Shi,2 Haiyan Qin,2 Di Qin,2 Wei Cao,2 Zihao Zou,2 Lu Wang,2 Rongjiang Jin,1 Ying Li,2 Junpeng Yao,2 Juan Li1,3 1School of Health Preservation and Rehabilitation, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, People’s Republic of China; 2Acupuncture and Tuina School, Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, 610075, People’s Republic of China; 3Affiliated Sichuan Provincial Rehabilitation Hospital of Chengdu University of TCM, Chengdu, Sichuan, 611135, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junpeng Yao; Juan Li, Email yjp@cdutcm.edu.cn; 785939016@qq.comBackground: Emerging evidence links gut microbiota and their by-products, notably short-chain fatty acids (SCFAs), to urticaria. This study employs multiple Mendelian Randomization (MR) analyses to unravel the complex interactions among gut microbiota, SCFAs, and different subtypes of urticaria, aiming to elucidate the underlying mechanisms and enhance future clinical research.Methods: We analyzed published genome-wide association study (GWAS) summary statistics to identify associations between gut microbiota and three common subtypes of urticaria: spontaneous, dermatographic, and temperature-triggered. Initial two-sample and reverse MR analyses explored the causality in these relationships. Subsequent multivariate MR analyses investigated the role of SCFAs in modulating these interactions, with multiple sensitivity analyses to ensure robustness.Findings: Specific taxa were differently associated with various urticaria subtypes. From microbiota to urticaria: one taxon was negatively associated with dermatographic urticaria; seven taxa were negatively associated and four positively associated with temperature-triggered urticaria; four taxa were negatively associated and six positively associated with spontaneous urticaria. Conversely, from urticaria to microbiota: five taxa were negatively associated with dermatographic urticaria; four were negatively and two positively associated with temperature-triggered urticaria; and two were negatively associated with spontaneous urticaria. These associations were observed at a nominal significance level (P < 0.05). After applying Bonferroni correction for multiple testing, these associations did not reach statistical significance. The observed trends, however, provide insights into potential microbiota-urticaria interactions. Multivariate MR analyses elucidated the role of SCFAs, particularly acetate, which plays a crucial role in modulating immune response. Adjusting for acetate revealed direct effects of Actinobacteria, Bifidobacteriales, and Bifidobacteriaceae on spontaneous urticaria, with corresponding mediation effects of − 22%, − 24.9%, and − 24.9% respectively. Similarly, adjustments for Alcaligenaceae and Betaproteobacteria indicated significant negative effects of acetate on dermatographic and spontaneous urticaria, with mediation effects of − 21.7% and − 23.7%, respectively.Conclusion: This study confirms the interconnected roles of gut microbiota, SCFAs, and urticaria. It highlights SCFAs’ potential mediating role in influencing urticaria through microbiota, providing insights for future therapeutic strategies.Keywords: urticaria, short-chain fatty acids, gut microbiota, gut-skin axis, Mendelian randomization

Zhiying Yang,1,&ast; Shun Yao,1,2,&ast; Yichong Xu,1 Xiaoqing Zhang,1,2 Yuan Shi,1,2 Lijun Wang,1,2 Donghong Cui1,2 1Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Shanghai Key Laboratory of Psychotic Disorders, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Donghong Cui, Email manyucc@126.comBackground: Schizophrenia is a devastating mental disease with high heritability. A growing number of susceptibility genes associated with schizophrenia, as well as their corresponding SNPs loci, have been revealed by genome-wide association studies. However, using SNPs as predictors of disease and diagnosis remains difficult. Here, we aimed to uncover susceptibility SNPs in a Chinese population and to construct a prediction model for schizophrenia.Methods: A total of 210 participants, including 70 patients with schizophrenia, 70 patients with bipolar disorder, and 70 healthy controls, were enrolled in this study. We estimated 14 SNPs using published risk loci of schizophrenia, and used these SNPs to build a model for predicting schizophrenia via comparison of genotype frequencies and regression. We evaluated the efficacy of the diagnostic model in schizophrenia and control patients using ROC curves and then used the 70 patients with bipolar disorder to evaluate the model’s differential diagnostic efficacy.Results: 5 SNPs were selected to construct the model: rs148415900, rs71428218, rs4666990, rs112222723 and rs1716180. Correlation analysis results suggested that, compared with the risk SNP of 0, the risk SNP of 3 was associated with an increased risk of schizophrenia (OR = 13.00, 95% CI: 2.35– 71.84, p = 0.003). The ROC-AUC of this prediction model for schizophrenia was 0.719 (95% CI: 0.634– 0.804), with the greatest sensitivity and specificity being 60% and 80%, respectively. The ROC-AUC of the model in distinguishing between schizophrenia and bipolar disorder was 0.591 (95% CI: 0.497– 0.686), with the greatest sensitivity and specificity being 60% and 55.7%, respectively.Conclusion: The SNP risk score prediction model had good performance in predicting schizophrenia. To the best of our knowledge, previous studies have not applied SNP-based models to differentiate between cases of schizophrenia and other mental illnesses. It could have several potential clinical applications, including shaping disease diagnosis, treatment, and outcomes.Keywords: schizophrenia, SNP, diagnostic model, bipolar disorder, differential diagnosis

Fujie Jiang,1,&ast; Shuling Liu,1,&ast; Lu Wang,1 Huifang Chen,1 Yao Huang,2 Ying Cao,2 Xiaoxia Wang,1 Meng Lin,1 Jiuquan Zhang1 1Department of Radiology, Chongqing University Cancer Hospital, Chongqing Key Laboratory for Intelligent Oncology in Breast Cancer (iCQBC), Chongqing, 400030, People’s Republic of China; 2School of Medicine, Chongqing University, Chongqing, 400030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiuquan Zhang; Meng Lin, Department of Radiology Chongqing University Cancer Hospital, No. 181 Hanyu Road, Shapingba District, Chongqing, 400030, People’s Republic of China, Tel/Fax +86-23-65079339, Email zhangjq_radiol@foxmail.com; 15823113338@139.comPurpose: Chemotherapy mediated by Reactive oxygen species (ROS)-responsive drug delivery systems can potentially mitigate the toxic side effects of chemotherapeutic drugs and significantly enhance their therapeutic efficacy. However, achieving precise targeted drug delivery and real-time control of ROS-responsive drug release at tumor sites remains a formidable challenge. Therefore, this study aimed to describe a ROS-responsive drug delivery system with specific tumor targeting capabilities for mitigating chemotherapy-induced toxicity while enhancing therapeutic efficacy under guidance of Fluorescence (FL) and Magnetic resonance (MR) bimodal imaging.Methods: Indocyanine green (ICG), Doxorubicin (DOX) prodrug pB-DOX and Superparamagnetic iron oxide (SPIO, Fe3O4) were encapsulated in poly(lactic-co-glycolic acid) (PLGA) by double emulsification method to prepare ICG/ pB-DOX/ Fe3O4/ PLGA nanoparticles (IBFP NPs). The surface of IBFP NPs was functionalized with mammaglobin antibodies (mAbs) by carbodiimide method to construct the breast cancer-targeting mAbs/ IBFP NPs (MIBFP NPs). Thereafter, FL and MR bimodal imaging ability of MIBFP NPs was evaluated in vitro and in vivo. Finally, the combined photodynamic therapy (PDT) and chemotherapy efficacy evaluation based on MIBFP NPs was studied.Results: The multifunctional MIBFP NPs exhibited significant targeting efficacy for breast cancer. FL and MR bimodal imaging clearly displayed the distribution of the targeting MIBFP NPs in vivo. Upon near-infrared laser irradiation, the MIBFP NPs loaded with ICG effectively generated ROS for PDT, enabling precise tumor ablation. Simultaneously, it triggered activation of the pB-DOX by cleaving its sensitive moiety, thereby restoring DOX activity and achieving ROS-responsive targeted chemotherapy. Furthermore, the MIBFP NPs combined PDT and chemotherapy to enhance the efficiency of tumor ablation under guidance of bimodal imaging.Conclusion: MIBFP NPs constitute a novel dual-modality imaging-guided drug delivery system for targeted breast cancer therapy and offer precise and controlled combined treatment options.Keywords: targeted drug delivery, photodynamic therapy, ROS-responsive chemotherapy, bimodal imaging

Luyang Zhang,1,&ast; Yuan Luo,1,&ast; Jiewen Long,1 Yan Yin,1 Qin Fu,2 Lei Wang,1 Sandip Patil1 1Department of Haematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China; 2Department of Nursing, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sandip Patil; Lei Wang, Department of Haematology and Oncology, Shenzhen Children’s Hospital, 7019 Yitian Road, Shenzhen, Guangdong Province, People’s Republic of China, Tel +86-755-83008283, Email sandippatil1309@yahoo.com; 405112310@qq.comBackground: Oral mucositis (OM) poses a significant challenge in children undergoing hematopoietic stem cell transplantation (HSCT). There is a gap between clinical practice and the evidence, and nursing practices is not standardized.Objective: This study aims to evaluate the effectiveness of applying the evidence for preventing HSCT chemotherapy-induced OM in children and to elevate the nurses’ compliance to the evidence.Methods: Following the clinical evidence practice application model of the Joanna Briggs Institute (JBI) evidence-Based Care Center. The process included reviewing literature, extracting evidence, identifying gaps, developing audit criteria, conducting a baseline audit, creating an action plan, implementing evidence-based interventions, and assessing outcomes.Results: After the evidence implementation, 6 out of 12 audit criteria with poor compliance are significantly improved, with statistically significant differences (P< 0.05). The incidence of OM decreases, with a statistically significant difference (66.6% vs 36.7%, P=0.02). The incidence of grade I, II, III, and IV OM also decreases (30% vs 23.3%, 23.3% vs 13.4%, 10% vs 0%, and 3.3% vs 0%). Ultimately, the standardized oral care practice routine and workflows to prevent OM were established.Conclusion: Bridging the gap between evidence and clinical practice can standardize nurse behavior, decrease the incidence of OM, and lower the OM severity in children undergoing HSCT.Keywords: children, hematopoietic stem cell transplantation, oral mucositis, evidence-based practice

Dan Liu, Juan Tong, Erling Chen, Li Wang, Lei Xue, Xuhan Zhang, Na Zhao, Xing Hu, Changcheng Zheng Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui Province, People’s Republic of ChinaCorrespondence: Changcheng Zheng, Department of Hematology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Lujiang Road No. 17, Hefei, Anhui Province, 230001, People’s Republic of China, Email zhengchch1123@ustc.edu.cnBackground: The aim of the study was to evaluate the efficacy and safety of induction and consolidation with all-trans retinoic acid (ATRA) +arsenic trioxide (ATO) +anthracyclines and maintenance with ATRA +Realgar-Indigo naturalis formula (RIF) for high-risk APL.Methods: Twenty-one patients with high-risk APL treated with ATRA+ATO+ anthracyclines for induction and consolidation and ATRA+RIF for maintenance from 2012 to 2021 were analyzed. Endpoints include morphological complete remission (CR) and complete molecular remission (CMR), early death (ED) and relapse, survival and adverse events (AEs).Results: After induction treatment, all 21 patients (100%) achieved morphological CR and 14 people (66.7%) achieved CMR. Five of the 21 patients did not undergo immunological minimal residual disease (MRD) examination after induction; however, 14 of the remaining 16 patients were MRD negative (87.5%). The median time to achieve CR and CMR was 26 days (range: 16– 44) and 40 days (range: 22– 75), respectively. The cumulative probability of achieving CR and CMR in 45 days was 100% and 76.2% (95% CI: 56.9– 91.3%), respectively. All patients achieved CMR and MRD negativity after the three courses of consolidation treatment. The median follow-up was 66 months (25– 142), with no central nervous system relapse and bone marrow morphological or molecular relapse until now, and all patients survived with 100% overall survival and 100% event-free survival. Grade 4 adverse events (AEs) were observed in 3 patients (14.3%) during the induction period including arrhythmia (n = 1), pulmonary infection (n = 1) and respiratory failure (n = 1); and the most frequent grade 3 AEs were pulmonary infection, accounting for 62.0% and 28.6%, respectively, during induction and consolidation treatment, followed by neutropenia, accounting for 42.9% and 38.1%, respectively.Conclusion: For newly diagnosed high-risk APL patients, induction and consolidation with ATRA+ATO+anthracyclines and maintenance with ATRA+RIF is a highly curative treatment approach.Keywords: high-risk acute promyelocytic leukemia, all-trans retinoic acid, arsenic trioxide, realgar–Indigo naturalis formula, anthracyclines, event-free survival

