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

Mengyao Shi,1,&ast; Xueyu Mao,2,&ast; Xuechun Wu,2 Min Chu,2 Huicong Niu,2 Lulu Sun,1 Xinyue Chang,1 Yu He,1 Yi Liu,1 Daoxia Guo,3 Yonghong Zhang,1 Zhengbao Zhu,1 Jing Zhao2,4 1Department of Epidemiology, School of Public Health, Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, MOE Key Laboratory of Geriatric Diseases and Immunology, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 2Department of neurology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China; 3School of Nursing, Suzhou Medical College of Soochow University, Suzhou, People’s Republic of China; 4Institute of Healthy Yangtze River Delta, Shanghai Jiao Tong University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jing Zhao, Department of Neurology, Minhang Hospital, Fudan University, Shanghai, People’s Republic of China, Email zhao_jing@fudan.edu.cn Zhengbao Zhu, Department of Epidemiology, School of Public Health and Jiangsu Key Laboratory of Preventive and Translational Medicine for Geriatric Diseases, Suzhou Medical College of Soochow University, 199 Renai Road, Industrial Park District, Suzhou, Jiangsu Province, 215123, People’s Republic of China, Email zbzhu@suda.edu.cnBackground: Prealbumin is a symbol of protein nutrition and is involved in anti-inflammatory and neuron regeneration, but its association with the prognosis of ischemic stroke remains unclear. We aimed to prospectively explore the associations between serum prealbumin levels and adverse clinical outcomes after ischemic stroke in a large-scale cohort study.Methods: We measured serum prealbumin levels among 6609 ischemic stroke patients admitted at Minhang hospital. The primary outcome was composite of death and major disability (modified Rankin Scale [mRS] score ≥ 3) at 3 months after stroke onset, and secondary outcomes included death and the ordered 7-level categorical score of mRS.Results: During 3 months of follow-up, a total of 2118 patients developed the primary outcome. After multivariable adjustment, high prealbumin levels were associated with a decreased risk of primary outcome (odds ratio, 0.71; 95% CI, 0.59– 0.85; Ptrend< 0.0001) when 2 extreme quartiles were compared. Each unit increase of log-transformed prealbumin was associated with a 42% (95% CI, 28-53%) decreased risk of primary outcome. There was a better shift in the distribution of mRS score at 3 months with higher quartiles of serum prealbumin in ischemic stroke patients (Ptrend< 0.0001). Multivariable-adjusted spline regression model showed a linear relationship between prealbumin and the risk of primary outcome (P for linearity = 0.0036).Conclusion: High serum prealbumin level was independently associated with decreased risks of adverse clinical outcomes among ischemic stroke patients. Our findings suggested that prealbumin may be a valuable prognostic biomarker and indicated the importance of keeping nourished in the daily life.Keywords: prealbumin, ischemic stroke, prognosis, cohort study

Jie Wang,1 Yuanbo Wu,2 Meng Mao,3 Hailong Bing,1 Liwei Sun,1 Wei Xu,1 Wangli Tian,1 Zhengyuan Xia,4,5 Xiaogao Jin,1,6 Qinjun Chu1 1Department of Anesthesiology and Perioperative Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, People’s Republic of China; 2Department of Anesthesiology, Hubei Cancer Hospital, Wuhan, Hubei, People’s Republic of China; 3Center for Advanced Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450007, People’s Republic of China; 4Department of Anesthesiology, The First Affiliated Hospital, Jinan University, Guangzhou, People’s Republic of China; 5Department of Anesthesiology, The University of Hong Kong, Hong Kong; 6Department of Anesthesiology, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of ChinaCorrespondence: Xiaogao Jin; Qinjun Chu, Email jinxiaoagao@zzu.edu.cn; jimmynetchu@163.comPurpose: We aim to detect the effects of sivelestat on renal ischemia-reperfusion associated with AKI and also explore the underlying mechanism.Materials and Methods: Mice, aged between 8 and 12 weeks, were randomly allocated among four distinct groups, respectively normal saline sham group(C), normal saline surgery group(I), sivelestat (50 mg/kg) sham group(S), sivelestat (50 mg/kg) surgery group(SI) (n=6, each group). In the surgical groups, the renal pedicles of mice were clamped with non-traumatic micro-aneurysm clamps, resulting in ischemia of the kidneys for 45 minutes. This was followed by a period of reperfusion lasting 24 hours. Sham group mice underwent the identical surgery produced without clamping renal pedicles. Mice blood was obtained from eyeballs, and Serum creatinine and blood urea nitrogen levels were measured. After a 24-hour period of reperfusion, the mice were euthanized, and their kidneys were gathered for various analyses, including Western Blot (WB) analysis, RT-PCR, immunofluorescence (IF), hematoxylin and eosin (H&E) staining, and Tunel assay.Results: Pretreatments with sivelestat decreased renal Neutrophil elastase (NE), serum creatinine, and blood urea nitrogen levels after renal ischemia-reperfusion. Sivelestat also reduced histological damage and cell apoptosis in kidneys following ischemia-reperfusion injury (IRI). In addition, the sivelestat administration diminished the levels of mRNA expression of interleukin 6 (IL-6), Macrophage inflammatory protein-2 (MIP-2), monocyte chemoattractant protein-1 (MCP-1), and tumor necrosis factor (TNF)-α in the kidneys during IRI. The kidney tissues of the SI group had significantly mitigated TLR4, Myd88, and NF-κB p-p65 protein expression levels compared to the I group (all P< 0.05).Conclusion: We demonstrated a previously unidentified mechanism that sivelestat effectively attenuates AKI-induced renal dysfunction, possibly through suppressing the TLR4/Myd88/ NF-κB pathway.Keywords: neutrophil elastase, ischemia reperfusion injury, renal dysfunction, inflammation

Xinchen Wang,1,&ast; Haiwei Bu,1,2,&ast; Chen Wei,1 Jingyi Liu,1– 3 Yuewen Qi,3,4 Weichao Shan,1– 3 Ying Zhang,1– 3 Lixian Sun1– 3 1Department of Cardiology, The Affiliated Hospital of Chengde Medical University, Chengde, People’s Republic of China; 2The Cardiovascular Research Institute of Chengde, Chengde, People’s Republic of China; 3Hebei Key Laboratory of Panvascular Diseases, Chengde, People’s Republic of China; 4Central Laboratory of The Affiliated Hospital of Chengde Medical University, Chengde, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lixian Sun, Department of Cardiology, The Affiliated Hospital of Chengde Medical University, Chengde, China, No. 36, Nanyingzi Street, Shuangqiao District, Chengde, Hebei Province, People’s Republic of China, Tel +86 0314 227 9016, Fax +86 0314 227 4895, Email lixiansun01@126.comPurpose: To elucidate the predictive values of adipocytokines in patients with acute coronary syndrome (ACS).Patients and Methods: Overall, 297 patients with ACS were consecutively enrolled in this prospective cohort study between June 2015 and July 2017 and completed follow-up with a median follow-up time of 6.5 years. For consistency, the last visit date was June 20, 2023. Serum levels of retinol-binding protein-4 (RBP4), interleukin-1β (IL-1β), monocyte chemoattractant protein 1(MCP-1), adrenomedullin (ADM), netrin 1 (NTN 1), and omentin were measured using enzyme-linked immunosorbent assay. Follow-up data were collected during clinical visits or through telephone interviews at 1, 3, 6, 12 months, and annually. The primary endpoint was defined as major adverse cardiovascular events (MACEs), including all-cause mortality, rehospitalization for percutaneous coronary intervention, and severe angina requiring rehospitalization.Results: All biomarkers displayed a good diagnostic ability of MACEs. The Kaplan–Meier curve showed that the cumulative survival rates of high level of RBP4, IL-1β, and MCP-1 and low level of the ADM, NTN1, and omentin had lower cumulative survival rates (Log rank tests: all p< 0.05). After adjustment in the Cox hazard proportional model, the results were RBP4 ≥ 6.87 ng/mL, hazard ratio (HR)=2.512, p=0.003; IL-1β≥ 58.95 pg/mL, HR=3.809, p< 0.001; MCP-1 ≥ 401.75 pg/mL, HR=4.047, p< 0.001; ADM≤ 120.01 ng/mL, HR=3.930, p=0.008; NTN1 ≤ 63.7 pg/mL, HR=3.345, p=0.007; omentin ≤ 4.54 ng/mL, HR=2.830, p=0.004. P-values for interaction were > 0.05 in the sex, age, and dyslipidemia subgroups.Conclusion: Pro-inflammation adipocytokines RBP4, IL-1β, and MCP-1 increased and anti-inflammation biomarkers ADM, NTN1, and omentin decreased were independently associated with a higher risk of MACEs in patients with ACS.Keywords: acute coronary syndrome, adipocytokines, prognosis

Liying Sun, Xuhui Ye, Junping Yu, Linlin Wang, Yan Wu, Jing Cui, Lihua Dai Intensive Care Unit, Shidong Hospital, Shanghai, People’s Republic of ChinaCorrespondence: Lihua Dai, Intensive Care Unit, Shidong Hospital, Yangpu District, Shanghai, 200438, People’s Republic of China, Tel +86 18917059757, Email gg790516@163.comPurpose: Previous studies have reported that lymphocyte-to-monocyte ratio (LMR) is associated with the prognosis of patients with acute ischemic stroke (AIS); however, the relationship between LMR and early neurological deterioration (END) in AIS patients has not been elucidated.Patients and Methods: Patients were divided into two groups according to LMR by using receiver operating characteristic (ROC) curve analysis. Patients with END were confirmed as the National Institutes of Health Stroke Scale (NIHSS) increased ≥ 4 points between hospital days 0 and 5. Multivariate logistic regression analysis was used to analyze the factors independently related to END in patients with AIS.Results: In total, 202 patients diagnosed with AIS were enrolled in this retrospective study. Using ROC curve analysis, patients were divided into two groups according to LMR: low LMR group (LMR < 3.24, n = 95) and high LMR group (LMR ≥ 3.24, n = 107). The frequencies of END were significantly higher in the low LMR group compared to the high LMR group (41.05 vs.15.89%, p < 0.001). Multivariate logistic regression showed that age (OR = 1.03, 95% CI 1.01– 1.06, p = 0.04), infarct volume (OR = 1.01, 95% CI 1.00– 1.02, p = 0.001), neutrophil count (OR = 1.17, 95% CI 1.03– 1.33, p = 0.018), and LMR (OR = 2.49, 95% CI 1.01– 9.11, p = 0.018) were independently associated with END in AIS patients.Conclusion: A peripheral LMR levels at admission were significantly associated with END and LMR < 3.24 is an independent predictive factor of END in patients with AIS.Keywords: lymphocyte-to-monocyte ratio, acute ischemic stroke, early neurological deterioration, national institutes of health stroke scale

Ruyu Han,1,&ast; Leijuan Gan,1,&ast; Liyu Sun,1 Mengran Lang,2 Xindi Tian,1 Kangwei Zhu,1 Lu Chen,1 Guangtao Li,1 Tianqiang Song1 1Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, People’s Republic of China; 2Hepatobiliary Surgery Department, National Cancer Center, National Clinical Research Center for Cancer, Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianqiang Song, Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, People’s Republic of China, Tel +86-22-23340123, Fax +86-22-23537796, Email songtianqiangtj@163.comPurpose: This study aimed to investigate the benefit of conversion therapy for patients with unresectable hepatocellular carcinoma (HCC).Patients and Methods: A retrospective cohort study was conducted involving 40 patients initially deemed unresectable HCC (uHCC). They received surgery following successful conversion therapy involving lenvatinib. The patients were matched in a 1:1 ratio to with a control group who underwent direct surgery, based on pre-treatment clinical data.Results: The median recurrence-free survival (RFS) duration for the conversion therapy cohort was notably longer than that of the direct surgery cohort (25 months vs 11 months). Furthermore, the 1- and 2-year RFS rates were significantly higher in the conversion therapy group compared to the direct surgery group (1 year: 70.5% vs 40.1%; 2 years: 49.0% vs 19.1%). The survival curves indicated a statistically significantly longer RFS in the conversion therapy cohort compared to the direct surgery cohort (P = 0.007). While patients achieving good remission based on both RECIST 1.1 and mRECIST criteria showed superior median RFS, no significant disparity was observed in the survival curves. The subgroup analysis revealed significantly improved prognosis among patients in the conversion therapy group who were male, older, had a history of alcohol consumption, were non-smokers, had liver cirrhosis, possessed Child-Pugh A liver function, had a tumor diameter exceeding 5 cm, and had an AFP ≥ 400 ng/mL. Among the cohort of 40 patients, only 8 individuals encountered severe adverse reactions, which were managed through dose reduction. None of the patients experienced multiple severe adverse reactions concurrently.Conclusion: For patients with unresectable hepatocellular carcinoma, conversion therapy offers a significantly better prognosis than direct surgery for uHCC patients.Keywords: hepatocellular carcinoma, conversion therapy, recurrence-free survival, hepatic resection

Wenbin Guo,1,&ast; Lin Sun,1,&ast; Huijun Yue,1,&ast; Xueqin Guo,1 Lin Chen,1 Jinhong Zhang,1 Zhuqi Chen,1 Yiming Wang,1 Jiao Wang,2 Wenbin Lei1 1Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 510080, People’s Republic of China; 2School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiao Wang, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, Guangdong, People’s Republic of China, Email wangj836@mail.sysu.edu.cn Wenbin Lei, Otorhinolaryngology Hospital, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, 510080, Guangdong, People’s Republic of China, Email leiwb@mail.sysu.edu.cnPurpose: Clinical studies focusing on the association between the gut microbiota and obstructive sleep apnea (OSA) are limited. This study aimed to explore the relationship between intermittent hypoxia and the composition of gut microbiota in adults by analyzing the differences in the characteristics and functional distribution of gut microbiota between patients with different severities of OSA and healthy individuals.Patients and Methods: A cohort of 113 individuals from the First Affiliated Hospital of Sun Yat-sen University underwent overnight polysomnography from July 2019 to August 2021. The individuals included 16 healthy controls and 97 patients with OSA, categorized by the apnea-hypopnea index into mild, moderate, and severe groups. Fecal samples were analyzed using high-throughput sequencing of the 16S rRNA V3–V4 region to assess gut microbiota composition and function. Correlation analysis was used to evaluate the association between clinical indicators and microbiota markers.Results: In patients with OSA, the gut microbiota diversity and the abundance of specific microbes that produce short-chain fatty acids decreased (P< 0.05). The phyla Verrucomicrobia and Candidatus Saccharibacteria, genera Gemmiger and Faecalibacterium, and the species Gemmiger formicilis exhibited decreasing abundance with increasing OSA severity. Correlation analysis revealed a robust association between the proportion of total sleep time, characterized by nighttime blood oxygen saturation below 90%, and the alterations in the gut microbiota, demonstrating that elevated levels of desaturation are correlated with pronounced microbiota dysbiosis (P< 0.05).Conclusion: Compared to the control group, the intermittent hypoxia exhibited by patients with OSA may be related to alterations in the composition and structure of the gut microbiota. Our results demonstrate the importance of monitoring hypoxia indicators in future clinical practice.Keywords: obstructive sleep apnea, gut microbiota, 16S rRNA, intermittent hypoxia

