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Wenxian Lin,1– 4 Lizhu Tang,1,2,5 Chenyi Zhuo,1 Xiuli Mao,1– 4 Jiajia Shen,6 Shaoang Huang,3 Shangyang Li,3,7 Yujuan Qin,3,4 Ju Liao,2,3 Yuhong Chen,8 Xiamin Zhang,3,4 Yuting Li,9 Jian Song,4 Lingzhang Meng,4 Xiaofeng Dong,10 Yueyong Li2 1Key Laboratory of Molecular Pathology for Hepatobiliary Diseases of Guangxi, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, The People’s Republic of China; 2Department of Interventional Oncology, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, The People’s Republic of China; 3Graduate School, Youjiang Medical University for Nationalities, Baise, 533000, The People’s Republic of China; 4Institute of Cardiovascular Sciences, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530016, The People’s Republic of China; 5Department of Radiation Oncology, The First Affiliated Hospital of Jinan University, Guangzhou, 510632, The People’s Republic of China; 6Department of Laboratory Medicine, Nanning Maternity and Child Health Hospital & Nanning Women and Children’s Hospital, Nanning, 530011, The People’s Republic of China; 7Department of Laboratory Medicine, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530016, The People’s Republic of China; 8Department of Nephrology, the Second Affiliated Hospital of Guangxi Medical University, Nanning, 530007, The People’s Republic of China; 9Graduate School, Guangxi University of Chinese Medicine, Nanning, 530200, The People’s Republic of China; 10Department of Hepatobiliary, Pancreas and Spleen Surgery, Guangxi Academy of Medical Sciences & The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530016, The People’s Republic of ChinaCorrespondence: Yueyong Li; Xiaofeng Dong, Email 305017674@qq.com; gandanyingcai@163.comBackground: Cancer-associated fibroblasts (CAFs) play a pivotal role in shaping the microenvironment of hepatocellular carcinoma (HCC). However, the mechanisms through which CAFs influence the progression of HCC remain incompletely understood.Methods: Single-cell RNA sequencing datasets (GSE158723 and GSE112271) were retrieved from the Gene Expression Omnibus (GEO) database at the National Center for Biotechnology Information (NCBI) and analyzed using R software. Our analysis suggested that CAFs may promote liver cancer cell development, possibly through the interaction of pleiotrophin (PTN) and syndecan-2 (SDC2). Clinical samples from HCC patients were collected and processed into frozen sections and single-cell suspensions for Masson staining, immunofluorescence staining, and flow cytometry. Additionally, Huh7 liver cancer cells and LO2 normal liver cells were cultured and subjected to immunofluorescence assays using cell slides.Results: The proportion of CAFs in cancerous tissues was higher than in adjacent non-cancerous tissues, and pleiotrophin (PTN) expression was elevated in cancer tissues compared to adjacent tissues. These findings aligned with the results of the single-cell RNA sequencing (scRNA-seq) analysis. Furthermore, SDC2 expression was significantly upregulated in Huh7 liver cancer cells compared to LO2 normal liver cells.Discussion: This study suggests that CAFs may contribute to HCC progression via the PTN/SDC2 signaling pathway. Our findings provide deeper insights into the interactions between CAFs and HCC cells within the tumor microenvironment (TME).Keywords: CAFs, HCC, PTN, scRNA-seq, TME

Chuxiao Zhang, Yuelan Qin, Yangguang Song, Yingying Liu, Xiaodong Zhu Department of Radiation Oncology, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, People’s Republic of ChinaCorrespondence: Xiaodong Zhu, Department of Radiation OncologyGuangxi Medical University Cancer Hospital, No. 71 hedi Road, Nanning, Guangxi, 530021, People’s Republic of China, Email xdzhu1466@hotmail.comPurpose: There are insufficient data about the optimal treatment for older patients with recurring medium or large hepatocellular carcinoma (HCC). The study intended to assess the effect of transcatheter arterial chemoembolization combined with microwave ablation (TACE-MWA) in an elderly cohort through a retrospective analysis.Methods: From 2011 to 2018, a cohort of individuals (age ≥ 70 years) with recurrent HCC tumors ranging from 3.1 cm to 7 cm underwent either a combination treatment of TACE and MWA (n = 43) or surgical intervention (n = 33). Using the Inverse Probability of Treatment Weighting (IPTW) technique, factors of disease-free survival (DFS), overall survival (OS), and rates of major adverse events were analyzed, retrospectively.Results: The group that underwent surgery had a greater history of alcohol use before treatment (P= 0.001), as well as a higher Barcelona Clinic Liver Cancer (BCLC) stage for the primary tumor before treatment (P= 0.014) and a higher primary tumor location before treatment (P= 0.045). The TACE-MWA group had DFS rates of 86.2%, 68.8%, and 60.4% at 1, 3, and 5 years, while the surgery group had rates of 53.0%, 42.2%, and 25.8% at the same time points. In the TACE-MWA treatment group, survival rates at 1 year, 3 years, and 5 years post-treatment were recorded as 93.0%, 80.8%, and 65.7%, respectively, while in the surgery group, they were 62.7%, 46.9%, and 42.6%. In the univariate analysis using IPTW, the type of treatment was found to have a significant correlation with disease progression (hazard ratio [HR] 0.41, 95% CI 0.20– 0.86, P=0.017). IPTW multivariate analysis showed that treatment modality (HR, 0.35; 95% CI, 0.17 to 0.79; P= 0.011) was the only significant prognostic factor for OS.Conclusion: In elderly patients with recurrent 3.1 cm≤ HCC ≤ 7 cm, TACE-WMA was superior to surgery in the respects of DFS and OS.Keywords: elderly patients, hepatocellular carcinoma, transcatheter arterial chemoembolization, microwave ablation, treatment modality

Yu Qin, Jingjing Ye, Haoxiang Li, Xunan Wu, Yue Xia, Xia Deng Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of ChinaCorrespondence: Xia Deng, Department of Endocrinology, Affiliated Hospital of Jiangsu University, Zhenjiang, 212000, People’s Republic of China, Email dengxia11@outlook.comPurpose: This study aimed to investigate the relationship between weight-adjusted waist index (WWI) and albuminuria in patients with type 2 diabetes mellitus (T2DM) in the Chinese population.Patients and Methods: A total of 860 adult patients in the Department of Endocrinology of the Affiliated Hospital of Jiangsu University were retrospectively analyzed from June 2018 to September 2023. Correlations between WWI and albuminuria (albumin-to-creatinine ratio (UACR) ≥ 30 mg/g were defined as albuminuria) were analyzed using the Pearson and Spearman methods. The associations between albuminuria and Age, gender, body mass index (BMI), waist circumference/ hip circumference (WHR), systolic blood pressure(SBP), diastolic blood pressure (DBP), fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2h PG), fasting plasma insulin (FIns), 2-h postprandial insulin (2hINS), glycosylated hemoglobin (HbA1c), WWI, homeostasis model assessment of insulin resistance (HOMA-IR) were analyzed via binary logistic regression.Results: Compared with the normal albumin group, serum urea nitrogen, serum creatinine, UACR, and WWI levels in the albuminuria group were significantly increased, while estimated glomerular filtration rate (eGFR) levels were significantly decreased (P < 0.05). Correlation analyses revealed that WWI was positively correlated with UACR but negatively correlated with urea nitrogen, serum creatinine, and eGFR (P < 0.05). Binary logistic regression analyses indicated that WWI was an independent risk factor for albuminuria in T2DM patients. Receiver operating characteristic curve results showed that the area under the curve for albuminuria as predicted by WWI was 0.605 [95% CI = (0.563– 0.646), P < 0.001].Conclusion: WWI is independently associated with albuminuria in the Chinese patients with type 2 diabetes and may serve as a simple indicator for albuminuria risk assessment.Keywords: weight-adjusted waist index, kidney function, albuminuria, type 2 diabetes

Yuexiang Qin,1,2 Shanhu Yao,3,4 Gaoyuan Wang,5 Ziyuan Xu,6,7 Gangcai Zhu,8 Ying Li,1,2 Pingting Yang,1,2 Jiangang Wang,1,2 Chunbo Zou,5 Changhan Chen7,9 1Department of Health Management Medicine, The Third Xiangya Hospital of Central South University, Changsha, Hunan Province, 410013, People’s Republic of China; 2Hunan Chronic Disease Health Management Medical Research Center, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, 410013, People’s Republic of China; 3Department of Radiology, The Third Xiangya Hospital, Central South University, Changsha, Hunan Province, 410013, People’s Republic of China; 4Key Laboratory of Medical Information Research, Central South University, Changsha, Hunan Province, 410013, People’s Republic of China; 5Department of Nephrology, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, People’s Republic of China; 6Department of Otolaryngology, Head and Neck Surgery, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, People’s Republic of China; 7National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, Hunan, People’s Republic of China; 8Department of Otolaryngology, Head and Neck Surgery, The Second Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, People’s Republic of China; 9National Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, Hunan Province, 410008, People’s Republic of ChinaCorrespondence: Changhan Chen, National Medical Metabolomics International Collaborative Research Center, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, People’s Republic of China, Tel +86-13875974606, Email changhanchen@csu.edu.cnObjective: Inflammation plays a crucial role in the development of metabolic syndrome (MetS). However, the roles of pepsinogens (PGs) and gastrin, known biomarkers linked to gastric inflammation, in MetS and the transition of MetS status are unclear. This research aimed to explore the relationship between MetS, the transition of MetS status, and levels of gastric biomarkers.Methods: This large-scale cross-sectional study included 19162 participants aged 18– 80 years between August 2021 and March 2024. Serum levels of the gastric biomarkers PGI, PGII, and gastrin-17 were analyzed using enzyme-linked immunosorbent assay. In addition, the relationship between transitions of MetS status based on 1032 MetS-negative participants from baseline to the second health exam after 2 years was considered. The association between MetS and the transitions of MetS status and gastric biomarkers was analyzed using logistic regression models.Results: The prevalence of MetS in the study population was 31.4%, with higher rates in males (35.2%) than females (24.6%). Gastrin-17 levels were markedly elevated in participants with MetS, a trend observed in both genders. In the logistic regression analysis, after adjusting for confounding factors, gastrin-17 levels were strongly and positively correlated with MetS in the entire cohort and in males but not in females. Male participants with MetS had lower levels of PGI and PGII than those without MetS, whereas the opposite trend was observed in females. Logistic regression analysis indicated that PGI and PGII were not independently associated with MetS. During the follow-up of 2 years, 199 (19.28%) of the 1032 MetS-negative participants transitioned to MetS-positive status. As compared to the stable MetS-negative subjects, transition from MetS-negative to MetS-positive was associated with higher levels of gastrin-17, especially in males, but not in females.Conclusion: Gastrin-17 is a promising biomarker for MetS, exhibiting potential utility in monitoring the transition of MetS status and revealing gender difference.Keywords: gastric biomarkers, gastrin-17, metabolic syndrome, transition, gender difference

Xiang Huo,1 Zhongming Tan,1,2 Huimin Qian,1,2 Yuanfang Qin,1,2 Chen Dong,1,2 Chuchu Li,1,2 Xiaoxiao Kong,1,2 Jie Hong1,2 1National Health Commission (NHC) Key Laboratory of Enteric Pathogenic Microbiology, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People’s Republic of China; 2Department of Acute Infectious Disease Control and Prevention, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People’s Republic of ChinaCorrespondence: Jie Hong, Department of Acute Infectious Disease Control and Prevention, Jiangsu Provincial Center for Disease Control and Prevention, 172 Jiangsu Road, Gulou Distrct, Nanjing, People’s Republic of China, Email hongjie@jscdc.cnBackground: Streptococcus pneumoniae is a significant etiological agent of infection and commonly inhabits the human nasopharynx, alongside other potentially pathogenic bacteria. In this study, S. pneumoniae strains were obtained from a community population and subjected to investigation of their phenotypes, genotypes, and vaccine coverage.Methods: S. pneumoniae was isolated from nasopharyngeal swab samples of a healthy population in the Guangfu Community. Capsular serotypes and genotypes were identified using Quellung reaction and multilocus sequence typing (MLST), respectively. The antimicrobial susceptibility was tested using minimum inhibitory concentrations.Results: In total, 500 unvaccinated people were sampled. Ninety-four S. pneumoniae strains were identified. Common serotypes were 19F, 6A, and 9V. The strain coverages of PCV13 and PPV23 were 61.7% and 58.5%, respectively. About 27.6% isolates were non-susceptible to penicillin, and over 80% were resistant to erythromycin and doxycycline. Among 27 novel sequence types (STs) identified in all strains, the most common STs were ST236 (6/94, 6.4%) and ST12669 (6/94, 6.4%). Nearly half of the strains were grouped into four clone complexes (CC12665, CC271, CC6011, and CC180), of which CC271 showed the highest resistance to PEN.Conclusion: In our study, various drug-resistant clone complexes of Streptococcus pneumoniae were found in the healthy population, the elderly, and children. Consequently, pneumococcal vaccines should be included in the national immunization schedule to prevent disease spread.Keywords: vaccine, Streptococcus pneumonia, serotype, antibiotics, STs

Yao Qin,1 Xingwu Zou,1 Yanghui Jin,2 Jinmeng Li,3 Qingshan Cai1 1Department of Tuberculosis, Hangzhou Red Cross Hospital, Hangzhou, People’s Republic of China; 2Department of Orthopaedic, Hangzhou Red Cross Hospital, Hangzhou, People’s Republic of China; 3Department of Pharmacy, Hangzhou Red Cross Hospital, Hangzhou, People’s Republic of ChinaCorrespondence: Qingshan Cai, Department of Tuberculosis, Hangzhou Red Cross Hospital, Hangzhou, People’s Republic of China, Email caiqs66@163.comAim: Cryptococcus neoformans osteomyelitis coupled with tuberculosis and tuberculous lymphadenitis, is a rare occurrence in clinical. Diagnostic challenges arise due to the clinical radiological similarity of this condition to other lung infections and the limited and sensitive nature of traditional approaches. Here, we present a case of co-infection diagnosed using Metagenomic Next-Generation Sequencing, highlighting the effectiveness of advanced genomic techniques in such complex scenarios.Case Presentation: We present a case of a 67-year-old female infected with cryptococcal osteomyelitis and presented with swelling and pain in the right ankle. Following a biopsy of the right ankle joint, Metagenomic Next-Generation Sequencing (mNGS) of the biopsy tissue revealed Cryptococcus neoformans infection. Positive results for Cryptococcus capsular antigen and pathological findings confirmed the presence of Cryptococcus neoformans. The patient underwent surgical debridement, coupled with oral fluconazole treatment (300mg/day), leading to the resolution of symptoms.Conclusion: Cryptococcus neoformans is an uncommon cause of ankle infection. Metagenomic Next-Generation Sequencing (mNGS) serves as a valuable diagnostic tool, aiding clinicians in differentiating cryptococcal osteomyelitis from other atypical infections.Keywords: Cryptococcus neoformans, tuberculosis, diagnosis, metagenomic next-generation sequencing, mNGS

