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Wenjuan Qiu,1 Ruifang Wang,1 Lili Liang,1 Yuning Sun,1 Rong Zhou,2 Xiaoli Wang,2 Wen Sun,3 Xuefan Gu1 1Department of Pediatric Endocrinology and Genetic Metabolism, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute for Pediatric Research, Shanghai, 200092, People’s Republic of China; 2Medical Affairs, GeneScience Pharmaceuticals Co. Ltd. (Gensci), Shanghai, 200233, People’s Republic of China; 3Beijing Intelligent Decision Medical Technology Co. Ltd., Beijing, 100028, People’s Republic of ChinaCorrespondence: Xuefan Gu, Email gu_xfan@163.comIntroduction: Growth hormone (GH) is crucial for immune system development and regulation, potentially benefiting COVID-19 outcomes. However, there are limited studies on the role of GH treatment in COVID-19 in children with short stature.Methods: We conducted a survey study to evaluate the association between GH treatment and COVID-19 risk in short stature children aged 7 to 18 years. Two groups were defined: GH Treated and GH Untreated. The primary endpoint was the proportion of children with COVID-19 histories. Secondary endpoints included the presence, severity, and duration of COVID-19 symptoms. Exploratory endpoints included the frequency of common colds after GH treatment. We further performed two-sample Mendelian randomization (MR) analyses to explore the causal relationship between GH levels and COVID-19 susceptibility, hospitalization, and severity using genome-wide association study summary-level data.Results: Of the 201 children, 113 (56.2%) reported COVID-19 history, and 149 (74.1%) used GH. The mean age was 11.02 ± 2.10 years. GH treatment was associated with a somewhat lower proportion of COVID-19 history (− 9.77%, 95% confidence interval [CI] − 26.41% to 6.87%; P = 0.289), and the odds ratio (OR) is 0.58 (95% CI 0.29 to 1.14, P = 0.120) after adjusting for confounders. Among the 113 children with COVID-19 histories, the highest body temperature was significantly lower in the GH Treated group (P = 0.040). In the MR analyses, for one unit increase in GH level, the OR was 0.95 (95% CI 0.92 to 0.99, P = 0.022) for COVID-19 susceptibility, 0.86 (95% CI 0.77 to 0.96, P = 0.007) for COVID-19 hospitalization, and 0.95 (95% CI 0.84 to 1.07, P = 0.392) for COVID-19 severity.Conclusion: GH treatment was associated with somewhat decreased COVID-19 susceptibility but was not statistically significant. Higher GH levels were causally associated with a significantly lower rate of COVID-19 susceptibility and hospitalization.Keywords: Mendelian randomization analysis, growth hormone treatment, COVID-19, children with short stature

Chengbin Zheng,1 Leilei Liang,1 Marhaba Kiyum,1 Tongshuang Yuan,1 Junsong Fei,1 Huimin Wang,1 Jiaying Gao,1 Xiaoying Liu,1 Songli Mei,1 Na Du2 1Department of Social Medicine and Health Management, School of Public Health of Jilin University, Changchun, 130021, People’s Republic of China; 2Center of Infectious Disease and Pathogen Biology, Department of Infectious Diseases, The First Hospital of Jilin University, Changchun, 130061, People’s Republic of ChinaCorrespondence: Songli Mei, Jilin University, Department of Social Medicine and Health Management, School of Public Health of Jilin University, Changchun, 130021, People’s Republic of China, Email meisongli@sina.com Na Du, The First Hospital of Jilin University, Center of Infectious Disease and Pathogen Biology, Department of Infectious Diseases, The First Hospital of Jilin University, Changchun, 130061, People’s Republic of China, Email du_na@jlu.edu.cnBackground: With the increasing popularity of ARVs, physical symptoms of people living with HIV/AIDS (PLWHA) have been effectively improved. Improving mental health and quality of life has gradually become the focus of attention in the treatment. The aim of this study is to explore the association between death anxiety and depression in men living with HIV/AIDS (MLWHA) from the perspective of network analysis.Methods: This study recruited 701 MLWHA in Jilin Province, China. Participants were asked to complete a questionnaire. The average age of the participants was 37.4 years old. Among them, there were 54 heterosexual participants, 