Rong Huang,1,&ast; Jun Zeng,1,&ast; Xiaoze Yu,1 Yunke Shi,2 Na Song,1 Jie Zhang,1 Peng Wang,1 Min Luo,1 Yiming Ma,2 Chuang Xiao,1 Lueli Wang,1 Guanhua Du,3 Hongyan Cai,4 Weimin Yang1 1School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 2The First Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China; 3Key Laboratory of Drug Target Research and Drug Screen, Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, People’s Republic of China; 4The Second Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weimin Yang, School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural Products, Kunming Medical University, Kunming, Yunnan, 650500, People’s Republic of China, Email ywmbessie@yeah.net Hongyan Cai, The Second Department of Cardiology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan, 650032, People’s Republic of China, Email caihy@ydyy.cnPurpose: Luteolin is a promising candidate for diabetic nephropathy due to its potential anti-inflammatory and anti-fibrotic properties. This study explored the molecular mechanisms through which luteolin combats fibrosis in DN.Methods: Potential targets affected by luteolin and genes associated with DN were collected from databases. Overlapping targets between luteolin and diabetic nephropathy were identified through Venn analysis. A protein-protein interaction network was constructed using these common targets, and critical pathways and targets were elucidated through GO and KEGG analysis. These pathways and targets were confirmed using a streptozotocin-induced mouse model. Luteolin was administered at 45 mg/kg and 90 mg/kg. Various parameters were evaluated, including body weight, blood glucose levels, and histopathological examinations. Protein levels related to energy metabolism, inflammation, and fibrosis were quantified.Results: Fifty-three targets associated with luteolin and 36 genes related to diabetic nephropathy were extracted. The AGE-RAGE signaling pathway was the key pathway impacted by luteolin in diabetic nephropathy. Key molecular targets include TGF-β, IL-1β, and PPARG. Luteolin reduced body weight and blood glucose levels, lowered the left kidney index, and improved insulin and glucose tolerance. Furthermore, luteolin mitigated inflammatory cell infiltration, basement membrane thickening, and collagen deposition in the kidney. Luteolin up-regulated the protein expression of p-AMPKα (Th172) while simultaneously down-regulated the protein expression of p-NF-&kgreen;B (p65), NLRP3, TGF-β 1, α-SMA, and Collagen I.Conclusion: Luteolin mitigated renal fibrosis by alleviating energy metabolism disruptions and inflammation by modulating the AMPK/NLRP3/TGF-β signaling pathway.Keywords: diabetic nephropathy, network pharmacology, inflammation, TGF-β, fibrosis

Wenguang Deng, Zhiming Zeng, Qingyan Liu, Jingjing Deng, Liyu Wang, Hui Li, Yuenong Zhang The Anesthesiology Surgery Center of The Third Affiliated Hospital of Sun Yat-sen University-Yuedong Hospital, Guangdong, People’s Republic of ChinaCorrespondence: Yuenong Zhang, Email 36856665@qq.comBackground: This study explored the effects of different doses of remimazolam tosilate (RT) and propofol combined with remifentanil anesthesia on hemodynamic and inflammatory responses in patients undergoing laparoscopic surgery.Subjects and Methods: Ninety patients with a BMI of less than 35 kg/m², classified as ASA II–III and scheduled for laparoscopic surgery, were enrolled in this study. Patients were divided into three groups: low-dose RT group (A), high-dose RT group (B), and propofol group (C). The changes in hemodynamic indices such as SBP, DBP, HR, MAP, and inflammatory response indices such as IL-6, SAA, CRP, and PCT, along with extubation time and doses of sufentanil, remifentanil, urapidil, and phenylephrine, were compared among the three groups.Results: There were no statistically significant differences in extubation time, doses of sufentanil and remifentanil, or the usage rates and average doses of urapidil and phenylephrine between the three groups. The average dose of phenylephrine in group A was lower than in group B and group C, with a statistically significant difference. There were no statistically significant differences among the groups in SBP, DBP, HR, and MAP from T0 to T2, nor in IL-6, SAA, CRP, or PCT levels.Conclusion: Using RT for induction and maintenance of anesthesia in laparoscopic surgery ensures stable hemodynamic and inflammatory responses in patients. Low-dose RT may reduce the usage rate and dose of vasopressors such as phenylephrine during surgery.Keywords: remimazolam tosilate, propofol, remifentanil, hemodynamic, inflammatory, laparoscopic surgery

Rui Shen,1,2,&ast; Kebin Cheng,3,&ast; Guanyi Li,1 Zhendong Pan,4 Xijier Qiaolongbatu,1 Yuting Wang,1 Cui Ma,1 Xucong Huang,1 Li Wang,1 Wenjing Li,1 Yuanyuan Wang,2 Lili Jing,1 Guorong Fan,2 Zhenghua Wu2 1School of Pharmaceutical Sciences, Shanghai Jiao Tong University, Shanghai, 200240, People’s Republic of China; 2Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200080, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, 200433, People’s Republic of China; 4Department of Clinical Pharmacy, Eye and ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhenghua Wu, Department of Clinical Pharmacy, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, No. 85 Wujin Road, Shanghai, 200080, People’s Republic of China, Tel +86-159-0161-7923, Email wuzhenghua@sjtu.edu.cnPurpose: Alisma orientale (AO, Alisma orientale (Sam). Juzep) has been widely employed for the treatment of macular edema (ME) in traditional Chinese medicine due to its renowned water-relief properties. Nonetheless, the comprehensive investigation of AO in alleviating ME remained unexplored. This study aims to identify the active components of AO that target the eye and investigate its pharmacological effects and mechanisms on ME.Methods: The study commenced with UPLC-Triple-TOF/MS analysis to identify the primary constituents of AO. Zebrafish eye tissues were then analyzed after a five-day administration of AO to detect absorbed components and metabolites. Subsequently, network pharmacology, molecular docking, and molecular dynamics simulations were employed to predict the mechanisms of ME treatment via biological target pathways. In vivo experiments were conducted to corroborate the pharmacological actions and mechanisms.Results: A total of 7 compounds, consisting of 2 prototype ingredients and 5 metabolites (including isomers), were found to traverse the blood-eye barrier and localized within eye tissues. Network pharmacology results showed that AO played a role in the treatment of ME mainly by regulating the pathway network of PI3K-AKT and MAPK with TNF-α centered. Computational analyses suggested that 11-dehydro-16-oxo-24-deoxy-alisol A, a metabolite of alisol A, mitigates edema through TNF-α inhibition. Furthermore, zebrafish fundus confocal experiments and HE staining of eyes confirmed the attenuating effects of alisol A on fundus angiogenesis and ocular edema, representing the first report of AO’s ME-inhibitory effects.Conclusion: In this study, computational analyses with experimental validation were used to understand the biological activity and mechanism of alisol A in the treatment of ME. The findings shed light on the bioactive constituents and pharmacological actions of AO, offering valuable insights and a theoretical foundation for its clinical application in managing ME. Keywords: Alisma orientale, macular edema, network pharmacology, zebrafish, TNF-&#x03B1

Yuan Huang,1,&ast; Hong Yang,2,&ast; Rui Ding,1,&ast; Li Wang,3 Ji Li,2 Wenbo Li,4 Xuzhen Qin,1 Yingchun Xu,1 Jiaming Qian2 1Department of Laboratory Medicine, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 2Department of Gastroenterology, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China; 3Department of Epidemiology and Health Statistics, Institute of Basic Medicine, Peking Union Medical College, Beijing, People’s Republic of China; 4Department of Ultrasound, Peking Union Medical College Hospital & Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuzhen Qin; Jiaming Qian, Email qxz_01@163.com; qianjiaming1957@126.comObjective: Serum pepsinogen (PG) is a good indicator of atrophic changes in the gastric mucosa. Gastric mucosal atrophy is a high-risk factor for gastric cancer. Serological testing for PG combined with endoscopy can help to improve gastric cancer screening. In this study, we established the reference ranges of serum PG-I, PG-II, and the PG-I/II ratio (PGR) in the Chinese population by chemiluminescence immunoassay (CLIA) and enzyme-linked immunosorbent assay (ELISA). Besides, in the real world, doctors are often confused by the results of different testing platforms. Thus, a comparison of methods CLIA and ELISA was performed.Methods: 2904 individuals were enrolled from six regions in China as part of the Chinese Adult Digestive Diseases Surveillance (2016) program. The individuals completed questionnaires and volunteered to undergo examinations, including gastroscopy, urea breath test, abdominal ultrasound examination and routine serologic tests. Serum was collected to measure PGs (including PG-I, PG-II and PGR) by CLIA and ELISA. Participants who were found obvious abnormalities or absent from the examinations were excluded. Ultimately, 747 healthy individuals were enrolled in this study. The Kolmogorov–Smirnov test was used to assess the distribution of variables. The Kruskal–Wallis H or Mann–Whitney U-tests were used to compare different sex, age, and geographical groups. The 95% reference ranges of PGs obtained by the two methods were established according to document CLSI-EP28-A3, with covariates of sex, age, and region. Spearman correlation analysis, linear regression analysis and allowable total error (ATE) zone analysis were utilized for comparing the two methods.Results: On overall, the 95% reference ranges of PG-I, PG-II, and PGR measured by CLIA were 23.00– 110.64 ng/mL, 2.50– 19.13 ng/mL, and 3.87– 13.30, respectively. Meanwhile, the reference ranges of PG-I, PG-II, and PGR measured by ELISA were 36.93– 205.06 ng/mL, 1.65– 17.96 ng/mL, and 7.50– 33.60, respectively. Both PG-I and PG-II levels measured by the two platforms were found to be influenced by sex and age. PGR measured by CLIA was influenced by age but not by sex, while PGR measured by ELISA was not affected by either age or sex. Regional factors did not significantly impact the PG results, except for PG-I detected by ELISA. Ultimately, reference ranges for PGs were established based on age and sex stratification. Additionally, the Spearman correlation analysis revealed that the correlation coefficients for PG-I, PG-II, and PGR detected by the two methods were 0.899, 0.887, and 0.777, respectively, indicating a strong correlation between the two methods. The regression equation for the PG levels detected by two methods was obtained through linear regression analysis. The ATE analysis provided a visual depiction of the consistency between the two methods, clearly indicating the poor agreement between them.Conclusion: This study established the reference ranges of PGs by strict and intact enrollment standard. In addition, the results indicated a strong linear relationship between the two methods, yet with a clear bias, which was valuable for laboratory interpretation.Keywords: pepsinogen, reference range, gastric cancer

Hui Sun,&ast; Yan Liu,&ast; Ling Wang, Xiaoling Liu, WenHui Wang Department of Tuberculosis, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Wang; Xiaoling Liu, Department of Tuberculosis, The Second Hospital of Nanjing, Nanjing University of Chinese Medicine, No. 1-1 Zhongfu Road, Nanjing, Jiangsu Province, 210000, People’s Republic of China, Tel +86 83626512, Email liuxiaoling15l@163.comObjective: Accurate diagnosis is very important to block the transmission of tuberculosis. The quality of sputum culture affects the diagnostic accuracy. The quality of sputum samples is not optimistic. Therefore, this study investigated whether health care failure mode and effect analysis (HFMEA) can improve specimen quality and detection efficiency in sputum specimen management in tuberculosis departments.Methods: This study is a non-randomized controlled trial study. A convenience sampling method was used to select 110 patients who visited the Department of Tuberculosis of the Second Hospital of Nanjing from September to November 2022 and December 2022 to February 2023 as the control group and the experimental group. Control groups followed standard operating procedures for sputum specimen collection. In the experimental group, HFMEA model was used to control the quality on this basis. After 3 months of intervention, the qualified rate and positive detection rate of sputum samples were compared between the two groups.Results: A total of 634 sputum specimens were included in the experimental group and 647 in the control group. Compared with the control group, the qualification rate of sputum specimens was higher in the experimental group (84.54% vs 79.13%); the positive detection rates of the X-Pert assay (27.88% vs 16.19%), sputum culture (20.29% vs 12.68%), and sputum smear (22.29% vs 15.81%) were all higher in the experimental group (all P < 0.05). Patients in the experimental group had higher knowledge mastery and nurse sputum sample management scores (P < 0.05). However, patient satisfaction with sputum specimen management in the experimental group was lower than in the control group (7.72 ± 0.74 vs 8.38 ± 0.85, P < 0.001).Conclusion: The application of the HFMEA model in sputum specimen management can effectively improve specimen quality and positive detection rates.Keywords: healthcare failure mode and effect analysis (HFMEA), tuberculosis, sputum, nursing care, risk management

Xiaowei Zhou, Liyong Zou, Haoyue Deng, Yuanqun Zhou, Yue Wu, Xingnan Ouyang, Liangming Liu, Li Wang,&ast; Tao Li&ast; Department of Shock and Transfusion, Army Medical Center of Army Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Wang; Tao Li, Department of Shock and Transfusion, Army Medical Center of Army Medical University, Chongqing, People’s Republic of China, Email wangli8134@163.com; lt200132@tmmu.edu.cnPurpose: Cold seawater immersion aggravates hemorrhagic shock-induced homeostasis imbalance and organ dysfunction, leading to increased mortality. Previous studies have shown that treatments targeting oxidative stress and mitochondrial dysfunction have limited efficacy for cold seawater immersion combined with hemorrhagic shock (SIHS). Thus, the mechanisms responsible for SIHS need further investigation.Methods and Results: Data from the hemorrhagic shock transcriptome and cold seawater immersion targets used for bioinformatics analysis revealed the involvement of endoplasmic reticulum stress (ERS) in SIHS occurrence and progression. Based on these findings, the effects and possible mechanism of inhibiting ERS in SIHS rats were investigated. SIHS causes a lethal triad and impairment of vital organ function, leading to death. Compared to lactated Ringer’s solution, the ERS inhibitor 4-phenylbutyric acid (PBA)significantly ameliorated acidosis and coagulopathy and protected vital organ function while prolonging survival and the golden treatment time. Through target screening and validation, 7 targets were identified for the ERS inhibitor PBA for the treatment of SIHS, among which S1PR1, MMP8 and CFTR may play more important roles.Conclusion: ERS plays a crucial role in the progression of SIHS. Inhibition of ERS caused by SIHS alleviates the lethal triad, protects organ function, and prolongs survival and the golden treatment time. The ERS inhibitor PBA may be an effective therapeutic measure for treating SIHS.Keywords: cold seawater immersion, hemorrhagic shock, lethal triad, organ function, ER stress, 4-phenylbutyric acid