Tiefa Guan,1,2,&ast; Yibing Qin,3,&ast; Nini Qu,3 Yushuo Pan1 1First Clinical College, Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning Province, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, the Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning Province, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Affiliated Hospital of Liaoning University of Traditional Chinese Medicine, Shenyang, Liaoning Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Nini Qu, Email qvnini@sina.comBackground: The immune cells play a substantial role in the development and progression of chronic obstructive pulmonary disease (COPD). We aim to investigate the causal involvement of immune cells in COPD via a Mendelian randomization (MR) analysis.Methods: Published genome-wide association studies (GWAS) statistics on immune cells were analyzed, with genetic variants identified as instrumental variables (IVs). Inverse-variance weighting (IVW), weighted median, and MR-Egger regression methods were employed, along with simple mode and weighted mode adopted in the two-sample MR analysis. Sensitivity analysis was conducted to examine the heterogeneity, horizontal pleiotropy, and stability of the causal relationship.Results: IVW results suggested that CCR2 on CD62L+ plasmacytoid dendritic cells (DC), CCR2 on plasmacytoid DC, CD11b on CD66b++ myeloid cells, CD19 on CD20− CD38− CD24+ memory B cell subset, CD25 on transitional B cells, and CD25++CD8br %CD8br T cells were risk factors for the development of COPD. Besides, CD127 on effector memory-like cytotoxic T lymphocytes lacking expression of co-stimulatory molecule 28 (CD28-EM CTLs) and HLA DR+ NK ACs expressing human leukocyte antigen DR molecules while being natural killer cells (%NK ACs) were protective factors for COPD.Conclusion: This study unveiled a causal relationship between immune cell phenotype and COPD. These findings offer new insights for the prevention and treatment of COPD using COPD-associated immune cells.Keywords: chronic obstructive pulmonary disease, immune cells, causal inference, Mendelian randomization

Zhenyi Wang, Shimin Dong, Yanjun Qin Department of Emergency, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, People’s Republic of ChinaCorrespondence: Yanjun Qin; Shimin Dong, Department of Emergency, the Third Hospital of Hebei Medical University, Shijiazhuang, Hebei Province, 05000, People’s Republic of China, Email qyj778899@163.com; dsm_123@163.comPurpose: The aim of this study was to investigate the relationship between ARF and coagulopathy in patients with sepsis and to explore the prognostic value of these conditions.Patients and Methods: The data of 271 patients with sepsis-associated coagulopathy admitted from June 2021 to June 2022 were reviewed. The patients were divided into a survival group and a nonsurviving group according to patient prognosis. Independent sample t tests were utilized to compare laboratory parameters within 24 hours of admission, as well as the APACHE II and SOFA scores, between the two patient groups. According to the sepsis-associated coagulation dysfunction (SAC) grading criteria for grading, Spearman correlation analysis was used to study the relationship between blood creatinine and SAC grading and assignment scores, and receiver operating characteristic (ROC) curves and Cox’s proportional risk regression model were used to explore the factors affecting the prognosis of SAC patients.Results: Spearman correlation analysis revealed strong associations between serum creatinine (Scr) concentration, SAC classification, and SAC score, with coefficients above 0.7. SAC classification outcomes varied significantly with severity: mild severity had a 77.6% survival rate versus 22.4% mortality; moderate severity had 21.5% survival versus 78.5% mortality; and severe cases had a 0.7% survival rate versus 99.3% mortality (P< 0.01 for all). Multivariate analysis revealed significant predictors of outcome, including multiple organ dysfunction syndrome (MODS), with an OR of 2.070 (P=0.019); the SOFA score (OR=1.200, P< 0.01); the international normalized ratio (INR) (OR=0.72, P=0.013); and the Scr level (OR=0.995, P< 0.01). The areas under the ROC curves for the SOFA score, APACHE II score, and SAC classification were > 0.8, all P < 0.05.Conclusion: In patients with sepsis, SAC grade 3 or a SAC score of 4 or higher is associated with poorer prognosis, and the interaction of acute kidney injury exacerbates the degree of SAC, consequently affecting prognosis.Plain Language Summary: To investigate the relationship between acute renal dysfunction and coagulation dysfunction in patients with sepsis and to explore the prognostic value of these conditions. We collected information and laboratory indicators from 271 patients, classified these two groups of patients according to the grading criteria for sepsis-associated coagulation dysfunction (SAC), and compared the differences between them. We utilized Spearman correlation analysis to investigate the relationship between blood creatinine and the severity of sepsis-associated coagulation dysfunction (SAC). Additionally, we employed a Cox proportional hazards regression model to study the factors influencing the prognosis of SAC patients. This study revealed a significant positive correlation between blood creatinine levels and SAC grade. Furthermore, the presence of MODS, INR, blood creatinine, and SOFA score can serve as independent predictive factors for mortality. We can infer that there is a significant correlation between coagulation function parameters and blood creatinine levels, which play a crucial role in the diagnosis and prognostic analysis of sepsis. In patients with sepsis, a higher grade of SAC or an SAC score of 4 or higher indicates a poorer prognosis. Additionally, the interaction with acute kidney injury exacerbates the severity of SAC, thereby impacting patient prognosis.Keywords: sepsis, sepsis shock, acute kidney injury, sepsis-induced coagulopathy, multiple organ dysfunction syndrome

Liang Ruan,1,2 Shuailei Xu,1,2 Yuhan Qin,2 Huihong Tang,1,2 Xudong Li,1,2 Gaoliang Yan,2 Dong Wang,2 Chengchun Tang,2 Yong Qiao2 1School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Department of Cardiology, Zhongda Hospital, Southeast University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Chengchun Tang; Yong Qiao, Department of Cardiology, Zhongda Hospital, Southeast University, 87 Dingjiaqiao, Nanjing, 210009, People’s Republic of China, Email tangchengchun@hotmail.com; jinyong8866@163.comPurpose: Red blood cell distribution width to albumin ratio (RAR) is a novel inflammatory biomarker that independently predicts adverse cardiovascular events and acute kidney injury. This study aimed to assess the predictive value of RAR for cardio-renal syndrome type I (CRS-I) risk in acute myocardial infarction (AMI) patients.Patients and methods: This study retrospectively enrolled 551 patients who were definitively diagnosed as AMI between October 2021 and October 2022 at the Affiliated Zhongda Hospital of Southeast University. Participants were divided into two and four groups based on the occurrence of CRS-I and the quartiles of RAR, respectively. Demographic data, laboratory findings, coronary angiography data, and drug utilization were compared among the groups. Logistic regression and receiver operating characteristic curve (ROC) analysis were performed to identify independent risk factors for CRS-I and evaluated the predictive value of RAR for CRS-I.Results: Among the cohort of 551 patients, 103 (18.7%) developed CRS-I. Patients with CRS-I exhibited significantly elevated RAR levels compared to those without the condition, and the incidence of CRS-I correlated with escalating RAR. Univariate and multivariate logistic regression analyses identified RAR as an independent risk factor for CRS-I. ROC curves analysis demonstrated that RAR alone predicted CRS-I with an area under the curve (AUC) of 0.683 (95% CI=0.642– 0.741), which was superior to the traditional inflammatory marker C-reactive protein (CRP). Adding the variable RAR to the model for predicting the risk of CRS-I further improved the predictive value of the model from 0.808 (95% CI=0.781– 0.834) to 0.825 (95% CI=0.799– 0.850).Conclusion: RAR is an independent risk factor for CRS-I, and high levels of RAR are associated with an increased incidence of CRS-I in patients with AMI. RAR emerges as a valuable and readily accessible inflammatory biomarker that may play a pivotal role in risk stratification in clinical practice.Keywords: acute myocardial infarction, cardio-renal syndrome type I, red blood cell distribution width to albumin ratio, inflammatory

Jianmei Lu,1,2,&ast; Yongzhu Zeng,1,&ast; Huashuai Zhong,1 Wei Guo,1 Yuyan Zhang,1 Wanting Mai,3 Yucui Qin,4 Xiaodan Su,3 Bo Zhang,5 Weisen Wu,1 Yu Zhu,1 Qiujie Huang,6 Yong Ye1,7– 9 1Department of Pharmacy, Guangxi Medical University, Nanning, People’s Republic of China; 2The Second Nanning People’s Hospital, Nanning, People’s Republic of China; 3The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 4Maternity and Child Health Care of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 5Scientific Research Center, Guilin Medical University, Guilin, People’s Republic of China; 6Department of Pharmacy, Guangxi University of Traditional Chinese Medicine, Nanning, People’s Republic of China; 7Guangxi Key Laboratory of Bioactive Molecules Research and Evaluation, Nanning, People’s Republic of China; 8Guangxi Key Laboratory of Pharmaceutical Precision Detection and Screening, Nanning, People’s Republic of China; 9Key Laboratory of Micro-Nanoscale Bioanalysis and Drug Screening of Guangxi Education Department, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qiujie Huang, Department of Pharmacy, Guangxi University of Traditional Chinese Medicine, Nanning, People’s Republic of China, Email hqj8@163.com Yong Ye, Department of Pharmacy, Guangxi Medical University, Nanning, People’s Republic of China, Email yong-ye@163.comBackground and Purpose: Nitidine chloride (NC) is a botanical drug renowned for its potent anti-inflammatory, antimalarial, and hepatocellular carcinoma-inhibiting properties; however, its limited solubility poses challenges to its development and application. To address this issue, we have devised a colon-targeted delivery system (NC-CS/PT-NPs) aimed at modulating the dysbiosis of the gut microbiota by augmenting the interaction between NC and the intestinal microbiota, thereby exerting an effect against nonalcoholic fatty liver disease.Methods: The NC-CS/PT-NPs were synthesized using the ion gel method. Subsequently, the particle size distribution, morphology, drug loading efficiency, and release behavior of the NC-CS/PT-NPs were characterized. Furthermore, the impact of NC-CS/PT-NPs on non-alcoholic fatty liver disease (NAFLD) induced by a high-fat diet (HFD) in mice was investigated through serum biochemical analysis, ELISA, and histochemical staining. Additionally, the influence of NC-CS/PT-NPs on intestinal microbiota was analyzed using 16S rDNA gene sequencing.Results: The nanoparticles prepared in this study have an average particle size of (255.9± 5.10) nm, with an encapsulation rate of (72.83± 2.13) % and a drug loading of (4.65± 0.44) %. In vitro release experiments demonstrated that the cumulative release rate in the stomach and small intestine was lower than 22.0%, while it reached 66.75% in the colon. In vivo experiments conducted on HFD-induced NAFLD mice showed that treatment with NC-CS/PT-NPs inhibited weight gain, decreased serum aspartate aminotransferase (AST), Alanine aminotransferase (ALT) and lipid levels, improved liver and intestinal inflammation, and altered the diversity of gut microbiota in mice.Conclusion: This study provides new evidence for the treatment of NAFLD through the regulation of gut microbiota using active ingredients from traditional Chinese medicine.Keywords: nanoparticles, colonic targeting, metabolic disorders, gut microbiota

Fei Wang,1,2 Chun Yue Yan,3 Yuan Qin,4 Zheng Ming Wang,1 Dan Liu,1 Ying He,1 Ming Yang,2 Li Wen,1 Dong Zhang1 1Department of Radiology, XinQiao Hospital of Army Medical University, Chongqing, 400037, People’s Republic of China; 2Department of Medical Imaging, Luzhou People’s Hospital, Luzhou, 646000, People’s Republic of China; 3Department of Emergency Medicine, Luzhou People’s Hospital, Luzhou, 646000, People’s Republic of China; 4Department of Radiology, Chongqing University Three Gorges Hospital, Chongqing, 404031, People’s Republic of ChinaCorrespondence: Dong Zhang, Department of Radiology, Xin Qiao Hospital, Army Medical University, Chongqing, 400037, People’s Republic of China, Tel +86-23-68774676, Email hszhangd@tmmu.edu.cnBackground: Currently, it is still confused whether preoperative aminotransferase-to-platelet ratio (APRI) and gamma-glutamyl transferase-to-platelet ratio (GPR) can predict microvascular invasion (MVI) in solitary hepatocellular carcinoma (HCC). We aimed to develop and validate a machine-learning integration model for predicting MVI using APRI, GPR and gadoxetic acid disodium (Gd-EOB-DTPA) enhanced MRI.Methods: A total of 314 patients from XinQiao Hospital of Army Medical University were divided chronologically into training set (n = 220) and internal validation set (n = 94), and recurrence-free survival was determined to follow up after surgery. Seventy-three patients from Chongqing University Three Gorges Hospital and Luzhou People’s Hospital served as external validation set. Overall, 387 patients with solitary HCC were analyzed as whole dataset set. Least absolute shrinkage and selection operator, tenfold cross-validation and multivariate logistic regression were used to gradually filter features. Six machine-learning models and an ensemble of the all models (ENS) were built. The area under the receiver operating characteristic curve (AUC) and decision curve analysis were used to evaluate model’s performance.Results: APRI, GPR, HBPratio3 ([liver SI‒tumor SI]/liver SI), PLT, peritumoral enhancement, non-smooth margin and peritumoral hypointensity were independent risk factors for MVI. Six machine-learning models showed good performance for predicting MVI in training set (AUCs range, 0.793– 0.875), internal validation set (0.715– 0.832), external validation set (0.636– 0.746) and whole dataset set (0.756– 0.850). The ENS achieved the highest AUCs (0.879 vs 0.858 vs 0.839 vs 0.851) in four cohorts with excellent calibration and more net benefit. Subgroup analysis indicated that ENS obtained excellent AUCs (0.900 vs 0.809 vs 0.865 vs 0.908) in HCC > 5cm, ≤ 5cm, ≤ 3cm and ≤ 2cm cohorts. Kaplan‒Meier survival curves indicated that ENS achieved excellent stratification for MVI status.Conclusion: The APRI and GPR may be new potential biomarkers for predicting MVI of HCC. The ENS achieved optimal performance for predicting MVI in different sizes HCC and may aid in the individualized selection of surgical procedures.Keywords: hepatocellular carcinoma, microvascular invasion, inflammatory biomarker, magnetic resonance imaging, machine learning