494 homosexual participants, 139 bisexual participants, and 14 asexual/other participants. Network analysis was used to identify central symptoms, key bridge symptoms, and the strongest edge among symptoms in the death anxiety and depression network.Results: In this study, 18.1% of MLWHA may suffer from severe depression. The severity of depression in homosexual MLWHA was severer than in heterosexuals. Death anxiety was severer among unmarried and married/cohabiting MLWHA compared to divorced/separated/widowed MLWHA. This study found that item DAS10 (The topic of post death is very confusing to me) was the most central symptom. The edge DAS2 – PHQ9 (Rarely think of death – Suicide ideation) was the strongest edge between death anxiety and depression. Item DAS2 (Rarely think of death) was the strongest bridge symptom.Conclusion: Psychological symptoms such as distress over the topic of death, thoughts of death, and suicidal ideation play an important influential and connecting role in the death anxiety-depression network among MLWHA. Implementing appropriate interventions for these symptoms—such as popularizing correct knowledge of death and providing more psychological counseling services for this group—can effectively reduce the co-occurrence of death anxiety and depression, thereby improving the mental health of MLWHA.Keywords: death anxiety, depression, men living with HIV/AIDS, network analysis, comorbid psychological symptoms

Zhenren Peng,1– 6,* Jie Wei,1,2,* Xiuning Huang,1,2,* Biyan Chen,1,2 Lifang Liang,1,2 Baoying Feng,1,2 Pengshu Song,1,2 Jiajia He,1,2 Ting Que,1,2 Jingjue Lan,1,2 Jie Qin,1,2 Sheng He,1– 6 Qiufen Wei1– 6 1Birth Defects Research Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530002, People’s Republic of China; 2Birth Defects Research Laboratory, Birth Defects Prevention and Control Institute of Guangxi Zhuang Autonomous Region, Nanning, 530002, People’s Republic of China; 3Birth Defects Research Laboratory, Guangxi Key Laboratory of Reproductive Health and Birth Defect Prevention, Nanning, 530002, People’s Republic of China; 4Birth Defects Research Laboratory, Guangxi Key Laboratory of Birth Defects Research and Prevention, Nanning, 530002, People’s Republic of China; 5Birth Defects Research Laboratory, Guangxi Clinical Research Center for Fetal Diseases, Nanning, 530002, People’s Republic of China; 6Birth Defects Research Laboratory, Guangxi Clinical Research Center for Pediatric Diseases, Nanning, 530002, People’s Republic of China*These authors contributed equally to this workCorrespondence: Sheng He; Qiufen Wei, Birth Defects Research Laboratory, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, No. 59 Xiangzhu Avenue, Nanning, Guangxi Zhuang Autonomous Region, 530002, People’s Republic of China, Email heshengbiol@163.com; Wqf2024@163.comPurpose: To explore the changing trends in the prevalence and epidemiological characteristics of congenital heart defects (CHDs) in perinatal infants (PIs) in Guangxi, China.Patients and Methods: During 2016 and 2020, the Guangxi Birth Defects Monitoring Network (GXBDMN) monitored a total of 3627108 PIs in this study. The CHDs data for PIs can be obtained from the GXBDMN. The study analyzed the changing trends of total CHDs prevalence and each subtype of CHDs prevalence per year using prevalence-rate ratios (PRR). The correlation between characteristics (such as year, infant gender, maternal age, and quarter) and the prevalence of CHDs was also examined by the PRR.Results: Between 2016 and 2020, 10817 PIs were diagnosed with CHDs, resulting in an overall CHDs prevalence of 29.82 [95% confidence intervals (CI): 29.26– 30.38] per 10000 PIs. CHDs accounted for 24.50% of all types of BDs, making them the most common type of BDs. Atrial septal defect / patent foramen ovale (ASD/PFO), patent ductus arteriosus (PDA), ventricular septal defect (VSD), atrioventricular septal defect (AVSD), persistent left superior vena cava (PLSVC), and tetralogy of Fallot (TOF) were the 6 most common subtypes of CHDs. Together they accounted for 86.24% of all CHDs cases, with a total prevalence of 25.72 (95% CI: 25.20– 26.24) per 10000 PIs. The study period saw a significant increase in the prevalence of CHDs (PRR = 1.300, 95% CI: 1.283– 1.318), and the maternal age also played a significant role in this increase (PRR = 2.738, 95% CI: 2.428– 3.087).Conclusion: The prevalence of CHDs in Guangxi is rising and has an upward trend with maternal age. ASD/PFO, PDA, VSD, AVSD, PLSVC, and TOF were the top six subtypes of CHDs.Keywords: congenital heart defects, perinatal infants, pregnant women, prevalence