Qingqing Shen,1– 3,&ast; Qing Zhang,2,3,&ast; Yunxiao Liu,1– 3,&ast; Yingao Cui,1– 3 Jingwen Shang,1– 3 Xiaoping Yuan,2,3 Feng Geng,4 Liang Sun,5 Zhiwei Liu,5 Rongchun Yang,5 Kai Zhang,2,3 Huanzhong Liu2,3,6 1Department of Psychiatry, School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 2Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 3Anhui Psychiatric Center, Anhui Medical University, Hefei, Anhui, People’s Republic of China; 4Department of Psychology and Sleep Medicine, the Second Affiliated Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China; 5Department of Psychiatry, Fuyang Third People’s Hospital, Fuyang, Anhui, People’s Republic of China; 6Brain Bank Construction and Resource Utilization, Anhui Provincial Key Laboratory, Anhui, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Kai Zhang; Huanzhong Liu, Department of Psychiatry, Chaohu Hospital of Anhui Medical University, Hefei, Anhui, People’s Republic of China, Email zhangkai@ahmu.edu.cn; huanzhongliu@ahmu.edu.cnPurpose: The purpose of this study was to further explore the association of pain intensity and sensitivity with suicidal ideation in adolescents with depressive disorder by comparing the differences in pain intensity and sensitivity between adolescent patients with depressive disorders and healthy controls.Patients and Methods: A consecutive enrollment method was used to select 158 adolescent patients with depressive disorders from three hospitals in Anhui Province as the MDD group, and 47 healthy adolescents were recruited as the Control group. The subjects’ suicidal ideation was assessed using the Positive and Negative Suicide Ideation scale (PANSI), and the intensity of somatic pain was assessed using the Numerical Rating Scale-11 (NRS-11). Subjects were assessed for forearm and tibial pain sensitivity using a hand-held pressure pain instrument, and experimental pain sensitivity measures included pressure pain threshold (PPT) and pressure pain tolerance (PTO). Differences in pain intensity and sensitivity between the MDD group and the Control group were compared, and the association of pain intensity and sensitivity with suicidal ideation was analyzed.Results: The incidence of physical pain in adolescent depressive disorder was higher at 88.6%, which was significantly higher than the Control group (P< 0.001), and the pain intensity in the MDD group (3.77± 2.48) was significantly higher than the Control group (0.617± 0.99) (P < 0.001).The Pain tolerance was significantly higher in the MDD group (forearm 105.37 ± 41.46; tibia 121.29 ± 41.60) than in the Control group (forearm 91.92 ± 37.62; tibia 105.47 ± 35.52) (P < 0.05).Linear regression analysis showed that the greater the pain intensity and pain tolerance, the higher the total PANSI score.Binary logistic regression showed that pain intensity was an influencing factor for suicidal ideation.Conclusion: Adolescents with depressive disorders have higher pain intensity and lower pain sensitivity than healthy adolescents. Increased pain intensity and pain tolerance were positively correlated with suicidal ideation.Keywords: adolescents, depressive disorder, pain intensity, pain sensitivity, suicidal ideation

Liyan Sun,1 Jinshuai Lan,1,2 Zhe Li,1,2 Ruifeng Zeng,1,2 Yi Shen,1 Tong Zhang,1,2 Yue Ding1– 3 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2State Key Laboratory of Integration and Innovation of Classic Formula and Modern Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 3National Innovation Platform for Medical Industry-Education Integration, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of ChinaCorrespondence: Yue Ding; Tong Zhang, Email dingyue-2001@hotmail.com; zhangtongshutcm@hotmail.comAbstract: Berberine (BBR), recognized as an oncotherapeutic phytochemical, exhibits its anti-cancer properties via multiple molecular pathways. However, its clinical application is hindered by suboptimal tumor accumulation, rapid systemic elimination, and diminished bioactive concentration owing to extensive metabolic degradation. To circumvent these limitations, the strategic employment of nanocarriers and other drugs in combination with BBR is emerging as a focus to potentiate its anti-cancer efficacy. This review introduced the expansive spectrum of BBR’s anti-cancer activities, BBR and other drugs co-loaded nanocarriers for anti-cancer treatments, and evaluated the synergistic augmentation of these amalgamated modalities. The aim is to provide an overview of BBR for cancer treatment based on nano-delivery. Berberine (BBR), recognized as an oncotherapeutic phytochemical, exhibits its anti-cancer properties via multiple molecular pathways. However, its clinical application is hindered by suboptimal tumor accumulation, rapid systemic elimination, and diminished bioactive concentration owing to extensive metabolic degradation. To circumvent these limitations, the strategic employment of nanocarriers and other drugs in combination with BBR is emerging as a focus to potentiate its anti-cancer efficacy. Nano-delivery systems increase drug concentration at the tumor site by improving pharmacological activity and tissue distribution, enhancing drug bioavailability. Organic nanocarriers have advantages for berberine delivery including biocompatibility, encapsulation, and controlled release of the drug. While the advantages of inorganic nanocarriers for berberine delivery mainly lie in their efficient loading ability of the drug and their slow release ability of the drug. This review introduced the expansive spectrum of BBR’s anti-cancer activities, BBR and other drugs co-loaded nanocarriers for anti-cancer treatments, and evaluated the synergistic augmentation of these amalgamated modalities. The aim is to provide an overview of BBR for cancer treatment based on nano-delivery.Keywords: berberine, anti-cancer, nano drug delivery system, combination therapy

Lisha Sun,1,&ast; Xiaoran Zhang,1,&ast; Jiao Yang,1,&ast; Jun Yuan,2 Xingxing Lei1 1Department of Endocrinology, Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China; 2Chengdu University of Traditional Chinese Medicine, Chengdu, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xingxing Lei, Email iopmj38169@tom.comObjective: Visceral fat area (VFA) levels have been found to exhibit a strong association with various conditions such as insulin resistance (IR), inflammation, oxidative stress, metabolic syndrome (MetS), hyperlipidemia, diabetes, and its vascular complications. These complications include hypertension, cardiovascular disease, diabetic retinopathy (DR), albuminuria, and cardiovascular autonomic dysfunction, which is considered one of the main types of diabetic neuropathy. This study aimed to investigate the correlation between visceral fat and peripheral neuropathy in patients with type 2 diabetes (T2DM).Methods: A retrospective analysis of clinical data of patients diagnosed with type 2 diabetes admitted to our hospital was conducted. After excluding 28 cases, a total of 488 patients were included, divided into the group with peripheral neuropathy (207 cases) and the control group without peripheral neuropathy (281 cases). The correlation between VFA and the presence of DPN was assessed using correlation and multiple logistic regression analyses.Results: In terms of general information, the group with peripheral neuropathy had lower BMI but longer duration of diabetes compared to the control group. Regarding biochemical indicators, VFA were lower in the group with peripheral neuropathy, while FPG and HbA1c levels were higher (all P< 0.05). Spearman correlation analysis showed a negative correlation between VFA, and the presence of peripheral neuropathy in patients with type 2 diabetes (P< 0.05). Logistic regression analysis indicated that VFA, duration of diabetes, and HbA1c level were influencing factors for the occurrence of peripheral neuropathy in patients with type 2 diabetes (P< 0.05).Conclusion: This study revealed a correlation between visceral fat and peripheral neuropathy in patients with type 2 diabetes, highlighting the importance of monitoring visceral fat in such patients. In addition to lower levels of VFA, factors such as duration of diabetes and glycated hemoglobin (HbA1c) level were also associated with peripheral neuropathy in patients with T2DM.Keywords: type 2 diabetes, visceral fat, peripheral neuropathy, correlation, metabolic complications

Lili Huang,1,&ast; Yesong Liu,2,&ast; Tingting Geng,1,&ast; Nannan Zhang,2 Liang Sun,1 Shouling Wu,3 Xiang Gao1 1Department of Nutrition and Food Hygiene, School of Public Health, Institute of Nutrition, Fudan University, Shanghai, People’s Republic of China; 2Department of Neurology, Kailuan General Hospital, Tangshan, People’s Republic of China; 3Department of Cardiology, Kailuan General Hospital, Tangshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiang Gao, Department of Nutrition and Food Hygiene, School of Public Health, Institute of Nutrition, Fudan University, 130 Dongan Road, Shanghai, 200032, People’s Republic of China, Email xiang_gao@fudan.edu.cn Shouling Wu, Department of Cardiology, Kailuan General Hospital, 57 Xinhua East Road, Tangshan, 063000, People’s Republic of China, Tel +86 315 3025655, Fax +86 315 3725312, Email drwusl@163.comBackground: Sleep complaints were reported to be associated with stroke, however, the evidence on the association between healthy sleep pattern and stroke risk in Chinese is limited.Objective: The aim of this study was to investigate the association between healthy sleep pattern and stroke in Chinese, and the influence of metabolic diseases on the association.Methods: A total of 11,851 participants from the Kailuan study in China without stroke at baseline were included. We calculated a healthy sleep score according to four sleep factors, and defined the low-risk groups as follows: no insomnia, no excessive daytime sleepiness, no frequent snoring, and sleep 7– 8h/d. Each low-risk sleep factor was assigned a score of 1. Cox proportional hazard models were used to assess the association between healthy sleep score and stroke. Mediation analysis was used to estimate the role of metabolic diseases (obesity, diabetes, and hypertension) in the healthy sleep score-stroke association.Results: During a mean follow-up period of 7.7 years, 504 cases of stroke were identified. A higher healthy sleep score was associated with a lower risk of stroke in a dose-response manner (P-trend=0.03). The adjusted hazard ratio (HR) for participants with a healthy sleep score of 4 versus ≤ 2 was 0.75 (95% confidence interval [CI]: 0.56, 0.96). In addition, obesity, diabetes, and hypertension collectively explained 21.9% (95% CI: 17.2, 26.5) of the association between healthy sleep score and stroke.Conclusion: Adherence to healthy sleep pattern was associated with a lower risk of stroke, and the favorable association was partially mediated by metabolic diseases.Keywords: healthy sleep pattern, metabolic disease, stroke, mediation

Chang Shang,1,&ast; Mengfei Yuan,1,&ast; Yue Wang,1,&ast; Yahui Wang,2 Wujisiguleng Bao,2 Shuanghui Zeng,2 Dandan Zhang,2 Ping Liu,2,3 Luying Sun2,3 1Department of Nephropathy and Endocrine, Dongzhimen Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 2Fangshan Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 3Integrated Chinese and Western Medicine Metabolic Disease Research Center, Fangshan Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Luying Sun; Ping Liu, Fangshan Hospital, Beijing University of Chinese Medicine, No. 4, Health Care Road, Chengguan Street, Fangshan District, Beijing, 102499, People’s Republic of China, Email luyingsun@outlook.com; liuping000000@sina.cnPurpose: To investigate the association between visceral obesity and glycemic control in patients with type 2 diabetes mellitus.Patients and Methods: A retrospective analysis involved 714 patients diagnosed with type 2 diabetes mellitus from the National Metabolic Management Center from November 2021 to February 2024. Medical data included sociodemographic data, lifestyle behaviors, and anthropometric and biochemical measurements. Multivariate logistic regression analysis was used to analyze their associations.Results: Among the patients, 251 (35.2%) achieved good glycemic control (HbA1c < 7.0%). On univariate analysis, higher diastolic blood pressure, longer duration of type 2 diabetes mellitus, tobacco smoking, alcohol drinking, insulin treatment, higher levels of fasting plasma glucose, homeostasis model assessment of insulin resistance, triglyceride, total cholesterol, and low-density lipoprotein cholesterol, visceral obesity (visceral fat area ≥ 100cm2) and diabetic peripheral neuropathy were all positively correlated with poor glycemic control; female, older age, higher levels of C peptide and serum uric acid were inversely associated with poor glycemic control (all P < 0.05). On multivariate logistic regression analysis, the results suggested that higher diastolic blood pressure [OR: 1.021, 95% CI (1.002, 1.040), P = 0.030], insulin treatment [currently used: OR = 2.156, 95% CI (1.249, 3.724), P = 0.006], higher level of fasting plasma glucose [OR: 1.819, 95% CI (1.598, 2.069), P < 0.001], and visceral obesity [OR: 1.876, 95% CI (1.158, 3.038), P = 0.011] were risk factors for poor glycemic control.Conclusion: This study indicated that visceral obesity (visceral fat area ≥ 100cm2) is positively associated with poor glycemic control, and serves as an independent risk factor for poor glycemic control (HbA1c ≥ 7.0%) in patients with type 2 diabetes mellitus. Screening for visceral obesity should be emphasized, and targeted interventions should be taken to improve glycemic control in patients with type 2 diabetes mellitus.Keywords: type 2 diabetes mellitus, glycemic control, influencing factors, visceral obesity, visceral fat area

Beibei Luo,1 Baolong Pan,2 Guancheng Zhao,1 Jiefen Li,1 Li Sun1 1Clinical Laboratory, People’s Hospital of Yuxi City, the Sixth Affiliated Hospital of Kunming Medical University, Yuxi City, Yunnan Province, 653100, People’s Republic of China; 2Physical Examination Center, People’s Hospital of Yuxi City, the Sixth Affiliated Hospital of Kunming Medical University, Yuxi City, Yunnan Province, 653100, People’s Republic of ChinaCorrespondence: Baolong Pan, Physical Examination Center, People’s Hospital of Yuxi City, the Sixth Affiliated Hospital of Kunming Medical University, 21 Nieer Road, Yuxi City, Yunnan Province, 653100, People’s Republic of China, Email pbl1210@126.comIntroduction: Serum magnesium is a crucial mineral within the human body. It is imperative for diabetic patients to maintain optimal serum magnesium levels. We focus on the relationship between glycemic control and serum magnesium in type 2 diabetes mellitus (T2DM).Methods: The retrospective, observational, cross-sectional study comprised 1694 patients recruited from the People’s Hospital of Yuxi. Fasting blood samples were collected for analysis, accompanied by the recording of participants’ demographic characteristics. Patients were categorized into two groups based on whether their glycosylated hemoglobin (HbA1c) levels < 7%. A t-test was employed to identify significant differences between the two groups. Correlation coefficients were calculated using Pearson’s method. A Logistic regression analysis was conducted to assess the association between variables and glycemic control. A linear regression analysis was performed to assess the relationship between serum magnesium levels and HbA1c.Results: Patients with poor glycemic control exhibited elevated age, low-density lipoprotein (LDL-C), fasting plasma glucose (FPG), and homeostasis model assessment (HOMA-IR) compared to those with good glycemic control (P < 0.001). Additionally, total cholesterol (TC) levels were significantly higher in patients with poor glycemic control. Conversely, high-density lipoprotein (HDL-C) and serum magnesium levels were lower in patients with poor glycemic control. Serum magnesium levels exhibited negative correlations with HOMA-IR (r = − 0.05, P < 0.05), HbA1c (r = − 0.29, P < 0.05), and FPG (r = − 0.20, P < 0.05). Moreover, serum magnesium was significantly associated with reduced odds of glycemic control (OR = 0.0005, 95% CI 0.0001– 0.0027, P < 0.001).Conclusion: The serum magnesium level in patients with T2DM is closely associated with glycemic control.Keywords: serum magnesium, glycaemic control, diabetes