Yuxin Liang,1,&ast; Deyuan Zhong,1,&ast; Qinyan Yang,1 Yuan Tang,1 Yingying Qin,2 Yuhao Su,1 Xiaolun Huang,1 Jin Shang1 1Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China; 2School of Pharmacy, Faculty of Medicine, Macau University of Science and Technology, Macau, SAR, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jin Shang; Xiaolun Huang, Liver Transplantation Center and HBP Surgery, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology of China, Chengdu, People’s Republic of China, Email 935516165@qq.com; huangxiaolun@med.uestc.edu.cnBackground: Tumor metastasis is the leading cause of high mortality in hepatocellular carcinoma (HCC). The metastasis-related HCC microenvironment is characterized by high heterogeneity. Single-cell RNA sequencing (scRNA-seq) may aid in determining specific cell clusters involved in regulating the immune microenvironment of HCC.Methods: The scRNA-seq data of 10 HCC samples were collected from the Gene Expression Omnibus (GEO) database GSE124395. Correlations between key gene expression and clinicopathological data were determined using public databases. HCC tissues and matched tumor-adjacent and normal tissue samples were obtained by surgical resection at Sichuan Cancer Hospital. Immune cell infiltration analysis was performed and verified by immunohistochemistry and immunofluorescent staining.Results: Nine malignant hepatocyte clusters with different marker genes and biological functions were identified. C3_Hepatocyte-SERF2 and C6_Hepatocyte-IL13RA2 were mainly involved in the regulation of the immune microenvironment, which was also a significant pathway in regulating HCC metastasis. Key genes in malignant hepatocyte clusters that associated with HCC metastasis were further screened by LASSO regression analysis. TPI1, a key gene in C6_Hepatocyte-IL13RA2 and HCC metastasis, could participate in regulating the HCC immune microenvironment in The Cancer Genome Atlas (TCGA) and Tumor Immune Estimation Resource (TIMER) databases. Moreover, immunohistochemistry analysis demonstrated that TPI1 expression was positively correlated with HCC metastasis and poor prognosis, while negatively correlated with CD8+ T cell infiltration. The negative correlation between TPI1 expression and CD8+ T cell infiltration was further confirmed by immunofluorescence staining.Conclusion: In summary, a cluster of TPI1+ malignant hepatocytes was associated with the suppression of CD8+ T cell infiltration and HCC metastasis, providing novel insights into potential biomarkers for immunotherapy in HCC.Keywords: single-cell RNA sequencing, malignant hepatocyte, hepatocellular carcinoma, immune microenvironment, metastasis

Ying Qin,1 Jingwen Zhao,1 Yong Yang,1 Yanjing Liu,1 Hui Xiang,2 Jingfeng Tong,3 Chengchen Huang3 1Department of Psychiatry, the Second People’s Hospital of Guizhou Province, Guiyang, 550004, People’s Republic of China; 2Department of Psychology, Guizhou Provincial People’s Hospital, Guiyang, 550002, People’s Republic of China; 3Shanghai Conlight Medical Laboratory, Co, Ltd, Shanghai, 200032, People’s Republic of ChinaCorrespondence: Chengchen Huang, Shanghai Conlight Medical Laboratory Co, Ltd, Shanghai, People’s Republic of China, Email huangcc@kangliyixue.comPurpose: We investigate the association of HTR1A rs10042486 and rs6295 with efficacy and plasma concentrations of atypical antipsychotics in the treatment of male patients with schizophrenia.Patients and Methods: A total of 140 male patients diagnosed with schizophrenia who were treated with any single atypical antipsychotic between May 2020 and May 2022 were retrospectively included. Clinical symptoms were assessed using Positive and Negative Syndrome Scale (PANSS). All SNPs were typed using Agena Bioscience MassARRAY DNA mass spectrometry. Plasma concentrations of antipsychotics at week 3, 6 and 12 after treatment commence were analyzed using mass spectrometry.Results: For efficacy of atypical antipsychotics, we observed no significant difference between HTR1A rs10042486, rs6295 and positive symptom improvement, where the patients with heterozygous mutant at the rs10042486 and rs6295 locus were superior to those with wild-type or homozygous mutant genotypes on negative symptom improvement, especially at 12 weeks of follow-up when the difference between genotypes at the rs6295 locus have statistical significance (P = 0.037). For plasma concentration, we found that quetiapine plasma concentrations were significantly lower in patients with mutation-heterozygous types than in wild-type and homozygous mutation genotypes at week 6. In contrast, higher plasma concentrations were found for mutant heterozygous than wild genotypes in the risperidone monotherapy analysis, and the difference among genotypes at the rs6295 locus was statistically significant at 6 weeks of follow-up.Conclusion: The assessment of the correlation of genetic polymorphisms of HTR1A rs6295 and rs10042486 in male patients with schizophrenia with the monitoring of therapeutic drug concentrations and therapeutic efficacy provides a constructive foundation for the clinical individualization of antipsychotics, such as quetiapine and risperidone, which is important in selecting the dose of the medication and improving the improvement of negative symptoms.Keywords: schizophrenia, HTR1A, polymorphism, plasma concentration, atypical antipsychotics, asian male patients

Yuhua Mai,1,2 Liheng Meng,1 Ganlu Deng,2,3 Yingfen Qin1 1Department of Endocrinology, The First Affiliated Hospital of GuangXi Medical University, Nanning, Guangxi, 530021, People’s Republic of China; 2Guangxi Key Laboratory of Enhanced Recovery after Surgery for Gastrointestinal Cancer (Guangxi Medical University), Ministry of Education, Nanning, Guangxi, 530021, People’s Republic of China; 3Department of Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of ChinaCorrespondence: Yingfen Qin, Department of Endocrinology, The First Affiliated Hospital of GuangXi Medical University, Nanning, 530021, Guangxi, People’s Republic of China, Tel/Fax +86-13607862619, Email yingfenq@126.com Ganlu Deng, Department of Oncology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Tel/Fax +86-15676132389, Email dengganlu@gxmu.edu.cnAbstract: With changes in modern lifestyles, type 2 diabetes mellitus (T2DM) has become a global epidemic metabolic disease, and hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related deaths worldwide. T2DM is a complex metabolic disorder and has been considered an independent risk factor for HCC. Growing evidence supports that T2DM-related risk factors facilitate hepatocarcinogenesis via abundant mechanisms. With the wide implementation of microbiomics, transcriptomics, and immunotherapy, the understanding of the complex mechanisms of intestinal flora and immune cell subsets have advanced tremendously in T2DM-related HCC, uncovering new findings in T2DM-related HCC patients. In addition, reports have indicated the different effects of anti-DM drugs on the progression of HCC. In this review, we summarize the effects of major T2DM-related risk factors (including hyperglycemia, hyperinsulinemia, insulin, chronic inflammation, obesity, nonalcoholic fatty liver disease, gut microbiota and immunomodulation), and anti-DM drugs on the carcinogensis and progression of HCC, as well as their potential molecular mechanisms. In addition, other factors (miRNAs, genes, and lifestyle) related to T2DM-related HCC are discussed. We propose a refined concept by which T2DM-related risk factors and anti-DM drugs contribute to HCC and discuss research directions prompted by such evidence worth pursuing in the coming years. Finally, we put forward novel therapeutic approaches to improve the prognosis of T2DM-related HCC, including exploiting novel diagnostic biomarkers, combination therapy with immunocheckpoint inhibitors, and enhancement of the standardized management of T2DM patients.Keywords: type 2 diabetes mellitus, hepatocellular carcinoma, NAFLD, gut microbiota, inflammatory, immunotherapy

Wei W, Mo X, Yan L, et al. Cancer Manag Res. 2020;12:15–30. We, the Editor and Publisher of the journal Cancer Management and Research have retracted the published article. Following publication, concerns were raised regarding the use of non-verifiable cell lines described in the article. The concerns related specifically to the use of cell lines which were found to be either contaminated, wrongly identified, improperly indexed, unavailable through external cell line repositories, and/or lacking publications describing their establishment. Overall, these concerns raised doubts about the validity of the findings described in the article. The corresponding author did not respond to our queries and was unable to provide information relating to the use of these cell lines or provide original data relating to the study. As verifying the validity of published work is core to the integrity of the scholarly record, the Publisher and Editor requested to retract the article and the corresponding author was notified of this decision. We have been informed in our decision-making by our editorial policies and COPE guidelines. The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as “Retracted”.

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

Yifan Qin, Huiyu She, Wenrui Peng, Xiaofeng Zhou, Yiting Wang, Peng Jiang, Jin Wu Department of Anesthesiology, Affiliated Hospital of Jiangsu University, Zhenjiang, People’s Republic of ChinaCorrespondence: Jin Wu, Department of Anesthesiology, Affiliated Hospital of Jiangsu University, 438 Jie Fang Road, Zhenjiang, Jiangsu, 212001, People’s Republic of China, Email wujin914@hotmail.comPurpose: Multiple regional nerve blocks proved no additional benefit in total laparoscopic hysterectomy in multimodal analgesia, as postoperative pain may mainly originate from the vaginal cuff. Theoretically, caudal block can relieve pain from the vaginal cuff by a sacral spinal nerve block. We aimed to verify whether a caudal block with ropivacaine and morphine can achieve an analgesic effect without additional adverse effects after a total laparoscopic hysterectomy.Patients and Methods: Forty-eight patients undergoing total laparoscopic hysterectomy were randomly allocated to receive preoperative caudal block with 20 mL of mixture including 0.25% ropivacaine and 2 mg morphine (caudal block group) or sham block (sham group). The primary outcome was the postoperative 24 h cumulative sufentanil consumption.Results: Median (IQR) sufentanil consumption in the first 24 postoperative hours of the caudal block group and the sham group was 0.00 (0.00 to 0.05) μg/kg vs 0.13 (0.04 to 0.21) μg/kg, respectively, p < 0.001. The majority of patients felt that visceral pain was more intense than incisional pain at 1, 6, 12, and 24 h post-surgery in the sham group (95.8% at 1 h, 95.8% at 6 h, 95.8% at 12 h, and 75% at 24 h post-surgery). Compared to the sham group, the caudal block reduced visceral pain scores at rest and during movement at 1 h (p < 0.001), 6 h (p < 0.001), 12 h (p < 0.001), and 24 h (p < 0.001) post-surgery. Intraoperative remifentanil consumption was significantly lower in the caudal block group than in the sham group (p = 0.004). There were no significant differences in other secondary outcomes between the two groups.Conclusion: A caudal block with ropivacaine and morphine could provide a satisfactory analgesic effect for 24 h postoperatively without additional adverse effects after total laparoscopic hysterectomy.Keywords: anesthesia, caudal, visceral pain, hysterectomy, pain, postoperative, postoperative nausea and vomiting, gynecologic surgical procedures

Qiumei Lin,1,&ast; Zongwei Jiang,1,&ast; Dan Mo,2,&ast; Fengfei Liu,1 Yuling Qin,1 Yihua Liang,1 Yuchen Cheng,3 Hao Huang,1 Min Fang1,4 1Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China; 2Department of Breast, Guangxi Zhuang Autonomous Region Maternal and Child Health Care Hospital, Nanning, 530025, People’s Republic of China; 3Department of Clinical Laboratory, Wuzhou Maternal and Child Health-Care Hospital, Wuzhou, People’s Republic of China; 4Engineering Research Center for Tissue & Organ Injury and Repair Medicine, Guangxi Medical University Cancer Hospital, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Huang; Min Fang, Email 1057226867@qq.com; fangmin@sr.gxmu.edu.cnBackground: Accurate prognosis is crucial for improving hepatocellular carcinoma (HCC) patients, clinical management, and outcomes post-liver resection. However, the lack of reliable prognostic indicators poses a significant challenge. This study aimed to develop a user-friendly nomogram to predict HCC patients’ post-resection prognosis.Methods: We retrospectively analyzed the data from 1091 HCC patients, randomly split into training (n=767) and validation (n=324) cohorts. Receiver operating characteristic (ROC) curves determined the optimal cut-off value for alpha1-microglobulin (α 1MG) and Beta2-microglobulin (β 2MG). Kaplan–Meier analysis assessed microglobulin’s impact on survival, followed by Cox regression to identify prognostic factors and construct a nomogram. The predictive accuracy and discriminative ability of the nomogram were measured by the concordance index (C-index), calibration curves, area under the ROC curve (AUC), and decision curve analysis (DCA), and were compared with the BCLC staging system, Edmondson grade, or BCLC stage plus Edmondson grade.Results: Patients with high β 2MG (≥ 2.395mg/L) had worse overall survival (OS). The nomogram integrated β 2MG, BCLC stage, Edmondson grade, microvascular invasion (MVI), and serum carbohydrate antigen 199 (CA199) levels. C-index for training and validation cohorts (0.712 and 0.709) outperformed the BCLC stage (0.660 and 0.657), Edmondson grade (0.579 and 0.564), and the combination of BCLC stage with Edmondson grade (0.681 and 0.668), improving prognosis prediction. Calibration curves demonstrated good agreement between predicted and observed survival. AUC values exceeded 0.700 over time, highlighting the nomogram’s discriminative ability. DCA revealed superior overall net income compared to other systems, emphasizing its clinical utility.Conclusion: Our β 2MG-based nomogram accurately predicts HCC patients’ post-resection prognosis, aiding intervention and follow-up planning. Significantly, our nomogram surpasses existing prognostic indicators, including BCLC stage, Edmondson grade, and the combination of BCLC stage with Edmondson grade, by demonstrating superior predictive performance.Keywords: hepatocellular carcinoma, nomogram, microglobulin, prognosis

Linghang Zhou, Jin Tan, Yuzhe Dai, Keke Zhu, Yanbo Xiao, Dan Wu, Zongkang Wang, Yisi Tan, Yijie Qin Department of Stomatology, The First Affiliated Hospital of Hunan University of Chinese Medicine, Changsha, Hunan, 410007, People’s Republic of ChinaCorrespondence: Jin Tan, Department of Stomatology, The First Affiliated Hospital of Hunan University of Chinese Medicine, 95 Shaoshan Middle Road, Changsha, Hunan, People’s Republic of China, Email 310176@hnucm.edu.cnPurpose: Arecoline is one of the main toxic components of arecoline to cause oral mucosal lesions or canceration, which seriously affects the survival and life quality of patients. This study analyzed the mechanism of Jiawei Danxuan Koukang (JDK) in alleviating arecoline induced oral mucosal lesions, to provide new insights for the treatment of oral submucosal fibrosis (OSF) or cancerosis.Methods: Metabolomics was applied to analyze the composition of JDK and serum metabolites. The active ingredients of JDK were analyzed by the combined ultra-high performance liquid chromatography and mass spectrometry. The target network of JDK, metabolites and OSF was analyzed by network pharmacology, and molecular docking. Oral mucosal lesions and fibrosis were analyzed by HE and Masson staining. Cell differentiation, proliferation and apoptosis were detected. The expressions of α-SMA, Collagen I, Vimentin, Snail, E-cadherin, AR and NOTCH1 were detected by Western blot.Results: Arecoline induced the gradual atrophy and thinning of rat oral mucosal, collagen accumulation, the increase expressions of fibrosis-related proteins and Th17/Treg ratio. JDK inhibited arecoline-induced oral mucosal lesions and inflammatory infiltration. Arecoline induced changes of serum metabolites in Aminoacyl-tRNA biosynthesis, Alanine, aspartate and glutamate metabolism and Arginine biosynthesis pathways, which were reversed by M-JDK. Quercetin and AR were the active ingredients and key targets of JDK, metabolites and OSF interaction. Arecoline promoted the expression of AR protein, and the proliferation of oral fibroblasts. Quercetin inhibited the effect of arecoline on oral fibroblasts, but was reversed by AR overexpression. Arecoline induced NOTCH1 expression in CAL27 and SCC-25 cells, and promoted cell proliferation, but was reversed by M-JDK or quercetin.Conclusion: JDK improved the arecoline-induced OSF and serum metabolite functional pathway. Quercetin targeted AR protein to improve arecoline-induced OSF. JDK and quercetin inhibited arecoline-induced NOTCH1 protein expression in CAL27 and SCC-25 cells to play an anti-oral cancer role.Graphical Abstract: Keywords: oral submucous fibrosis, Jiawei Danxuan Koukang, arecoline, pharmacology, metabolomics