Mengli Li,1,&ast; Tongtong Yin,1,&ast; Jiaying Qi,1 Minhao Shi,1 Fangfang Wang,1 Zhiyu Mao,1 Hui Zhang,1,2 Li Wang1 1School of Nursing, Suzhou Medical College of Soochow University, Suzhou, Jiangsu, People’s Republic of China; 2School of Nursing, Suzhou Vocational Health College, Suzhou, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Wang; Hui Zhang, Email li-wang-1@suda.edu.cn; zhanghuichange@sina.comObjective: To explore the cut-off values and health evaluations of upper arm circumference (AC) and calf circumference (CC) on sarcopenia in Chinese community-dwelling older people.Methods: In this cross-sectional study, AC, CC, handgrip strength, muscle mass and gait speed were measured in 1537 Chinese community-dwelling older people in Sub-study 1. Correlation analysis, receiver operator characteristic curve (ROC curve) analysis, and consistency analysis were used for determination of AC and CC cut-off values for sarcopenia diagnosis (sarcopenia-AC and CC). Thereafter, 269 participants accepted additional assessments on physical function, body composition and muscle strength in Sub-study 2. T-test or Mann-Whitney U-test was used to explore the differential effects of sarcopenia-AC and CC on health indicators between sarcopenic and non-sarcopenic participants.Results: In Sub-study 1, the Area Under ROC (AUC) of AC and CC for sarcopenia screening were greater than 0.700 (P< 0.05). The cut-off values, sensitivity and specificity of AC and CC on sarcopenia in males were 25.9 cm (86.0%, 83.6%) and 33.7 cm (90.7%, 81.4%) whereas in females were 26.5 cm (70.8%, 69.7%) and 33.0 cm (86.5%, 69.4%), respectively. In Sub-study 2, the participants with sarcopenia-AC or sarcopenia-CC showed lower muscle strength and lower fat and muscle mass than the ones without (P< 0.05). Additionally, males instead of females with sarcopenia-AC or sarcopenia-CC showed worse performance in time-up and go test and 6-Minute Walk Test (P< 0.05). However, the 30-second chair stand test was not different between participants with and without sarcopenia-AC or sarcopenia-CC in both sexes.Conclusion: We found accurate and Chinese population targeted cut-off values of AC and CC on sarcopenia diagnosis (25.9 cm and 33.7 cm in males; 26.5 cm and 33.0 cm in females) and a good evaluation effect of AC and CC on fat and muscle mass, muscle strength and physical functions in males, not females.Keywords: sarcopenia, upper arm circumference, calf circumference, health assessment

Lei Liu,1,&ast; Shanshan Liu,2,&ast; Fuyan Bai,1 Yangxin Deng,1 Xinhuan Zhang,1 Li Wang3 1Department of Endocrinology, the Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, People’s Republic of China; 2General Gynecology, the Tai ‘an Central Hospital, Taian, Shandong, People’s Republic of China; 3Department of Pharmacy, the Second Affiliated Hospital of Shandong First Medical University, Taian, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinhuan Zhang; Li Wang, Email zhangxh22009@126.com; suxinlan1027@126.comBackground: An important factor in the pathogenesis of polycystic ovary syndrome (PCOS) is chronic low-grade inflammation. However, the exact pathophysiology of PCOS is currently unknown, which makes clinical diagnosis and the development of effective treatments more difficult. We aimed to investigate the role of the inflammatory response in initiating and progressing PCOS.Methods: 13 control granulosa cell samples and 15 granulosa cell samples from patients with PCOS were obtained from the GSE102293, GSE34526, and GSE5850 datasets. The gene set variation analysis (GSVA) method was used to calculate the inflammatory response score. Subsequently, the genes associated with inflammation in the hub were identified using differential expression analysis and weighted gene co-expression network analysis (WGCNA). The findings were confirmed by analysis of independent datasets and examination of clinical samples by qRT-PCR analysis. A consensus cluster analysis was conducted to categorize the PCOS samples into subtypes related to inflammation. Functional enrichment and analysis of immune cell infiltration were conducted to explore the potential mechanisms involved. Additionally, the CMap database was utilized to predict potential drugs, and the results were confirmed through molecular docking.Results: During the training cohort analysis, we identified five distinct genes (TGFBR2, ICAM3, WIPF1, SLC11A1, and NCF2) that could serve as potential diagnostic markers for PCOS. The expression levels of these genes were confirmed through validation in both the test set and clinical samples. In training cohort, two distinct inflammatory patterns (C1 and C2) were identified, and the C2 subtype exhibited activated immune- and inflammation-related pathways. Esmolol was shown to have potential as a drug to treat PCOS and it showed good results for molecular binding at TGFBR2, ICAM3, WIPF1, SLC11A1, and NCF2 proteins.Conclusion: Five diagnostic biomarkers and two inflammation-related molecular types associated with PCOS were identified, and esmolol was a potential drug for PCOS treatment. Our findings provided new diagnostic markers and potential small-molecule drugs for PCOS diagnosis and prevention.Keywords: polycystic ovary syndrome, inflammatory response, diagnostic biomarkers, molecular subtypes, esmolol

Lingling Wang,1 Huiguo Liu,1 Ling Zhou,1 Pengdou Zheng,1 Hai Li,2,3 Huojun Zhang,4,&ast; Wei Liu2,3,&ast; 1Department of Respiratory and Critical Care Medicine, Key Laboratory of Pulmonary Diseases of Health Ministry, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Geriatrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 3Key Laboratory of Vascular Aging, Ministry of Education, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 4Department of Respiratory and Critical Care Medicine, Renmin Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huojun Zhang, Email hjzhang@whu.edu.cn; Wei Liu, Email 404793938@tjh.tjmu.edu.cnAbstract: Obstructive sleep apnea (OSA), a common sleep-disordered breathing condition, is characterized by intermittent hypoxia (IH) and sleep fragmentation and has been implicated in the pathogenesis and severity of nonalcoholic fatty liver disease (NAFLD). Abnormal molecular changes mediated by IH, such as high expression of hypoxia-inducible factors, are reportedly involved in abnormal pathophysiological states, including insulin resistance, abnormal lipid metabolism, cell death, and inflammation, which mediate the development of NAFLD. However, the relationship between IH and NAFLD remains to be fully elucidated. In this review, we discuss the clinical correlation between OSA and NAFLD, focusing on the molecular mechanisms of IH in NAFLD progression. We meticulously summarize clinical studies evaluating the therapeutic efficacy of continuous positive airway pressure treatment for NAFLD in OSA. Additionally, we compile potential molecular biomarkers for the co-occurrence of OSA and NAFLD. Finally, we discuss the current research progress and challenges in the field of OSA and NAFLD and propose future directions and prospects.Keywords: intermittent hypoxia, hypoxia-inducible factor 1 alpha, nonalcoholic fatty liver disease, oxidative stress, dyslipidemia, leptin resistance

Chenguang Jia,1,&ast; Xiaowei Yao,1,&ast; Zhaoliang Dong,1 Lianbo Wang,1 Fangchao Zhao,2,&ast; Jianguo Gao,1,&ast; Tao Cai3,&ast; 1Department of Orthopedics, Hebei Chest Hospital, Shijiazhuang, Hebei, People’s Republic of China; 2Department of Thoracic Surgery, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, People’s Republic of China; 3Hebei Chest Hospital, Shijiazhuang, Hebei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Cai, Hebei Chest Hospital, No. 372, Shengli North Street, Shijiazhuang, Hebei, People’s Republic of China, Tel/Fax +86-311-86911080, Email caitaoxiongke@163.comBackground: Post-translational modifications (PTM) significantly influence the pathogenesis and progression of diverse neoplastic conditions. Nevertheless, there has been limited research focusing on the potential of PTM-related genes (PTMRGs) as tumor biomarkers for predicting the survival of specific patients.Methods: The datasets utilized in this research were obtained from the TARGET and GEO repositories, respectively. The gene signature was constructed through the utilization of LASSO Cox regression method. GSEA and GO was used to identify hub pathways associated with risk genes. The functionality of risk genes in osteosarcoma (OS) cell lines was verified through the implementation of the CCK-8 assay, cell cycle analysis, and immunofluorescence assay.Results: Two distinct PTM patterns and gene clusters were finally determined. Significant differences in the prognosis of patients were found among two different PTM patterns and gene clusters, so were in the function enrichment and the landscape of TME immune cell infiltration. Moreover, we examined two external immunotherapy cohorts and determining that patients in the low-risk group was more likely to profit from immunotherapy. In addition, we mapped the expression of the genes in the signature in distinct cells using single-cell analysis. Finally, CCK-8 assay, cell cycle analysis, and immunofluorescence assay were utilized to confirm that RAD21 was expressed and functioned in OS.Conclusion: In conclusion, this study elucidated the potential link between PTM and immune infiltration landscape of OS for the first time and provided a new assessment protocol for the precise selection of treatment strategies for patients with advanced OS.Keywords: post-translational modifications, osteosarcoma, immune microenvironment, immune therapy, RAD21

Shixin Ma,1,2 Fei Li,2 Lunqing Wang2 1Graduate School, Dalian Medical University, Dalian, Liaoning, 116000, People’s Republic of China; 2Department of Thoracic Surgery, Qingdao Municipal Hospital, Qingdao, Shandong, 266071, People’s Republic of ChinaCorrespondence: Lunqing Wang, Department of Thoracic Surgery, Qingdao Municipal Hospital, No. 5 Donghai Middle Road, Qingdao, People’s Republic of China, Tel +86 532 87077952, Email wanglunqing1973@163.comPurpose: The purpose of this study was to investigate the predictive value of Pan-Immune-Inflammation Value (PIV) combined with the PILE score for immunotherapy in patients with advanced non-small cell lung cancer (NSCLC) and to construct a nomogram prediction model to provide reference for clinical work.Patients and Methods: Patients with advanced NSCLC who received ICIs treatment in Qingdao Municipal Hospital from January 2019 to December 2021 were selected as the study subjects. The chi-square test, Kaplan-Meier survival analysis, and Cox proportional risk regression analysis were used to evaluate the prognosis. The results were visualized by a nomogram, and the performance of the model was judged by indicators such as the area under the subject operating characteristic curve (AUC) and C-index. The patients were divided into high- and low-risk groups by PILE score, and the prognosis of patients in different risk groups was evaluated.Results: Multivariate Cox regression analysis showed that immune-related adverse events (irAEs) were prognostic factors for overall survival (OS) improvement, and ECOG PS score ≥ 2, bone metastases before treatment, and high PIV expression were independent risk factors for OS. The C index of OS predicted by the nomogram model is 0.750 (95% CI: 0.677– 0.823), and the Calibration and ROC curves show that the model has good prediction performance. Compared with the low-risk group, patients in the high-risk group of PILE were associated with a higher inflammatory state and poorer physical condition, which often resulted in a poorer prognosis.Conclusion: PIV can be used as a prognostic indicator for patients with advanced NSCLC treated with ICIs, and a nomogram prediction model can be constructed to evaluate the survival prediction of patients, thus contributing to better clinical decision-making and prognosis assessment.Keywords: non-small cell lung cancer, immune checkpoint inhibitors, pan-immune-inflammation value, prognosis, nomogram

Leitong Wang, Baoshan Li, Dongkai Cheng Embryo Laboratory, Jinghua Hospital of Shenyang, Shenyang, Liaoning Province, 110000, People’s Republic of ChinaCorrespondence: Dongkai Cheng, Embryo Laboratory, Jinghua Hospital of Shenyang, No. 83, Zhongshan Road, Heping District, Shenyang, Liaoning Province, 110000, People’s Republic of China, Tel +86 17766533209, Email cheng_dongkai@126.comAbstract: Recent research findings have highlighted the pivotal roles played by lncRNAs in both normal human development and disease pathogenesis. LncRNAs are expressed in oocytes and early embryos, and their expression levels change dynamically once the embryonic genome is activated during early human embryonic development. Abnormal expression of lncRNAs was found in follicular fluid, granulosa cells and oocytes of patients, and these lncRNAs were related to cell proliferation and apoptosis, nuclear maturation and follicle development. The expression levels of some lncRNAs in cumulus cells demonstrate correlations with the quality of oocytes and early embryos. This paper aims to present a comprehensive overview of the influence of LncRNAs on the developmental process of human oocytes as well as their involvement in certain infertility-related diseases.Keywords: cumulus cells, female infertility, lncRNA, oocyte