Yunpeng Cui,1 Qiwei Wang,1 Chuan Mi,1 Bing Wang,1 Yuanxing Pan,1 Yunfei Lin,1 Rui He,2 Liying Sun,3 Bo Zheng,4 Xuedong Shi1 1Department of Orthopaedics, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Plastic Surgery and Burn, Peking University First Hospital, Beijing, People’s Republic of China; 3Department of Clinical Laboratory, Peking University First Hospital, Beijing, People’s Republic of China; 4Department of Clinical Pharmacology, Peking University First Hospital, Beijing, People’s Republic of ChinaCorrespondence: Xuedong Shi, Department of Orthopedic, Peking University First Hospital, Beijing, People’s Republic of China, Email pku_ortho@163.comBackground: This retrospective cohort study explores a practical approach to acquiring pathogenic microorganisms in patients with bone and joint infections.Methods: From Aug 2018 to Mar 2022, 68 consecutive patients (87 cultures) with bone and joint infection were recruited in this study. All cultures followed the Peking University First Hospital Procedure of Culturing Pathogenic microorganisms for bone and joint infection. Tissue samples were obtained through fluoroscopy-guided biopsy or open debridement. Tissue samples were divided into manual homogenization (MH), manual mixture (MM), and pathological examination. The baseline, antibiotic exposure, laboratory, surgical, and microbial data were reviewed. Independent sample T-test, Mann–Whitney U-test, and Chi-square test were used to detect the difference between patients who received different processing measures.Results: The average age was 55.8± 2.4 years old. Thirty-nine patients were male. The total positive culture rate of the manual homogenization group was 80.5% (70/87). Thirty-five patients had mixed infections with more than one microorganism cultured. Staphylococci accounted for 60.23% of all microorganisms. Staphylococcus aureus (18.2%) and Staphylococcus epidermidis (15.9%) were the two most common bacteria cultured in this study. Patients with positive culture in the manual mixture group had significantly higher WBC (p = 0.006), NE% (p = 0.024), ESR (p = 0.003), CRP (p = 0.020) and IL6 (0.050) compared to patients with negative culture. After tissue homogenization, only ESR is still statistically different. Patients without SIRS had a low positive culture rate (59.4%). Tissue homogenization could significantly increase the positive culture rate of patients without SIRS. Pre-culture antibiotic exposure was not an independent risk factor for culture results.Conclusion: Peking University First Hospital Procedure for Culturing Pathogenic microorganisms for Bone and Joint Infections was a practical approach for obtaining pathogenic microorganisms.Keywords: bone and joint infection, systemic inflammatory response syndrome, antibiotic, tissue homogenization

Yi Tang,1,&ast; Zemin Wei,1,&ast; Ning Li,2 Chao Jiang,2 Chen Liang,1 Lulu Sun,2 Lufeng Tian,3 Zhengyu Jin,4 Zhe Wu,2,&ast; Hao Sun4,&ast; 1Department of Endocrinology, Fushun Central Hospital, Fushun, Liaoning Province, People’s Republic of China; 2Department of Radiology, Fushun Central Hospital, Fushun, Liaoning Province, People’s Republic of China; 3Department of Internal Medicine, Fushun Central Hospital, Fushun, Liaoning Province, People’s Republic of China; 4Department of Radiology, State Key Laboratory of Complex Severe and Rare Disease, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hao Sun, No. 1 Shuaifuyuan, Wangfujing Street, Dongcheng District, Beijing, 100730, People’s Republic of China, Tel +86-10-69159537, Email sunhao_robert@126.com Zhe Wu, Fushun Central Hospital, Xincheng Road, Shuncheng District, Fushun, Liaoning Province, 113006, People’s Republic of China, Tel +86-156-42018778, Email wuzhe0306@163.comPurpose: To examine the risk of type 2 diabetes mellitus in non-obese patients with pancreatic fatty infiltration through abdominal computed tomography (CT) quantitation.Patients and Methods: We carried out a retrospective analysis of abdominal CT and inpatient medical records of 238 inpatients from July 2019 to April 2021. The patients were divided into a normal non-obese group (BMI < 25, n = 135) and diabetic non-obese group (BMI < 25, n = 103). Abdominal CT-related parameters included body width; mean CT values of the pancreas, liver, and spleen; difference between pancreas and spleen CT values (P−S); pancreas-to-spleen attenuation ratio (P/S); and liver-to-spleen attenuation ratio (L/S). Logistic regression was used to estimate the risk factors for comorbid diabetes in a non-obese population.Results: The P-values of the pancreas CT value, P−S, P/S, body width, and L/S were all < 0.05 and correlated to comorbid diabetes in non-obese patients. Worsening pancreatic fatty infiltration increased the risk of developing diabetes. Using a P/S of 1.0 as reference, every successive decrease in this ratio by 0.1 increases patient risk by 3.981, 4.452, 6.037, and 12.937 times.Conclusion: The risk of developing type 2 diabetes mellitus in non-obese patients increases with the degree of pancreatic fatty infiltration as assessed by CT.Keywords: computed tomography, non-obese patients, pancreatic fatty infiltration, type 2 diabetes mellitus

Jiaying Lao,1,2,&ast; Hang Tan,3,&ast; Yuyu Wu,2,&ast; Ting Ding,4 Xinqian Liu,1 Lanrong Sun,2 Xiyi Chen,2 Chongrong Zhu,2 Yiming Kang,5 Yu-Hsin Chen,2,6 Chonghui Tang,1 Fan Wang,7 Yanlong Liu2,6 1Department of Neurosurgery, Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, People’s Republic of China; 2School of Mental Health, Wenzhou Medical University, Wenzhou, People’s Republic of China; 3Department of neurosurgery, Hangzhou Mingzhou Brain Rehabilitation Hospital, Hangzhou, People’s Republic of China; 4Department of Infectious Diseases, The Affiliated Xiangshan Hospital of Wenzhou Medical University, Ningbo, People’s Republic of China; 5Psychosomatic Medicine Research Division, Inner Mongolia Medical University, Huhhot, People’s Republic of China; 6Zhejiang Provincial Clinical Research Center for Mental Disorders, The Affiliated Wenzhou Kangning Hospital, Wenzhou Medical University, Wenzhou, People’s Republic of China; 7Beijing Hui−Long−Guan Hospital, Peking University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yanlong Liu, School of Mental Health, Medical University, Wenzhou, 325035, People’s Republic of China, Email benjaminlyl@wmu.edu.cn Chonghui Tang, Department of Neurosurgery, Affiliated Cixi Hospital, Wenzhou Medical University, Ningbo, 315300, People’s Republic of China, Email tangegg@163.comObjective: Cigarette smoking and low peripheral nitric oxide synthase (NOS) levels are strongly associated with sleep disorders. However, whether cerebrospinal fluid (CSF) NOS relates to sleep disorders and whether CSF NOS mediates the relationship between cigarette smoking and sleep disorders is unclear.Methods: We measured CSF levels of total NOS (tNOS) and its isoforms (inducible NOS [iNOS] and constitutive NOS [cNOS]) in 191 Chinese male subjects. We applied the Pittsburgh Sleep Quality Index (PSQI).Results: The PSQI scores of active smokers were significantly higher than those of non-smokers, while CSF tNOS, iNOS, and cNOS were significantly lower (all p < 0.001). CSF tNOS, iNOS, and cNOS were negatively associated with PSQI scores in the general population (all p < 0.001). Mediation analysis suggested that CSF tNOS, iNOS, and cNOS mediate the relationship between smoking and PSQI scores, and the indirect effect accounted for 78.93%, 66.29%, and 81.65% of the total effect, respectively.Conclusion: Cigarette smoking is associated with sleep disorders. Active smokers had significantly lower CSF levels of tNOS, iNOS, and cNOS. Furthermore, tNOS, iNOS, and cNOS mediate the relationship between cigarette smoking and sleep quality. This study provides insights into how cigarette smoke affects sleep disorders.Keywords: cerebrospinal fluid nitric oxide synthase, cigarette smoking, Pittsburgh Sleep Quality Index, sleep disorders, mediation

Guoqin Wang,1,&ast; Xiaoying Hu,1,&ast; Nan Ye,1 Xiaoyi Xu,1 Weiyi Guo,1 Lijun Sun,1 Hongrui Dong,1 Xiaoyi Zhao,2 Hong Cheng1 1Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Division of Nephrology, Affiliated Hospital of Chifeng University, Neimenggu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hong Cheng, Division of Nephrology, Beijing Anzhen Hospital, Capital Medical University, No. 2 Anzhen Road, Beijing, 100029, People’s Republic of China, Email drchengh@163.comPurpose: In recent years, the incidence of malignancy patients with membranous nephropathy (MN) has gradually increased, but the clinical and pathological characteristics of these patients are still unclear. Our study aims at elucidating the clinical and pathological characteristics of malignancy patients with MN, especially the expression patterns of MN-specific antigens in both kidney and tumor tissue.Patients and Methods: A retrospective analysis was performed to summarize the clinical and pathological data of MN patients with malignancy at Beijing Anzhen Hospital from January 1, 2012, to December 31, 2022, followed by a thorough review of relevant literature published between May 1, 2000 to May 1, 2023 and case aggregation.Results: 19 patients in our center’s MN cohort and 21 patients from literature review were diagnosed with malignancy either before or after being diagnosed with MN. Among them, 16 (40.0%) and 17 (42.5%) patients tested PLA2R-only and THSD7A-only positive in renal tissue, respectively. And 16 of 26 patients showed similar staining in tumor and kidney tissues. Compared to the idiopathic membranous nephropathy (IMN) patients at our center, patients with malignancy were older, had a lower estimated glomerular filtration rate, and had a lower rate of partial or complete response to treatment. Renal tissue from MN patients with concomitant malignancy was less frequently PLA2R-positive, more frequently THSD7A-positive, and more often glomerular IgG subclass IgG2 (P = 0.033) but less frequently IgG4 (P < 0.001).Conclusion: The clinical and pathological characteristics of MN patients with concomitant malignancy are different from those of IMN patients. Active screening for malignancy should be performed in non-PLA2R-positive elderly MN patients with a poor therapeutic response. Staining for MN target antigens in kidney and tumor tissues may be inconsistent, and the role of MN target antigens needs to be further explored.Keywords: malignancy, membranous nephropathy, PLA2R, THSD7A, NELL-1

Liwei Sun,1,&ast; Hailong Bing,1,&ast; Chenxi Zhang,1,&ast; Lin Lin,2 Hongkai Lian,2 Qinjun Chu,1 Xiaogao Jin1,3 1Department of Anesthesiology and Perioperative Medicine, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, People’s Republic of China; 2Research of Trauma Center, Zhengzhou Central Hospital Affiliated to Zhengzhou University, Zhengzhou, 450007, People’s Republic of China; 3Department of Anesthesiology, The Second Affiliated Hospital of Guangdong Medical University, Zhanjiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaogao Jin; Liwei Sun, Email jinxiaoagao@zzu.edu.cn; sunliwei2972@163.comObjective: Insulin attaches insulin receptor to activate the PI3-kinase/Akt signaling to maintain glucose homeostasis and inhibit apoptosis. This study determined whether preconditioning with insulin and glucose protects the kidney against ischemia-reperfusion injury (IRI).Methods: Kidney IRI was performed in C57BL/6 mice by clamping the renal vessels for 30 min, followed by reperfusion for 24 h. A total subcutaneous 0.1 unit of insulin along with 10% glucose in drinking water was treated on the mice for 24 h before kidney IRI. The kidney function and injuries were investigated through the determination of BUN and Cr in blood plasma, as well as the apoptosis and the expression of P-AKT, BAX, and caspase-3 in the kidneys. The role of P-AKT in insulin-treated IRI kidneys was tested using an AKT inhibitor. The effects of the preconditional duration of insulin and glucose on IRI kidneys were investigated by expanding the treatment duration to 1, 3, and 6 days.Results: Preconditioning with insulin and glucose protected the kidney against IRI as manifested by a decrease in creatinine and BUN and a reduction of kidney tubular injury. The protection effect was mediated by P-AKT-BAX-caspase-3 signaling pathway resulting in suppression of apoptotic cell death. An AKT inhibitor partially reversed the protective effects of preconditional insulin. The preconditional duration for 1, 3, and 6 days had no differences in improving kidney functions and pathology.Conclusion: A short-term preconditioning with insulin and glucose protected the kidney from IRI through the activation of p-AKT and subsequent reduction of BAX-caspase-3-induced apoptosis. The short-term precondition provides a practicable strategy for protecting the kidney against predictable IRI, such as kidney transplant and major surgical operations with high risk of hypotension.Keywords: kidney, insulin, ischemia-reperfusion injury, AKT, Bax, caspase-3

Mingming Li,1,2,&ast; Xin Zhou,1,&ast; Doudou Huang,1,&ast; Yingkui Zhao,2 Jiani Chen,2 Zhiying Dong,1 Wansheng Chen,1,2 Feng Zhang,2 Lianna Sun1 1School of Pharmacy, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China; 2Department of Pharmacy, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lianna Sun; Wansheng Chen, School of Pharmacy, Shanghai University of Traditional Chinese Medicine, 1200 Cailun Road, Shanghai, 201203, People’s Republic of China, Tel +86-13818946096 ; +86-15901818646, Email sssnmr@163.com; chenwansheng@shutcm.edu.cnBackground: Polygonum capitatum Buch.-Ham. ex D. Don (P. capitatum), a traditional herb used in Miao medicine, is renowned for its heart-clearing properties. Davidiin, the primary bioactive component (approximately 1%), has been used to treat various conditions, including diabetes. Given its wide range of effects and the diverse biomolecular pathways involved in diabetes, there is a crucial need to study how davidiin interacts with these pathways to better understand its anti-diabetic properties.Materials and Methods: Diabetic rats were induced using a high-fat diet and streptozotocin (STZ) administered intraperitoneally at 35 mg/kg. Out of these, 24 rats with blood glucose levels ≥ 11.1 mmol/L and fasting blood glucose levels ≥ 7.0 mmol/L were selected for three experimental groups. These groups were then treated with either metformin (gavage, 140 mg/kg) or davidiin (gavage, 90 mg/kg) for four weeks. After the treatment period, we measured body weight, blood glucose levels, and conducted untargeted metabolic profiling using UPLC-QTOF-MS.Results: Davidiin has been shown to effectively treat diabetes by reducing blood glucose levels from 30.2 ± 2.6 mmol/L to 25.1 ± 2.4 mmol/L (P < 0.05). This effect appears stronger than that of metformin, which lowered glucose levels to 26.5 ± 2.6 mmol/L. The primary outcomes of serum metabolomics are significant changes in lipid and lipid-like molecular profiles. Firstly, davidiin may affect phosphatide metabolism by increasing levels of phosphatidylinositol and sphingosine-1-phosphate. Secondly, davidiin could influence cholesterol metabolism by reducing levels of glycocholic acid and glycochenodeoxycholic acid. Lastly, davidiin might impact steroid hormone metabolism by increasing hepoxilin B3 levels and decreasing prostaglandins.Conclusion: Our study demonstrates that davidiin modulates various lipid-related metabolic pathways to exert its anti-diabetic effects. These findings offer the first detailed metabolic profile of davidiin’s action mechanism, contributing valuable insights to the field of Traditional Chinese Medicine in the context of diabetes treatment.Keywords: diabetes mellitus, streptozotocin, metformin, davidiin, metabolomics