Zi-Qiang Li,1,&ast; Ye Qin,2,&ast; Wen-Peng Cai,1,&ast; Si-Qi Deng,3 Xiao-Fei Mao,1 Jian-Guo Zhang,1 Tian-Ya Hou,1 Yu Pan,4 Yi Cui,1 Ying-Nan Ge,5 Wei Dong,1,&ast; Yun-Xiang Tang1,&ast; 1Faculty of Psychology, Naval Medical University, Shanghai, 200433, People’s Republic of China; 2The School of Mechanical Engineering, Changzhou University, Changzhou, 210046, People’s Republic of China; 3Department of Clinical Psychological Counseling, Shanghai Tongxinjici Health Couseling Center, Shanghai, 200433, People’s Republic of China; 4Department of Medical Psychology, Chinese PLA General Hospital, Beijing, 100830, People’s Republic of China; 5Department of Hepatopancreatobiliary Surgery, the First Affiliated Hospital of Shenzhen University, Shenzhen Second People’s Hospital, Shenzhen, 518000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Dong; Yun-Xiang Tang, Faculty of Psychology, Naval Medical University, No. 800 Xiangyin Road, Shanghai, 200433, People’s Republic of China, Tel/Fax +86-13524435414 ; +86-13386271042, Email sophiedongwei@163.com; tangyun7633@sina.comPurpose: This study aims to examine the impact of sleep deprivation on individual cognitive reappraisal ability using a standardized behavioral paradigm.Methods: A randomized pretest-posttest control group design was conducted. Thirty-nine participants were eventually enrolled and randomly assigned to receive either the sleep control (SC: n = 17) or the sleep deprivation (SD: n = 22). Both of them were required to perform a standardized behavioral paradigm of measuring cognitive reappraisal ability one time under sleep-rested condition and another time under the condition of different sleep manipulation a week later.Results: Mean valence ratings of SD group were more negative than SC group’s (p < 0.05) and mean arousal ratings of SD group were higher than SC group’s (p < 0.01).Conclusion: Sleep deprivation may impair individual cognitive reappraisal ability and could potentially undermine the efficacy of cognitive therapy in terms of emotion regulation.Keywords: sleep deprivation, emotion regulation, cognitive reappraisal, IAPS, CRA

Heng Rong,1,&ast; Weixin Dai,1,&ast; Yinying Qin,1,&ast; Zhikeng Meng,2 Xia Zou,3 Binbin Wang,4 Qiufeng Wei,1 Yubo Xie1,5 1Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 2Department of Anesthesiology, The First People’s Hospital of Yulin, Yulin, People’s Republic of China; 3Department of Anesthesiology, The People’s Hospital of Guangxi Zhuang Autonomous Region, Nanning, People’s Republic of China; 4Department of Anesthesiology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China; 5Guangxi Key Laboratory of Enhanced Recovery After Surgery for Gastrointestinal Cancer, The First Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yubo Xie, Department of Anesthesiology, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuang-Yong Road, Nanning, Guangxi, 530021, People’s Republic of China, Email xybdoctor@163.comPurpose: In this prospective observational study, an ultrasonographic measurement of antral cross-sectional area (ACSA) was conducted to evaluate the gastric content and volume as well as to identify high-risk stomach in non-pregnant adult surgical patients adhering to preanesthetic fasting guidelines.Patients and Methods: Fasted patients undergoing gastrointestinal endoscopy under sedation were included. Ultrasonographic measurements of ACSA were conducted in both semi-recumbent and right lateral decubitus positions before endoscopic procedures. Gastroscopy was employed to guide the measurement of suctioned gastric volume (GV). Ultrasonography was performed to assess gastric contents and identify patients with high-risk stomach. The relationship between ACSA and suctioned GV was also evaluated.Results: ACSA was evaluated in 736 out of 782 patients. A significant positive correlation was discovered between ACSA in the right lateral decubitus position and suctioned GV, which was more reliable than in the semi-recumbent position. To analyze high-risk stomach with a GV > 100 mL, the cutoff value of ACSA in the right lateral decubitus was found to be 7.5 cm2, with the AUC, sensitivity and specificity of 0.80 (95% CI, 0.76– 0.82; P< 0.001), 82.4% and 67.3%, respectively. A novel mathematical model based on ACSA to estimate GV in non-pregnant fasted adults was presented.Conclusion: Ultrasonographic measurement of ACSA can assist anesthesiologists in estimating the risk of pulmonary aspiration of gastric contents during general anesthesia and sedation.Keywords: gastroscopy, antrum, gastric content, pulmonary aspiration, ultrasonography

Qinglin Ye,&ast; Guiling Xu,&ast; Haizhen Huang,&ast; Shuting Pang, Boji Xie, Bingmei Feng, Peng Liang, Yijie Qin, Siji Li, Yin Luo, Chao Xue, Wei Li Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li; Chao Xue, Department of Nephrology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of China, Email liwei030514@126.com; xccqh@126.comPurpose: Chronic kidney disease (CKD) progression is complex. There are not standardized methods for predicting the prognosis of CKD. Nicotinamide N-methyltransferase (NNMT) has been shown to be associated with renal fibrosis. This study aimed to validate NNMT as a prognostic biomarker of progressive CKD.Patients and Methods: We explored the relationship between NNMT expression and CKD-related outcome variables using the NephroseqV5 and GEO databases. Additionally, a validation set of 37 CKD patients was enrolled to measure the correlation between NNMT expression levels and CKD outcomes. Furthermore, single-cell RNA sequencing data and the Human Protein Atlas were reanalyzed to investigate the expression specificity of NNMT in the kidney. Finally, to detect the status of NNMT expression with tubular fibrosis in vivo, we constructed a unilateral ureteral obstruction (UUO) mouse treated with an NNMT inhibitor.Results: Analyzing the datasets showed that NNMT was expressed mainly in proximal tubule compartments. And patients with high NNMT expression levels had a significantly lower overall survival rate compared to those with low NNMT expression levels (P = 0.013). NNMT was independent of prognosis factors in the multivariate Cox regression model, and the AUCs for CKD progression at 1, 3, and 5 years were 0.849, 0.775, and 0.877, respectively. Pathway enrichment analysis indicated that NNMT regulates the biological processes of tubulointerstitial fibrosis (TIF). In the validation group, NNMT levels were significantly higher in the CKD group combined with interstitial fibrosis. In vivo, NNMT was a high expression in the UUO group, peaking at postoperative day 21. Treatment with an NNMT inhibitor improved renal tubular interstitial fibrosis, and expression levels of FN, α-SMA, VIM, and TGF-β 1 were decreased compared with UUO (P < 0.05).Conclusion: NNMT was expressed mainly in tubular renal compartments, and associated with CKD prognosis. It holds potential as a diagnostic biomarker for tubular fibrosis in CKD.Graphical Abstract: Keywords: nicotinamide N-methyl transferase, tubular fibrosis, chronic kidney disease, biomarker diagnosis

Zhongjie Wang,1,&ast; Yanru Qin,1,&ast; Xueyuan Wang,2 Tianyu Zhang,1 Yixue Hu,2 Dongna Wang,1 Liefeng Zhang,1 Yongqiang Zhu1,2 1School of Food and Pharmaceutical Engineering, Nanjing Normal University, Nanjing, 210023, People’s Republic of China; 2College of Life Science, Nanjing Normal University, Nanjing, 210023, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liefeng Zhang; Yongqiang Zhu, Nanjing Normal University, Wenyuan Road 1&num;, Qixia District, Nanjing, 210023, People’s Republic of China, Tel/Fax +86-25-85898184 ; +86-25-85891591, Email lfzhang@njnu.edu.cn; zhyqscu@hotmail.comIntroduction: Mitochondria are a significant target of lonidamine (LND). However, its limited solubility and inability to specifically target mitochondria, LND can lead to hepatic toxicity and has shown only modest anticancer activity. The objective of this study is to establish a glutathione programmed mitochondria targeted delivery of LND for the effective treatment of triple negative breast cancer (TNBC).Methods: In this study, LND was encapsulated in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) wrapped with mitochondria-targeting short-chain triphenylphosphonium-tocopherol polyethylene glycol succinate (TPP-TPGS, TPS) and tumor-targeting long-chain 1, 2-distearoyl-sn-glycero-3-phosphoethanolamine-S-S-polyethylene glycol-R6RGD (DSPE-S-S-PEG2000-R6RGD, DSSR), which were designated as LND-PLGA/TPS/DSSR NPs. The release behavior was evaluated, and cellular uptake, in vitro and in vivo antitumor activity of nanoparticles were investigated. The mechanism, including apoptosis of tumor cells and mitochondrial damage and respiratory rate detection, was also further investigated.Results: LND-PLGA/TPS/DSSR NPs were successfully prepared, and characterization revealed that they are globular particles with smooth surfaces and an average diameter of about 250 nm. Long-chain DSSR in LND-PLGA/TPS/DSSR NPs prevented positively charged LND-PLGA/TPS NPs from being cleared by the reticuloendothelial system. Furthermore, LND release rate from NPs at pH 8.0 was significantly higher than that at pH 7.4 and 5.5, which demonstrated specific LND release in mitochondria and prevented LND leakage in cytoplasm and lysosome. NPs could locate in mitochondria, and the released LND triggered apoptosis of tumor cells by damaging mitochondria and releasing apoptosis-related proteins. In addition, in TNBC mice model, programmed mitochondria targeted NPs improved efficacy and reduced LND toxicity.Conclusion: LND-PLGA/TPS/DSSR NPs may be a useful system and provide an effective approach for the treatment of TNBC.Keywords: alkaline-responsive drug release, GSH-responsive, programmed mitochondria targeting, triple negative breast cancer, lonidamine

Jiarui Zhang,1,&ast; Yichun Qin,2,&ast; Chen Zhou,3 Yuanming Luo,4 Hailong Wei,5 Huiqing Ge,6 Hui-Guo Liu,7 Jianchu Zhang,8 Xianhua Li,9 Pinhua Pan,10 Mengqiu Yi,11 Lina Cheng,11 Liang Liu,12 Adila Aili,1 Lige Peng,1 Yu Liu,1 Jiaqi Pu,1 Qun Yi,1,13,&ast; Haixia Zhou1,&ast; 1Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 2State Key Laboratory of Oral Diseases and National Clinical Research Center for Oral Diseases, West China Hospital of Stomatology, Sichuan University, Chengdu, People’s Republic of China; 3West China School of Medicine, West China Hospital, Sichuan University, Chengdu, Sichuan Province, People’s Republic of China; 4State Key Laboratory of Respiratory Disease, Guangzhou Medical University, Guangzhou, Guangdong Province, People’s Republic of China; 5Department of Respiratory and Critical Care Medicine, People’s Hospital of Leshan, Leshan, Sichuan Province, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang Province, People’s Republic of China; 7Department of Respiratory and Critical Care Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 8Department of Respiratory and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei Province, People’s Republic of China; 9Department of Respiratory and Critical Care Medicine, The First People’s Hospital of Neijiang City, Neijiang, Sichuan Province, People’s Republic of China; 10Department of Respiratory and Critical Care Medicine, Xiangya Hospital, Central South University, Changsha, Hunan Province, People’s Republic of China; 11Department of Emergency, First People’s Hospital of Jiujiang, Jiujiang, Jiangxi Province, People’s Republic of China; 12Department of Respiratory and Critical Care Medicine, The Affiliated Hospital of Chengdu University, Chengdu, Sichuan Province, People’s Republic of China; 13Sichuan Cancer Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Haixia Zhou; Qun Yi, Department of Respiratory and Critical Care Medicine, West China Hospital, Sichuan University, Guo-Xue-Xiang 37&num;, Wuhou District, Chengdu, Sichuan Province, 610041, People’s Republic of China, Tel/Fax +86-28-85422571, Email zhouhaixia@wchscu.cn; yiqun925@126.comBackground: High blood urea nitrogen (BUN) is observed in a subset of patients with acute exacerbation of COPD (AECOPD) and may be linked to clinical outcome, but findings from previous studies have been inconsistent.Methods: We performed a retrospective analysis of patients prospectively enrolled in the MAGNET AECOPD Registry study (ChiCTR2100044625). Receiver operating characteristic (ROC) was used to determine the level of BUN that discriminated survivors and non-survivors. Univariate and multivariate Cox proportional hazards regression analyses were performed to assess the impact of BUN on adverse outcomes.Results: Overall, 13,431 consecutive inpatients with AECOPD were included in this study, of whom 173 died, with the mortality of 1.29%. The non-survivors had higher levels of BUN compared with the survivors [9.5 (6.8– 15.3) vs 5.6 (4.3– 7.5) mmol/L, P < 0.001]. ROC curve analysis showed that the optimal cutoff of BUN level was 7.30 mmol/L for in-hospital mortality (AUC: 0.782; 95% CI: 0.748– 0.816; P < 0.001). After multivariate analysis, BUN level ≥ 7.3 mmol/L was an independent risk factor for in-hospital mortality (HR = 2.099; 95% CI: 1.378– 3.197, P = 0.001), also for invasive mechanical ventilation (HR = 1.540; 95% CI: 1.199– 1.977, P = 0.001) and intensive care unit admission (HR = 1.344; 95% CI: 1.117– 1.617, P = 0.002). Other independent prognostic factors for in-hospital mortality including age, renal dysfunction, heart failure, diastolic blood pressure, pulse rate, PaCO2 and D-dimer.Conclusion: BUN is an independent risk factor for in-hospital mortality in inpatients with AECOPD and may be used to identify serious (or severe) patients and guide the management of AECOPD.Clinical Trial Registration: MAGNET AECOPD; Chinese Clinical Trail Registry NO.: ChiCTR2100044625; Registered March 2021, URL: http://www.chictr.org.cn/showproj.aspx?proj=121626.Keywords: AECOPD, inpatients, blood urea nitrogen, mortality, adverse outcomes