Li`ao Wang,1 Zhiming Zheng,2 Jia Zheng,2 Guifeng Zhang,3 Zheng Wang4 1Clinical College of Neurology, Neurosurgery and Neurorehabilitation, Tianjin Medical University, Tianjin, 300203, People’s Republic of China; 2Department of Neurosurgery, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, 250021, People’s Republic of China; 3Department of Neurology, Liaocheng People’s Hospital, Liaocheng, 252004, People’s Republic of China; 4Department of Neurosurgery, Liaocheng Traditional Chinese Medicine Hospital, Liaocheng, 252000, People’s Republic of ChinaCorrespondence: Guifeng Zhang, Department of Neurology, Liaocheng People’s Hospital, Liaocheng, 252004, People’s Republic of China, Tel +86 18063513155, Email GFZhangNo.1@gmail.com Zheng Wang, Department of Neurosurgery, Liaocheng Traditional Chinese Medicine Hospital, Liaocheng, 252000, People’s Republic of China, Tel +86 18063560328, Email zhengyimingdao@gmail.comPurpose: Low-grade gliomas (LGG) are common brain tumors with high mortality rates. Cancer cell invasion is a significant factor in tumor metastasis. Novel biomarkers are urgently needed to predict LGG prognosis effectively.Methods: The data for LGG were obtained from the Bioinformatics database. A consensus clustering analysis was performed to identify molecular subtypes linked with invasion in LGG. Differential expression analysis was performed to identify differentially expressed genes (DEGs) between the identified clusters. Enrichment analyses were then conducted to explore the function for DEGs. Prognostic signatures were placed, and their predictive power was assessed. Furthermore, the invasion-related prognostic signature was validated using the CGGA dataset. Subsequently, clinical specimens were procured in order to validate the expression levels of the distinct genes examined in this research, and to further explore the impact of these genes on the glioma cell line LN229 and HS-683.Results: Two invasion-related molecular subtypes of LGG were identified, and we sifted 163 DEGs between them. The enrichment analyses indicated that DEGs are mainly related to pattern specification process. Subsequently, 10 signature genes (IGF2BP2, SRY, CHI3L1, IGF2BP3, MEOX2, ABCC3, HOXC4, OTP, METTL7B, and EMILIN3) were sifted out to construct a risk model. Besides, the survival (OS) in the high-risk group was lower. The performance of the risk model was verified. Furthermore, a highly reliable nomogram was generated. Cellular experiments revealed the ability to promote cell viability, value-addedness, migratory ability, invasive ability, and colony-forming ability of the glioma cell line LN229 and HS-683. The qRT-PCR analysis of clinical glioma samples showed that these 10 genes were expressed at higher levels in high-grade gliomas than in low-grade gliomas, suggesting that these genes are associated with poor prognosis of gliomas.Conclusion: Our study sifted out ten invasion-related biomarkers of LGG, providing a reference for treatments and prognostic prediction in LGG.Keywords: LGG, prognosis, invasion, overall survival, EMILIN3

Hong-Mei Shu,1,&ast; Chang-Qing Lin,1 Bei He,1 Wang Wang,1 Ling Wang,1 Ting Wu,1 Hai-Juan He,1 Hui-Juan Wang,1 He-Ping Zhou,2 Guo-Zheng Ding1,&ast; 1Department of Pulmonary and Critical Care Medicine, Anqing Municipal Hospital, Anhui, People’s Republic of China; 2Neurosurgery Department, Anqing Municipal Hospital, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong-Mei Shu, Email shuxin501@163.comBackground: Chronic obstructive pulmonary disease (COPD) stands as a predominant cause of global morbidity and mortality. This study aims to elucidate the relationship between pyroptosis-related genes (PRGs) and COPD diagnosis in the context of immune infiltration, ultimately proposing a PRG-based diagnostic model for predicting COPD outcomes.Methods: Clinical data and PRGs of COPD patients were sourced from the GEO database. The “ConsensusClusterPlus” package was employed to generate molecular subtypes derived from PRGs that were identified through differential expression analysis and LASSO Cox analysis. A diagnostic signature including eight genes (CASP4, CASP5, ELANE, GPX4, NLRP1, GSDME, NOD1and IL18) was also constructed. Immune cell infiltration calculated by the ESTIMATE score, Stroma scores and Immune scores were also compared on the basis of pyroptosis-related molecular subtypes and the risk signature. We finally used qRT – PCR to detect the expression levels of eight genes in COPD patient and normal.Results: The diagnostic model, anchored on eight PRGs, underwent validation with an independent experimental cohort. The area under the receiver operating characteristic (ROC) curves (AUC) for the diagnostic model showcased values of 0.809, 0.765, and 0.956 for the GSE76925, GSE8545, and GSE5058 datasets, respectively. Distinct expression patterns and clinical attributes of PRGs were observed between the comparative groups, with functional analysis underscoring a disparity in immune-related functions between them.Conclusion: In this study, we developed a potential as diagnostic biomarkers for COPD and have a significant role in modulating the immune response. Such insights pave the way for novel diagnostic and therapeutic strategies for COPD.Keywords: chronic obstructive pulmonary disease, pyroptosis, gene, biomarkers, immune Infiltration

Yan Zhang,1,&ast; Senlu Wang,1,&ast; Xinqi Wang,2 Nianqiang Liu,2 Le Wang,2 Xiaomin Wang,1 Zhichao Liang,1 Junan Wang,1 Abulikemu Aili,1 Mingqin Cao1 1Department of Epidemiology and Health Statistics, College of Public Health, Xinjiang Medical University, Urumqi, Xinjiang, 830011, People’s Republic of China; 2The Center for Disease Control and Prevention of Xinjiang Uygur Autonomous Region, Urumqi, Xinjiang, 830002, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Mingqin Cao, Department of Epidemiology and Health Statistics, College of Public Health, Xinjiang Medical University, No. 393 Xinyi Road, Urumqi, 830011, People’s Republic of China, Tel +86-13319912419, Email 573596229@qq.comObjective: To analyze the effectiveness of the “Xinjiang Model” for tuberculosis prevention and control in Kashgar Prefecture, Xinjiang, and to explore the determinants of the policy implementation effect.Methods: The registration data of pulmonary tuberculosis (PTB) patients in Kashgar Prefecture from 2012 to 2021 were collected to describe the temporal trend of registered incidence. A questionnaire survey was conducted among PTB patients registered and treated in the tuberculosis management information system in Zepu and Shache Counties from January 2022 to July 2023 to collect and analyze “Xinjiang model” determinants of effectiveness.Results: The PTB registered incidence in Kashgar Prefecture showed a significant increasing trend from 2012 to 2018 (APC=18.7%) and a significant decreasing trend from 2018– 2021 (APC=− 28.8%). Among the Kashgar Prefecture, compared with average registered incidence in 2012– 2017, registered incidence in 2021 in Shufu, Maigaiti, and Zepu Counties had a greater decline rate of 58.68%, 57.16%, and 54.02%, respectively, while the registered incidence in 2021 in Shache County increased by 6.32%. According to the comprehensive analysis of the factors affecting the effect of policy implementation, the proportion of PTB patients in Zepu County whose health status has now significantly improved compared with that before treatment was significantly greater than that in Shache County (P< 0.05); patients in Shache County were significantly less aware than those in Zepu County of how to take tuberculosis drugs, precautions, adverse reactions, and regular reviews during treatment; the factors that accounted for the greater proportion of heavy treatment burden in both Shache and Zepu Counties were discomfort caused by taking or injecting drugs, accounting for 12.8% and 8.7%, respectively.Conclusion: The “Xinjiang model” can effectively control the epidemic situation of tuberculosis in Kashgar, and the knowledge of tuberculosis treatment, adverse reactions to tuberculosis drugs, and treatment costs were the determinants of the effectiveness of policy implementation.Keywords: pulmonary tuberculosis, implementation effect, registered incidence, determinants, Xinjiang

Qianhui Zhou,1 Yi Liu,1 Yan Gao,1 Lingli Quan,1 Lin Wang,1 Hao Wang2 1Department of Respiratory and Critical Care Medicine, Zhuzhou Central Hospital, Zhuzhou, 412000, People’s Republic of China; 2Department of Urology, The First Affiliated Hospital, Hengyang Medical School, University of South China, HengYang, Hunan, 421005, People’s Republic of ChinaCorrespondence: Hao Wang, Email wanghao872013@163.comBackground: Lung cancer is the leading cause of cancer deaths worldwide, primarily due to lung adenocarcinoma (LUAD). However, the heterogeneity of programmed cell death results in varied prognostic and predictive outcomes. This study aimed to develop an LUAD evaluation marker based on cuproptosis-related lncRNAs.Methods: First, transcriptome data and clinical data related to LUAD were downloaded from the Cancer Genome Atlas (TCGA), and cuproptosis-related genes were analyzed to identify cuproptosis-related lncRNAs. Univariate, LASSO, and multivariate Cox regression analyses were conducted to construct cuproptosis-associated lncRNA models. LUAD patients were categorized into high-risk and low-risk groups using prognostic risk values. Kaplan-Meier analysis, PCA, GSEA, and nomograms were employed to evaluate and validate the results.Results: 7 cuproptosis-related lncRNAs were identified, and a risk model was created. High-risk tumors exhibited cuproptosis-related gene alterations in 95.54% of cases, while low-risk tumors showed alterations in 85.65% of cases, mainly involving TP53. The risk value outperformed other clinical variables and tumor mutation burden as a predictor of 1-, 3-, and 5-year overall survival. The cuproptosis-related lncRNA-based risk model demonstrated high validity for LUAD evaluation, potentially influencing individualized treatment approaches. Expression analysis of four candidate cuproptosis-related lncRNAs (AL606834.1, AL161431.1, AC007613.1, and LINC02835) in LUAD tissues and adjacent normal tissues revealed significantly higher expression levels of AL606834.1 and AL161431.1 in LUAD tissues, positively correlating with tumor stage, lymph node metastasis, and histopathological grade. Conversely, AC007613.1 and LINC02835 exhibited lower expression levels, negatively correlating with these factors. High expression of AL606834.1 and AL161431.1 indicated poor prognosis, while low expression of AC007613.1 and LINC02835 was associated with unfavorable outcomes. Univariate and multivariate analyses confirmed these lncRNAs as independent risk factors for LUAD prognosis.Conclusion: The 4 cuproptosis-related (lncRNAsAL606834.1, AL161431.1, AC007613.1, and LINC02835) can accurately predict the prognosis of patients with LUAD and may provide new insights into clinical applications and immunotherapy.Keywords: lung adenocarcinoma, tumor mutation load, cuproptosis, long noncoding RNA, immunotherapeutic response

Jing Luo,1,2 Yi Luo,2 Maoru Zhao,3 Yulong Liu,2 Jiayin Liu,2 Zhulin Du,2 Hong Gong,2 Lian Wang,2 Jinghui Zhao,2 Xiaqing Wang,2 Zhanjun Gu,3 Wenhui Zhao,1 Tianyao Liu,2 Xiaotang Fan2 1School of Life Sciences, Chongqing University, Chongqing, 401331, People’s Republic of China; 2Department of Military Cognitive Psychology, School of Psychology, Third Military Medical University (Army Medical University), Chongqing, 400038, People’s Republic of China; 3Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety and CAS Center for Excellence in Nanoscience, Institute of High Energy Physics and National Center for Nanoscience and Technology, Chinese Academy of Sciences, Beijing, 100049, People’s Republic of ChinaCorrespondence: Xiaotang Fan; Tianyao Liu, Email fanxiaotang2005@163.com; squall277@163.comBackground: Autism Spectrum Disorder (ASD) is a neurodevelopmental condition that affects social interaction and communication and can cause stereotypic behavior. Fullerenols, a type of carbon nanomaterial known for its neuroprotective properties, have not yet been studied for their potential in treating ASD. We aimed to investigate its role in improving autistic behaviors in BTBR T+Itpr3tf/J (BTBR) mice and its underlying mechanism, which could provide reliable clues for future ASD treatments.Methods: Our research involved treating C57BL/6J (C57) and BTBR mice with either 0.9% NaCl or fullerenols (10 mg/kg) daily for one week at seven weeks of age. We then conducted ASD-related behavioral tests in the eighth week and used RNA-seq to screen for vital pathways in the mouse hippocampus. Additionally, we used real-time quantitative PCR (RT-qPCR) to verify related pathway genes and evaluated the number of stem cells in the hippocampal dentate gyrus (DG) by Immunofluorescence staining.Results: Our findings revealed that fullerenols treatment significantly improved the related ASD-like behaviors of BTBR mice, manifested by enhanced social ability and improved cognitive deficits. Immunofluorescence results showed that fullerenols treatment increased the number of DCX+ and SOX2+/GFAP+ cells in the DG region of BTBR mice, indicating an expanded neural progenitor cell (NPC) pool of BTBR mice. RNA-seq analysis of the mouse hippocampus showed that VEGFA was involved in the rescued hippocampal neurogenesis by fullerenols treatment.Conclusion: In conclusion, our findings suggest that fullerenols treatment improves ASD-like behavior in BTBR mice by upregulating VEGFA, making nanoparticle- fullerenols a promising drug for ASD treatment. Keywords: fullerenols, BTBR, neurogenesis, autism spectrum disorder, hippocampus