Tielong Chen,1,&ast; Jianwu Zheng,1,&ast; Cheng Bao,1 Yu Wang,1 Shiwang Wang,1 Lu Liang,1 Li Zhang,2 Hui Zhang,2 Chaoxia Ji,2 Jian Wang,2 Xudong Zhang,1 Guangli Zhu,1 Houyong Zhu1 1Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China; 2Zhejiang Chinese Medical University, Hangzhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tielong Chen; Houyong Zhu, Department of Cardiology, Hangzhou TCM Hospital Affiliated to Zhejiang Chinese Medical University, No. 453 Stadium Road, Hangzhou, Zhejiang, 310007, People’s Republic of China, Email ctlppp@foxmail.com, ctlppp@163.com; houyongzhu@foxmail.comBackground: Despite statins and other medications central to atherosclerotic cardiovascular disease (ASCVD) secondary prevention, stable coronary artery disease (SCAD) patients remain at significant cardiovascular risk, partly due to residual inflammation risk (RIR). This study aims to assess if adding Guanxinning to standard ASCVD therapy further mitigates RIR in SCAD patients.Methods: In a prospective, randomized, single-blind endpoint design, 50 patients with SCAD who received ASCVD standardized treatment strategy were randomly assigned to either take Guanxinning tablets (4 tablets, thrice daily) or no Guanxinning tablets and were followed up for an average of 12 weeks. The primary outcomes were changes in inflammation-related indicators, including interleukin-2 (IL-2), IL-4, IL-6, tumor necrosis factor-α (TNF-α), and high sensitivity C-reactive protein (hs-CRP).Results: Compared with the control group, the intervention group showed significantly greater decreases in the levels of IL-2, IL-6, TNF-α, and hs-CRP (all P < 0.05). However, there was no significant difference in the IL-4 level between the two groups (P > 0.05). Compared with the control group, there were also significant improvements in endothelial function-related indicators (vascular endothelial growth factor (VEGF), nitric oxide (NO), and peroxisome proliferator-activated receptor-γ (PPAR-γ)), blood lipid profile (total cholesterol (Tch), low-density lipoprotein cholesterol (LDL-C)), and chest pain related scores (angina and Traditional Chinese medicine syndrome scores) in the intervention group (all P< 0.05). There was no significant difference in the triglyceride (TG) and carotid intima-media thickness between the two groups (P< 0.05). Compared to the control group, there was no significant difference in the white blood cell line, liver and kidney function, anemia, and bleeding in the intervention group (all P< 0.05).Conclusion: The addition of Guanxinning tablets (4 tablets, thrice daily) to the standard treatment strategy for ASCVD was associated with a reduction in the RIR in patients with SCAD and demonstrated good safety.Plain Language Summary: In the quest for a heart-healthy life, even with statins at our side, some folks with stable heart troubles still face a sneaky foe: lingering inflammation. Our study explored whether adding Guanxinning, a traditional Chinese medicine, to the standard treatment might help. Over 12 weeks, patients who took Guanxinning along with their usual heart meds showed promising signs of reduced inflammation and improved heart health markers. These preliminary positive signs hint at the potential benefits of Guanxinning, which, however, need further studies to confirm. Fortunately, it appears to be safe to use Guanxinning alongside conventional treatments for now. As we delve deeper into the mysteries of heart health, every promising discovery brings us one step closer to developing better therapeutic strategies.Keywords: Guanxinning, stable coronary artery disease, risk of residual inflammation, secondary prevention