Chen Chen,&ast; Zehua Wang,&ast; Yanru Qin Department of Oncology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanru Qin, Department of Oncology, The First Affiliated Hospital of Zhengzhou University, No. 1 Jianshe East Road, Erqi District, Zhengzhou, Henan, 450052, People’s Republic of China, Tel +86 13676932999, Email yanruqin@163.comPurpose: This study aims to construct a novel hematological inflammation-nutrition score (HINS) and investigate its prognostic value in patients with advanced gastric cancer (AGC). We investigated the risk stratification performance of HINS and developed a HINS-based nomogram model to predict overall survival by combining traditional predictors.Patients and Methods: We conducted a retrospective study on 812 AGC patients who received first-line platinum- or fluoropyrimidine-containing chemotherapy at The First Affiliated Hospital of Zhengzhou University Hospital between 2014 and 2019. Patients were randomly divided into a training cohort (N=609) and a validation cohort (N=203). HINS (0– 2) was constructed based on a pre-chemotherapy systemic immune-inflammation index (SII) and albumin (ALB). Prognostic factors were screened by univariate and multivariate COX proportional regression models. Significant factors were used to construct a nomogram model. Internal validation was performed by calibration curves, time-dependent receiver operating characteristics (ROC) curves, and decision curve analysis (DCA), evaluating its prediction consistency, discrimination ability, and clinical net benefit.Results: HINS was constructed based on SII and ALB. HINS showed a better stratification ability than JCOG prognostic index, with significant differences between groups. Multivariate analysis showed that ECOG ≥ 1 (HR: 1.379; P=0.005), Stage IV (HR: 1.581; P < 0.001), diffuse-type histology (HR: 1.586; P < 0.001), number of metastases ≥ 2 (HR: 1.274; P=0.038), without prior gastrectomy (HR: 1.830; P < 0.001), ALP ≥ULN (HR: 1.335; P=0.034), HINS (P < 0.001) were independent factors of OS. We successfully established a HINS-based nomogram model that showed a strong discriminative ability, accuracy, and clinical utility in training and validation cohorts.Conclusion: HINS shows a superior risk stratification ability, which might be a potential prognostic biomarker for AGC patients receiving palliative first-line palliative chemotherapy. The HINS-based nomogram model is a convenient and efficient tool for managing prognosis and follow-up treatments.Keywords: hematological inflammation-nutrition score, nomogram model, advanced gastric cancer, prognosis

Yi Liang,1,2 Xiaohong Li,1 Fang Wang,2 Zongting Yan,2 Yuhuan Sang,2 Yuan Yuan,2 Yun Qin,1 Xuefei Zhang,1 Mei Ju2 1Health Management Center, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China; 2Nursing College, Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of ChinaCorrespondence: Mei Ju; Xiaohong Li, Email 593576753@qq.com; 1848922774@qq.comBackground: Thyroid nodules (TNs) are among the most common thyroid lesions, and rates of these nodules have risen over the past three decades. As the majority of TN patients remain asymptomatic when these nodules are in the early stages of development, malignant nodules may continue to develop into thyroid cancer when not detected. As such, early screening and diagnosis-based strategies represent the most promising means of preventing or treating TNs and associated cancers. The present study was thus developed to explore TN prevalence among individuals in Luzhou, China.Methods: Here, thyroid ultrasonography and metabolic-related indicators from 45,023 adults undergoing routine physical examinations in the Health Management Center of a large Grade A hospital in Luzhou over the last three years were retrospectively reviewed in an effort to identify factors associated with TN risk and the detection of these nodules through univariate and multivariate logistic regression analyses.Results: In total, 13,437 TNs were detected in these 45,023 healthy adults for an overall 29.8% detection rate. This TN detection rate rose with age, and multivariate logistic regression analyses revealed that independent risk factors associated with TNs included greater age (≥ 31 years old), female (OR = 2.283, 95% CI: 2.177– 2.393), central obesity (OR = 1.115, 95% CI: 1.051– 1.183), impaired fasting glucose (OR = 1.203, 95% CI: 1.063– 1.360), overweight status (OR = 1.085, 95% CI: 1.026– 1.147), and obesity (OR = 1.156, 95% CI: 1.054– 1.268), while low BMI was a protective factor associated with lower rates of TN incidence (OR = 0.789, 95% CI: 0.706– 0.882). When results were stratified by gender, impaired fasting glucose was not an independent predictor of TN risk among males, while high LDL levels were an independent predictor of TNs among females, and other risk factors were not significantly changed.Conclusion: TN detection rates were high among adults in Southwestern China. Female, elderly individuals, individuals exhibiting central obesity, and those with high levels of fasting plasma glucose are more likely to develop TN.Keywords: thyroid nodules, detection rate, influence factors

Lei Huang,1,2 Chengcheng Liu,1,2 Zhanjie Li,3 Xu Huang,1,4 Ruiying Zheng,1,2 Zhixin Shi,1,2 Xin Hong,1,2 Yufeng Qin,5 Genyan Liu1,2 1Department of Laboratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Branch of National Clinical Research Center for Laboratory Medicine, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Infection Control, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Laboratory Medicine, the Children’s Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 5School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of ChinaCorrespondence: Genyan Liu, Department of Laboratory Medicine, The First Affiliated Hospital with Nanjing Medical University, Nanjing, 210029, People’s Republic of China, Tel +86 25 68308025, Fax +86 25 83724440, Email liugenyan@njmu.edu.cnObjective: To investigate the transmission pathway of a MRSA prevalence in a pancreatic surgery ward in a Chinese teaching hospital.Methods: Molecular epidemiology investigations were carried out combined PFGE, MLST, SCCmec typing and whole-genome sequencing for 20 successive MRSA isolates (2 isolates from the ward environment). Resistance and virulence genes were detected using specific PCR. Bacterial identification and AST were performed using the Vitek 2 Compact System. Clinical data of enrolled cases were retrieved from electronic case records.Results: From January 2020 to May 2020, successive isolated 20 MRSA strains were clarified to 2 PFGE patterns (A = 19, B = 1) in the ward. Both isolates from environment and patients belonged to sequence type ST5-SCCmec II-spa type t311. MRSA-related resistance genes mecA, blaZ, ermA, ant(4’)-Ia and norA were found in each clone. All 20 isolates carried tst, hlg, hla, eta, eap, fnbA and seo virulence genes, other virulence genes such as sea, sec, seb, seg, sei, sem, sen, ebpS and fnbB were also found in partial stains. All patients had fever symptom, 27.8% were accompanied by diarrhea, 88.9% had undergone surgery or invasive procedures within 30 days. Finally, 94.4% of these patients recovered.Conclusion: This study confirmed a prevalence of ST5-MRSA-II-t311 clone in a surgery ward, indicated MRSA is a risk factor for post-surgery nosocomial infection and hand hygiene and environmental surveillance should not be ignored.Keywords: methicillin-resistantStaphylococcus aureus, ST5, SCCmec II, spa type t311, diarrhea, virulence genes

Yanan Liu, Shuo Zhang, Rongrong Hu, Chao Li, Gang Chen, Xiaoxiao Shi, Yan Liu, Ke Zheng, Hang Li, Yubing Wen, Xuemei Li, Xuewang Li, Peng Xia, Yan Qin Department of Nephrology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, People’s Republic of ChinaCorrespondence: Peng Xia; Yan Qin, Department of Nephrology, Peking Union Medical College Hospital, Peking Union Medical College, Chinese Academy of Medical Sciences, Beijing, 100730, People’s Republic of China, Tel +86 01069155058, Email 7-xp@163.com; qinyanbeijing@126.comPurpose: There are increasing reports of atypical membranous nephropathy (AMN) cases with similar pathological characteristics to secondary membranous nephropathy (SMN) without definite underlying causes. Although rituximab has become a first-line option in treating idiopathic membranous nephropathy (IMN), the efficacy and safety of rituximab-based regimen for AMN is not clear.Patients and Methods: This is a retrospective, single-center study. AMN patients who received rituximab-based therapy were included. IMN patients treated with rituximab during the same period were selected as the control group matched by gender, sex, baseline urinary protein and albumin levels. Baseline data and follow-up data were collected.Results: A total of 20 AMN patients and 40 IMN patients were included. The baseline levels of urinary protein were comparable between the two groups [6.77 (IQR 3.34, 11.49) g/24 h vs 6.47 (IQR 3.4, 10.76) g/24 h, P=0.944]. The baseline levels of serum albumin were 26.15± 6.71 g/L and 26.8± 5.54 g/L (P=0.689) respectively. The cumulative remission rate for rituximab-based treatment at the 12th month was lower in AMN group than IMN group [13 (65%) vs 36 (90%), P=0.045]. In AMN group, non-responders showed a higher level of proteinuria and a worse renal function at baseline than those of responders. There was no significant difference in the overall adverse events or serious adverse events between the two groups.Conclusion: In our study, AMN patients obtained proteinuria remission in a lower percentage compared with IMN patients. In general, rituximab-based therapy is effective in AMN patients with an acceptable safety profile.Keywords: rituximab, atypical membranous nephropathy, idiopathic membranous nephropathy, efficacy

Cong You,1 Kun Wang,1 Mingyi Liao,1 Luying Zhang,1 Mintong He,1 Xiaoying Ye,1 Yongzhang Qin,2 Tao Yang1 1Department of Dermatology and Venereology; Candidate Branch of National Clinical Research Centre for Skin and Immune Diseases, The First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China; 2Department of Endocrinology, The First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of ChinaCorrespondence: Tao Yang, Department of Dermatology and Venereology, Candidate Branch of National Clinical Research Centre for Skin and Immune Diseases, The First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China, Tel +8618720732351, Email danny20021068@sina.comAbstract: Condylomata lata are flat-topped, moist papules or plaques usually found in the anogenital area as cutaneous manifestations of secondary syphilis. Here, we present a unique case of a solitary interdigital condyloma latum of secondary syphilis in a 16-year-old female sex worker without other cutaneous findings. Sexual contact history, histopathology, including direct detection of Treponema pallidum, and serological tests were essential for the diagnosis of this case. The patient reached serological cure with two doses of intramuscularly delivered penicillin G benzathine. Owing to the dramatic rise in the incidence of primary and secondary syphilis, medical workers should be aware of the atypical skin manifestations of secondary syphilis in adolescents who are at risk of acquiring sexually transmitted diseases to avoid the progression to late syphilis and further transmission to sexual partners.Keywords: interdigital condyloma latum, secondary syphilis, female adolescent

Fei Guo,1,&ast; Yuting Yan,1,&ast; Li Sun,1 Ruili Han,1 Lanlan Zheng,1 Yuan Qin,1 Shuang Wang,1 Xude Sun,1 Zhaohua Ji,2 Changjun Gao1 1Department of Anesthesiology, Second Affiliated Hospital of Air Force Medical University, Xi’an, 710038, People’s Republic of China; 2Department of Epidemiology, School of Public Health, Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environment, Air Force Medical University, Xi’an, 710032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Changjun Gao, Department of Anesthesiology, Second Affiliated Hospital of Air Force Medical University, Xin Si Road & 569, Xi’an City, Shaanxi, 710038, People’s Republic of China, Tel/Fax +86 2984777439, Email gaocj74@163.com Zhaohua Ji, Department of Epidemiology, School of Public Health, Ministry of Education Key Laboratory of Hazard Assessment and Control in Special Operational Environment, Air Force Medical University, ChangLe Road & 169, Xi’an City, Shaanxi, 710032, People’s Republic of China, Tel/Fax +86 2884711316, Email hellojzh@msn.comObjective: This meta-analysis of randomized controlled trials (RCTs) aims to evaluate the efficacy and safety of transcutaneous electrical acupoint stimulation (TEAS) for postoperative delirium (POD) in surgical patients.Methods: Based on database searches of the Wanfang, China National Knowledge Infrastructure (CNKI), VIP, Chinese Biology Medicine (CBM), PubMed, Cochrane Library, and Web of Science, relevant RCTs published before December 30, 2022, were extracted. Outcome indicators included the incidence of POD, changes in Confusion Assessment Method (CAM) scores, Visual Analogue Scale (VAS) scores, and the intraoperative consumption of anesthetics. Data were pooled and analyzed by Review Manager 5.3, and publication bias detection was conducted using Stata 17.0.Results: A meta-analysis containing 715 experimental and 717 control participants from 12 RCTs was performed. The overall results showed that TEAS had obvious superiority with a lower incidence of POD on any day during the postoperative 1 week. In subgroup analyses, the CAM scores on the third postoperative day were significantly lower in the TEAS group than in the control group (MD = − 0.52, 95% CI: − 1.02 to − 0.03, P = 0.04), the VAS scores on the first postoperative day were significantly lower in the TEAS group than in the control group (MD = − 0.19, 95% CI: − 0.36 to − 0.02, P = 0.03), the consumption of propofol and remifentanil were both significantly lower in the TEAS group compared with the control group (MD = − 23.1, 95% CI: − 37.27 to − 8.94, P = 0.001; MD = − 105.69, 95% CI: − 174.20 to − 37.19, P = 0.002). No serious adverse events of TEAS were reported in any of the referenced studies.Conclusion: TEAS has an obvious curative effect in preventing POD and pain in the earlier stage of surgical patients. It could be a promising assisted anesthesia technique in the future.Keywords: transcutaneous electrical acupoint stimulation, TEAS, postoperative delirium, POD, meta-analysis

Yanyan Yang,1 Yao Qin,2 Ziyi Wang,3 Angyu Sun4 1School of Business Administration, Jiangxi University of Finance and Economics, Nanchang, Jiangxi, People’s Republic of China; 2School of Business, Macau University of Science and Technology, Macau, People’s Republic of China; 3School of Business Administration, Zhongnan University of Economics and Law, Wuhan, Hubei, People’s Republic of China; 4Faculty of Arts and Social Science, Dalhousie University, Halifax, NS, CanadaCorrespondence: Ziyi Wang, Email 15999955121@163.comPurpose: The purpose of this study is to investigate whether the emotional labor of service employees affects customer service misbehavior and repurchase intention and to explore the mechanism and boundary conditions.Methods: We collected a total of 252 pairs of employee–customer valid matching data and used SPSS 24.0 and Mplus7.0 statistical analysis tools to perform statistical analysis and hypothesis testing.Results: The results showed that employees’ surface acting has a significant positive impact on customer misbehavior and negative impact on repurchase intention via perceived face threat, while deep acting has a significant negative impact on customer misbehavior and positive impact on repurchase intention via perceived face threat. And customer face threat sensitivity not only moderates the relationship between service employee emotional labor and customer perceived face threat but also moderates the indirect effect of surface acting on customer misbehavior and repurchase intention via customer perceived face threat.Conclusion: Based on face theory, this study explained how and when emotional labor of service employees may affect customer service misbehavior and repurchase intention. These results contribute to the emotional labor and customer service misbehavior literature by introducing perceived face threat as an underlying mechanism and face threat sensitivity as a boundary condition. In addition, this study suggests that service-oriented enterprises should pay attention to the management and guidance of employees’ emotional labor and try their best to let employees show deep acting rather than surface acting.Keywords: emotional labor, customer perceived face threat, face threat sensitivity, customer misbehavior, repurchase intention