Zheng Wang,1,&ast; Guangzhong Xu,1,&ast; Guanyang Chen,2,3,&ast; Buhe Amin,1 Liang Wang,1 Zhehong Li,1 Jing Wang,1 Weijian Chen,1 Chengyuan Yu,3 Chenxu Tian,1 Qiqige Wuyun,1 Qing Sang,3 Mingyue Shang,1 Dongbo Lian,1 Nengwei Zhang1 1Surgery Centre of Diabetes Mellitus, Capital Medical University Affiliated Beijing Shijitan Hospital, Beijing, People’s Republic of China; 2Department of Critical Care Medicine, Peking University People’s Hospital, Beijing, People’s Republic of China; 3Surgery Centre of Diabetes Mellitus, Peking University Ninth School of Clinical Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongbo Lian; Nengwei Zhang, Shijitan Hospital, Tieyi Road, Haidian District, Beijing, People’s Republic of China, Tel +8613681299755 ; +8613801068802, Email lian.dongbo@126.com; zhangnw1@sohu.comBackground: Some research have indicated that Bariatric and metabolic surgery (BMS) can reduce the risk of cardiovascular disease (CVD) among individuals with obesity. However, there are few reports available that focuses on assessing effect of BMS on the risk of CVD in Chinese population using multiple models.Objective: This research aims to assess the function of BMS on the risk of CVD in Chinese patients with obesity using multiple CVD risk models.Methods: We performed a retrospective analysis of the basic data and glycolipid metabolism data preoperatively and postoperatively from patients with obesity at our hospital. Subgroup analysis was carried out according to different surgical procedures. Then, the function of BMS on the risk of CVD in the Chinese population was assessed using four models, including: China-PAR risk model, Framingham risk score (FRS), World Health Organization (WHO) risk model, and Globorisk model.Results: We enrolled 64 patients, 24 (37.5%) of whom underwent laparoscopic sleeve gastrectomy (LSG) while 40 (62.5%) underwent Roux-en-Y gastric bypass (RYGB). The 10-year CVD risk for patients calculated using the China-PAR risk model decreased from 6.3% preoperatively to 2.0% at 1 year postoperatively and was statistically significantly different. Similarly, the 10-year CVD risk of patients calculated using the FRS, WHO, Global risk model decreased significantly at 1 year postoperatively compared to preoperatively. When the FRS risk model was used to calculate the patients’ 30-year postoperative CVD risk, there was a significant decrease at 1 year after surgery compared to the preoperative period. When employing various models to evaluate the 10-year CVD risk for LSG and RYGB, no statistically significant difference was found in the 1-year postoperative RRR between the procedures.Conclusion: The CVD risk after BMS was significantly reduced compared to preoperatively. In terms of improving cardiovascular risk, SG and RYGB appear to be equally effective.Keywords: obesity, metabolic surgery, T2DM, CVD risk model

Lei Wang,1 Xinbao Li,2 Yan Li,2 Zhongying Bao,1 Shuhong Duan,1 Jie Zhang1 1Department of Infectious Diseases, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 2Department of Peritoneal Cancer Surgery, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of ChinaCorrespondence: Lei Wang, Department of Infectious Diseases, Beijing Shijitan Hospital, Capital Medical University, NO. 10, Tie Yi Road, Yang Fang Dian, Haidian District, Beijing, 100038, People’s Republic of China, Tel + 86 10 63926121, Email wanglei2489@bjsjth.cnObjective: In this study we aimed to evaluate the postoperative safety of cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for the treatment of peritoneal surface malignancies (PSM), and analyzed the risk factors and pathogen resistance associated with bloodstream infections.Methods: We retrospectively analyzed the incidence of postoperative bloodstream infections in 1500 patients undergoing CRS and HIPEC for PSM. We utilized univariate and multivariate analyses to screen for independent risk factors associated with postoperative bloodstream infections in CRS combined with HIPEC.Results: Among the 1500 cases of individuals undergoing CRS combined with HIPEC, 207 cases (13.8%) experienced bloodstream infections. A total of 233 strains of pathogens were isolated and cultured, consisting of 151 gram-positive cocci, 52 gram-negative bacilli, and 30 fungi. Coagulase-negative staphylococci (SCN) were the gram-positive cocci (54.94%), while Klebsiella pneumoniae subsp. Pneumoniae (7.30%) and Escherichia coli (5.58%) dominated the Gram-negative bacilli. Candida albicans was the predominant fungus. Staphylococci exhibited high sensitivity to tigecycline, linezolid, vancomycin, and quinupristin/dalfopristin. However, K. pneumoniae and E. coli were resistant to imipenem. Furthermore, five parameters were associated with the development of bloodstream infections: age (P = 0.040), surgical history (P = 0.033), prior tumor treatment (P < 0.001), tumor tissue type (P = 0.034), and completeness of cytoreduction (CC) score (P = 0.004). Among these, age (P = 0.013), prior tumor treatment (P = 0.001), tumor tissue type (P = 0.032), and CC score (P = 0.002) emerged as independent risk factors for postoperative bloodstream infections in patients undergoing CRS combined with HIPEC.Conclusion: Postoperative bloodstream infections in patients with PSM undergoing CRS combined with HIPEC are predominantly attributed to SCN, K. pneumoniae subsp. Pneumoniae, and C. albicans. Notably, Enterobacteriaceae exhibited resistance to carbapenem. Independent risk factors for postoperative infections in PSM include age, prior tumor treatment, tumor tissue type, and completeness of cytoreduction score.Keywords: bloodstream infections, cytoreductive surgery, hyperthermic intraperitoneal chemotherapy, pathogens drug resistance, pathogens

Lan Hong,1,&ast; Huihui Xu,2,&ast; Jiaqi Zheng,2 Xiujian Lin,2 Lijun Wang,2 Chengjia Zhao,3 Xiaolian Tu,4 Jingjing Zhang,5 Ke Zhao,1,6 Guohua Zhang6,7,&ast; 1Lishui Second People’s Hospital Affiliated to Wenzhou Medical University, Lishui, 323000, People’s Republic of China; 2School of Mental Health, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 3School of Education, Renmin University of China, Beijing, 100872, People’s Republic of China; 4School of Renji, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 5School of Nursing, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 6Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China; 7Institute Of Aging, Key Laboratory Of Alzheimer’s Disease Of Zhejiang Province, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guohua Zhang, Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, 325035, People’s Republic of China, Email zghcnu@wmu.edu.cn Ke Zhao, Lishui Second People’s Hospital Affiliated to Wenzhou Medical University, Lishui, 323000, People’s Republic of China, Email cocozk1986@163.comBackground: Bedtime procrastination (BP) has become an important factor affecting individual well-being. This study aimed to assess the stability and changes in BP and examine risk and protective factors.Methods: The study recruited 1423 respondents. Latent profile analysis was used to identify subgroups of BP and latent transition analysis to determine transition probabilities for each subgroup. Logistic regression examined associations between identified classes and related factors.Results: Three subgroups of BP were identified. In terms of stability and changes, the moderate bedtime procrastination group showed the highest stability (66%), followed by the severe bedtime procrastination group (62.4%), and the mild bedtime procrastination group had a 52% probability of switching to moderate bedtime procrastination. In terms of influencing factors, more problematic phone use (PSU) (OR: 1.08; 95% CI = 1.05– 1.12), more depression (OR: 1.17; 95% CI = 1.06– 1.29) and anxiety (OR: 1.16; 95% CI = 1.05– 1.28) are all factors that aggravate the transition from mild to moderate sleep procrastination. Similarly, PSU (OR: 1.15; 95% CI = 1.12– 1.19), anxiety (OR: 1.10; 95% CI = 1.06– 1.14), and depression (OR: 1.10; 95% CI = 1.06– 1.14) increased the risk of severe bedtime procrastination. Self-control emerged as a protective factor against BP.Conclusion: This study identified three subgroups of BP at two time points and the rule of transition for each subgroup. Our findings indicate that BP were relatively stable, with some changes over time. The results also highlight the important function that PSU, depression, anxiety, and self-control can play in preventing and intervening in BP.Keywords: bedtime procrastination, latent profile analysis, latent transition analysis, problematic smartphone use, depression, anxiety, self-control

Huiying Xu,1 Lizhen Wang,2 Wenchao Zhu,1 Chunguang Ren,1 Guoying Liu,1 Yanchao Liu1 1Department of Anaesthesiology, Liaocheng People’s Hospital, Liaocheng, People’s Republic of China; 2Department of Tuberculosis, Liaocheng Infectious Disease Hospital, Liaocheng, People’s Republic of ChinaCorrespondence: Yanchao Liu, Email lycxyl9@sina.comObjective: Remimazolam besylate is a novel ultra-short-acting benzodiazepine that is rapidly hydrolyzed to zolpidem propionic acid by tissue lipases. We designed this study to compare the safety and efficacy of remimazolam besylate alfentanil versus dexmedetomidine–alfentanil for fiberoptic bronchoscopy (FB).Methods: One hundred and twenty patients undergoing FB into this prospective randomized controlled trial were divided into two groups. The anesthesia induction consisted of 6 mg/kg/h of remimazolam besylate in the RA group and 0.5 μg/kg of dexmedetomidine in the DA group. 1– 2 mg/kg/h of remimazolam besylate or 0.2– 0.7 μg/kg/h of dexmedetomidine were administered to maintain during FB. The lowest oxygen saturation, success rate of FB, hemodynamics, time metrics, bronchoscopy feasibility, drug dose requirements, patient and bronchoscopist satisfaction scores, occurrence of intraoperative awareness, number of patients willing to repeat FB with the same sedation regimen, and occurrence and severity of adverse events.Results: The lowest oxygen saturation during the FB was significantly higher in the RA group (P = 0.001). Compared with the variables in the DA group, peripheral oxygen saturation, systolic blood pressure, and diastolic blood pressure were significantly lower at T2 and T3 in the RA group (P < 0.05). Heart rates were significantly higher from T2 to T4 in the DA group (P < 0.05). More patients experienced bradycardia in the DA group (P = 0.041). Compared with time metrics in the DA group, the induction time, fully-alert time, and recovery room-leaving time were all significantly shorter in the RA group (P < 0.05). The bronchoscopy feasibility scores in the RA group were significantly lower at T2, whereas they were lower at T3 in the DA group (P < 0.05).Conclusion: Remimazolam besylate is superior to dexmedetomidine when combined with alfentanil during FB, promoting faster patients’ recovery, better operative conditions and respiratory stability with similar rates of occurrence and severity of adverse events.Keywords: remimazolam besylate, dexmedetomidine, fiberoptic bronchoscopy, alfentanil, propofol

Lin Wang,1,2 Fulan Wang,1,2 Hong Qin,2 Li Hou,2 Shiqiong Zhu,3 Fang He,2 Chao Zeng2 1Department of Nursing, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 2Gynecology Department, The First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China; 3Gynecology Department, Sichuan Provincial People’s Hospital, Chengdu, Sichuan, 610031, People’s Republic of ChinaCorrespondence: Fulan Wang, Department of Nursing, the First Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, People’s Republic of China, Tel +86-13012370558, Email WFL3076@163.comBackground: Bladder dysfunction is a common complication following radical hysterectomy, affecting patients’ QOL. Exploring interventions, particularly IC continuity care, is crucial for identifying strategies to enhance postoperative outcomes. This study aimed to assess the impact of continuous intermittent catheterization (IC) care on bladder function recovery and quality of life (QOL) in patients undergoing radical hysterectomy for cervical cancer.Methods: The primary outcome measured was the time to bladder function recovery, with secondary outcomes comprising EORTC QLQ-C30 assessments at 3 and 6 months post-surgery, as well as EORTC QLQ-CX24 evaluations. Meanwhile, urinary complications, readmissions, and outpatient follow-up were also compared.Results: Among the 128 participants, with 64 in each group, indwelling catheterization durations were similar. However, the IC continuity care group exhibited significantly shorter IC duration and bladder recovery time. This group demonstrated superior QOL, lower occurrence rates post-IC, reduced urethral injuries, and higher readmission and outpatient follow-up rates.Conclusion: This study underscores continuous IC care emerges as a beneficial intervention, facilitating accelerated bladder function recovery and improved QOL in patients following radical hysterectomy for cervical cancer.Keywords: intermittent urethral catheterization, cervical cancer, urinary bladder neurogenic dysfunction, continuity of patient care, rehabilitation

Ya-Ping Chen,1,2 Heng Wang,1,3 Lei Wang,4 Dan Xie,4 Min Guo,4 Jiang-Fen Wu,5 Bang-Quan An,6 Sheng-Wen Huang1,5 1School of Clinical Laboratory Science, Guizhou Medical University, Guiyang, Guizhou, People’s Republic of China; 2Department of Clinical Laboratory, the Second People’s Hospital of Guiyang, Guiyang, Guizhou, People’s Republic of China; 3Guiyang Public Health Clinical Center, Guiyang, Guizhou, People’s Republic of China; 4Medical College of Guizhou University, Guiyang, Guizhou, People’s Republic of China; 5Medical Genetics Department, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of China; 6Department of Blood Transfusion, Guizhou Provincial People’s Hospital, Guiyang, Guizhou, People’s Republic of ChinaCorrespondence: Sheng-Wen Huang, Medical Genetics Department, Guizhou Provincial People’s Hospital, No. 83, East Zhongshan Road, Nanming District, Guiyang, Guizhou, 550002, People’s Republic of China, Tel +86-851-85935128, Fax +86-851-85937194, Email hsw713@sina.comPurpose: To analyze the composition of abnormal hemoglobin and the relationship between genotype and phenotype by screening abnormal hemoglobin in a subpopulation of Guizhou, China.Patients and Methods: Routine blood evaluation, capillary electrophoresis of hemoglobin, and mutation of α - and β - thalassemia genes were evaluated in 19,976 individuals for thalassemia screening in Guizhou. Sanger sequencing of HBA1, HBA2 and HBB genes was performed in samples with abnormal bands or unexplained increases of normal bands. The types of abnormal hemoglobin were obtained by sequence analysis.Results: Abnormal hemoglobin was detected in 84 individuals (detection rate, 0.42%). Ten types each of α and β globin chain variants were detected, including most commonly Hb E, Hb New York and Hb Port Phillip. In this study, the abnormal Hb Mizuho was identified for the first time in a Chinese population, and a novel abnormal hemoglobin Hb Guiyang (HBA2: c.151C > A) was detected for the first time. Except for Hb Mizuho, other abnormal hemoglobin heterozygotes without thalassemia or iron deficiency had no significant hematological changes.Conclusion: This study enriched the molecular epidemiological data of abnormal hemoglobin in Guizhou, China and provided reference data for genetic counseling and prenatal diagnosis of abnormal hemoglobin.Keywords: abnormal hemoglobin, routine blood examination, capillary electrophoresis, DNA sequencing, Hb Mizuho, HBA2