Liu Liang,1 Xuemin Guo,1 Wei Ye,1 Yuxiang Liu2 1Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou, People’s Republic of China; 2Department of Medical Oncology, Meizhou People’s Hospital, Meizhou, People’s Republic of ChinaCorrespondence: Liu Liang, Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou, People’s Republic of China, Email 19926117315@163.comBackground: The efficacy of targeted therapy for colorectal cancer (CRC) is affected by hub genes of epidermal growth factor receptor (EGFR) signaling pathways, such as KRAS. Immune cell infiltration may lead to gene mutation, but the relationship between KRAS status and peripheral immune-inflammatory indices has not been clarified in CRC.Methods: Clinical records of CRC patients were collected. The relationship between KRAS status and clinicopathological characteristics, peripheral immune-inflammatory indices (pan-immune inflammation value (PIV) (monocyte×neutrophil×platelet/lymphocyte), systemic immune inflammation index (SII) (platelet×neutrophil/lymphocyte), and system inflammation response index (SIRI) (monocyte×neutrophil/lymphocyte)) were analyzed.Results: 1033 CRC patients were collected, there were 514 (49.8%) patients with KRAS wild-type and 519 (50.2%) with KRAS mutation. Patients with KRAS mutation had higher proportions of female, III-IV stage, and lymph node metastasis and lower proportion of low grade of tumor budding (the presence of single tumor cells or small clusters of up to 5 cells in mesenchyma at the front of tumor invasion) than those with KRAS wild-type. The PIV, SII, and SIRI levels in KRAS mutation patients were significantly higher than those in KRAS wild-type patients. The proportion of aged ≥ 65 years old, dMMR, distant metastasis, and KRAS mutation were high in patients with high PIV, SII, and SIRI levels. Logistic regression analysis showed that non-low grade of tumor budding (odds ratio (OR): 1.970, 95% confidence interval (CI): 1.287– 3.016, p=0.002), and high SII level (≥ 807.81 vs < 807.81, OR: 1.915, 95% CI: 1.120– 3.272, p=0.018) were independently associated with KRAS mutation.Conclusion: Non-low grade of tumor budding, and high SII level were independently associated with KRAS mutation in CRC. It provides additional references for diagnosis and treatment options for patients with CRC.Keywords: colorectal cancer, KRAS, systemic immune inflammation index, tumor budding

Junyu Chen,1,&ast; Yupei Yuan,2,&ast; Ying Hu,1 Liang Liang1,3 1Department of Psychology, The Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China; 2Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China; 3Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, Hubei, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Liang Liang, Department of Psychology, The Fourth Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang, People’s Republic of China, Tel +8609915848029, Email 79023556@qq.comBackground: The adjunctive therapeutic potential of simvastatin in schizophrenia treatment has generated interest due to its anti-inflammatory and neuroprotective properties. This meta-analysis aims to assess the efficacy of simvastatin as an adjunct treatment for schizophrenia, synthesizing results from various controlled trials.Methods: We performed a comprehensive search of databases including PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) evaluating the efficacy of simvastatin as an adjunct therapy in patients with schizophrenia. The primary outcome measures were improvements in the Positive and Negative Syndrome Scale (PANSS) scores. Secondary outcomes included changes in overall clinical condition and level of functioning. Data were pooled using random-effects models, and heterogeneity was assessed through I² statistics.Results: The four RCTs included in the analysis represented 425 participants. The combined results demonstrated no significant advantage of simvastatin over placebo in reducing PANSS total scores with a pooled effect size (Standard Mean Difference, SMD) of − 0.36 (95% Confidence Interval, CI: − 0.82 to 0.11) at 1 month, and − 1.80 (95% Confidence Interval, CI: − 4.82 to 1.21) at 3 months, indicating minimal to no effect. Similarly, analyses of secondary outcomes showed no significant improvements in overall clinical condition and level of functioning. The studies exhibited low heterogeneity (I² = 0%).Conclusion: This meta-analysis provides evidence that simvastatin, used as adjunctive therapy, does not significantly improve the symptomatic outcomes of schizophrenia compared to placebo. Although simvastatin is well-tolerated, its role in enhancing antipsychotic treatment efficacy in patients with schizophrenia appears limited. These findings suggest that simvastatin should not be recommended as an adjunctive treatment in the clinical management of schizophrenia. Further research may explore the potential subgroups that could benefit from such treatment or identify the biological reasons for the lack of efficacy.Keywords: schizophrenia, simvastatin, adjunctive therapy, meta-analysis, randomized controlled trials, efficacy

Lijuan Liang,1,&ast; Ming Jia,2,3,&ast; Min Zhao,4,&ast; Yiping Deng,5,&ast; Jun Tang,5 Xinghui He,2 Yilin Liu,2 Kexin Yan,2 Xin Yu,6 Hong Yang,7 Chunhong Li,2 Yao Li,2,8 Tao Li4 1Department of Pharmacy, Hejiang County People’s Hospital, Luzhou, Sichuan, People’s Republic of China; 2Department of Pharmaceutical Sciences, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Nanchong Institute for Food and Drug Control, Nanchong, Sichuan, People’s Republic of China; 4Key Laboratory of Medical Electrophysiology of Ministry of Education, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Analysis and Testing Center, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 6Chinese Pharmacy Laboratory, School of Pharmacy, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 7Department of Pediatrics, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 8Science and Technology department, Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yao Li; Tao Li, Email lnetyao@163.com; leta49@swmu.edu.cnAbstract: As a pivotal transition metal oxide, manganese dioxide (MnO2) has garnered significant attention owing to its abundant reserves, diverse crystal structures and exceptional performance. Nanosizing MnO2 results in smaller particle sizes, larger specific surface areas, optimized material characteristics, and expanded application possibilities. With the burgeoning research efforts in this field, MnO2 has emerged as a promising nanomaterial for tumor diagnosis and therapy. The distinctive properties of MnO2 in regulating the tumor microenvironment (TME) have attracted considerable interest, leading to a rapid growth in research on MnO2-based nanomaterials for tumor diagnosis and treatment. Additionally, MnO2 nanomaterials are also gradually showing up in the regulation of chronic inflammatory diseases. In this review, we mainly summarized the recent advancements in various MnO2 nanomaterials for tumor diagnosis and therapy. Furthermore, we discuss the current challenges and future directions in the development of MnO2 nanomaterials, while also envisaging their potential for clinical translation.Keywords: manganese dioxide nanoparticles, tumors, inflammation, biomedicine, research progress

Liping Zou,1,&ast; Wanli Kang,2,&ast; Chunhui Guo,3,&ast; Juan Du,4,&ast; Qing Chen,1 Zhengyu Shi,1 Xianzhen Tang,1 Li Liang,1 Peijun Tang,5 Qing Pan,6 Qingdong Zhu,7 Song Yang,8 Zhanlin Chang,9 Zhouli Guo,1 Guihui Wu,1 Shenjie Tang2 1Department of Tuberculosis, Public Health Clinical Center of Chengdu, Chengdu, People’s Republic of China; 2Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, People’s Republic of China; 3Department of Tuberculosis, Harbin Chest Hospital, Harbin, People’s Republic of China; 4Department of Tuberculosis, Wuhan Pulmonary Hotel, Wuhan, People’s Republic of China; 5Department of Tuberculosis, the Fifth People’s Hospital of Suzhou, Suzhou, People’s Republic of China; 6Department of Respiratory and Critical Care Medicine, Anqing Municipal Hospital, Anqing, People’s Republic of China; 7Department of Tuberculosis, the Fourth People’s Hospital of Nanning, Nanning, People’s Republic of China; 8General Internal Medicine Department, Chongqing Public Health Medical Center, Chongqing, People’s Republic of China; 9Department of Surgery, the Third People’s Hospital of Tibet Autonomous Region, Lasa, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guihui Wu, Department of Tuberculosis, Public Health Clinical Center of