Min Sun,1,2 Lei Gao,1 Hongmei Bai,1 Weiwei Hu,1 Xiaofang Zhang,1 Jin Xiao,1 Xiangliang Deng,1 Hongmei Tao,1 Ping Ge,2 Yuhong Qin,1,&ast; Dongying Zhang1,&ast; 1Department of Cardiovascular Medicine, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Health Management Center, The First Branch of the Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dongying Zhang; Yuhong Qin, Tel +86-23-13608398395 ; +86-23-13068357151, Email zhangdongying@cqmu.edu.cn; 798213639@qq.comPurpose: To investigate the association of visceral fat with arterial stiffness of heart failure patients with preserved ejection fraction (HFpEF) and to evaluate the extent to which this association is mediated by blood pressure (BP).Patients and Methods: This cross-sectional descriptive study (clinicaltrials.gov identifier: NCT04535726) recruited 94 patients with HFpEF totally from October to December 2020. The obesity-related measurements included visceral fat area (VFA), body mass index (BMI), waist circumference (WC), hip circumference (HC), waist–hip ratio (WC/HC), abdominal circumference (AC), body fat mass and fat percentage. Brachial-ankle pulse wave velocity (baPWV) was used to estimate the degree of arterial stiffness. Mediation analysis was performed to reveal whether the effect of visceral fat area on arterial stiffness can be mediated by BP in patients with HFpEF and the extent to which this association was mediated by BP.Results: About 93.6% of HFpEF patients were accompanied with abdominal obesity. Patients in baPWV ≥ 1800cm/s group were older, with a higher incidence of type 2 diabetes mellitus (T2DM), hypertension and abdominal obesity. VFA, systolic BP (SBP), diastolic BP (DBP) and pulse pressure (PP) were correlated with baPWV in total group. Adjusted for age ≥ 75 years old, gender, smoking, T2DM, calcium channel blocker and statins, the mediation effect of systolic SBP and PP on the VFA-baPWV association were 53.3% (indirect effect was 2.28, 95% CI 0.62– 4.73) and 48.4% (indirect effect was 2.07, 95% CI 0.51– 4.38), respectively. DBP failed to mediate the association between VFA and baPWV (indirect effect was 0.50, 95% CI − 0.41– 2.14).Conclusion: The association of visceral fat with baPWV in HFpEF patients may be partly accounted for SBP or PP. Elevated SBP and PP might be important potential targets for preventing arterial stiffness in HFpEF patients.Keywords: mediation analysis, blood pressure, visceral fat area, brachial-ankle pulse wave velocity, HFpEF

Mei Wang,1 Leran Zhao,2 Kun Wang,3 Yongzhang Qin,4 Jingji Jin,1 Dong Wang,1 Huimin Yan,1 Cong You3 1Department of Dermatology, Tianjin First Central Hospital, School of Medicine, Nankai University, Tianjin, People’s Republic of China; 2Department of Dermatology and Venereology, The General Hospital of Tianjin Medical University, Tianjin, People’s Republic of China; 3Department of Dermatology and Venereology, Candidate Branch of National Clinical Research Centre for Skin and Immune Diseases, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China; 4Department of Endocrinology, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of ChinaCorrespondence: Cong You, Department of Dermatology and Venereology, Candidate Branch of National Clinical Research Centre for Skin and Immune Diseases, First Affiliated Hospital of Gannan Medical University, Ganzhou, People’s Republic of China, Tel +8615979766532, Email youcong1987@tmu.edu.cnPurpose: Omalizumab is a humanized anti-immunoglobulin (Ig) E monoclonal antibody that is effective in treating some patients with chronic spontaneous urticaria (CSU) who do not respond to antihistamines. Gut microbiome plays a role in the pathogenesis of allergies and autoimmune diseases. Here, we investigated differences in the gut microbiome of adolescent CSU patients before and after omalizumab treatment, which has not been previously reported.Patients and Methods: Ten adolescent CSU patients were given 300 mg omalizumab subcutaneously in three treatments at 4-week intervals. Urticaria Activity Score (UAS7) was applied to evaluate the efficacy of each omalizumab treatment during follow-up. Fecal samples were collected before and 12 weeks after the first treatment. Total DNA of the gut microbiota in all fecal samples were extracted. The 16S rRNA gene-targeted sequencing technology was used for the analysis of the diversity and distribution of gut microbiome, followed by bioinformatics analysis.Results: UAS7 scores decreased significantly after each treatment compared with the baseline (all P < 0.0001). There were five well-controlled responders and five non-responders after three treatment sessions of omalizumab. The dominant bacteria phyla in all fecal samples were Firmicutes, Bacteroidetes, Proteobacteria, and Actinobacteria. Alpha diversity analysis showed no significant difference before and after treatment (P > 0.05), whereas beta diversity analysis revealed a significant difference in the bacterial abundance before and after treatment (P < 0.01). The relative abundance of Alphaproteobacteria and Betaproteobacteria at the class level and Burkholderia, Rhodococcus, and Sphingomonas at the genus level decreased significantly after treatment (linear discriminant analysis > 4, P

Yuanyuan Zhang,1,* Tong Ge,1,* Meijuan Huang,1 Yun Qin,2 Tianjiao Liu,3 Wei Mu,1 Gaoxiang Wang,1 Lijun Jiang,1 Tongjuan Li,1 Lei Zhao,1 Jue Wang1 1Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Hematology, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Department of Hematology, Harbin Medical University Cancer Hospital, Harbin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lei Zhao; Jue Wang, Email zl103311@tjh.tjmu.edu.cn; Jeff_wangjue@hotmail.comBackground: CAR-T cell therapy is effective in the treatment of certain hematological malignancies, and the expansion and functional persistence of CAR-T cells in vivo are crucial to clinical efficacy. The aim of this study was to investigate the potential of extracellular vesicles (EVs) modified with the CAR antigen to promote the efficacy of CAR-T cells in vivo.Methods: We generated HEK293T-derived EVs to present the CD19 antigen as the CAR target. In vitro, EVs expressing CD19 antigen (CD19 EVs) were co-incubated with anti-CD19 CAR-T cells. Then, proliferation, cytokine secretion, CD107a expression, tumor killing, subsets, and immune checkpoint expression were measured to assess CAR-T cell function. After infusion of CD19 EVs pretreated CAR-T cells into a lymphoma xenograft mouse model, flow cytometry and digital PCR were used to measure the expansion of CAR-T cells, and tumor volumes were continuously monitored to assess the anti-tumor efficacy of CAR-T cells in vivo. Another mouse model was created to investigate the effect of in vivo injection of CD19 EVs on the functional persistence of CAR-T cells, and safety was determined by histopathology of the main organs.Results: CD19 EVs activated CAR-T cells in an antigen-specific and dose-dependent manner and promoted the selective expansion and cytokine secretion of co-cultured CAR-T cells. Specifically, CD19 EVs preferably increased the expansion of the CAR-T subpopulation with a high surface CD19-CAR density and consequently enhanced the anti-tumor activity of CAR-T cells. Futhermore, CD19-EVs-primed CAR-T cells achieved superior proliferation and anti-tumor effects in a mouse model with lymphoma xenograft. In vivo administration of CD19 EVs promoted the functional persistence of CAR-T cells in the xenograft mouse model.Conclusion: Our findings indicate that antigen-expressing EVs can be utilized as a boost to improve CAR-T cell efficacy in vitro and in vivo.Keywords: immunotherapy, chimeric antigen receptor T-cell, extracellular vesicles, CD19 antigen

Xiang Li,1– 3 Yijing Yang,2,3 Yan Song,1– 3 Fujiao Nie,1– 3 Chaojun Fu,2,3 Yuhui Qin2– 4 1Ophthalmology Department, the First Affiliated Hospital, Hunan University of Chinese Medicine, Changsha, 410007, People’s Republic of China; 2Hunan Provincial Key Laboratory for the Prevention and Treatment of Ophthalmology and Otolaryngology Diseases with Chinese Medicine, Hunan University of Chinese Medicine, Changsha, 410208, People’s Republic of China; 3Hunan Engineering Technological Research Center for the Prevention and Treatment of Otolaryngologic Disease and Protection of Visual Function with Chinese Medicine, Changsha, 410208, People’s Republic of China; 4Institute of Chinese Medicine of Hunan Province, Changsha, 410006, People’s Republic of ChinaCorrespondence: Yuhui Qin, Institute of Chinese Medicine of Hunan Province, Lushan Road, Yuelu District, Changsha, 410006, People’s Republic of China, Tel +86 13873120865, Email 1243695133@qq.comPurpose: To evaluate the effects of Shuangdan Mingmu (SDMM) capsule on diabetic retinopathy in rats by regulating miRNAs.Materials and Methods: Streptozotocin (STZ) (50 mg/kg) was successfully used to induce diabetes in male Sprague-Dawley rats, which were randomly assigned to a group taking SDMM capsules (“diabetic+SDMM”) or a control group (“diabetic”), and the normal group (n=10/group). The diabetic+SDMM capsule group received 1.89g/kg/d of SDMM capsule by gavage, whereas the other groups received the same amount of distilled water. After 12-weeks of gavage, the retina was removed from all rats for histopathological analysis, and miRNA sequencing experiments were carried out to identify the differential expression of miRNAs. These results were then confirmed by quantitative real-time polymerase chain reaction (qRT-PCR).Results: SDMM capsules improved retinal morphology, restored the number of cells in the ganglion cell layer (p< 0.0001) and reduced apoptosis in all retinal layers (p values in the outer nuclear layers, inner nuclear layers and ganglion cell layers 0.0001, 0.0147, 0.0034, respectively). In addition, miRNA expression was changed in rats taking SDMM capsules. Compared with the diabetic group, six miRNAs were up-regulated and four miRNAs were down-regulated in the diabetic+SDMM capsule group. The qRT-PCR validation results showed that the expression levels of miR-450b-5p, miR-1249 and miR-155-5p were consistent with the trend of miRNA sequencing results, and were all up-regulated after SDMM capsule treatment. Target gene prediction and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis of differentially expressed miRNAs showed that these pathways were mainly concentrated in the focal adhesions and PI3K/Akt, MAPK, and neural factor signaling pathways.Conclusion: SDMM capsules may prevent and treat diabetic retinopathy by regulating the expression of miR-450b-5p, miR-1249 and miR-155-5p.Keywords: SDMM capsule, diabetic retinopathy, traditional Chinese medicine, miRNAs, bioinformatics analysis

Weijie Cao,&ast; Jieyong Zhang,&ast; Zhilei Bian, Li Li, Suping Zhang, Yang Qin, Dingming Wan, Zhongxing Jiang, Ran Zhang Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ran Zhang; Zhongxing Jiang, Department of Hematology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, 450002, People’s Republic of China, Tel +86 137 8359 0246 ; +86 185 3805 3607, Fax +86 370 66295122, Email zhangran19880310@126.com; jiangzx@zzu.edu.cnPurpose: To investigate the prevalence, risk factors of intestinal carbapenem-resistant Enterobacteriaceae (CRE) colonization and bloodstream infection (BSI) caused by CRE in allogeneic hematopoietic stem cell transplantation (allo-HSCT) recipients.Methods: We analyzed the clinical data of 185 patients with hematological malignancies who underwent allo-HSCT from May 2019 to December 2021. All patients received regular CRE monitoring by rectal swab during allo-HSCT, and some CRE strains were further identified for carbapenemase phenotypes. The rates, distribution and risk factors of CRE colonization, CRE-induced BSI were analyzed.Results: CRE was detected in 44 of 185 recipients, with colonization rate of 23.8%. A total of 46 strains of CRE were isolated, including 22 Escherichia coli, 17 Klebsiella pneumoniae, three Klebsiella oxytoca, two Enterobacter hormaechei, and two other Enterobacteriaceae. Among the 19 strains identified with carbapenemase phenotypes, eight strains of E. coli produced metal β-lactamase, five K. pneumoniae produced serine carbapenemase, two K. pneumoniae produced metal β-lactamase, two K. oxytoca produced metal β-lactamase, a Citrobacter malonic acid-free produced metal β-lactamase and a Citrobacter freundii produced metal β-lactamase. In 10 patients developed with CRE-related BSI, the types and combined drug sensitivity of strains detected by rectal swab were highly consistent with blood culture. Multivariate analysis revealed that pulmonary infection, perianal infection and carbapenem application in the 3 months pre-transplant were independent risk factors for rectal CRE colonization, while rectal colonization with carbapenem-resistant K. pneumoniae (CR-KP) was an independent risk factor for CRE-induced BSI. The mortality rate within 30 days of CRE-related BSI was 50.0%, and patients receiving multi-drug therapy within 24 hours showed slightly lower mortality than that in the single-drug treatment group.Conclusion: Allo-HSCT patients with CRE-induced BSI have poor prognosis, and CR-KP rectal colonization is an independent risk factor for CRE-related BSI. Rectal swab screening during allo-HSCT could provide early warning for later CRE-induced BSI.Keywords: allogeneic hematopoietic stem cell transplantation, carbapenem-resistant enterobacteriaceae, bloodstream infection, intestinal colonization

Yuan Zhang,1,&ast; Hongli Yue,1,&ast; Yirui Qin,1 Jiajing Wang,1 Chenyang Zhao,1 Miao Cheng,1 Bo Han,2 Ruquan Han,1 Weihua Cui1,&ast; 1Department of Anesthesiology, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Neurosurgery, Beijing Tian Tan Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruquan Han; Weihua Cui, Department of Anesthesiology, Beijing Tian Tan Hospital, Capital Medical University, No. 119, Nan Si Huan Xi Lu, Fengtai District, Beijing, 100070, People’s Republic of China, Tel +8613701285393 ; Tel +8613701285393, Fax +861059976658, Email ruquan.han@ccmu.edu.cn; weihuacui@ccmu.edu.cnPurpose: Patients undergoing intraspinal tumor resection usually experience severe postoperative pain. Inadequate postoperative analgesia usually leads to severe postsurgical pain, which could cause patients to suffer from many other related complications. Recently, an increasing number of studies have found that gabapentin can relieve hyperalgesia, postoperative pain, and postoperative inflammation. However, there have been no reports on the use of gabapentin combined with sufentanil preoperatively for acute pain following intraspinal tumor resection.Study Design and Methods: This is a protocol for a randomized, placebo-controlled, and double-blinded trial. One-hundred and sixty-eight participants with chronic pain related to the intraspinal tumor will be randomized into the gabapentin and placebo groups in a 1:1 ratio. In the gabapentin group, patients will be given 300 mg gabapentin orally 36 h, 24 h, and 12 h before surgery; the placebo group will receive a placebo orally at the same time points preoperatively. To estimate the efficacy and safety endpoints, all the researchers and patients will be blinded until the completion of this study. The primary outcome will be the consumption of sufentanil within 48 h postoperatively. The secondary outcomes include the visual analog scale pain score and Von Frey mechanical pain threshold 36 h and 24 h before and 24 h and 48 h after surgery, the incidence of postoperative nausea, vomiting, and drowsiness, the length of hospital stay and medical expenses.Discussion: This trial is to evaluate the efficacy and safety of gabapentin combined with sufentanil for postoperative analgesia in patients who complain of pain before intraspinal tumor resection. The findings will provide a new strategy for multimode perioperative analgesia management in these patients.Keywords: gabapentin, intraspinal tumor resection, multimode perioperative analgesia, opiates