Qianfeng Li,1,&ast; Bo Wang,2,&ast; Jun Yang,3 Yuan Wang,1 Faliang Duan,1 Ming Luo,1 Chungang Zhao,4 Wei Wei,2 Lei Wang,3 Sha Liu2,5 1Department of Neurosurgery, Wuhan No.1 Hospital, Wuhan, People’s Republic of China; 2Brain Research Center, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China; 3Huanggang Central Hospital of Yangtze University, Huanggang, People’s Republic of China; 4Jilin Jianda Modern Agricultural Research Institute, Changchun, People’s Republic of China; 5Department of General Practice, Zhongnan Hospital of Wuhan University, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Wang; Sha Liu, Email wanglei@hgyy.org.cn; sha.liu@whu.edu.cnBackground: Aging is recognized as the key risk for intracerebral hemorrhage (ICH). The detailed mechanisms of aging in ICH warrant exploration. This study aimed to identify potential aging-related genes associated with ICH.Methods: ICH-specific aging-related genes were determined by the intersection of differentially expressed genes (DEGs) between perihematomal tissues and corresponding contralateral parts of four patients with ICH (GSE24265) and 349 aging-related genes obtained from the Aging Atlas database. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Set Enrichment Analysis (GSEA) analyses were performed to identify the potential biological functions and pathways in which these ICH-specific aging-related genes may be involved. Then, PPI network was established to identify the hub genes of ICH-specific aging-related genes. Meanwhile, miRNA-mRNA and transcription factor (TF)-mRNA regulatory networks were constructed to further explore the ICH-specific aging-related genes regulation. The relationship between these hub genes and immune infiltration was also further explored. Additional single-cell RNA-seq analysis (scRNA-seq, GSE167593) was used to locate the hub genes in different cell types. Besides, expression levels of the hub genes were validated using clinical samples from our institute and another GEO dataset (GSE206971).Results: This study identified 24 ICH-specific aging-related genes, including 22 up-regulated and 2 down-regulated genes. The results of GO and KEGG suggested that the ICH-specific aging-related genes mainly enriched in immunity and inflammation-related pathways, suggesting that aging may affect the ich pathogenesis by regulating inflammatory and immune-related pathways.Conclusion: Our study revealed 24 ICH-specific aging-related genes and their functions highly pertinent to ICH pathogenesis, providing new insights into the impact of aging on ICH.Keywords: intracerebral hemorrhage, aging, immune infiltration, single-cell RNA sequencing, molecular docking

Ying Wang,1,&ast; Yiyan Xu,2,&ast; Jiayu Song,1 Xueting Liu,1 Sijia Liu,1 Nan Yang,1 Le Wang,1 Yujie Liu,1 Yiwei Zhao,1 Wenhu Zhou,3,4 Yunyan Zhang1 1Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, Harbin, Heilongjiang, 150081, People’s Republic of China; 2Department of Vascular Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong, 510120, People’s Republic of China; 3Xiangya School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, 410013, People’s Republic of China; 4Hunan Key Laboratory of The Research and Development of Novel Pharmaceutical Preparations, School of Pharmaceutical Science, Changsha Medical University, Changsha, 410219, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunyan Zhang, Department of Gynecological Radiotherapy, Harbin Medical University Cancer Hospital, No. 150, Haping Road, Nangang District, Harbin, Heilongjiang Province, 150081, People’s Republic of China, Tel +86 13604843878, Fax +86 451 85718392, Email zhangyunyan@hrbmu.edu.cn Wenhu Zhou, Xiangya School of Pharmaceutical Sciences, Central South University, 172 Tongzipo Road, Changsha, Hunan, 410013, People’s Republic of China, Tel +86 15111469284, Fax +86 731 88710591, Email zhouwenhuyaoji@163.comPurpose: Phototherapy, known for its high selectivity, few side effects, strong controllability, and synergistic enhancement of combined treatments, is widely used in treating diseases like cervical cancer.Methods: In this study, hollow mesoporous manganese dioxide was used as a carrier to construct positively charged, poly(allylamine hydrochloride)–modified nanoparticles (NPs). The NP was efficiently loaded with the photosensitizer indocyanine green (ICG) via the addition of hydrogen phosphate ions to produce a counterion aggregation effect. HeLa cell membrane encapsulation was performed to achieve the final M-HMnO2@ICG NP. In this structure, the HMnO2 carrier responsively degrades to release ICG in the tumor microenvironment, self-generates O2 for sensitization to ICG-mediated photodynamic therapy (PDT), and consumes GSH to expand the oxidative stress therapeutic effect [chemodynamic therapy (CDT) + PDT]. The ICG accumulated in tumor tissues exerts a synergistic PDT/photothermal therapy (PTT) effect through single laser irradiation, improving efficiency and reducing side effects. The cell membrane encapsulation increases nanomedicine accumulation in tumor tissues and confers an immune evasion ability. In addition, high local temperatures induced by PTT can enhance CDT. These properties of the NP enable full achievement of PTT/PDT/CDT and targeted effects.Results: Mn2+ can serve as a magnetic resonance imaging agent to guide therapy, and ICG can be used for photothermal and fluorescence imaging. After its intravenous injection, M-HMnO2@ICG accumulated effectively at mouse tumor sites; the optimal timing of in-vivo laser treatment could be verified by near-infrared fluorescence, magnetic resonance, and photothermal imaging. The M-HMnO2@ICG NPs had the best antitumor effects among treatment groups under near-infrared light conditions, and showed good biocompatibility.Conclusion: In this study, we designed a nano-biomimetic delivery system that improves hypoxia, responds to the tumor microenvironment, and efficiently loads ICG. It provides a new economical and convenient strategy for synergistic phototherapy and CDT for cervical cancer.Keywords: phototherapy, reactive oxygen species, hypoxia relief, collaborative therapy

Yang Chong,1,2 Dong Yu,1,2 Rui Han,3 Yanxu Li,2 Yali Gu,3 Zhaoyu Lu,1,2 Fengsong Nie,1,2 Lingli Wang,1 Hengmi Cui4 1Department of Traditional Chinese Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, 225000, People’s Republic of China; 2Department of General Surgery, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, 225000, People’s Republic of China; 3Institute of Translational Medicine, Medical College, Yangzhou University, Yangzhou, 225009, People’s Republic of China; 4Institute of Epigenetics and Epigenomics and College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, 225009, People’s Republic of ChinaCorrespondence: Yang Chong, Department of Traditional Chinese Medicine, The Affiliated Hospital of Yangzhou University, Yangzhou University, Yangzhou, Jiangsu, 225000, People’s Republic of China, Email 092016@yzu.edu.cn Hengmi Cui, Institute of Epigenetics and Epigenomics and College of Animal Science and Technology, Yangzhou University, Yangzhou, Jiangsu, 225009, People’s Republic of China, Email hmcui@yzu.edu.cnPurpose: Incorporation of luvangetin in nanoemulsions for antimicrobial and therapeutic use in infected wound healing.Patients and Methods: Luvangetin nanoemulsions were prepared by high-speed shear method and characterized based on their appearance structure, average droplet size, polydispersity index (PDI), electric potential, storage stability. Optimized formulation of luvangetin nanoemulsion by Box-Behnken design (BBD). The antimicrobial activity and antimicrobial mechanism of luvangetin nanoemulsions against common hospital pathogens, ie, Staphylococcus aureus (S. aureus) and Escherichia coli (E. coli), were investigated using luvangetin nanoemulsions. The biosafety of luvangetin nanoemulsion was evaluated through cytotoxicity, apoptosis, and reactive oxygen species (ROS) assay experiments using human normal epidermal cells and endothelial cells. Finally, the effect of luvangetin nanoemulsion on healing of infected wounds was investigated in B6 mice.Results: Luvangetin nanoemulsion formulation consists of 2.5% sunflower seed oil, 10% emulsifier Span-20 and 7 minutes of shear time, and with good stability. Luvangetin nanoemulsion produces antibacterial activity against S. aureus and E. coli by disrupting the structure of bacterial cell membranes. Luvangetin nanoemulsion are biologically safe for HaCat and HUVEC. Luvangetin nanoemulsion showed good therapeutic effect on MRSA infected wounds in mice.Conclusion: For the first time, developed a new formulation called luvangetin nanoemulsion, which exhibited superior antibacterial effects against Gram-positive bacteria. Luvangetin nanoemulsion has a favorable effect in promoting infected wound healing. We have combined luvangetin, which has multiple activities, with nanoemulsions to provide a new topical fungicidal formulation, and have comprehensively evaluated its effectiveness and safety, opening up new possibilities for further applications of luvangetin. Keywords: luvangetin, nanoemulsion, antimicrobial mechanism, infected wound healing

Yiyue Xu,1,&ast; Haoqian Li,1,&ast; Xiaoqing Wang,2 Butuo Li,1 Aiqin Gao,1 Qian Zhao,1 Linlin Yang,1 Wenru Qin,1 Linlin Wang1 1Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, People’s Republic of China; 2Department of Portal Hypertension, Shandong Public Health Clinical Center, Shandong University, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Linlin Wang, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, 440 JiYan Road, Jinan, 250117, People’s Republic of China, Tel +86-13793187739, Email wanglinlinatjn@163.comBackground: COVID-19 has spread worldwide, becoming a global threat to public health and can lead to complications, especially pneumonia, which can be life-threatening. However, in lung cancer patients, the prediction of pneumonia and severe pneumonia has not been studied. We aimed to develop effective models to assess pneumonia after SARS-CoV-2 infection in lung cancer patients to guide COVID-19 management.Methods: We retrospectively recruited 621 lung cancer patients diagnosed with COVID-19 via SARS-CoV-2 RT-PCR analysis in two medical centers and divided into training and validation group, respectively. Univariate and multivariate logistic regression analysis were used to identify independent risk factors of all-grade pneumonia and ≥ grade 2 pneumonia in the training group. Nomograms were established based on independent predictors and verified in the validation group. C-index, ROC curves, calibration curve, and DCA were used to evaluate the nomograms. Subgroup analyses in immunotherapy or thoracic radiotherapy patients were then conducted.Results: Among 621 lung cancer patients infected with SARS-CoV-2, 203 (32.7%) developed pneumonia, and 66 (10.6%) were ≥ grade 2. Multivariate logistic regression analysis showed that diabetes, thoracic radiotherapy, low platelet and low albumin at diagnosis of COVID-19 were significantly associated with all-grade pneumonia. The C-indices of the prediction nomograms in the training group and validation group were 0.702 and 0.673, respectively. Independent predictors of ≥ grade 2 pneumonia were age, KPS, thoracic radiotherapy, platelet and albumin at COVID 19 diagnosis, with C-indices of 0.811 and 0.799 in the training and validation groups. In the thoracic radiotherapy subgroup, 40.8% and 11% patients developed all-grade and ≥grade 2 pneumonia, respectively. The rates in the immunotherapy subgroup were 31.3% and 6.6%, respectively.Conclusion: We developed nomograms predicting the probability of pneumonia in lung cancer patients infected with SARS-CoV-2. The models showed good performance and can be used in the clinical management of COVID-19 in lung cancer patients. Higher-risk patients should be managed with enhanced protective measures and appropriate intervention.Keywords: COVID-19, pneumonia, lung cancer, risk factor, nomogram

Wenya Shan,1– 3 Liangping Wang,1,4 Jiayi Qin,1– 3 Wenhan Peng,5 Kuifen Ma1– 3 1Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Zhejiang Provincial Key Laboratory for Drug Evaluation and Clinical Research, Hangzhou, People’s Republic of China; 3Zhejiang Provincial Key Laboratory of Traditional Chinese Medicine for Clinical Evaluation and Translational Research, Hangzhou, People’s Republic of China; 4Department of Pharmacy, Hangzhou Linping District Hospital of Integrated Chinese and Western Medicine, Hangzhou, People’s Republic of China; 5Kidney Disease Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of ChinaCorrespondence: Wenhan Peng, Kidney Disease Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Tel +8687233411, Email 1198027@zju.edu.cn Kuifen Ma, Department of Clinical Pharmacy, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China, Email makuifen@zju.edu.cnBackground: The administration of trimethoprim-sulfamethoxazole (TMP-SMX) for the prophylaxis of Pneumocystis jirovecii pneumonia (PJP) has proven to be highly efficacious in individuals who have undergone kidney transplantation. Nevertheless, the potential for severe adverse reactions associated with this treatment cannot be overlooked, and the determination of an optimal dosage regimen continues to be a matter of investigation. The current study evaluated the effectiveness of low-dose TMP-SMX for PJP prophylaxis in kidney transplant patients and conducted an analysis of the clinical characteristics and epidemiological trends in patients with PJP infection.Methods: This retrospective analysis studied electronic medical records of 1763 kidney transplant recipients from 2017 to 2020. These patients were initially prescribed a daily half-strength TMP-SMX (40 mg/200 mg), and the efficacy of this regimen was assessed during a follow-up period of 3– 51 months.Results: Under our PJP prevention and adjustment strategy, 24 patients were infected with PJP. The overall morbidity of PJP infection in our study was 1.36%, corroborates with findings from previously published studies. Among these 24 patients, up to 87.5% had their dosage adjusted due to increased creatinine or other adverse reactions, the most frequent dose was daily quarter-strength TMP-SMX (20 mg/100 mg). TMP-SMX prophylaxis successfully postponed and distributed the onset of PJP, with the mean duration from transplantation to the occurrence of PJP being 13.50± 7.11 months.Conclusion: Daily administration of half-strength TMP-SMX can effectively prevent PJP, and prolonging prophylaxis with this medication may potentially reduce the incidence of infection.Keywords: efficacy, kidney transplant recipients, Pneumocystis jirovecii pneumonia, trimethoprim-sulfamethoxazole