Lin Sun,1,2,&ast; Xu Zhao,1 Yunting Guo,1,&ast; Xiaomin Hou,3– 5 Jieru Li,6 Xiaoxia Ren,7 Lin Dong,1 Ruifeng Liang,1 Jisheng Nie,1 Yiwei Shi,2 Xiaojiang Qin1,2,4,5,8 1School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, The First Hospital of Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 3Department of Pharmacology, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 4China Key Laboratory of Cellular Physiology, Shanxi Medical University, Taiyuan, Shanxi, China; 5Environmental Exposures Vascular Disease Institute, Taiyuan, Shanxi, People’s Republic of China; 6Department of Foreign Languages, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China; 7Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 8Key Laboratory of Coal Environmental Pathogenicity and Prevention, Shanxi Medical University, Taiyuan, Shanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiaojiang Qin, School of Public Health, Shanxi Medical University, 56 Xinjian South Road, Taiyuan, Shanxi, 030001, People’s Republic of China, Tel +86-18735379826, Email sph@sxmu.edu.cn Yiwei Shi, Department of Respiratory and Critical Care Medicine, The First Hospital of Shanxi Medical University, 85 Jiefang South Road, Taiyuan, Shanxi, 030001, People’s Republic of China, Tel +86-13835193132, Email chinasyw225@163.comPurpose: Smoking is a major risk factor for the group 3 PH. NT-proBNP is a biomarker for risk stratification in PH. This study aims to investigate the effects of smoking status and smoking index (SI) on group 3 PH and to evaluate the value of SI and SI combined with NT-proBNP in early diagnosis and prediction of disease severity.Patients and Methods: Four hundred patients with group 3 PH at the First Hospital of Shanxi Medical University between January 2020 and December 2021 were enrolled and divided into two groups: mild (30 mmHg ≤ pulmonary artery systolic pressure (PASP)≤ 50 mmHg) and non-mild (PASP > 50 mmHg). The effect of smoking on group 3 PH was analyzed using univariate analysis, and logistic analysis was conducted to evaluate the risk of group 3 PH according to smoking status and SI. Spearman correlation coefficient was used to test the correlation between SI and the index of group 3 PH severity. The predictive value of SI was evaluated using a receiver operating characteristic (ROC) curve.Results: Correlation and logistic analyses showed that SI was associated with PH severity. Smoking status (P=0.009) and SI (P=0.039) were independent risk factors for non-mild group 3 PH, and ROC showed that the predictive value of SI (AUC:0.596) for non-mild PH was better than that of the recognized pro-brain natriuretic peptide (NT-proBNP) (AUC:0.586). SI can be used as a single predictive marker. SI and NT-proBNP can be formulated as prediction models for screening non-mild clinical cases (AUC:0.628).Conclusion: SI is a potentially ideal non-invasive predictive marker for group 3 PH. SI and NT-proBNP could be used to develop a prediction model for screening non-mild PH cases. This can greatly improve the predictive specificity of the established PH marker, NT-proBNP.Keywords: smoking index, NT-proBNP, pulmonary hypertension, chronic lung disease, predictive value

Tingting Liu,1,&ast; Haojie Wu,1,&ast; Lin Sun,2 Jianshe Wei1 1Institute for Brain Sciences Research, School of Life Sciences, Henan University, Institute of Neurourology and Urodynamics, Huaihe Hospital of Henan University, Kaifeng, 475004, People’s Republic of China; 2College of Chemistry and Molecular Sciences, Henan University, Kaifeng, 475004, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lin Sun; Jianshe Wei, Email sunlin@vip.henu.edu.cn; jswei@henu.edu.cnBackground: The coronavirus disease 2019 (COVID-19) can lead to neurological symptoms such as headaches, confusion, seizures, hearing loss, and loss of smell. The link between COVID-19 and Parkinson’s disease (PD) is being investigated, but more research is needed for a definitive connection.Methods: Datasets GSE22491 and GSE164805 were selected to screen differentially expressed gene (DEG), and immune infiltration and gene set enrichment analysis (GSEA) of the DEG were performed. WGCNA analyzed the DEG and selected the intersection genes. Potential biological functions and signaling pathways were determined, and diagnostic genes were further screened using gene expression and receiver operating characteristic (ROC) curves. Screening and molecular docking of ibuprofen as a therapeutic target. The effectiveness of ibuprofen was verified by constructing a PD model in vitro, and constructing “COVID19-PD” signaling pathway, and exploring the role of angiotensin-converting enzyme 2 (ACE2) in PD.Results: A total of 13 DEG were screened from the GSE36980 and GSE5281 datasets. Kyoto encyclopedia of genes and genomes (KEGG) analysis showed that the DEG were mainly associated with the hypoxia-inducible factor (HIF-1), epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance, etc. After analysis, it is found that ibuprofen alleviates PD symptoms by inhibiting the expression of nuclear factor kappa-B (NF-κB), interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α). Based on signal pathway construction, the importance of ACE2 in COVID-19-induced PD has been identified. ACE2 is found to have widespread distribution in the brain. In the 1-methyl-4-phenyl-1,2,3,6-te-trahydropyridine (MPTP)-induced ACE2-null PD mice model, more severe motor and non-motor symptoms, increased NF-κB p65 and α-synuclein (α-syn) expression with significant aggregation, decreased tyrosine hydroxylase (TH), severe neuronal loss, and neurodegenerative disorders.Conclusion: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection increases the risk of PD through an inflammatory environment and downregulation of ACE2, providing evidence for the molecular mechanism and targeted therapy associated with COVID-19 and PD.Keywords: Parkinson’s disease, COVID-19, ibuprofen, nuclear factor kappa-B, angiotensin-converting enzyme 2

Longjun Sun,1,&ast; Wenjuan Chen,2,&ast; Peixi Zhao,3 Bin Zhao,4 Guangyan Lei,1 Le Han,1,&ast; Yili Zhang2,&ast; 1Department of Thoracic Surgery, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China; 2Department of Oncology, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China; 3Department of Department of Pharmacy, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China; 4Department of Epidemiology, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Le Han, Department of Thoracic Surgery, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China, Email millyhan1@sohu.com Yili Zhang, Department of Oncology, Cancer Hospital of Shaanxi Province, Xi’an, 710061, People’s Republic of China, Email doctor_z2023@stu.xjtu.edu.cnIntroduction: Hepatocellular carcinoma (HCC) is a common and deadly malignancy. Traditional Chinese medicine, such as the compound Astragalus (wild Baicalin), has shown promise in improving outcomes for HCC patients. This study aimed to investigate the effects of wild Baicalin on the human hepatoma cell line HepG2 and elucidate the underlying mechanisms, particularly the role of the AKR1B10 and PI3K/AKT signaling pathways.Methods: HepG2 cells were treated with varying concentrations of wild Baicalin. Cell proliferation, apoptosis, migration, invasion, and cell cycle were evaluated using CCK-8, flow cytometry, scratch, Transwell, and clonogenic assays, respectively. Transcriptome sequencing was performed to analyze gene expression changes induced by wild Baicalin. Differentially expressed genes were identified and analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. The expression of AKR1B10 and PI3K was validated by qPCR.Results: Wild Baicalin inhibited HepG2 cell proliferation, induced apoptosis, suppressed migration and invasion, and caused cell cycle arrest in a dose-dependent manner. Transcriptome sequencing revealed 1202 differentially expressed genes, including 486 upregulated and 716 downregulated genes. GO analysis indicated that biological processes were pivotal in the anticancer mechanism of wild Baicalin, while KEGG analysis identified metabolic pathways as the most significantly regulated. AKR1B10 and PI3K, key genes in metabolic pathways, were downregulated by wild Baicalin, which was confirmed by qPCR.Discussion: The findings suggest that wild Baicalin exhibits potent anticancer effects against HepG2 cells by inducing apoptosis, inhibiting proliferation, migration, and invasion, and causing cell cycle arrest. The regulatory effects of wild Baicalin on the AKR1B10 and PI3K/AKT signaling pathways appear to be critical for its inhibitory effects on HCC cell proliferation. These results provide new insights into the mechanism of action of wild Baicalin and support its potential as a therapeutic approach for HCC treatment. Keywords: hepatocellular carcinoma, wild baicalin, transcriptome sequencing, apoptosis

Zhengyi Wu,&ast; Liang Sun,&ast; Yongkang Xu,&ast; He Huang, Zhipeng Wu, Bingbing Qiu, Jinlong Yan, Xiangbao Yin Hepatobiliary Surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xiangbao Yin; Jinlong Yan, Hepatobiliary surgery, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Nanchang, Jiangxi Province, People’s Republic of China, Email yxbefy@163.com; yjl19880608@126.comBackground: Chemokines and chemokine receptors (CCRs) are involved in a variety of anti-tumour and pro-tumour immune processes in vivo, such as angiogenesis, metastasis, proliferation and invasiveness, and influence patient prognosis and response to therapy.Methods: CCRs differentially expressed in HCC and associated with prognosis were extracted from TCGA and GEO databases, and the obtained CCRs were then used to construct signature genes, and the signature gene were selected for expression validation as well as functional experiments to explore the role of CCRs in the treatment and prognosis of HCC.Results: We constructed a prognostic model including five CCRs (CCL20, CCL23, CCR3, CCR10, and CXCR3) and validated the expression of signature genes. The model’s risk score is an independent prognostic factor for HCC. We have also developed prognostic model nomograms for clinical use. In addition, we validated that CCR3 expression is associated with poor prognosis in HCC, and the proliferation and migration ability of HCC cells was significantly inhibited after interfering with the expression of CCR3 in MHCC-LM3. We also looked at differences in pathway enrichment, immune infiltration and immune checkpoints. Finally, we found that risk scores were also correlated with drug sensitivity, the high-risk group had a better sensitivity to sorafenib.Conclusion: The CCRs-related gene signature may better assess HCC prognosis and response to immunotherapy and tyrosine kinase inhibitors such as sorafenib in HCC, providing prospective solutions for diagnosis and treatment.Keywords: chemokine, chemokine receptors, prognosis, signature, hepatocellular carcinoma

Haiyang Hu, Xiaoxiao Wang, Yangsheng Ren, Tishuo Zhang, Lin Sun Department of Gynecology, Affiliated Hospital of Jining Medical University, Jining, Shandong, 272029, People’s Republic of ChinaCorrespondence: Lin Sun Department of Gynecology, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, Shandong, 272029, People’s Republic of China, Tel +86 18678760870 ; +86-05372908731, Email sunlingyn@outlook.comPurpose: To evaluate the association between Composite Dietary Antioxidant Index (CDAI) and the risk of endometriosis (EM)-related rheumatoid arthritis (RA) in women of childbearing age.Methods: Using the data from the National Health and Nutrition Examination Survey database, this cross-sectional study included women of childbearing age. The CDAI was obtained by summing the standardized Z-values of the dietary intakes. EM was diagnosed based on a questionnaire-based survey. The outcome of this study was the presence of RA, which was defined by a questionnaire. The associations of CDAI and EM with the risk of RA were determined using weighted logistic analysis. Additive interaction was evaluated using the relative excess risk due to interaction (RERI), the attributable proportion due to interaction (AP), and the synergy index (S).Results: In total, 3803 patients were included, of which 74 patients (1.99%) were with RA. A lower CDAI [odds ratio (OR): 1.85, 95% confidence interval (CI): 1.12 to 3.04, P= 0.015] and the presence of EM (OR: 3.05, 95% CI: 1.19 to 7.81, P= 0.023) was associated with the risk of RA. The result demonstrated an additive interaction of a lower CDAI and the presence of EM on the risk of RA (OR: 6.19, 95% CI: 2.33 to 16.43, P < 0.001, P of trend =0.007). Nevertheless, there was no significant additive interaction after being assessed by the RERI, AP, and S. However, a joint effect of a lower CDAI and EM on the risk of RA (OR: 3.94, 95% CI: 1.35 to 11.51, P= 0.013) was observed.Conclusion: Our study identified EM, and lower CDAI, was related to the risk of RA. Lower CDAI score was also associated with the risk of EM-related RA. This study indicates the importance of antioxidant intake in daily diet for the management of EM-related RA.Keywords: composite dietary antioxidant index, endometriosis, rheumatoid arthritis, cross-sectional study

Chuihao Kong,1,2,&ast; Kaidi Wang,1,2,&ast; Lei Sun,1,3 Hongsu Zhao,1,2 Tongsheng Wang,1 Wuxi Zhou,1 Deling Wu,1,2 Fengqing Xu1,2 1School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, People’s Republic of China; 2Anhui Province Key Laboratory of New Manufacturing Technology for Traditional Chinese Medicine Decoction Pieces, Hefei, 230012, People’s Republic of China; 3Zhejiang CONBA Pharmaceutical Co. LTD, Hangzhou, 310052, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wuxi Zhou; Fengqing Xu, School of Pharmacy, Anhui University of Chinese Medicine, 350 Longzihu Road, Xinzhan District, Hefei, 230012, People’s Republic of China, Email zhouwuxi@ahtcm.edu.cn; xufengqing@ahtcm.edu.cnBackground: Mangiferin (MA), a bioactive C-glucosyl xanthone with a wide range of interesting therapeutic properties, has recently attracted considerable attention. However, its application in biomedicine is limited by poor solubility and bioavailability. Carbon dots (CDs), novel nanomaterials, have immense promise as carriers for improving the biopharmaceutical properties of active components because of their outstanding characteristics.Methods: In this study, a novel water-soluble carbon dot (MC-CDs) was prepared for the first time from an aqueous extract of Moutan Cortex Carbonisata, and characterized by various spectroscopies, zeta potential and high-resolution transmission electron microscopy (HRTEM). The toxicity effect was investigated using the CCK-8 assay in vitro. In addition, the potential of MC-CDs as carriers for improving the pharmacokinetic parameters was evaluated in vivo.Results: The results indicated that MC-CDs with a uniform spherical particle size of 1– 5 nm were successfully prepared, which significantly increased the solubility of MA in water. The MC-CDs exhibited low toxicity in HT-22 cells. Most importantly, the MC-CDs effectively affected the pharmacokinetic parameters of MA in normal rats. UPLC-MS analysis indicated that the area under the maximum blood concentration of MA from mangiferin-MC-CDs (MA-MC-CDs) was 1.6-fold higher than that from the MA suspension liquid (MA control) after oral administration at a dose of 20 mg/kg.Conclusion: Moutan Cortex-derived novel CDs exhibited superior performance in improving the solubility and bioavailability of MA. This study not only opens new possibilities for the future clinical application of MA but also provides evidence for the development of green biological carbon dots as a drug delivery system to improve the biopharmaceutical properties of insoluble drugs. Keywords: Moutan Cortex, carbon dots, mangiferin, solubility, bioavailability