Haoqiang Liu,1,&ast; Zeyidan Jiapaer,1,&ast; Fanxing Meng,1 Wanfeng Wu,1 Chengyi Hou,2 Mengjiao Duan,1 Yanan Qin,1 Shuxuan Shao,1 Minwei Zhang1 1Xinjiang Key Laboratory of Biological Resources and Gentic Engineering, College of Life Science & Technology, Xinjiang University, Urumqi, 830046, People’s Republic of China; 2State Key Laboratory for Modification of Chemical Fibers and Polymer Materials, College of Materials Science and Engineering, Donghua University, Shanghai, 201620, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shuxuan Shao; Minwei Zhang, Email Shaoshux@126.com; zhangmw@xju.edu.cnBackground: Natural bioactive substances have been widely studied for their superior anti-tumor activity and low toxicity. However, natural bioactive substances suffer from poor water-solubility and poor stability in the physiological environment. Therefore, to overcome the drawbacks of natural bioactive substances in tumor therapy, there is an urgent need for an ideal nanocarrier to achieve high bioactive substance loading with low toxicity.Materials and Methods: Face-centered cubic hollow mesoporous Prussian Blue (HMPB) NPs were prepared by stepwise hydrothermal method. Among them, PVP served as a protective agent and HCl served as an etching agent. Firstly, MPB NPs were obtained by 0.01 M HCl etching. Then, the highly uniform dispersed HMPB NPs were obtained by further etching with 1 M HCl.Results: In this work, we report a pH-responsive therapeutic nanoplatform based on HMPB NPs. Surprisingly, as-prepared HMPB NPs with ultra-high bioactive substances loading capacity of 329 μg mg− 1 owing to the large surface area (131.67 m2 g− 1) and wide internal pore size distribution (1.8– 96.2 nm). Moreover, with the outstanding photothermal conversion efficiency of HMPB NPs (30.13%), natural bioactive substances were released in the tumor microenvironment (TME). HMPB@PC B2 achieved excellent synergistic therapeutic effects of photothermal therapy (PTT) and chemotherapy (CT) in vivo and in vitro without causing any extraneous side effects.Conclusion: A biocompatible HMPB@PC B2 nanoplatform was constructed by simple physical adsorption. The in vitro and in vivo experiment results demonstrated that the synergy of PTT/CT provided excellent therapeutic efficiency for cervical cancer without toxicity. Altogether, as-designed nanomedicines based on natural bioactive substances may be provide a promising strategy for cancer therapy.Graphical Abstract: Keywords: HMPB NPs, natural bioactive substances, synergistic therapy, negligible side effect

Shuxin Lv,&ast; Jinghua Sun,&ast; Chunyan Guo, Yufei Qin, Ruiping Zhang The Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Taiyuan, 030032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ruiping Zhang, Email zrp_7142@sxmu.edu.cnBackground: Tumor derived cellular microvesicles (TDMVs), as excellent drug delivery vehicles in vivo, play an important role in the treatment of cancers. However, it is difficult to obtain intuitional biodistribution behavior and internalization mechanisms of TDMVs in vivo. Thus, it is very urgent and important to establish a stable and reliable visualization technology to track the biological behavior and function of TDMVs. As an endogenous biopolymer, melanin possesses natural biocompatibility and biodegradability, and various biological imaging could be realized by modifying it. Therefore, melanin-based nanoparticles are excellent candidates for in vivo visualization of TDMVs.Methods: In this work, the biodistribution and metabolic behavior of TDMVs were visualized by dual-modality imaging with PAI and MRI after incubation with gadolinium ion-chelated melanin nanoparticles.Results: In this study, MRI and PAI dual-modality imaging of the in vivo distribution behavior of TDMVs was achieved with the help of MNP-Gd. The good targeting ability of TDMVs at the homologous tumor site was observed, and their distribution and metabolism behavior in the whole body were studied at the meantime. The results indicated that TDMVs preferentially accumulated in syngeneic tumor sites and liver regions after intravenous injection and were eventually metabolized by the kidneys over time.Conclusion: This work proposed a novel dual-modal imaging strategy for the visualization of TDMVs, which is of great significance for further understanding the biological mechanisms of extracellular vesicles.Keywords: cellular microvesicles, magnetic resonance imaging, photoacoustic imaging, melanin nanoparticles

Zhenming Zhang,1,* Zhentao Hu,1,* Yujie Qin,2,* Jun Qian,3 Song Tu,1,3 Jiaxi Yao3,4 1Department of General Surgery II, Hexi University Affiliated Zhangye People’s Hospital, Zhangye, Gansu, 734000, People’s Republic of China; 2Department of Endoscopy Center, Hexi University Affiliated Zhangye People’s Hospital, Zhangye, Gansu, 734000, People’s Republic of China; 3Institute of Urology, Hexi University, Zhangye, Gansu, 734000, People’s Republic of China; 4Department of Urology, Hexi University Affiliated Zhangye People’s Hospital, Zhangye, Gansu, 734000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Jiaxi Yao; Song Tu, Department of Urology, Zhangye People’s Hospital, affiliated to Hexi University, No. 67, Xihuan Road, Ganzhou District, Zhangye City, Gansu, 734000, People’s Republic of China, Tel +86-18093616382, Email 16111210057@fudan.edu.cn; zytusong@126.comPurpose: To determine an accurate method of inspecting low anastomotic leakages and application of transurethral prostate resection instrumentation for treating low rectal anastomotic leakage.Patients and Methods: Clinical data of eight patients treated for anastomotic leakage after rectal cancer surgery at Zhangye People’s Hospital (affiliated to Hexi University), from August 2019 to November 2021, were retrospectively analyzed. Transanal prostate resection instrumentation was used to assess the leakage and surrounding conditions. Using prostate resection instrumentation, the presacral and perirectal residual cavities were washed and removed, and indwelling suprapubic presacral, transanal presacral, and rectal drainage tubes were placed. Continuous presacral saline irrigation and drainage and open negative-pressure suction in the rectal cavity were performed until the patients’ fistula healed.Results: Of the eight patients with anastomotic leakages, one had grade B and seven had grade C International Study Group of Rectal Cancer anastomotic leakage classifications following Dixon operation. Transanal prostate resection instrumentation showed that the leakage of the one patient with grade B was less than a third of the circumference of the anastomosis. Among the seven patients with grade C, one leakage was less than a third of the anastomotic circumference. One patient had complete separation of the anastomosis and one distal colon necrosis, which necessitated immediate descending colostomy. Conservative treatment was successful in six patients; the conservative overall cure rate was 75%, and the median healing time was 43 (21– 68) days.Conclusion: Transanal examination of rectal anastomotic leakage using prostate resection instrumentation is comprehensive, easy to perform, provides clear visualization, accurately guides catheter placement, and can be combined with continuous open negative-pressure drainage, which is a safe, convenient, and effective method for treating low rectal leakage.Keywords: anastomotic leakage, prostate resection instrumentation, catheter, negative-pressure drainage

Dan Wang,1 Jiaqi Wang,1 Jiali Liu,1 Yu Qin,2 Peian Lou,3 Yongqing Zhang,2 Yuqing Zhang,4 Quanyong Xiang1,2 1School of Public Health, Southeast University, Nanjing, People’s Republic of China; 2Department of Chronic Non-Communicable Disease Control, Jiangsu Provincial Center for Disease Control and Prevention, Nanjing, People’s Republic of China; 3Department of Chronic Non-communicable Disease Control, Xuzhou Center for Disease Control and Prevention, Xuzhou, People’s Republic of China; 4Department of Cardiology, Nanjing Jiangning Hospital, the Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing, People’s Republic of ChinaCorrespondence: Quanyong Xiang, School of Public Health, Southeast University, Nanjing, People’s Republic of China, Tel +86-25-83759469 ; +86-18118996918, Email quanyongxiang@vip.sina.comBackground: Mean arterial pressure (MAP) has been proved to be an independent risk factor for stroke. In this study, we explored whether cumulative exposure of MAP in patients with hypertension is more associated with the occurrence of stroke.Methods: In this prospective follow-up cohort study of hypertension from June 2010 to May 2020, 9136 participants without previous stroke at recruitment were included, of whom 492 (5.4%) had a first incident stroke during the study period (418 ischemic strokes and 74 hemorrhagic strokes). The study exposure factor was cumulative MAP, and was quartered from low to high (Q1, Q2, Q3, Q4). We analyzed the risk of first stroke using multivariable adjusted Cox regression models and used stratified analysis to further explore the risk of stroke in hypertensive patients with different characteristics.Results: Increased cumulative MAP in patients with hypertension were associated with risk for ischemic stroke (HR, Q2, 1.23 [95% CI, 0.91– 1.67]; Q3, 1.35 [95% CI, 1.01– 1.82]; Q4, 1.55 [95% CI, 1.15– 2.10]; P=0.035). Furthermore, this trend persisted after stratified analysis in men (HR, Q3, 1.76[1.10– 2.82]; Q4, 2.05[1.28– 3.28]), aged 60 or above (HR, Q4, 1.63[1.13– 2.35]) and higher body mass index (BMI) populations (HR, Q3, 1.48[1.02– 2.14]; Q4, 1.59[1.09– 2.32]). In contrast, cumulative MAP was not significantly associated with stroke in women, age under 60, and non-obese individuals.Conclusion: Increased cumulative MAP is an independent risk factor of ischemic stroke in patients with hypertension. Special attention should also be paid to men, aged 60 or older, or those with a higher BMI.Keywords: cumulative mean arterial pressure, stroke, hypertension, blood pressure, population science

Liyun Sun,1,&ast; Xinwei Guo,2,&ast; Yeping Qin,3 Ping Li,4 Chunxia Yu,2 Xuesong Gao,2 Xinran Xie,4 Xuying Xu5 1Dermatology Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China; 2Beiyuan Rehabilitation Department, Beijing Longfu Hospital, Beijing, 100010, People’s Republic of China; 3Dermatology Department, Guang’anmen Hospital, China Academy of Chinese Medical Sciences, Beijing, 100053, People’s Republic of China; 4Beijng Institute of Traditional Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China; 5Ulcers Surgical Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xuying Xu, Ulcers Surgical Department, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China, Tel +86 1-87906642, Email xxying@126.com.cn Xinran Xie, Beijng Institute of Traditional Chinese Medicine, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, 100010, People’s Republic of China, Tel +86 1-87906565, Email xiexinran@bjzhongyi.comPurpose: Psoriasis is an immune-mediated chronic inflammatory disease. Metabolic syndrome (MetS) is characterized by central obesity, hypertension, dyslipidemia, diabetes and insulin resistance (IR). Increasing evidence indicates that psoriasis is associated with MetS. This study aimed to explore some metabolite indexes which could evaluate the severity or predict the risk of psoriasis patients associated with MetS.Patients and methods: It was a case-control study conducted in Beijing Hospital of Traditional Chinese Medicine. Sixty healthy volunteers (HC), 100 patients with psoriasis (Ps), 100 patients with MetS (MetS) and 80 patients with both psoriasis and MetS (Ps+MetS) were entered between January 2016 and December 2018. Blood samples were taken after at least 12 hours fasting and the contents of trimethylamine N-oxide (TMAO), carnitine, choline and betaine in serum were measured by Liquid Chromatography Mass Spectrometry (LC-MS/MS). Besides, the serum levels of low-density lipoprotein (LDL), high-density lipoprotein (HDL), cholesterol (CHO), triglyceride (TG), blood glucose (BG), creatinine (Cr), urea nitrogen (BUN), uric acid (UA) were determined.Results: The non-healthy groups had different degrees of dyslipidemia, Ps-MetS> Ps >MetS. Compared with HC, the Ps had a higher level of TG; The MetS had the lowest level of HDL; The Ps+Mets had the highest level of TG and CHO. The Ps and Ps+MetS both had high level of UA, but there was no difference between the two groups. As for intestinal metabolites, the Ps had significant differences in TMAO, carnitine, and betaine in comparison with HC. The MetS had the highest level of TMAO. There was positive correlation between PASI and TMAO and betaine.Conclusions: TMAO and betaine could serve as indexes reflecting the severity of psoriasis. TG, CHO, LDL and UA could serve as risk factors of MetS in psoriatic patients.Keywords: psoriasis, metabolic syndrome, TMAO

Yu Qin,1,2,&ast; Rui Liu,1,2,&ast; Yongxiang Wang,1– 3 Jiyou Tang,4 Lin Cong,1– 3 Juan Ren,1,2 Shi Tang,1– 3 Yifeng Du1– 3 1Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China; 2Department of Neurology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, People’s Republic of China; 3Shandong Provincial Clinical Research Center for Neurological Diseases, Jinan, Shandong, People’s Republic of China; 4Department of Neurology, The First Affiliated Hospital of Shandong First Medical University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yifeng Du; Shi Tang, Department of Neurology, Shandong Provincial Hospital, Cheeloo College of Medicine, Shandong University, No. 324 Jingwuweiqi Road, Jinan, Shandong, 250021, People’s Republic of China, Tel +86 531 68776354 ; +86-18678780912, Fax +86 531 68776354, Email duyifeng2013@163.com; tangshi@sdfmu.edu.cnPurpose: To investigate the cross-sectional associations of self-reported sleep characteristics with cardiovascular diseases (CVDs) and cardiovascular multimorbidity in older adults living in rural Eastern China.Patients and Methods: This population-based study included 4618 participants (age ≥ 65 years; 56.5% women) living in rural Eastern China. In March–September 2018, data were collected through interviews, clinical examinations, neuropsychological testing, and laboratory tests. Sleep parameters were assessed using the Pittsburgh Sleep Quality Index, Epworth Sleepiness Score, and Berlin questionnaire. Coronary heart disease (CHD), heart failure (HF), and stroke were defined according to in-person interviews, clinical and neurological examinations, and electrocardiogram examination. Data were analyzed using logistic regression and restricted cubic spline regression.Results: CHD was diagnosed in 991 participants, HF in 135 participants, and stroke in 696 participants. The multivariable-adjusted odds ratio (OR) of CHD was 1.27 (95% CI, 1.09– 1.49) for sleep duration ≤ 6 hours/night (vs > 6– 8 hours/night), 1.40 (1.20– 1.62) for poor sleep quality, and 1.22 (1.04– 1.43) for high risk for obstructive sleep apnea (OSA). The OR of HF was 2.16 (1.38– 3.39) for sleep duration > 8 hours/night, and 1.76 (1.22– 2.54) for high risk for OSA. In addition, the OR of stroke was 1.23 (1.04– 1.46) for poor sleep quality, 1.32 (1.01– 1.72) for excessive daytime sleepiness, and 1.42 (1.19– 1.70) for high risk for OSA. The associations of poor sleep with cardiovascular multimorbidity (≥ 2 CVDs) were stronger than that of sleep problems with a single CVD.Conclusion: Extreme sleep duration, high risk for OSA, and other sleep problems were associated with CVDs, especially cardiovascular multimorbidity.Keywords: sleep, coronary heart disease, heart failure, stroke, cardiovascular multimorbidity