Jiayi Wang,1,&ast; Yuanyuan Wang,1,&ast; Bangguo Zhou,2 Lin Wang,3 Zhangqi Lai1 1The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Hangzhou, People’s Republic of China; 2Department of Medical Ultrasound, Shanghai Tenth People’s Hospital, Shanghai, People’s Republic of China; 3Key Laboratory of Exercise and Health Sciences (Shanghai University of Sport), Ministry of Education, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Wang, Key Laboratory of Exercise and Health Sciences (Shanghai University of Sport), Ministry of Education, Shanghai, People’s Republic of China, Email wanglin@sus.edu.cn Zhangqi Lai, The Third School of Clinical Medicine (School of Rehabilitation Medicine), Zhejiang Chinese Medical University, Binwen Road 548, Binjiang District, Hangzhou, People’s Republic of China, Email laizhangqi@126.comIntroduction: The risk of falls among the elderly significantly increases, which has become a serious public health concern. Falls can not only lead to serious complications such as fractures and brain injuries but also limit their mobility function, reducing quality of life. Foot intrinsic muscles (FIMs) are an essential part of foot core stability even overall postural stability. This study aimed to investigate the effects of aging on the function of FIMs and to explore the influence of FIMs on postural control in the elderly.Materials and Methods: 56 healthy old participants (60– 75 years) and 57 healthy young participants (18– 29 years) joined this study. An ergoFet dynamometer was used to determine foot muscle strength (Doming, T1, T23 and T2345), and ankle muscle strength (plantarflexion and dorsiflexion). The morphology of FIMs and extrinsic foot muscle was determined using a Doppler ultrasound system, whereas the postural stability was assessed through Limits of Stability test. Independent samples t-test was used to determine the differences in strength and morphological parameters and Spearman correlation analysis was used to determine whether an association existed between muscle strength and postural stability parameters in the elderly.Results: Compared with young adults, foot muscle strength and ankle muscle strength (Doming, T1, T23, T2345, dorsiflexion, and plantarflexion, all p < 0.05) and the morphology of foot muscles (all p < 0.05) were significantly reduced in the elderly. The strength of FIMs and the limit of stability (r = 0.302– 0.424, all p < 0.05) were significantly correlated in the elderly.Conclusion: Compared with young adults, the weakness of strength as well as the morphological decline of the intrinsic and extrinsic foot muscles were found in the elderly. In addition, a correlation was observed between FIM’s strength and postural stability in the elderly, suggesting their potential role in posture stability.Keywords: postural stability, aging, foot core system, fall, foot intrinsic muscle, FIMs

Nan Mei,1,&ast; Sha Gong,1,&ast; Lizhao Wang,2 Lu Wang,1 Jincheng Wang,1 Jianpeng Li,3 Yingying Bao,4 Huanming Zhang,1 Huaiyu Wang1 1Department of Hematology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 2Department of Breast Surgery, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 3Department of Urology, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China; 4Institute of Gene and Cell Therapy, the First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Huaiyu Wang, Department of Hematology, the First Affiliated Hospital of Xi’an Jiaotong University, 277 West Yanta Road, Xi’an, Shannxi, 710061, People’s Republic of China, Email why@xjtufh.edu.cn; whymed@126.comBackground: Multiple myeloma (MM), an incurable plasma cell malignancy. The significance of the relationship between natural killer (NK) cell-related genes and clinical factors in MM remains unclear.Methods: Initially, we extracted NK cell-related genes from peripheral blood mononuclear cells (PBMC) of healthy donors and MM samples by employing single-cell transcriptome data analysis in TISCH2. Subsequently, we screened NK cell-related genes with prognostic significance through univariate Cox regression analysis and protein-protein interaction (PPI) network analysis. Following the initial analyses, we developed potential subtypes and prognostic models for MM using consensus clustering and lasso regression analysis. Additionally, we conducted a correlation analysis to explore the relationship between clinical features and risk scores. Finally, we constructed a weighted gene co-expression network analysis (WGCNA) and identified differentially expressed genes (DEGs) within the MM cohort.Results: We discovered that 153 NK cell-related genes were significantly associated with the prognosisof MM patients (P < 0.05). Patients in NK cluster A exhibited poorer survival outcomes compared to those in cluster B. Furthermore, our NK cell-related genes risk model revealed that patients with a high risk score had significantly worse prognoses (P < 0.05). Patients with a high risk score were more likely to exhibit adverse clinical markers. Additionally, the nomogram based on NK cell-related genes demonstrated strong prognostic performance. The enrichment analysis indicated that immune-related pathways were significantly correlated with both the NK subtypes and the NK cell-related genes risk model. Ultimately, through the combined use of WGCNA and DEGs analysis, and by employing Venn diagrams, we determined that ITM2C is an independent prognostic marker for MM patients.Conclusion: In this study, we developed a novel model based on NK cell-related genes to stratify the prognosis of MM patients. Notably, higher expression levels of ITM2C were associated with more favorable survival outcomes in these patients.Keywords: multiple myeloma, NK cell-related genes, NK subtypes, prognostic model, ITM2C

Wang L, Li D, Hao Y, et al. Int J Nanomedicine. 2017;12:3059-3075. The authors have advised Figures 9 and 11 on pages 3070 and 3071, respectively, are incorrect. The H&E staining image of tumor tissue in the PLGA/DTX@MnO2 group in Figure 9C and the X-ray CT images in Figure 11C were inadvertently misused during data acquisition. The correct Figure 9 is as follows. Figure 9 Inhibition of tumor growth in vivo by the drug delivery system.Abbreviations: H&E, hematoxylin and eosin; AuNR, gold nanorod; DTX, docetaxel; MnO2, manganese dioxide; PLGA, poly(lactic-co-glycolic acid); RF, radiofrequency.Notes: (A) Relative volumes of tumor-bearing mice; (B) body weight of the mice models (mean ± standard deviation; n=6); (C) H&E-stained tumor tissue sections: (a) control, (b) DTX, (c) PLGA/DTX@MnO2, (d) PLGA/DTX@MnO2 + RF, (e) PLGA/AuNR/DTX@MnO2, and (f) PLGA/AuNR/DTX@MnO2 + RF. The correct Figure 11 is as follows. Figure 11 Dual-mode imaging in vivo.Abbreviations: MR, magnetic resonance; CT, computed tomography.Notes: (A, B) T1-weighted MR images; (C) X-ray CT images: (a) control; (b) 4 h; (c) 8 h. The authors apologize for these errors and advise they do not affect the results and conclusions of the paper.

Jiaqi He,1,&ast; Xiuhui Lu,2,&ast; Chenchen Yuan,1 Yali Zheng,2 Fangzhou Chen,2 Jing Luo,2 Kejiao Ma,2 Fan Yang,2 Peng Wang,2 Dongsheng Zhou,2 Li Wang,1 Zhe Yin2 1Department of Clinical Laboratory, The First Affiliated Hospital of Henan University, Kaifeng, 475000, People’s Republic of China; 2State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Li Wang, Department of Clinical Laboratory, The First Affiliated Hospital of Henan University, Kaifeng, 475000, People’s Republic of China, Email wangli851217@163.com Zhe Yin, State Key Laboratory of Pathogen and Biosecurity, Academy of Military Medical Sciences, Beijing, 100071, People’s Republic of China, Email jerry9yin@163.comPurpose: Pseudomonas aeruginosa is a common causative bacteria in nosocomial infections. This study aims to describe the structure and evolutionary characteristics of mobile genetic elements (MGEs) carrying antibiotic resistance genes (ARGs) from P. aeruginosa and to conduct bioinformatics and comparative genomic analysis to provide a deeper understanding of the genetic characteristics and diversity of MGEs in P. aeruginosa.Methods: Fifteen clinical isolates of P. aeruginosa from China were collected and sequenced in this study, and 15 novel MGEs were identified. Together with four MGEs from GenBank, a total of 19 MGEs were used to perform detailed modular structure dissection and sequence comparison. Then, the biological experiments were carried out to verify the biological characteristics of these isolates and MEGs.Results: The novel MGEs identified in this study displayed diversification in modular structures, which showed complex mosaic natures. The seven types of 19 MGEs included in this study were divided into three groups: i) novel MGEs (firstly identified in this study): four IncpSE5381-aadB plasmids and three Tn 7495-related integrative and mobilizable elements (IMEs); ii) newly defined MGEs (firstly designated in this study, but with previously determined sequences): four Tn 7665-related IMEs; iii) novel transposons with reference prototypes identified in this study: two Tn 6417-related integrative and conjugative elements (ICEs), two IS-based transposition units, two Tn 501-related unit transposons, two Tn 1403-related unit transposons. At least 36 ARGs involved in resistance to 11 different classes of antimicrobials and heavy metals were identified. Additionally, three novel blaOXA variants were identified. Antimicrobial susceptibility testing showed that these variants were resistant to some β-lactamase antibiotics and blaOXA-1204 was additionally resistant to cephalosporins.Conclusion: The continuous evolution of ARG-carrying MGEs during transmission, leading to the emergence of novel MGEs or ARGs, which facilitates the spread of antibiotic resistance in P. aeruginosa and enhances the diversity of transmission modes of bacterial resistance.Keywords: Pseudomonas aeruginosa, genome sequencing, mobile genetic elements, antimicrobial resistance, OXA

Jiangying Li,1 Lu Chen,2 Lichun Wang3 1Department of Cardiology, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300, People’s Republic of China; 2Department of Emergency, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300, People’s Republic of China; 3Department of Nursing, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, Taizhou, 225300, People’s Republic of ChinaCorrespondence: Lichun Wang, Department of Nursing, The Affiliated Taizhou People’s Hospital of Nanjing Medical University, Taizhou School of Clinical Medicine, Nanjing Medical University, No. 366 Taihu Road, Taizhou Pharmaceutical High-Tech Zone, Taizhou, 225300, People’s Republic of China, Tel +86 13775704547, Email lichunwangwlc@126.comAbstract: Heart failure, a chronic condition, often manifests with reduced physical function and an overall decline in quality of life. It is considered critical that patients with heart failure recover as soon as possible; exercise training, which includes aerobic exercise, resistance exercise, inspiratory muscle training, traditional mind-body exercise, and combined training, facilitates this. The research progress on the impact of various exercise modalities on the physical function and quality of life of patients with heart failure is systematically reviewed in this article. The objective is to augment the understanding of healthcare personnel regarding the status of implementation and outcomes associated with varied exercise modalities. This endeavor seeks to provide a point of reference for the development of exercise rehabilitation programs tailored to individuals contending with heart failure.Keywords: exercise modalities, heart failure, physical function, quality of life, review

Dawei Ren,1 Yan Zhang,1 Bo Du,1 Lina Wang,2 Meiheng Gong,1 Wei Zhu1 1Department of Otorhinolaryngology, the First Hospital of Jilin University, Changchun, People’s Republic of China; 2Department of Pediatric Respiration, the First Hospital of Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Wei Zhu, Email zhuwei@jlu.edu.cnBackground: Electrical stimulation (ES) can effectively promote skin wound healing; however, single-electrode-based ES strategies are difficult to cover the entire wound area, and the effectiveness of ES is often limited by the inconsistent mechanical properties of the electrode and wound tissue. The above factors may lead to ES treatment is not ideal.Methods: A multifunctional conductive hydrogel dressing containing methacrylated gelatin (GelMA), Ti3C2 and collagen binding antimicrobial peptides (V-Os) was developed to improve wound management. Ti3C2 was selected as the electrode component due to its excellent electrical conductivity, the modified antimicrobial peptide V-Os could replace traditional antibiotics to suppress bacterial infections, and GelMA hydrogel was used due to its clinical applicability in wound healing.Results: The results showed that this new hydrogel dressing (GelMA@Ti3C2/V-Os) not only has excellent electrical conductivity and biocompatibility but also has a durable and efficient bactericidal effect. The modified antimicrobial peptides V-Os used were able to bind more closely to GelMA hydrogel to exert long-lasting antibacterial effects. The results of cell experiment showed that the GelMA@Ti3C2/V-Os hydrogel dressing could enhance the effect of current stimulation and significantly improve the migration, proliferation and tissue repair related genes expression of fibroblasts. In vitro experiments results showed that under ES, GelMA@Ti3C2/V-Os hydrogel dressing could promote re-epithelialization, enhance angiogenesis, mediate immune response and prevent wound infection.Conclusion: This multifunctional nanocomposite hydrogel could provide new strategies for promoting infectious wound healing. Keywords: MXene, GelMA, electrical stimulation, antimicrobial peptides, wound healing