Han Wu,1,&ast; Hui Wang,2,&ast; Lixia Sun,3,&ast; Mengchen Liu,1 Haoran Wang,1 Xianchang Sun,4 Wenjuan Zhang1 1Center for Reproductive Medicine, The Second Affiliated Hospital of Shandong First Medical University, Taian, 271000, People’s Republic of China; 2Gynecological Minimally Invasive Surgery Center, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, People’s Republic of China; 3Department of Hematology, The Affiliated Taian City Central Hospital of Qingdao University, Taian, 271000, People’s Republic of China; 4Department of Physiology, Shandong First Medical University & Shandong Academy of Medical Sciences, Jinan, 250117, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenjuan Zhang, Center for Reproductive Medicine, The Second Affiliated Hospital of Shandong First Medical University, 366 Taishan Street, Taian, 271000, People’s Republic of China, Email wenjuanzhang1119@163.com Xianchang Sun, Department of Physiology, Shandong First Medical University & Shandong Academy of Medical Sciences, 6699 Qingdao Road, Jinan, 250117, People’s Republic of China, Email hotsss@163.comPurpose: To study the relationship between the single nucleotide polymorphism (SNP) rs2278426 in the angiopoietin-like protein 8 gene (ANGPTL8) and polycystic ovary syndrome (PCOS).Patients and methods: A total of 122 patients with PCOS and 108 controls were recruited for comparison of glucose, lipid, insulin, sex hormone, and ANGPTL8 levels. Polymerase chain reaction (PCR) and gene sequencing were performed for comparison of the frequency of the CC, CT, and TT rs2278426 genotypes and the rs2278426 allele distributions between the PCOS and control groups and between the obese and non-obese subgroups of the PCOS and control groups.Results: The frequency of the T allele was significantly higher in the PCOS group than that in the controls (P = 0.037). In the dominant genetic model, the proportion of the CT+TT genotype in the PCOS group was significantly higher than that in the controls (P = 0.047). Subgroup analysis demonstrated that the T allele proportion was significantly higher in obese PCOS group than obese control group (P = 0.027). PCOS with the CT+TT genotype had significantly higher body mass index (BMI; P = 0.001), triglyceride (TG; P = 0.005), homeostasis model assessment of insulin resistance (HOMA-IR; P = 0.035), testosterone (P = 0.041), and ANGPTL8 (P = 0.037) levels and significantly lower high-density lipoprotein (HDL) levels (P = 0.025) than PCOS with the CC genotype. Obese PCOS group with the CT+TT genotype had significantly higher TG (P = 0.015), luteinizing hormone (LH; P = 0.030), fasting insulin (FINS; P = 0.039), HOMA-IR (P = 0.018), and ANGPTL8 (P = 0.049) levels than obese PCOS group with the CC genotype.Conclusion: Polymorphisms of rs2278426 may induce glycolipid metabolic disorders by affecting ANGPTL8 levels and functions in Han Chinese females with obesity from the Shandong region, increasing the risk of PCOS in this population.Keywords: angiopoietin-like protein 8, insulin resistance, metabolic disorder, obesity, polycystic ovary syndrome, single nucleotide polymorphism

Ailin Zou,1,&ast; Tingting Xiao,1,&ast; Boyu Chi,1,2 Yu Wang,1 Lipeng Mao,1,2 Dabei Cai,1,2 Qingqing Gu,1 Qianwen Chen,1 Qingjie Wang,1 Yuan Ji,1 Ling Sun1,2 1Department of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, People’s Republic of China; 2Changzhou Clinical Medical College, Dalian Medical University, Dalian, Liaoning, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ling Sun; Qingjie Wang, Department of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213003, People’s Republic of China, Email sunling85125@hotmail.com; wang-qingjie@hotmail.comBackground: Cardiac repair remains a thorny issue for survivors of acute myocardial infarction (AMI), due to the regenerative inertia of myocardial cells. Cell-free therapies, such as exosome transplantation, have become a potential strategy for myocardial injury. The aim of this study was to investigate the role of engineered exosomes in overexpressing Growth Differentiation Factor-15 (GDF-15) (GDF15-EVs) after myocardial injury, and their molecular mechanisms in cardiac repair.Methods: H9C2 cells were transfected with GDF-15 lentivirus or negative control. The exosomes secreted from H9C2 cells were collected and identified. The cellular apoptosis and autophagy of H2O2-injured H9C2 cells were assessed by Western blotting, TUNEL assay, electron microscopy, CCK-8 and caspase 3/7 assay. A rat model of AMI was constructed by ligating the left anterior descending artery. The anti-apoptotic, pro-angiogenic effects of GDF15-EVs treatment, as well as ensuing functional and histological recovery were evaluated. Then, mRNA sequencing was performed to identify the differentially expressed mRNAs after GDF15-EVs treatment.Results: GDF15-EVs inhibited apoptosis and promoted autophagy in H2O2 injured H9C2 cells. GDF15-EVs effectively decreased the infarct area and enhanced the cardiac function in rats with AMI. Moreover, GDF15-EVs hindered inflammatory cell infiltration, inhibited cell apoptosis, and promoted cardiac angiogenesis in rats with AMI. RNA sequence showed that telomerase reverse transcriptase (TERT) mRNA was upregulated in GDF15-EVs-treated H9C2 cells. AMPK signaling was activated after GDF15-EVs. Silencing TERT impaired the protective effects of GDF15-EVs on H2O2-injured H9C2 cells.Conclusion: GDF15-EVs could fulfil their protective effects against myocardial injury by upregulating the expression of TERT and activating the AMPK signaling pathway. GDF15-EVs might be exploited to design new therapies for AMI.Keywords: exosomes, growth differentiation factor-15, telomerase reverse transcriptase, acute myocardial infarction

Xue Du,1,2 Qi Dong,1,2 Le Sun,1,2 Xiaoyi Chen,1,2 Jun Jiang3 1College of Educational Science, Chongqing Normal University, Chongqing, People’s Republic of China; 2Key Laboratory of Applied Psychology, Chongqing Normal University, Chongqing, People’s Republic of China; 3Department of Basic Psychology, School of Psychology, Third Military Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Xue Du, Tel +86-23-65910354, Email 714789425@qq.com; duxue@cqnu.edu.cnBackground: It is well known that parents play an important role in the family, particularly the mental health literacy of parents is essential for the growth and development of children. As the parents of children with special needs, they are facing more difficulties and psychological pressure, resulted in more mental health problems.Purpose: The current study examined the effect of social support on mental health literacy, and its underlying mechanisms regarding the mediating role of coping styles and moderating role of social comparison.Methods: Using a cross-sectional design, 165 parents of children with special needs (22– 67 years old, M=37.72, SD=8.78) participated in the study. The general information questionnaire, Mental Health Literacy Scale (MHLS), Social Support Rating Scale, Simplified Coping Style Questionnaire, and Social Comparison Orientation Scale were used.Results: We found that objective support positively predicted the mental health literacy, positive coping style played a mediating role between objective support and mental health literacy. In addition, the relationship between objective support and positive coping styles was moderated by social comparisons; for lower levels of opinion social comparison, the effect of objective support on positive coping styles was significantly stronger.Conclusion: We revealed the underlying mechanisms between social support and mental health literacy. The present study has profound implications for mental health literacy services for parents who have children with special needs.Keywords: parents of children with special needs, social support, mental health literacy, coping styles, social comparison orientation

Qianwen Chen,1,&ast; Qingqing Gu,1,&ast; Anwen Yin,2,&ast; Dabei Cai,1 Tingting Xiao,1 Yu Wang,1 Yuan Ji,1 Qingjie Wang,1 Jun Wei,3 Ling Sun1 1Department of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, Changzhou, Jiangsu, 213000, People’s Republic of China; 2Department of Cardiology, the Affiliated Wuxi People’s Hospital of Nanjing Medical University, Wuxi, Jiangsu, 214023, People’s Republic of China; 3Department of Cardiovascular Surgery, the First Affiliated Hospital of Wannan Medical College, Wuhu, Anhui, 241000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Qingjie Wang; Ling Sun, Department of Cardiology, the Affiliated Changzhou Second People’s Hospital of Nanjing Medical University, 29 Xinglong Alley, Changzhou, Jiangsu, 213003, People’s Republic of China, Email wang-qingjie@hotmail.com; sunling85125@hotmail.comObjective: This study aimed to explore the association of preoperative neutrophil percentage (NEUT%) with the risk of acute kidney injury (AKI) in patients with acute myocardial infarction (AMI) having undergone coronary interventional therapy.Methods: A single-center, retrospective and observational study was conducted. From December 2012 to June 2021, patients with AMI were enrolled and divided into AKI group and non-AKI group. The NEUT% in the two groups was compared. The association between NEUT% with the risk of post-AMI AKI was analyzed by univariate and multivariable logistic regression. Kaplan-Meier survival curve was drawn to evaluate the prognostic ability of NEUT% for short-term all-cause death following AMI.Results: A total of 3001 consecutive patients were enrolled with an average age of 64.38 years. AKI occurred in 327 (10.9%) patients. The NEUT% was higher in the AKI group than in the non-AKI group ([76.65± 11.43]% versus [73.22± 11.83]%, P< 0.001). NEUT% was also identified as an independent risk factor for AKI in AMI patients after adjustment (OR=1.021, 95% CI: 1.010– 1.033, P < 0.001). Compared with those at the lowest quartile of NEUT%, the patients at quartiles 2– 4 had a higher risk of AKI (P for trend = 0.003). The odds of AKI increased by 29.0% as NEUT% increased by 1 standard deviation (OR=1.290, 95% CI: 1.087– 1.531, P = 0.004). After a median of 35 days follow-up, 93 patients died. Patients with a higher NEUT% presented a higher risk of all-cause death after AMI (Log rank: χ2 =24.753, P< 0.001).Conclusion: In AMI patients, the peripheral blood NEUT% was positively associated with the odds of AKI and short-term all-cause mortality. NEUT% may provide physicians with more information about disease development and prognosis.Keywords: neutrophil percentage, acute kidney injury, acute myocardial infarction

Kuihan Tang,1 Li Sun,2 Long Chen,2 Xiaobo Feng,1 Jiarui Wu,2 Hao Guo,2 Yong Zheng1 1Department of Orthopedics, Beijing Jishuitan Hospital Guizhou Hospital, Guiyang, 550014, People’s Republic of China; 2Department of Orthopedics, Guizhou Provincial People’s Hospital, Guiyang, 550000, People’s Republic of ChinaCorrespondence: Yong Zheng, Email 1210244258@qq.comBackground: Mitochondrial autophagy is closely related to the pathogenesis of osteoarthritis, In order to explore the role of mitochondrial autophagy related genes in knee osteoarthritis (KOA) and its molecular mechanism.Methods: KOA-related transcriptome data were extracted from the Gene Expression Omnibus (GEO) database. Differentially expressed mitochondrial autophagy gene (DEMGs) were screened in patients with KOA by differential expression analysis. The STRING website was used to construct a protein-protein interaction (PPI) network among DEMGs. Molecular complex detection (MCODE) method in Cytoscape software was performed to identify hub DEMGs. Support vector machine recursive feature elimination (SVM-RFE) method was used to construct the hub DEMG diagnosis model. Genes with diagnostic value were identified as biomarkers by plotting receiver operating characteristic (ROC) curves and Expression validation. CIBERSORT algorithm was used to calculate the proportion of 22 immune cells in each sample in the GSE114007 dataset. Finally, biomarker expression was verified by qPCR.Results: A total of 15 DEMGs were obtained and enrichment analyses showed that these DEMG strains were mainly enriched in the mitophagy-animal, shigellosis, autophagy-animal and FoxO signal pathways. The PPI network unveiled 13 DEMGs with interactions. In addition, 8 hub DEMGs (ULK1, CALCOCO2, MAP1LC3B, BNIP3L, GABARAPL1, BNIP3, FKBP8 and FOXO3) were obtained for KOA. And 5 model DEMGs (BNIP3L, BNIP3, MAP1LC3B, ULK1 and FOXO3) were screened. The ROC curves revealed that BNIP3 and FOXO3 has strong diagnostic value in these models of DEMG. Immune-infiltration and correlation analysis showed that BNIP3 and FOXO3 were significantly correlated with three different immune cells, including primary B cells, M0 macrophage and M2 macrophage. The cartilage tissue samples qPCR verification results show that FOXO3 and BNIP3 were all down-regulated in KOA (p < 0.01), and the validation results are consistent with the above analysis.Conclusion: BNIP3 and FOXO3 have been identified as biomarkers for the diagnosis of KOA, which might supply a new insight for the pathogenesis and treatment of KOA.Keywords: Gene Expression Omnibus, diagnostic, bioinformatics analysis, immune infiltration, biomarkers