Juan Li,1,2 Qianwen Lv,1 Haili Sun,1 Yunyun Yang,1,3 Xiaolu Jiao,1,3 Song Yang,1 Huahui Yu,1,3 Yanwen Qin1,3 1Key Laboratory of Upper Airway Dysfunction-Related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung, and Blood Vessel Diseases, Beijing, 100029, People’s Republic of China; 2Emergency Department, Beijing Shijitan Hospital, Capital Medical University, Beijing, 100038, People’s Republic of China; 3Key Laboratory of Remodeling-related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, Beijing, 100029, People’s Republic of ChinaCorrespondence: Yanwen Qin, Key Laboratory of Upper Airway Dysfunction-Related Cardiovascular Diseases, Beijing An Zhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, No. 2 Anzhen Road, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86-10-64456529, Fax +86-10-64456095, Email qinyanwen@vip.126.com; qinyanwen@ccmu.edu.cnPurpose: Obstructive sleep apnea (OSA) is a common chronic polygenic disease. Multiple genetic markers associated with OSA have been identified by genome-wide association studies. Here, we aimed to construct a polygenic risk score (PRS) and examine the association with the presence of OSA in a Chinese Han Population.Patients and Methods: This study included 1057 individuals who were genotyped for nine susceptibility loci from three genes (ADIPOQ, PPARG, and TNF), from which each individual’s PRS was calculated by summing the number of risk alleles. The associations between PRS and OSA were determined by logistic regression analyses. Model discrimination was assessed by a receiver operating characteristic (ROC) curve using bootstrapping with 1000 resamples.Results: The subjects included 874 with OSA and 183 controls. A higher PRS was associated with an increased apnea-hypopnea index (AHI). The PRS was an important risk factor for the development of OSA (OR = 1.237 per SD, P = 0.030). Subjects with higher PRS had a 2.88-fold (95% CI: 1.393– 5.955, P = 0.004) and 5.402-fold (95% CI: 2.311– 12.624, P< 0.001) greater risk for having OSA and moderate-to-severe OSA, respectively, compared with those with lower genetic risk. More importantly, compared with determination of risk based solely on clinical factors, addition of the PRS increased discriminatory accuracy for both OSA (AUC from 0.75 to 0.78, P = 0.02) and moderate-to-severe OSA (AUC from 0.80 to 0.83, P = 0.02).Conclusion: Our study suggests that the PRS is independently associated with AHI and OSA. Combining PRS with conventional risk factors could improve the discrimination of OSA.Keywords: polygenic risk score, apnea-hypopnea index, single nucleotide polymorphisms, discriminatory accuracy

He Liu,&ast; Yan Qin,&ast; Jie Yang, Guoxiu Huang, Xiaoying Wei, Lulu Wang, Wei Li Department of Health Management, The People’s Hospital of Guangxi Zhuang Autonomous Region & Research Center of Health Management, Guangxi Academy of Medical Sciences, Nanning, 530021, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Li; Lulu Wang, Email lw6666gx@aliyun.com; pariswangll@163.comBackground: Helicobacter pylori (HP) infection is considered as a risk factor for nutritional and metabolic abnormalities, and serum protein is an important marker of the nutritional and immune status. It is still unknown whether HP infection affects serum protein levels.Methods: The participants who underwent health screening from July 2020 to August 2021 were included, among whom, 1485 subjects with 14C-urea breath test (14C-UBT) values ≥ 100 disintegrations per minute (dpm) were defined as HP-positive cases, and 4864 cases with 14C-UBT values < 100 dpm were defined as HP-negative cases. Anthropometric measurements were taken, and biochemical parameters of the blood were analyzed for all subjects. Categorical variables were compared using the χ 2 test and continuous variables using Student’s t test. Logistic regression analysis was used to determine the effect of HP infection on serum proteins.Results: Age, the proportion of female, globulin levels, total cholesterol levels, and low-density lipoprotein cholesterol levels were significantly higher in the HP infected group than in the non-infected group (P < 0.05). Height, weight, body mass index, hip circumference, albumin levels, albumin to globulin ratio, triglycerides levels, and uric acid levels were significantly higher in the non-infected group than in the infected group (P < 0.05). Multifactorial analysis revealed that HP infection was significantly associated with the risk of decreased serum albumin levels (odds ratio [OR] = 0.809, P = 3.51× 10− 4); HP infection was significantly associated with the risk of increased serum globulin levels (model 1: OR = 1.257, P = 1.39× 10− 4); and HP infection was significantly associated with the risk of decreased albumin/globulin ratio (OR= 0.775, P = 2.30× 10− 5).Conclusion: HP infection was significantly associated with lower serum albumin levels, elevated globulin levels, and lower albumin/globulin ratio. Thus, it is an important factor affecting nutritional metabolism.Keywords: Helicobacter pylori, nutrition, serum albumin, serum globulin, albumin/globulin ratio

Yukun Jia,1 Zhan Peng,1 Jin Li,1 Yuantian Qin,2 Guangye Wang1 1Spine Surgery, Affiliated Baoan Hospital of Shenzhen, Southern Medical University; The Second School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong Province, People’s Republic of China; 2Teaching Department, Nanjing University of Aeronautics and Astronautics, Nanjing, Jiangsu Province, People’s Republic of ChinaCorrespondence: Zhan Peng; Guangye Wang, Email 2505948667@qq.com; doctorwang521@126.comPurpose: To evaluate the efficacy and safety of unilateral O-arm navigation-assisted percutaneous kyphoplasty (PKP) for the treatment of Kümmell’s disease.Methods: The clinical data from patients with Kümmell’s disease who attended our hospital between January 2015 and January 2019 were retrospectively analyzed. For each patient, the visual analog scale (VAS) score, anterior height of the vertebral body, sagittal kyphotic angle, Oswestry Disability Index (ODI), and postoperative cement leakage rate were recorded before and after surgery. Any surgical complications were documented.Results: The patients were followed up for 12 to 18 months. The average preoperative VAS score, kyphotic angle, and ODI decreased from 8.6 ± 0.5, 18.0 ± 3.7°, and 86.027%, respectively, to 2.2 ± 0.2, 5.8 ± 0.8°, and 26.720% three days after surgery. The anterior height of the vertebral body increased significantly from 14.5 ± 1.2 mm preoperatively to 19.4 ± 1.2 mm three days after surgery, and this improvement was maintained until the last follow-up. After surgery, bone cement leakage occurred in one vertebral body; this patient exhibited leakage to the intervertebral disc space, a complete pedicle and spinal canal structure, no clinical symptoms, and required no treatment.Conclusion: This study shows that unilateral PKP assisted by O-arm navigation is safe and effective. Moreover, the observed improvements can be maintained over the longer term.Keywords: percutaneous kyphoplasty, navigation, unilateral, Kümmell’s disease, efficacy, safety

Yan Qin,1,&ast; He Liu,1,&ast; Xiaoliang Huang,2 Lihaoyun Huang,2 Lixian Liao,2 Jiasheng Li,2 Lihua Zhang,2 Wei Li,1 Jianrong Yang1 1Department of Health Management, The People’s Hospital of Guangxi Zhuang Autonomous Region & Research Center of Health Management, Guangxi Academy of Medical Sciences, Nanning, Guangxi, 530021, People’s Republic of China; 2Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianrong Yang; Wei Li, Health Examination Center, The People’s Hospital of Guangxi Zhuang Autonomous Region, Email gandansurgery2014@163.com; lw6666gx@aliyun.comBackground: GIMAP, a GTP enzyme of immune-related proteins, plays a crucial role in immune mechanisms. Investigating GIMAP7 expression in pan-cancer can provide efficient guidance for predicting clinical prognosis and identifying novel immunotherapy targets.Methods: Gene expression in different tumour types and stages was analysed based on The Cancer Genome Atlas and the Genotype-Tissue Expression database. An immunohistochemical assay was used to explore the differences in GIMAP7 protein levels in different tumour types and stages. Further, the cBioPortal was used to obtain the genetic variation characteristics of GIMAP7. Kaplan–Meier analysis and multivariable Cox regression analysis were performed to assess the prognostic value of GIMAP7. The pathways affected by GIMAP7 were studied based on gene set enrichment analysis, and the correlation between GIMAP7 expression and immune infiltration was determined using the TIMER2 database and the CIBERSORT method. ESTIMATE was used to analyse the correlation between GIMAP7 expression and ESTIMATE, immune and stromal scores. In addition, the correlation between GIMAP7 and immunoregulators was analysed. Furthermore, tumour mutational burden and microsatellite instability were evaluated using Spearman correlation assay.Results: GIMAP7 expression was significantly low and predicted better survival status in most tumour types. GIMAP7 was positively correlated with the abundance of CD8 + and CD4 + T cells in the tumour microenvironment. However, the high expression of GIMAP7 was negatively correlated with tumour mutations in uveal melanoma and colon adenocarcinoma. A correlation between GIMAP7 and microsatellite instability was found in rectal adenocarcinoma. Additionally, GIMAP7 presented a robust correlation between immune modulators and immunotherapeutic markers. Moreover, high GIMAP7 expression was significantly related to immune-relevant pathways.Conclusion: This study suggests the potential role of GIMAP7 as a prognostic and immunotherapeutic marker in pan-cancer, laying the groundwork for prospective functional and mechanistic experiments and their impact in the clinical setting.Keywords: immune-associated nucleotide-binding protein 7, pan-cancer analysis, immunoregulation, immunotherapy, CD8-positive T cells

Litong Shi, Zehua Wang, Lei Wang, Yongxu Jia, Jing Li, Yanru Qin Department of Oncology, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, People’s Republic of ChinaCorrespondence: Yanru QinDepartment of Oncology, Zhengzhou University First Affiliated Hospital, No. 1 Jianshe East Road, Erqi District, Zhengzhou, 450052, Henan, People’s Republic of China, Tel +86 13676932999, Email yanruqin@163.comPurpose: This study aimed to study the prognostic value of clinicopathological data, inflammation and nutritional indicators, and to design an effective prognostic nomogram and heat map to predict cancer-specific survival (CSS) and disease-free survival (DFS) of stage II/III GC patients who underwent curative gastrectomy with adjuvant chemotherapy.Patients and Methods: We retrospectively analyzed the data of 611 patients with stage II/III GC after curative gastrectomy followed by adjuvant chemotherapy from 3 GC disease centers. Patients were divided into a training cohort (n = 503) and an external validation cohort (n = 108). Nomograms were established based on independent predictors identified by Cox regression analysis in the training cohort. The consistency index (C-index) and the calibration curve were used to evaluate the discriminative ability and accuracy of the nomogram. Heat maps were constructed with the prognostic factors and the corresponding survival probability. We further divided the patients into low-risk and high-risk groups based on the risk score of the nomogram.Results: Through univariate and multivariate survival analysis, the independent risk factors common to CSS and DFS were identified. Then these predictors were incorporated into the nomograms, and the established nomograms used to predict CSS and DFS had high discriminative power in the training cohort. Meanwhile, the calibration curves of CSS and DFS probability also showed good agreement between the prediction based on the nomograms and the actual observation results. The above independent predictors were applied to establish heat maps. Compared with low-risk patients, the high-risk patients calculated according to the nomogram had a shorter survival time and a worse prognosis.Conclusion: We established a nomogram and heat map, which could be used to assess the survival rate of stage II/III GC patients who underwent curative gastrectomy with adjuvant chemotherapy. These tools had high prognostic prediction accuracy and provided inspiration for clinical decision-making.Keywords: heat map, nomogram, gastric cancer, adjuvant chemotherapy, prognosis, survival

Xian Zhang,1,&ast; Liting Chen,2,&ast; Gaoxiang Wang,2,&ast; Liwen Chen,1 Lifang Huang,2 Yang Cao,2 Xing Chen,2 Chaohua Deng,1 Xuhui Chen,1 Dandan Ke,1 Yuanjun Qin,1 Bo Chen,1 Xufang Sun1 1Department of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2Department of Hematology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bo Chen; Xufang SunDepartment of Ophthalmology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095 Jiefang Ave., Wuhan, 430030, People’s Republic of ChinaEmail eyechen@aliyun.com; sunxufang2016@163.comPurpose: This study detects SARS-CoV-2 in the ocular surface through one-step reverse-transcription droplet digital PCR (one-step RT-ddPCR) and evaluates the possibility of the ocular surface as a possible transmission route.Methods: A single-center prospective observational study was designed to investigate the viral loads in ocular surface. Specimens including the conjunctival swabs, nasopharyngeal swabs and blood were synchronously collected at a single time point for all COVID-19 patients. SARS-CoV-2 loads in nasopharyngeal swabs were tested by real-time polymerase chain reaction (PCR); the blood samples and conjunctival swabs were tested by real-time PCR and one-step RT-ddPCR.Results: Sixty-eight COVID-19 patients confirmed by nasopharyngeal real-time PCR were recruited. In the single time point test, 40 cases showed positive SARS-CoV-2 detection in either the blood, tears, or nasopharynx, of which four cases were triple-positive, 10 were dual-positive, and 26 were single-positive. The positive rate of nasopharyngeal swab real-time PCR test was 22.1% (15/68). The positive rate of blood and conjunctival swabs by one-step RT-ddPCR was 38.2% (26/68) and 25% (17/68), respectively, whereas real-time PCR was all negative. Positive conjunctival swabs were significantly correlated with positive nasopharyngeal swabs (P = 0.028). The sampling lags from illness onset to sampling day in 3 out of 4 triple-positive patients and in 9 out of 10 dual-positive patients were respectively less than 9 days and less than 20 days.Conclusion: Our results indicate that the positive rate of SARS-CoV-2 on the ocular surface is much higher than expected. Transmission possibility through the ocular surface may be greatly underestimated.Keywords: absolute quantification, virus detection, transmission, nasopharyngeal specimens, blood samples, tear samples