Chengdu, Jingjusi 18 Street, Jingjiang District, Chengdu, Sichuan, People’s Republic of China, Tel +86-28-8455-0573, Email wghwgh2584@sina.com Shenjie Tang, Beijing Chest Hospital, Capital Medical University, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing, 101149, People’s Republic of China, Tel +86-13621028338, Email tangsj1106@vip.sina.comObjective: Rifampin-resistant tuberculosis (RR-TB) remains a serious global public health concern. We assessed treatment outcomes and associated influencing factors among RR-TB patients in China.Methods: This research enrolled 1339 patients who started RR-TB treatment between May 2018 and April 2020 in China retrospectively. Data were collected from the electronic medical records. Multivariable logistic regression analysis was used to identify the influencing factors related to unfavorable outcomes.Results: Of the 1339 RR-TB patients, 78.8% (1055/1339) achieved treatment success (cured or treatment completed), 5.1% (68/1339) experienced treatment failure, 1.1% (15/1339) died during treatment, 10.1% (135/1339) were lost to follow-up, and 4.9% (66/1339) were not evaluated. About 67.7% (907/1339) of patients experienced at least one adverse event (AE). The most common AE was hypohepatia (507/1339, 37.9%), followed by hyperuricemia (429/1339, 32.0%), anemia (368/1339, 27.5%), electrolyte disturbance (318/1339, 23.7%), peripheral neuritis (245/1339, 18.3%), and gastrointestinal reactions (203/1339, 15.2%). Multivariate analysis showed that age ≥ 60 years [adjusted odds ratio (aOR): 1.96, 95% confidence interval (CI): 1.39– 2.77], national minority (aOR: 2.36, 95% CI: 1.42– 3.93), smoking (aOR: 1.50, 95% CI: 1.10– 2.04), cardiopathy (aOR: 2.90, 95% CI: 1.33– 6.31), tumors (aOR: 9.84, 95% CI: 2.27– 42.67), immunocompromise (aOR: 2.17, 95% CI: 1.21– 3.91), re-treated TB (aOR: 1.46, 95% CI: 1.08– 1.97), and experienced gastrointestinal reactions (aOR: 2.27, 95% CI: 1.52– 3.40) were associated with unfavorable outcomes. Body mass index (BMI) ≥ 18.5 kg/m2, regimens containing bedaquiline and experienced adverse events (AEs) such as hypohepatia, leukopenia, peripheral neuritis, and optic neuritis were associated with favorable outcomes.Conclusion: High rates of treatment success were achieved for RR-TB patients at tertiary tuberculosis hospitals in China. Age ≥ 60 years, national minority, smoking status, comorbidities, re-treated TB, and experienced gastrointestinal reactions were independent prognostic factors for unfavorable treatment outcomes.Keywords: RR-TB, treatment outcomes, influencing factors, China

Yan Wang,1 Lihua Liang,2,&ast; Ran Li,2,&ast; Yihua Wang,3 Changfu Hao1 1Department of Child and Adolescent Health, School of Public Health, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China; 2Primary and Secondary School Health Center, Zhengzhou Education Science Planning and Evaluation Center, Zhengzhou Municipal Education Bureau, Zhengzhou, Henan, People’s Republic of China; 3Institute of Science and Technology Information, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yihua Wang, Institute of Science and Technology Information, Zhengzhou University, Science Avenue, Zhengzhou, Henan Province, 450001, People’s Republic of China, Email wangyh2015@icloud.com Changfu Hao, Department of Child and Adolescent Health, School of Public Health, Zhengzhou University, Science Avenue, Zhengzhou, Henan Province, 450001, People’s Republic of China, Email haochangfu@126.comPurpose: Chatbots, which are based on large language models, are increasingly being used in public health. However, the effectiveness of chatbot responses has been debated, and their performance in myopia prevention and control has not been fully explored. This study aimed to evaluate the effectiveness of three well-known chatbots—ChatGPT, Claude, and Bard—in responding to public health questions about myopia.Methods: Nineteen public health questions about myopia (including three topics of policy, basics and measures) were responded individually by three chatbots. After shuffling the order, each chatbot response was independently rated by 4 raters for comprehensiveness, accuracy and relevance.Results: The study’s questions have undergone