Ying Zhu,1 Liyuan Jiang,2 Tiantian Ye,3 Yan Liu,4 Li Sun,2 Lijuan Xiao,5 Jiayu Chen,6 Ting Wang,7 Yinghua Ren,8 Hongjun Xu,8 Huihui Zhao,8 Xiaozhen Mao,8 Tiantian Shen9 1School of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 2Department of Acupuncture and Rehabilitation, Hangzhou Hospital of Traditional Chinese Medicine, Hangzhou, 310005, People’s Republic of China; 3The 1st Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 4The 2nd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 5Department of Rehabilitation, Chun’an County Hospital of Traditional Chinese Medicine, Chun’an, 311799, People’s Republic of China; 6Department of Rehabilitation, Huzhou Central Hospital, Huzhou, 313099, People’s Republic of China; 7The 3rd Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, 310053, People’s Republic of China; 8Department of Acupuncture and Tuina, Community Health Service Center of Zhuantang Street, Hangzhou, 310024, People’s Republic of China; 9Department of Acupuncture and Rehabilitation, Shengzhou Municipal Hospital of Traditional Chinese Medicine, Hangzhou, 312499, People’s Republic of ChinaCorrespondence: Liyuan Jiang, Department of Acupuncture and Rehabilitation, Hangzhou Hospital of Traditional Chinese Medicine, No. 453, Stadium Road, Xihu District, Hangzhou, 310005, People’s Republic of China, Tel +86-13018976755, Email Jiangliyuan520j@163.comPurpose: Diastasis recti abdominis (DRA) is a condition in which the linea alba is stretched and widened, and the abdominal muscles are separated from each other. DRA typically occurs in pregnant and postpartum women. We aimed to determine the risk factors and patient-reported outcomes (PROs) of DRA in Chinese postpartum women.Methods: This observational study was conducted in Hangzhou Hospital of Traditional Chinese Medicine, and involved 534 women who filled out the following risk-factor and PRO questionnaires: SF-MPQ-2, SF-ICIQ, LDQ, EPDS, MBIS, HerQles, and SF-36 (all Chinese versions). The inter-recti distance was measured by palpation. Statistical analyses were performed using SPSS v25.0 software and the Mann–Whitney U-test, chi-square test, binary logistic regression analysis (for risk factors of DRA), and the Kendall and Spearman tests (for correlation analysis).Results: After childbirth, 78.1% (417/534) of the enrolled women had DRA. Abdominal surgery (P = 0.002), number of pregnancies (P = 0.035), parity (P = 0.012), number of births (P = 0.02), fetal birth weight (P = 0.014), and waist-to-hip ratio in the supine position (P = 0.045) significantly differed between the DRA and non-DRA groups. Caesarean delivery was an independent risk factor for DRA. The PROs were significantly worse in the DRA group than in the non-DRA group.Conclusion: Caesarean delivery was an independent risk factor for DRA. Women with DRA are more likely to have limited physical activity or function after childbirth, lower self-confidence, and a decreased quality of life.Keywords: risk factors, patient-reported outcome measures, diastasis recti abdominis, postpartum period

Long Sun,&ast; Jing Wang,&ast; Pan Wei, Wen-Qing Ruan, Jun Guo, Zhi-Yu Yin, Xing Li, Jian-Gang Song Department of Anesthesiology, Shuguang Hospital Affiliated to Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian-Gang Song; Xing Li, Department of Anesthesiology, Shuguang Hospital affiliated to Shanghai University of Traditional Chinese Medicine, No. 528 of Zhangheng Road, Pudong District, Shanghai, 201203, People’s Republic of China, Tel +86 13761172886 ; +86 13585562895, Email songjiangang_sjg@126.com; lixinglx06@126.comBackground: Utilizing high-flow nasal cannula (HFNC) oxygen therapy may prevent the collapse of alveoli and improve overall alveolar ventilation. In this study, we aimed to investigate the impact of HFNC on postoperative atelectasis in individuals undergoing robotic-assisted laparoscopic surgery.Methods: Patients undergoing robotic-assisted laparoscopic surgery for rectal cancer were randomly assigned to the control or HFNC groups. After the surgical procedure was complete and the trachea was extubated, both groups underwent an initial lung ultrasound (LUS) scan. In the post-anesthesia care unit (PACU), the control group received conventional nasal cannula oxygen therapy, while the HFNC group received high-flow nasal cannula oxygen therapy. A second LUS scan was conducted before the patient was transferred to the ward. The primary outcome measured was the total LUS score at the time of PACU discharge.Results: In the HFNC group (n = 39), the LUS score and the incidence of atelectasis at PACU discharge were significantly lower compared to the control group (n = 39) [(5 vs 10, P < 0.001), (48.72% vs 82.05%, P = 0.002)]. None of the patients in the HFNC group experienced hypoxemia in the PACU, whereas six patients in the control group did (P = 0.03). Additionally, the minimum SpO2 value in the PACU was notably higher in the HFNC group compared to the control group [99 vs 97, P < 0.001].Conclusion: Based on the results, HFNC improves the extent of postoperative atelectasis and decreases the occurrence of atelectasis in individuals undergoing robotic-assisted laparoscopic surgery for rectal cancer.Keywords: general anesthesia, high-flow nasal cannula oxygen therapy, lung ultrasound, postoperative atelectasis, robotic-assisted laparoscopic surgery

Ruyu Han,&ast; Leijuan Gan,&ast; Mengran Lang,&ast; Guangtao Li, Lu Chen, Xindi Tian, Kangwei Zhu, Liyu Sun, Tianqiang Song Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tianqiang Song, Department of Hepatobiliary Cancer, Liver Cancer Center, Tianjin Medical University Cancer Institute & Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin’s Clinical Research Center for Cancer, Tianjin Key Laboratory of Digestive Cancer, Tianjin, 300060, People’s Republic of China, Tel +86-022-23340123, Fax +86-022-23537796, Email songtianqiangtj@163.comPurpose: This study aimed to investigate the potential benefits of radical therapy in patients with stage B disease.Patients and Methods: A retrospective analysis was conducted on a cohort of 437 patients diagnosed with stage B hepatocellular carcinoma, who underwent either hepatic resection (HR) or radiofrequency ablation (RFA) at the Cancer Institute and Hospital of Tianjin Medical University from May 2011 to May 2022. Multivariate COX regression analysis was performed to identify the independent prognostic factors related to recurrence-free survival (RFS). The performance of the developed nomogram was evaluated using various statistical measures, including the concordance index (C-index), receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA).Results: Multivariate analysis revealed that tumor diameter, number of tumors, number of involved liver segments, alpha-fetoprotein (AFP), carbohydrate antigen 19– 9 (CA19-9), lactate dehydrogenase (LDH), and systemic immune inflammation index (SII) were independent prognostic factors influencing patients’ RFS, and these factors were incorporated into the nomogram. The C-index of the nomogram in the training cohort was 0.721, and the AUC at 2 and 3 years was 0.772 and 0.790, respectively. These values were appreciably higher than commonly used clinic staging systems and other predictive models. The calibration curve and DCA demonstrated good calibration and net benefit. Survival analysis comparing stage B patients who received radical treatment with stage A patients with multiple lesions did not reveal a significant difference in Kaplan-Meier survival curves (P=0.91).Conclusion: The nomogram provided a precise prediction of the recurrence for stage B hepatocellular carcinoma patients undergoing radical treatment. Furthermore, certain stage B patients may benefit from radical treatment.Keywords: nomogram, Barcelona clinic Liver cancer system, recurrence-free survival, hepatic resection, radiofrequency ablation

Wentao Zhong,1– 3,&ast; Qianyu Wang,2,&ast; Xiaofei Shen,4,&ast; Yuan Lv,2,3 Liang Sun,2 Ran An,5 Hongyan Zhu,5 Huiyun Cai,2 Gang Chen,2,3 Aijun Liu,5 Junfeng Du1– 3 1The Second School of Clinical Medicine, Southern Medical University, Guangdong, 510515, People’s Republic of China; 2Department of General Surgery, The 7th Medical Center, Chinese PLA General Hospital, Beijing, 100700, People’s Republic of China; 3Medical Department of General Surgery, The 1st Medical Center, Chinese PLA General Hospital, Beijing, 100853, People’s Republic of China; 4Division of Gastric Surgery, Department of General Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, 210008, People’s Republic of China; 5Department of Pathology, the 7th Medical Center, Chinese PLA General Hospital, Beijing, 100700, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Aijun Liu, Department of Pathology, The 7th Medical Center, Chinese PLA General Hospital, NO. 5, Nanmen Cang, Beijing, 100700, People’s Republic of China, Email aliu301@126.com Junfeng Du, Department of General Surgery, the 7th Medical Center, Chinese PLA General Hospital, NO. 5, Nanmen Cang, Beijing, 100700, People’s Republic of China, Email dujf66@126.comPurpose: To demonstrate the intrinsic association of Neutrophil extracellular traps (NETs) with outcome and neoadjuvant therapy response of locally advanced rectal cancer (LARC), and the mechanisms.Patients and Methods: We enrolled 240 patients with LARC who underwent surgery without neoadjuvant therapy in two independent sets (training and validation), and 153 patients who received neoadjuvant therapy with biopsy followed by surgery. Immunohistochemistry, immunofluorescence staining and bioinformatics analysis were performed in formalin-fixed paraffin-embedded sections. NETs were identified by costaining for myeloperoxidase and citrullinated histone H3.Results: NETs were associated with recurrence-free survival in the surgical training and validation sets. High-NET density predicted poor postoperative survival of patients with LARC. Multivariate analysis identified NETs, TNM stage, and neutrophil-to-lymphocyte ratio as independent prognostic factors for recurrence-free survival. Low-NETs LARC demonstrated increased CD8+ T cell and lower T regulatory cell infiltration, which indicated a tumor immune microenvironment with strong antitumor capacity. High-NET density was associated with epithelial–mesenchymal transition, which is considered to contribute to tumor progression. In the neoadjuvant therapy cohort, high-NET density on biopsy was significantly associated with reduced likelihood of complete/near complete response.Conclusion: NET was an independent prognostic factor in LARC that were associated with patients’ survival, and NET density in pretreatment biopsies was an independent predictive biomarker of response to neoadjuvant therapy. This biomarker may be helpful in predicting survival in LARC with improved accuracy and selecting patients who will respond to neoadjuvant therapy.Keywords: NETs, tumor microenvironment, locally advanced rectal cancer, outcome

Lingyan Sun,1– 3,&ast; Yan Chen,4– 6,&ast; Tingting Qu,7,8 Keren Shi,4– 6 Xinhong Han,4– 6 Wenhao Wu,7,8 Yan Jiang,4– 6 Yunsong Yu4– 6 1Department of Laboratory Medicine, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 2Key Laboratory of Clinical in Vitro Diagnostic Techniques of Zhejiang Province, Hangzhou, People’s Republic of China; 3Institute of Laboratory Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 4Department of Infectious Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 5Key Laboratory of Microbial Technology and Bioinformatics of Zhejiang Province, Hangzhou, People’s Republic of China; 6Regional Medical Center for National Institute of Respiratory Diseases, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 7State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, National Clinical Research Center for Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China; 8Infection Control Department, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yunsong Yu, Tel +86 138 0579 0432, Email yvys119@zju.edu.cnPurpose: We aimed to characterize a novel blaNDM-5 and blaKPC-2 co-carrying hybrid plasmid from a clinical carbapenem-resistant Klebsiella pneumoniae (CRKP) strain.Methods: Antimicrobial susceptibility was determined by the broth microdilution method. Plasmid size and localization were estimated using S1 nuclease pulsed-field gel electrophoresis (S1-PFGE) and Southern blotting. Plasmid transfer ability was evaluated by conjugation experiments. Whole genome sequencing (WGS) was performed using Illumina NovaSeq6000 and Oxford Nanopore MinION platforms. Genomic characteristics were analyzed using bioinformatics methods.Results: Strain ZY27320 was a multidrug-resistant (MDR) clinical ST11 K. pneumoniae strain that confers high-level resistance to carbapenems (meropenem, MIC 128 mg/L; imipenem, MIC 64 mg/L) and ceftazidime/avibactam (MIC > 128/4 mg/L). Both S1-PFGE–Southern blotting and whole genome sequencing revealed that the carbapenemase genes blaKPC-2 and blaNDM-5 were carried by the same IncFIIpHN7A8:IncR:IncN hybrid plasmid (pKPC2_NDM5). Conjugation experiments indicated that pKPC2_NDM5 was a non-conjugative plasmid.Conclusion: This is the first report of a hybrid plasmid carrying both carbapenemase genes blaNDM-5 and blaKPC-2 in a clinical K. pneumoniae ST11 isolate that confers resistance to both ceftazidime/avibactam and carbapenems, thereby presenting a serious threat to treatment in clinical practice.Keywords: blaNDM-5, blaKPC-2, Klebsiella pneumoniae, hybrid plasmid, IS 26

Gang Guo,1,2,&ast; Yanling Zheng,3,&ast; Xuexian Ma,4 Li Sun,5 Qimanguli Wushouer,1 Bin Jia,1 Muladier Yusufu,5 Shu Wen,6 Tuerhong Abudureyimu,6 Xiaowang Peng,6 Zhenjiang Liu,6 Xirizat Mamut,6 Yanggui Chen,7 Jian Zhang,8 Yuling Yang,9 Liusheng Huangfu,9 Jun Li,1 Wenbao Zhang1 1State Key Laboratory Pathogenesis, Prevention and Treatment of High Incidence Diseases in Central Asian, First Affiliated Hospital of Xinjiang Medical University, Urumqi, People’s Republic of China; 2Suzhou Center for Disease Control and Prevention, Suzhou, People’s Republic of China; 3College of Medical Engineering and Technology, Xinjiang Medical University, Urumqi, People’s Republic of China; 4Shache People’s Hospital, Shache, People’s Republic of China; 5Yingjisha County Center for Disease Control and Prevention, Yingjisha, People’s Republic of China; 6Kashgar Regional Lung Hospital, Kashgar, People’s Republic of China; 7Urumqi Municipal Center for Disease Control and Prevention, Urumqi, People’s Republic of China; 8High-Tech District Center for Disease Control and Prevention of Urumqi, Urumqi, People’s Republic of China; 9Xinhuarui Information Co., LTD, Urumqi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenbao Zhang, Tel +86 15276692787, Email wenbaozhang2013@163.comPurpose: To increase pulmonary tuberculosis (PTB) treatment adherence in Xinjiang Region, an electronic DOTS (eDOTS) system developed was applied and evaluated.Methods: An eDOTS system comprised electronic medicine boxes, mobile phones and a central processing platform. Between April and June 2016, persons with active PTB (PAPTB) were recruited from villages and a city and were prescribed a six-month course of antibiotics using either DOTS or eDOTS. Treatment adherence rate and chest X-ray digital radiography (DR) score were used to evaluate usefulness of eDOTS.Results: A total 167 PAPTB were recruited with 81 participants from villages and 86 from neighbourhoods. Of the 81 village patients, 43 (53%) used eDOTS and 38 (47%) used DOTS. Among the 86 patients from neighbourhoods, 50 (58%) used eDOTS and 36 (42%) used DOTS. After 6 months of treatment, the average treatment compliance of the village patients who used eDOTS were 47.0%± 20.5% compared to 26.7%± 21.1% who used DOTS (t=− 4.475, p< 0.001). The patients using eDOTS from both the villages and city had significantly lower X-ray DR scores than the patients using DOTS by 1.81 points, 95% CI (0.72– 2.90) and 1.05 points, 95% CI (0.15– 1.95), respectively.Conclusion: eDOTS is an effective means of managing the treatment of active PTB patients through daily reminding and monitoring of patient compliance. Ease of contact with doctors and special education programs encouraged PAPTB to complete their treatment course as required.Keywords: tuberculosis, infection, drug treatment, prevention/control program