Yujie Xie,1 Fanglin Shao,1 Yuxiu Ji,1 Dechao Feng,1,2 Ling Wang,3 Zonghai Huang,3 Shengjian Wu,1 Fuhua Sun,1 Hong Jiang,4 Akira Miyamoto,5 Haiming Wang,6 Chi Zhang1 1Rehabilitation Medicine Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 2Department of Urology, Institute of Urology, West China Hospital, Sichuan University, Chengdu, Sichuan, People’s Republic of China; 3School of Information and Communication Engineering, University of Electronic Science and Technology, Chengdu, Sichuan, People’s Republic of China; 4Rehabilitation Medicine Department, Xichong County People’s hospital, Nanchong, Sichuan, People’s Republic of China; 5Faculty of Rehabilitation, Nishikyushu University, Kansaitama, Japan; 6Department of Rehabilitation Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Haiming Wang, Department of Rehabilitation Medicine, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China, Tel +868950771, Fax +86 830 8950771, Email wanghaiming866@163.com Chi Zhang, Rehabilitation Medicine Department, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China, Email chizhang_swmu@126.comPurpose: To provide a comprehensive analysis of associated genes with osteoarthritis (OA). Here, we reported a network analysis of OA progression by using a Steiner minimal tree algorithm.Methods: We collected the OA-related genes through screening the publications in MEDLINE. We performed functional analysis to analyze the associated biochemical pathways of the OA-related genes. Pathway crosstalk analysis was constructed to explore interactions of the enriched pathways. Steiner minimal tree algorithm was used to analyze molecular pathway networks. The average clustering coefficient was compared with the corresponding values of the Osteoarthritis-specific network. The new finding RNA was compared with former single-cell RNA-seq analysis results.Results: A gene set with 177 members reported to be significantly associated with Osteoarthritis was collected from 187 studies. Functional enrichment analysis revealed a specific related-OA gene including skeletal system development, cytokine-mediated signaling pathway, inflammatory response, cartilage development, and extracellular matrix organization. We performed a pathway crosstalk analysis among the 72 significantly enriched pathways. A total of 151 of the 177 genes in the Osteoarthritis gene set were included in the human interactome network. There were 31 genes in the former single-cell RNA-seq analysis results. The CLU, ENO1, SRRM1, UBC, HMGB1, NR3C1, NOTCH2NL, and CBX5 have significantly increased expression in seven molecularly defined populations of OA cartilage.Conclusion: The Steiner tree-based approach finds new biological molecules associated with OA genes.Keywords: network analysis, Steiner minimal tree, osteoarthritis, bioinformatics, osteoarthritis genes

Qiaomin Xu,1 Xintong Zou,2 Jimin Wu,1 Gongchen Duan,1 Haiyan Lan,1 Liangrong Wang2 1Department of Anesthesiology, Lishui People’s Hospital, Lishui, 323000, People’s Republic of China; 2Department of Anesthesiology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, 325000, People’s Republic of ChinaCorrespondence: Liangrong Wang, The First Affiliated Hospital of Wenzhou Medical University, No. 2, Fuxue Road, Lucheng District, Wenzhou City, Zhejiang Province, 325000, People’s Republic of China, Tel +86 13587884540, Email arerong1984@126.comBackground: Cough is one of the most common complications following intravenous administration of sufentanil during anesthesia induction. The study aimed to investigate the protective effect of alfentanil, afentanyl derivative with short onset time and short duration, in reducing sufentanil-induced cough.Patients and methods: Eighty patients that scheduled for thyroid surgery under general anesthesia were randomly divided into the alfentanil group and normal saline group, with 40 cases per group. Patients in the alfentanil group received intravenous administration of 2 μg/kg alfentanil prior to sufentanil injection during general anesthesia induction, while the same dose of normal saline was administered in the normal saline group. The outcomes measures included the incidence and severity of cough and common side effects of opioids following the administration of sufentanil during the induction of general anesthesia, intraoperative hemodynamics parameters and major adverse events during anesthesia recovery period.Results: The incidence of cough within one minute after the injection of sufentanil during anesthesia induction was 40% in the normal saline group, and the pretreatment of alfentanil significantly reduced the incidence of sufentanil-induced cough to 5% (p < 0.05). Correspondingly, the patients in the alfentanil group had decreased severity of sufentanil-induced cough compared with the normal saline group (p < 0.05). No significant differences in the incidences of common side effects of opioids (dizziness, nausea and vomiting, chest tightness and respiratory depression) within one minute after sufentanil injection were found (p > 0.05). Furthermore, there were no significant differences between the two groups in intraoperative hemodynamic parameters, extubation time, or the incidences of emergence agitation, respiratory depression, delayed recovery from anesthesia and postoperative nausea and vomiting during Postanesthesia Care Unit stay (p > 0.05).Conclusion: Pretreatment with low-dose alfentanil (2 μg/kg) effectively and safely reduced both the incidence and severity of sufentanil-induced cough during anesthesia induction.Clinical Trial Registration Number: Chinese Clinical Trial Registry (identifier: ChiCTR2300069286).Keywords: alfentanil, sufentanil, cough, anesthesia induction

Jian Zhou,1,2,&ast; Housheng Zheng,1,&ast; Huiru Zhang,1 Wenqiang Yu,1 Baoer Li,1 Liang Ye,1 Lu Wang1 1Hyperbaric Oxygen Department, International Cancer Center, Shenzhen University General Hospital, Shenzhen University Medical School, Shenzhen, 518055, People’s Republic of China; 2Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging, National-Regional Key Technology Engineering Laboratory for Medical Ultrasound, School of Biomedical Engineering, Shenzhen University Medical School, Shenzhen, 518060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lu Wang, Hyperbaric oxygen department, Shenzhen University General Hospital, Shenzhen University Medical School, Shenzhen, 518055, People’s Republic of China, Tel +86-0755-21839715, Email luwangszu@163.com Liang Ye, International Cancer Center, Shenzhen University Medical School, Shenzhen, 518055, People’s Republic of China, Tel +86-0755-26631420, Fax +86-0755-86671943, Email liangyeszu@163.comObjective: MCM5 is a DNA licensing factor involved in cell proliferation and has been previously established as an excellent biomarker in a number of malignancies. Nevertheless, the role of MCM5 in GBM has not been fully clarified. The present study aimed to investigate the potential roles of MCM5 in the treatment of GBM and to elucidate its underlying mechanism, which is beneficial for developing new therapeutic strategies and predicting prognosis.Methods: Firstly, we obtained transcriptomic and proteomic data from the TCGA and CPTAC databases on glioma patients. Employing the DeSeq2 R package, we then identified genes with joint differential expression in GBM tissues subjected to chemotherapy. To develop a prognostic risk score model, we performed univariate and multivariate Cox regression analyses. In vitro knockdown and overexpression of MCM5 were used to further investigate the biological functions of GBM cells. Additionally, we also delved into the upstream regulation of MCM5, revealing associations with several transcription factors. Finally, we investigated differences in immune cell infiltration and drug sensitivity across diverse risk groups identified in the prognostic risk model.Results: In this study, the chemotherapy-treated GBM samples exhibited consistent alterations in 46 upregulated and 94 downregulated genes at both the mRNA and protein levels. Notably, MCM5 emerged as a gene with prognostic significance as well as potential therapeutic relevance. In vitro experiments subsequently validated the role of increased MCM5 expression in promoting GBM cell proliferation and resistance to TMZ. Correlations with transcription factors such as CREB1, CTCF, NFYB, NRF1, PBX1, TEAD1, and USF1 were discovered during upstream regulatory analysis, enriching our understanding of MCM5 regulatory mechanisms. The study additionally delves into immune cell infiltration and drug sensitivity, providing valuable insights for personalized treatment approaches.Conclusion: This study identifies MCM5 as a key player in GBM, demonstrating its prognostic significance and potential therapeutic relevance by elucidating its role in promoting cell proliferation and resistance to chemotherapy.Keywords: glioblastoma, minichromosome maintenance protein 5, chemotherapeutic drug resistance

Luyang Zhang,1,&ast; Li Wang,2,&ast; Jiewen Long,1 Yan Yin,1 Sandip Patil1 1Department of Haematology and Oncology, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, 518000, People’s Republic of China; 2Department of Clinical Nutrition, Shenzhen Children’s Hospital, Shenzhen, Guangdong Province, 518000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Sandip Patil; Yan Yin, Department of Haematology and Oncology, Shenzhen Children’s Hospital, 7019 Yitian Road, Shenzhen, Guangdong Province, 518000, People’s Republic of China, Tel +86-755-83008283, Email sandippatil1309@yahoo.com; yinyan0915@sina.comObjective: This retrospective study evaluated nutritional status and body composition changes in paediatric β-thalassemia (β-TM) patients before and after hematopoietic stem cell transplantation (HSCT), using bioelectrical impedance analysis (BIA), and explored their relationship with HSCT outcomes.Methods: A cohort of 40 paediatric β-TM patients undergoing allogeneic HSCT was assessed for their nutritional status, anthropometric parameters, including body mass index (BMI), weight, and height, and body composition parameters pre-and post-HSCT, focusing on BIA measurements, including intracellular water (ICW), extracellular water (ECW), fat mass (FAT), fat-free mass (FFM), Skeletal Muscle Mass (SMM), soft Lean Mass (SLM), percent body fat (PBF), Body Cell Mass (BCM), Phase angle (PA) and muscle balance pre- and post-HSCT. Post-HSCT clinical outcomes, including acute graft-vs-host disease (aGVHD), engraftment time, oral mucositis (OM), sinusoidal obstruction syndrome (SOS), and diarrhoea in relation to nutrition status after HSCT were analysed.Results: After HSCT, 28.21% experienced diminished nutritional status, with 71.43% of those who were wasting before HSCT showing diminished nutritional status, significantly higher than the normal group (18.75%, P = 0.012). Anthropometric changes included significant weight reduction (87.5%, 22.15 ± 7.46 vs 20.74 ± 6.57, P < 0.001) and BMI decrease (90%, 15.19 ± 1.70 vs 14.05 ± 1.48, P < 0.001). Body composition parameters, which are FFM, SMM, SLM, ICW, ECW, BCM, and PA (18.26 ± 5.71 vs 17.27 ± 5.19, 8.68 ± 3.30 vs 7.93 ± 3.02, 17.11 ± 5.28 vs 16.06 ± 4.84, 8.19 ± 2.54 vs 7.62 ± 2.31, 5.15 ± 1.58 vs 4.94 ± 1.47, 11.74 ± 3.63 vs 10.92 ± 3.32, 4.42 ± 0.50 vs 3.90 ± 0.57, respectively, P < 0.001) analysis revealed significant decreases. No significant differences in clinical outcomes were observed based on nutritional status.Conclusion: Paediatric β-TM patients undergoing HSCT exhibit significant changes in nutrition status and body composition, emphasizing the need for focused attention on malnourished children who are more prone to diminished nutritional status. Comprehensive BIA aids in understanding the impact, urging consideration for extended follow-up and larger cohorts in future research.Keywords: paediatric β-thalassemia, hematopoietic stem cell transplantation, HSCT, bioelectrical impedance analysis, BIA, nutritional status, malnourished children

Lixia Wang,1,&ast; Yilai Pei,2,&ast; Yuanfei Zhu,1 Haiying Long,3 Weiguo Pang4 1Shanghai Teacher Institute, Shanghai, People’s Republic of China; 2China Institute of Education and Social Development, Beijing Normal University, Beijing, People’s Republic of China; 3Department of Educational Psychology, University of Kansas, Lawrence, KS, USA; 4School of Psychology and Cognitive Science, East China Normal University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haiying Long; Weiguo Pang, Email hlong@ku.edu; wgpang@psy.ecnu.edu.cnIntroduction: The schizotypy-creativity link has been studied from different perspectives over the past few decades, yet the results of this relationship are inconsistent in the literature. Previous studies have suggested that two basic motivational systems—Behavioral Inhibition System (BIS, avoidance motivation) and Behavioral Activation System (BAS, approach motivation)—underlie the relationship between schizotypy and creativity. Few empirical studies, however, have examined how the relationship interacts with other variables. This study fills these gaps and explores the role of the approach and avoidance motivation assessed by trait behavioral activation and inhibition in the link between schizotypy as a dimensional personality trait and creative ideational behavior as a measure of creativity.Method: Undergraduate students (N = 388) completed questionnaires including the Schizotypal Personality Questionnaire (SPQ) measuring 3 dimensions of schizotypy, Runco Ideational Behavior Scale (RIBS) measuring creative ideational behavior, and BIS/BAS Scales measuring trait behavioral motivation. Bivariate Pearson correlation was computed, and hierarchical linear regression was performed to explore the effects of schizotypy, BIS/BAS, and their interaction on creative ideational behavior. The conditional effect of schizotypy based on different levels of the moderator was further tested.Results: The total score, positive dimension and disorganized dimension of SPQ were all positively correlated with RIBS, BAS, and BIS. Negative dimension of SPQ was not significantly correlated with the RIBS score but was positively correlated with BIS. Additionally, after controlling gender and age, BAS significantly moderated the relationship between the positive and disorganized dimensions of schizotypy and creative ideational behavior measured by RIBS. However, BIS was not a significant moderator.Discussion: The findings of this study regarding the relationships between different dimensions of schizotypy, two motivational systems, and creative ideational behavior were mostly consistent with previous findings. The significant moderated effect of BAS on the relationship between two dimensions of schizotypy and creative ideational behavior made significant contributions to the understanding of the relationship between schizotypy and creativity.Keywords: schizotypy, creativity, creative ideational behavior, motivation