reliable testing. There was a significant difference among the word count responses of all 3 chatbots. From most to least, the order was ChatGPT, Bard, and Claude. All 3 chatbots had a composite score above 4 out of 5. ChatGPT scored the highest in all aspects of the assessment. However, all chatbots exhibit shortcomings, such as giving fabricated responses.Conclusion: Chatbots have shown great potential in public health, with ChatGPT being the best. The future use of chatbots as a public health tool will require rapid development of standards for their use and monitoring, as well as continued research, evaluation and improvement of chatbots.Keywords: chatbot, large language model, public health, myopia

Haisong Hou,1,2 Liu Liang,3 Lihong Deng,4 Wanping Ye,5 Yuanzhang Wen,6 Jun Liu1 1Laboratory of Pathogenic Biology, Guangdong Medical University, Zhanjiang, People’s Republic of China; 2Department of Blood Transfusion, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 4Department of Hepatology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 5Department of Gastroenterology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 6Department of Hepatobiliary Surgery, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Jun Liu, Laboratory of Pathogenic Biology, Guangdong Medical University, Zhanjiang, People’s Republic of China, Email liujungd6@163.comBackground: The aim of this study was to describe the demographic and clinical characteristics of hepatitis B virus (HBV) associated hepatocellular carcinoma (HCC), analyse the risk factors associated with HBV-associated HCC, and to provide some references to the diagnosis and treatment of HCC.Methods: This study retrospectively enrolled 730 patients, including 390 patients with chronic hepatitis B (CHB) as controls, and 340 patients with CHB complicated with HCC as patients. Relevant information and medical records of these participants were collected, including age, sex, cigarette smoking, alcoholism, diabetes mellitus (DM), hypertension, coronary heart disease (CHD), cirrhosis, occupation, ascites, HBV-DNA load, the qualitative analysis of HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb serological markers, and levels of alanine transaminase (ALT), aspartate aminotransferase (AST), total bilirubin (TBIL), direct bilirubin (DBIL), gamma-glutamyltransferase (GGT), TNM stage, tumor size and tumor number. The T test, Chi-square test, non-parametric rank-sum test, logistic regression analyses were used to explore the influencing factors and their degree of association with HCC in patients with HBV.Results: The proportion of smoking, alcoholism, married status, DM, hypertension, and the rate of HBV-DNA with a viral load of ≥ 500 copies/mL were significantly higher in the HCC group than in the controls (all p< 0.05). Cirrhosis was more common among patients with CHB+HCC than in controls (p=0.013). The proportion of patients with HBsAg, HBeAb, and HBcAb positive was greater in CHB+HCC group than that in CHB group. Logistic regression analysis indicated that age ≥ 60 years (OR: 1.835, 95% CI: 1.020– 3.302, p=0.043), HBeAb positive (OR: 9.105, 95% CI: 4.796– 17.288, p< 0.001), antiviral treatment with entecavir (OR: 2.209, 95% CI: 1.106– 4.409, p=0.025), and GGT (OR: 1.004, 95% CI: 1.001– 1.007, p=0.002) were risk factors for HCC in patients with CHB.Conclusion: Advanced age, HBeAb positive, antiviral treatment with entecavir, and GGT were independent risk factors for HCC in HBV patients.Keywords: chronic hepatitis B, hepatocellular carcinoma, cirrhosis, hepatitis B virus

Yanzhi Feng,1– 4,&ast; Litao Liang,1– 4,&ast; Wenbo Jia,1– 4 Jinyi Wang,1– 4 Chao Xu,1– 4 Deming Zhu,1– 4 Bin Xu,1– 4 Wenhu Zhao,1– 4 Xiangyu Ling,1– 4 Yongping Zhou,5 Lianbao Kong,1– 4,&ast; Wenzhou Ding1– 4,&ast; 1Hepatobiliary Center, the First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 2Key Laboratory of Liver Transplantation, Chinese Academy of Medical Sciences, National Health Commission Key Laboratory of Living Donor Liver Transplantation (Nanjing Medical University), Nanjing, Jiangsu, People’s Republic of China; 3Jiangsu Provincial Medical Innovation Center, Nanjing, Jiangsu, People’s Republic of China; 4Jiangsu