Xiaoyu Zhang,1– 3,&ast; Lan Ding,1– 3,&ast; Ling Sun,1– 3 Bingqing Sun,1– 3 Yangyi Huang,1– 3 Yishan Qian,1– 3,&ast; Xingtao Zhou1– 3,&ast; 1Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China; 2Key Laboratory of Myopia, Chinese Academy of Medical Sciences, Shanghai, 200031, People’s Republic of China; 3Shanghai Research Center of Ophthalmology and Optometry, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yishan Qian; Xingtao Zhou, Eye Institute and Department of Ophthalmology, Eye & ENT Hospital, Fudan University, Shanghai, 200031, People’s Republic of China, Tel +86-21-64377134, Fax +86-21-64377151, Email thronebird31@hotmail.com; doctzhouxingtao@163.comPurpose: To investigate the relationship between corneal tomographic or biomechanical parameters and risk of keratoconus in very asymmetric ectasia (VAE).Methods: This retrospective case-control single-centre study included patients with VAE and normal controls. The VAE group had clinical ectasia in one eye and normal topography (VAE-NT) in the fellow eye; VAE-NT eyes were selected for analysis. The control group was selected from corneal refractive surgery candidates; the right eye was enrolled. Scheimpflug-based corneal tomography (Pentacam) and corneal biomechanical assessment (Corvis ST) were performed. Univariate and multivariable logistic regression were performed using Cox proportional hazards models to evaluate keratoconus-associated risk factors. A two-piecewise linear regression model was applied to examine the threshold effect of selected vital paragmeters on the risk of keratoconus according to a smoothing plot.Results: Threshold effect between tomographic integration and risk of keratoconus was observed. Discrepancy between the central corneal thickness and thinnest corneal thickness (discrepancy CCT vs TCT) greater than 5 μm, discrepancy between the apex corneal thickness and thinnest corneal thickness (discrepancy ACT vs TCT) greater than 3 μm, vector distance between CCT and TCT (distance CCT vs TCT) greater than 0.65 mm indicated a significant increased risk of keratoconus. Risk of keratoconus decreased when distance CCT vs TCT was less than 0.65 mm.Conclusion: Discrepancy CCT vs TCT, discrepancy ACT vs TCT, and distance CCT vs TCT can be used as indicators for risk assessment of early keratoconus.Keywords: keratoconus, corneal tomographic, corneal biomechanical, very asymmetric ectasia

Abstract We report a series of 1,3-diphenylureido hydroxamate HDAC inhibitors evaluated against sensitive and drug-resistant P. falciparum strains. Compounds 8a–d show potent antiplasmodial activity, indicating that a phenyl spacer allows improved potency relative to cinnamyl and di-hydrocinnamyl linkers. In vitro, mechanistic studies demonstrated target activity for PfHDAC1 on a recombinant level, which agreed with cell quantification of the acetylated histone levels. Compounds 6c, 7c, and 8c, identified as the most active in phenotypic assays and PfHDAC1 enzymatic inhibition. Compound 8c stands out as a remarkable inhibitor, displaying an impressive 85% inhibition of PfHDAC1, with an IC50 value of 0.74 µM in the phenotypic screening on Pf3D7 and 0.8 µM against multidrug-resistant PfDd2 parasites. Despite its potent inhibition of PfHDAC1, 8c remains the least active on human HDAC1, displaying remarkable selectivity. In silico studies suggest that the phenyl linker has an ideal length in the series for permitting effective interactions of the hydroxamate with PfHDAC1 and that this compound series could bind as well as in HsHDAC1. Taken together, these results highlight the potential of diphenylurea hydroxamates as a privileged scaffold for the generation of potent antimalarial HDAC inhibitors with improved selectivity over human HDACs.

Man Li,1,2,&ast; Xintao Li,3,&ast; Hongwei Gao,4 Peng Li,1 Li Zhang,1 Xiaoling Zhang,1 Peipei Liu,5 Xuemei Yang,2 Lili Wu,6 Jiangwei Zeng,2 Shouling Wu,7 Lixia Sun1 1Department of Emergency, The Affiliated Hospital of North China University of Science and Technology, Tangshan, People’s Republic of China; 2Graduate School, North China University of Science and Technology, Tangshan, People’s Republic of China; 3Department of Cardiology, The First Hospital of Soochow University, Jiangsu, People’s Republic of China; 4Department of Emergency, Caofeidian District hospital of Tangshan City, Tangshan, People’s Republic of China; 5School of Public Health, North China University of Science and Technology, Tangshan, People’s Republic of China; 6Department of Cardiology, Shanghai Songjiang District Central Hospital, Shanghai, People’s Republic of China; 7Department of Cardiology, Kailuan Hospital, Tangshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lixia Sun, Department of Emergency, The Affiliated Hospital of North China University of Science and Technology, Tangshan, 063000, People’s Republic of China, Email 13323151999@189.cn Shouling Wu, Department of Cardiology, Kailuan General Hospital, Tangshan, 063000, People’s Republic of China, Email drwusl@163.comPurpose: Inflammation plays a critical role in the development of cardiac conduction block (CCB), which is associated with an increased risk of morbidity and mortality. The monocyte-lymphocyte ratio (MLR) acts as a novel inflammatory marker; however, its association with CCB has not yet been studied. This study aimed to investigate the association between MLR and CCB risk.Patients and Methods: In total, 82,472 CCB-free participants were identified from the Kailuan study. MLR was calculated using the monocyte count/lymphocyte count. The participants were stratified based on quartiles of MLR levels. Incident CCB and its subtypes were ascertained from electrocardiograms at biennial follow-up visits. The Cox proportional hazards model and restricted cubic spline analysis were used to investigate the association between MLR with CCB and its subtypes.Results: During a median follow-up of 10.4 years, 3222 incident CCB cases were observed. A U-shaped association was observed between MLR and CCB risk (Pnonlinearity < 0.05). After multivariate adjustment, individuals in the highest MLR quartile had a hazard ratio (HR) of 1.212 (95% CI: 1.097-1.340; Q4 vs Q2), while those in the lowest MLR quartile had an HR of 1.106 (95% CI: 1.000-1.224; Q1 vs Q2). Sensitivity and subgroup analyses yielded consistent results. The U-shaped association persisted for atrioventricular block (AVB) in subtype analyses.Conclusion: MLR was significantly associated with an increased risk of new-onset CCB. Assessing MLR may have clinical relevance for predicting CCB risk, providing valuable insights for preventive strategies and patient management.Pre-Registered Clinical Trial Number: The pre-registered clinical trial number is ChiCTR-TNC-11001489. Keywords: cardiac arrhythmia, cardiac conduction block, inflammation, monocyte-lymphocyte ratio, risk factors

Huaiyi Cheng,&ast; Yifan Zhao,&ast; Yue Wang,&ast; Yuxi Hou, Ran Zhang, Mingrui Zong, Lingxiang Sun, Yingyu Liu, Jin Qi, Xiuping Wu, Bing Li School and Hospital of Stomatology, Shanxi Medical University, Shanxi Province Key Laboratory of Oral Diseases Prevention and New Materials, Shanxi Medical University, Taiyuan, 030001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bing Li; Xiuping Wu, Email libing1975vip@163.com; 77wxp@163.comBackground: Carbon dots (CDs), a novel nanomaterial, have gained significant attention over the past decade due to their remarkable fluorescence properties, low toxicity, and biocompatibility. These characteristics make them promising in various applications, especially in biomedicine. However, most CDs are currently synthesized using chemical materials, and their biocompatibility falls short of natural compounds. Research on extracting CDs from natural sources is limited, and their potential in biomedicine remains largely unexplored.Methods: We extracted CDs from resveratrol, a natural plant compound, and enhanced their water solubility using citric acid. Characterization of resveratrol-based carbon dots (RES-CDs) was carried out using various techniques, including UV-Vis, SEM, TEM, FTIR, XRD, and fluorescence spectroscopy. Extensive biocompatibility tests, wound healing assays, cell migration studies, and angiogenesis experiments were conducted using human umbilical vein endothelial cells (HUVEC). In addition, we investigated the biocompatibility and wound healing potential of RES-CDs in an in vivo rat model of inflammation.Results: RES-CDs exhibited stable yellow-green fluorescence under 365-nanometer ultraviolet light and demonstrated excellent biocompatibility. In wound healing experiments, RES-CDs outperformed resveratrol in terms of cell scratch healing, migration, and tube formation. In a rat skin defect model, RES-CDs promoted wound healing and stimulated the formation of blood vessels and tissue regeneration near the wound site, as evidenced by increased CD31 and VEGF expression.Conclusion: Resveratrol-derived CDs with enhanced water solubility show superior performance in tissue healing compared to resveratrol. This discovery opens new possibilities for the clinical application of resveratrol-based carbon dots. Keywords: carbon dots, wound healing, resveratrol, fluorescence, bio-imaging, biocompatibility

Dawei Wang,1 Lingchao Sun,1 Yunru Shao,1 Xiaoyan Zhang,1 Phil Maguire,2 Yixin Hu1 1School of Psychology, Shandong Normal University, Ji’nan, Shandong, People’s Republic of China; 2Department of Computer Science, National University of Ireland, Galway, IrelandCorrespondence: Yixin Hu, School of Psychology, Shandong Normal University, Jinan, Shandong Province, 250358, People’s Republic of China, Email huyixin2005@163.comPurpose: Cyberchondria is a problematic or unhelpful behavior pattern that describes excessive or repetitive online health-related information searching related to an enhanced level of health anxiety. Such internet-derived medical anxiety can manifest itself in different ways across cultures. This study explores the unique nature of cyberchondria in the context of Chinese culture, identifying the risk factors for the condition and the possible negative outcomes.Methods: An exploratory factor analysis (EFA) was used to explore whether the structure of the Chinese version of the Cyberchondria Severity Scale (C-CSS) is different from that in western context. Subsequently, a confirmatory factor analysis (CFA) was used to verify the model fit of the C-CSS. Finally, a series of regression analysis were used to test the relationship between cyberchondria and its antecedent variables and consequence variables in Chinese context.Results: Retained 18 items and revised to 3 dimensions (Negative Effects, Excessiveness and Reassurance Seeking), the Chinese version of the Cyberchondria Severity Scale (C-CSS) was developed. In the context of China, the three antecedents were also effective predictors of cyberchondria, and C-CSS is also related to theoretically relevant outcomes.Conclusion: This study initially demonstrated the validity, reliability and applicability of C-CSS to assess the severity of cyberchondria among Chinese undergraduates.Keywords: cyberchondria severity scale, medical anxiety, Chinese health system, validity, reliability

Yuping Xu,1 Yanyi Huang,1 Lin Sun,2 Jing Yang1 1School of Management, Huazhong University of Science and Technology, Wuhan, People’s Republic of China; 2School of History, Culture and Tourism, Guangxi Normal University, Guilin, People’s Republic of ChinaCorrespondence: Lin Sun, School of History, Culture and Tourism, Guangxi Normal University, No. 1 Wangcheng, Xiufeng District, Guilin, People’s Republic of China, Email 15078364886@163.comPurpose: This paper aims to redefine happiness goals and explore the conditions and mechanisms through which these redefined happiness goals influence work-related outcomes.Methods: The study developed and validated scales for self-focused happiness and other-focused happiness through exploratory factor analyses of 244 employees and confirmatory factor analyses of 300 employees. The proposed theoretical model was subsequently tested using a time-lagged analysis with data from 556 supervisor-employee dyads.Results: The findings provide strong evidence for the categorization of happiness goals into self-focused happiness and other-focused happiness. Furthermore, both self-focused and other-focused happiness significantly contribute to work-related vigor, subsequently influencing employee creativity. Additionally, the impact of these happiness goals on vigor and creativity is contingent upon the availability of job resources.Conclusion: This study highlights the substantial role of self-focused and other-focused happiness in enhancing employee vigor and creativity. However, the extent of these effects depends on the level of available job resources. These outcomes carry notable implications for the fields of positive psychology, positive organizational behavior, and creativity.Keywords: self-focused happiness, other-focused happiness, work-related vigor, job resources, creativity

Lina Sun,1,2,&ast; Kexin Liu,1,2,&ast; Meijiao Li,3 Yongchang Sun,1,2 Xiang Zhu,4,5 Chun Chang1,2 1Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, People’s Republic of China; 2Research Center for Chronic Airway Diseases, Peking University Health Science Center, Beijing, People’s Republic of China; 3Department of Radiology, Peking University Third Hospital, Beijing, People’s Republic of China; 4Department of Pathology, Peking University Third Hospital, Beijing, People’s Republic of China; 5Department of Pathology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chun Chang, Department of Respiratory and Critical Care Medicine, Peking University Third Hospital, Beijing, People’s Republic of China, Tel +86-15810075362, Email doudou_1977@163.com Xiang Zhu, Department of Pathology, Peking University Third Hospital, Beijing, People’s Republic of China, Tel +86-13691281987, Email zhuxiangbjmu@163.comAbstract: Tracheobronchial amyloidosis is a rare disease characterized by amyloid deposits on the tracheal and bronchial tissue. Patients with tracheobronchial amyloidosis are asymptomatic or exhibit symptoms, such as chronic wheezing, dyspnea, and cough, that are common manifestations of other disorders, including asthma. A bronchoscopic tissue biopsy using Congo red staining is the key standard for diagnosing tracheobronchial amyloidosis. Treatment strategies vary depending on the degree of airway obstruction. If the obstruction is significant and the patient is symptomatic, repeated bronchoscopic treatment, including local resection, laser therapy, stent placement, and radiation therapy, is considered a safer and better option. It is often misdiagnosed as asthma, but cases of tracheobronchial amyloidosis accompanied with asthma have not been reported. We report a case of intermittent wheezing, cough for 33 years, and shortness of breath on exertion for 7 years, which had aggravated in the previous 22 days. A pulmonary examination revealed diffuse wheezing. Pulmonary function testing revealed an obstructive ventilation dysfunction. Computerized tomography (CT) imaging revealed circumferential and irregular thickening of the tracheobronchial wall tissue with calcification and atelectasis of the right middle and lower lobe of the lung. Bronchoscopy revealed diffuse thickening of the mucosa of the trachea and bilateral main bronchi, with multiple nodular protuberances and relatively narrow lumens. The bronchial biopsies revealed massive amyloid deposits under the bronchial mucosa. The deposits exhibited a green birefringence under crossed polarized light after Congo red positive staining. The patient received standard treatment for asthma, and remains in good general condition without wheezing. It is not difficult to distinguish tracheobronchial amyloidosis through chest CT examination for patients with wheezing as long as this disease was considered. It was interesting that we present a rarer case of patient with tracheobronchial amyloidosis accompanied with asthma which both can cause symptoms such as wheezing.Keywords: wheezing, trachea, bronchi, respiratory amyloidosis

Chaoe Zhou,1 Liying Sun,2 Haixia Li,2 Lei Huang,2,&ast; Xinmin Liu1,&ast; 1Department of Geriatrics, Peking University First Hospital, Beijing, People’s Republic of China; 2Department of Clinical Laboratory, Peking University First Hospital, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xinmin Liu, Department of Geriatrics, Peking University First Hospital, Beijing, 100034, People’s Republic of China, Tel +86-10-8357-2128, Email lxm2128@163.com Lei Huang, Department of Clinical Laboratory, Peking University First Hospital, Beijing, 100034, People’s Republic of China, Tel +86-10-8357-5546, Email leihuang2031@bjmu.edu.cnPurpose: Hospital-acquired pneumonia (HAP) caused by carbapenem-resistant K. pneumoniae (CRKP), especially in elderly patients, results in high morbidity and mortality. Studies on risk factors, mortality, and antimicrobial susceptibility of CRKP pulmonary infection among elderly patients are lacking.Patients and Methods: A retrospective case–control study was conducted from January 2019 to December 2021. The elderly inpatients (≥ 65 years) who were diagnosed with HAP caused by K. pneumoniae were enrolled. Clinical data were collected. Univariate and multivariate logistic regression analyses were used to identify risk factors. Propensity score matching was used to minimize the effect of potential confounding variables. Kaplan–Meier analysis was used to compare survival.Results: A total of 115 patients with CRKP infection and 78 patients with carbapenem-susceptible K. pneumoniae (CSKP) infection were recruited. There were four independent risk factors for CRKP infection: history of intensive care unit (ICU) stays from hospital admission to positive respiratory specimen culture for K. pneumoniae (odds ratio (OR)=2.530), Charlson comorbidity index score ≥ 3 (OR = 2.420), prior exposure to carbapenems (OR = 5.280), and prior K. pneumoniae infection or colonization in the preceding 3 years (OR = 18.529). The all-cause 30-day mortality was 22.3%, the mortality of CRKP and CSKP infection was 28.7% and 12.8%, respectively. Independent risk factors for mortality included: older age (OR = 1.107), immunocompromised patients (OR = 8.632), severe pneumonia (OR = 51.244), quick Sepsis-related Organ Failure Assessment (qSOFA) score ≥ 2 (OR = 6.187), exposure to tigecycline before infection (OR = 24.702), and prolonged ICU stay (OR = 0.987). Thirty-day mortality was significantly lower in patients receiving ceftazidime-avibactam (CAZ-AVI) containing regimens than patients receiving polymyxin B sulfate (PB) containing regimens (P = 0.048). qSOFA score had a good prognostic effect [area under receiver operating characteristic curve (AUROC) of 0.838].Conclusion: Active screening of CRKP for the high-risk populations, especially elderly patients, is significant for early detection and successful management of CRKP infection.Keywords: elderly, hospital-acquired pneumonia, CRKP, CSKP, ceftazidime-avibactam, qSOFA

Shu Cui,1,&ast; Zhiwei Liu,1,&ast; Yun Liu,1 Gaofeng Yao,1 Yanhai Wu,1 Juanjuan Li,1 Feng Sun,1,2 Liang Sun,1,2 Longlong Sun1,2 1Department of Psychiatry, Third People’s Hospital of Fuyang, Fuyang, Anhui, 236000, People’s Republic of China; 2School of Mental Health and Psychological Sciences, Anhui Medical University, Hefei, Anhui, 238000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gaofeng Yao; Yanhai Wu, Department of Psychiatry, Third People’s Hospital of Fuyang, Wenxing Road, Fuyang, Anhui, 236000, People’s Republic of China, Email yao_gaofeng@126.com; wyh0387@163.comObjective: This study aims to investigate the association between the systemic immune-inflammatory index (SII) and suicide attempt (SA) in children and adolescents with first-episode, drug-naïve Major Depressive Disorder (MDD) during the COVID-19 pandemic.Methods: A retrospective study was conducted on 263 MDD patients hospitalized at the Third Hospital of Fuyang City between 2020 and 2022. Patients were categorized into two groups based on the presence of previous SA. The study compared the differences in SII and clinical characteristics between the two groups and used the receiver operating characteristic (ROC) curve to determine the optimal critical value of SII and the area under the curve. Binary logistic regression was used to analyze the independent risk factors for SA.Results: Compared with the patients without SA history, the patients with a personal history of SA had a higher mean HDRS scores (Z=− 2.369, p=0.018), higher mean neutrophil count (Z=− 2.870, p=0.004), higher mean platelet count (Z=− 2.155, p=0.031), and higher mean SII (Z=− 3.170, p=0.002). The optimal critical SII determined by the ROC curve was 548.15 (sensitivity = 63.2%, specificity = 83.1%), and the area under the curve was 0.661. After adjusting for gender, age, BMI, illness duration and HDRS score, the risk of total SA in patients with high SII was 8.296 times higher than in those with low SII (OR = 8.296, 95% CI: 3.803– 18.095, P < 0.001), The risk of recent SA was 13.922 times higher in patients with high SII than in those with low SII (OR = 13.922, 95% CI: 5.587– 34.693, p < 0.001). However, high SII was not a risk factor for past SA (OR = 0.547, 95% CI: 0.062– 4.842, P=0.587).Conclusion: SII may be an inexpensive, easily accessible strategy that can assist in determining suicide risk in adolescents with MDD.Keywords: major depressive disorder, suicide attempt, children and adolescents, systemic immune-inflammation index, first-episode

Dawei Wang,&ast; Dong Han,&ast; Lingchao Sun,&ast; Mengmeng Zhou, Leilei Hao, Yixin Hu School of Psychology, Shandong Normal University, Jinan, Shandong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yixin Hu, School of Psychology, Shandong Normal University, Jinan, Shandong, People’s Republic of China, Email huyixin2005@163.comPurpose: The core question explored in this study was whether social value theory, which can explain the domain specificity of self-other differences, still was applicable when choice recipients change.Methods: A pre-experiment and three formal experiments were conducted to explore the differences in self-other risk decision-making in different domains and different recipients from the perspective of social value theory. Experiment 1 involved 152 participants who were asked to make decisions for themselves and a single other in three risk domains. In Experiment 2, 178 participants were recruited, with money loss domain added and the “others” divided into “intimate others” to explore the effect of social distance on self-others risk decision-making in four domains. In Experiment 3, 233 participants were involved, and the number of “others” was expanded to explore the differences between “individual decision-making” and “group decision-making”.Results: In the relationship domain, individuals were more risk-averse when making decisions for themselves, while in the money gain domain and personal safety domain, individuals’ risk-taking tendencies when making decisions for themselves were significantly higher than that for new friends. In the money loss domain, no significant difference was found among the three decision-maker roles. When making decisions for a group (including the decision-maker), individuals exhibit a “compromise effect” in the non-monetary domain, where their risk appetite falls between making decisions for themselves and for the group.Conclusion: The domain differences in self-other risk decision-making can be explained by the social value theory.Keywords: self-other difference, risk decision-making, domain specificity, decision-maker role, social value theory

Meng-Chuan Zhao,1 Chan Wen,2 Ling Sun,2 Su-xia Duan,1 Ke-xin Zang,3 Le Wang,1 Xiao-Wei Cui4 1Department of Laborotory Medicine, Children’s Hospital of Hebei Province, Shijiazhuang, People’s Republic of China; 2Department of Medical, Children’s Hospital of Hebei Province, Shijiazhuang, People’s Republic of China; 3Hebei Medical University, Shijiazhuang, People’s Republic of China; 4Children’s Hospital of Hebei Province, Shijiazhuang, People’s Republic of ChinaCorrespondence: Xiao-Wei Cui, Children’s Hospital of Hebei Province, No. 133 of JianHua Street, Shijiazhuang, 050031, People’s Republic of China, Tel +86 18503292016, Fax +86 031185911109, Email cuixiaoweicxw@126.comBackground: This study aimed to assess the impact of the COVID-19 pandemic on the prevalence and clinical characteristics of seasonal human coronavirus (HCoV) infections among children hospitalized in Hebei, China.Methods: We examined nasopharyngeal aspirate (NPA) specimens for seasonal HCoVs from January 2018 to December 2021, at the Children’s Hospital of Hebei Province. We used a GeXP-based multiplex reverse transcription PCR assay for the detection of 11 common respiratory viruses (including seasonal HCoVs), chlamydia, and Mycoplasma pneumoniae. The demographic and clinical characteristics of children who tested positive for seasonal HCoVs were recorded and analyzed.Results: A total of 377 (1.96%) of the 19,248 specimens from 2018 to 2019 and 263 (1.96%) of the 13,426 specimens from 2020 to 2021 exhibited seasonal HCoVs. Compared to 2018 and 2019, the positive rate of seasonal HCoVs was lower from January to July of 2020 and increased beginning in August 2020, peaking in the autumn and winter. In 2020– 2021, nasal blockage and swollen adenoids were detected more frequently in children who tested positive for seasonal HCoVs. During 2018– 2019, however, the duration of fever was significantly longer, and cough and dyspnea were more prominent among children who had fallen ill. In addition, seasonal HCoV-positive patients in 2018– 2019 were more likely to experience complications, had a higher risk of severe community-acquired pneumonia (CAP), and had a tendency to require a longer hospital stay than patients in 2020– 2021.Conclusion: According to our findings, there were significant changes in the epidemiology of seasonal HCoVs in Hebei, China during the COVID-19 pandemic, and children infected with seasonal HCoVs usually experienced milder clinical symptoms during the pandemic than before it.Keywords: children, clinical characteristics, COVID-19 pandemic, epidemiology, Seasonal human coronavirus

Lin Zhao,&ast; Yan Zeng,&ast; Lin Sun, ZengLei Zhang, KunQi Yang, ZuoZhi Li, Man Wang, XianLiang Zhou, WeiXian Yang Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yan Zeng; WeiXian Yang, Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 167, Beilishi Road, Beijing, 100037, People’s Republic of China, Email zyminny@163.com; ywx66@aliyun.comPurpose: The presence of elevated fibrinogen levels is associated with cardiovascular disease. However, whether fibrinogen level is associated with adverse clinical events in patients with psoriasis and coronary artery disease (CAD) is unknown. This study aimed to investigate the relationship between fibrinogen levels and cardiovascular adverse events in these patients.Patients and Methods: This retrospective cohort study collected consecutive patients with psoriasis and CAD between January 2017 and May 2022 in our hospital. The clinical records were collected, and comparisons were made between groups. The Cox regression analysis and Kaplan–Meier survival analysis were used to evaluate the association between variables.Results: Of the 267 participants, one hundred and forty-seven patients (55.1%) had elevated fibrinogen levels. Compared with patients in low fibrinogen group, white blood cell and platelet counts and high-sensitivity C-reactive protein levels were higher, whereas the left ventricular ejection fraction was lower in patients in high fibrinogen group. After a median follow-up of 35.5 months, the incidence of major adverse cardiovascular events (MACEs) was higher in patients in high fibrinogen group compared with patients in low fibrinogen group (31.4% vs 16.4%, p = 0.013). The Kaplan–Meier survival curves showed the same trend (log rank p = 0.020). Subgroup analysis revealed a positive association between elevated fibrinogen levels and MACEs in patients aged < 60 years (log-rank p = 0.013), those with diabetes (log-rank p = 0.027), and those who were not admitted for acute cardiovascular syndrome (log-rank p = 0.015).Conclusion: Elevated fibrinogen levels were associated with adverse clinical events in patients with psoriasis and CAD, especially among patients aged < 60 years, those with diabetes, and those not admitted for acute cardiovascular syndrome.Keywords: fibrinogen, coronary artery disease, major adverse cardiovascular events, psoriasis

Lei Sun,1,&ast; Qi Zhao,2,&ast; Yanning Wang,3,&ast; Yongsheng Wang,2 Ming Zheng,2 Xuansheng Ding,4 Liyun Miao2 1School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University Nanjing Drum Tower Hospital, Nanjing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 3Clinical Stem Cell Center, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 4School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liyun Miao, Department of Respiratory and Critical Care Medicine, Nanjing Drum Tower Hospital, The Affiliated Hospital of Nanjing University Medical School, Nanjing, 210008, People’s Republic of China, Tel +86 13813920964, Fax +86-25-68183333, Email liyunmiao462@163.comPurpose: Anlotinib is widely used in the clinical treatment of non-small cell lung cancer (NSCLC), alone or in combination with other anticancer drugs. The aim of this study was to investigate the real-world efficacy and safety of anlotinib-containing regimens.Patients and Methods: Confirmed advanced NSCLC patients who had received anlotinib alone or in combination were enrolled. An overall analysis of the efficacy and safety of anlotinib was performed in all patients, and then subgroup analysis was used to further compare the efficacy between anlotinib monotherapy and combination therapy. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were ADR, ORR, and DCR.Results: A total of 240 patients were included. The overall median PFS was 8.5 months (95% confidence interval [CI]: 7.1– 9.9 months). Anlotinib treatment regimens (monotherapy or combination therapy) and whether they received previous antiangiogenesis were associated with PFS. Anlotinib plus immunotherapy achieved longer PFS than anlotinib monotherapy (median PFS: 10.5 vs 6.5 months, p=0.007). Stratification analysis showed the PFS of anlotinib plus immunotherapy was significantly longer in male, adenocarcinoma,

Yu-Hsiang Shih, Lou Sun, Shih-Tien Hsu, Ming-Jer Chen, Chien-Hsing Lu Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, Taichung, TaiwanCorrespondence: Chien-Hsing Lu, Department of Obstetrics and Gynecology, Taichung Veterans General Hospital, 1650 Taiwan Boulevard Sect. 4, Taichung, Taiwan, Tel +886-4-23592525, Email chlu@vghtc.gov.twObjective: This study investigated whether random urine (RU) samples can be used to accurately identify human papillomavirus (HPV) and whether these samples can replace self-collected vaginal samples in HPV tests.Methods: A total of 167 patients with abnormal Pap smears were recruited. The patients provided self-collected vaginal and RU samples for HPV testing. Clinicians obtained cervical samples from the patients. Colposcopy examination and cervical biopsy were performed. Hybrid Capture II (HC II) and Cervista tests were used to detect HPV in the RU samples.Results: The results of tests on clinician-collected cervical samples were used as the benchmark. The sensitivities of the Cervista tests on vaginal samples and the HC II and Cervista tests on RU samples were 75.00%, 49.07%, and 44.44%, respectively. After we adjusted the HPV detection cutoff value for urine samples based on values in the receiver operating characteristic curve, the sensitivities of the HC II and Cervista tests increased to 63.89% and 58.33%, respectively. In 167 patients, 59 had cervix biopsies showing CIN2 or worse (CIN2+). For CIN2+, the sensitivity was 47.5% and 50.8% in the HC II and Cervista tests on RU samples, respectively.Conclusion: HPV tests on RU samples had approximately 60% sensitivity to HPV tests on clinician-collected cervical samples after the cutoff values were adjusted. For CIN2+, the sensitivity was only approximately 50%. Further studies and improvements in urine-based HPV testing are needed to establish it as a more convenient and accessible method for detecting HPV and cervical dysplasia in patients.Keywords: HPV, random urine, vaginal HPV test, cervical intraepithelial lesion, Hybrid Capture II, Cervista