Provincial Medical Key Laboratory, Nanjing, Jiangsu, People’s Republic of China; 5Jiangnan University Medical Center, JUMC, Department of Hepatobiliary, Wuxi, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wenzhou Ding; Lianbao Kong, Hepatobiliary Centre, The First Affiliated Hospital of Nanjing Medical University, 300 Guangzhou Road, Nanjing, 210029, People’s Republic of China, Email dingwenzhou@njmu.edu.cn; lbkong@njmu.edu.cnBackground: Circular RNAs (circRNAs) have been shown to play a crucial role in the initiation and development of Hepatocellular carcinoma (HCC). However, the mechanism and function of circ_0007386 in HCC are still unknown.Methods: Circ_0007386 expression level in HCC tissues, and HCC cell lines was further analyzed by qRT-PCR. Agarose gel electrophoresis and Sanger sequencing were used to figure out the structure of circ_0007386. The involvement of circ_0007386 in HCC development was evaluated by experimental investigations conducted in both laboratory settings (in vitro) and living organisms (in vivo). RNA immunoprecipitation, Western blotting, luciferase reporter assay and fluorescence in situ hybridization (FISH) were applied for finding out the interaction among circ_0007386, miR-507 and CCNT2. To assess the connection between circ_0007386 and lenvatinib resistance, lenvatinib-resistant HCC cell lines were employed.Results: The expression of circ_0007386 was found to increase in HCC tissues, and it was observed to be associated with a worse prognosis. Overexpression of circ_0007386 stimulated HCC cells proliferation, invasion, migration and the epithelial–mesenchymal transition (EMT) while silencing of circ_0007386 resulted in the opposite effect. Mechanistic investigations revealed that circ_0007386 acted as a competing endogenous RNA of miR-507 to prevent CCNT2 downregulation. Downregulating miR-507 or overexpressing CCNT2 could reverse phenotypic alterations that originated from inhibiting of circ_0007386. Importantly, circ_0007386 determines the resistance of hepatoma cells to lenvatinib treatment.Conclusion: Circ_0007386 advanced HCC progression and lenvatinib resistance through the miR-507/ CCNT2 axis. Meanwhile, circ_0007386 served as a potential biomarker and therapeutic target in HCC patients. Keywords: hepatocellular carcinoma, circ_0007386, miR-507, CCNT2, Lenvatinib

Jingzhan Huang,1,&ast; Jialong Liu,1,&ast; Jin Lan,1,&ast; Jingbo Sun,1 Kun Zhou,1 Yunyao Deng,1 Li Liang,2 Lixin Liu,1,&ast; Xiaolong Liu1 1Department of General Surgery, The Third Affiliated Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China; 2Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lixin Liu; Xiaolong Liu, Department of General Surgery, The Third Affiliated Hospital, Southern Medical University, 183 West Zhongshan Avenue, Guangzhou, Guangdong, 510630, People’s Republic of China, Email llx0129@i.smu.edu.cn; lxl1979@i.smu.edu.cnBackground: Guanine-rich RNA sequence binding factor 1 (GRSF1), part of the RNA-binding protein family, is now attracting interest due to its potential association with the progression of a variety of human cancers. The precise contribution and molecular mechanism of GRSF1 to colorectal cancer (CRC) progression, however, have yet to be clarified.Methods: Immunohistochemistry and Western Blot analysis was carried out to detect the expression of GRSF1 in CRC at both mRNA and protein levels and its subsequent effects on prognosis. A series of functional tests were performed to understand its influence on proliferation, migration, and invasion of CRC cells.Results: The universal downregulation of GRSF1 in CRC was identified, indicating a correlation with poor prognosis. Our functional studies unveiled that the elimination of GRSF1 enhances tumour activities such as proliferation, migration, and invasion of CRC cells, while GRSF1 overexpression curtailed these abilities.Conclusion: Notably, we uncovered that GRSF1 insufficiency modulates the PI3K/Akt signaling pathway and Ras activation in CRC. Therefore, our data suggest GRSF1 operates as a tumor suppressor gene in CRC and may offer promise as a potential biomarker and novel therapeutic target in CRC management. Keywords: GRSF1, CRC, proliferation, metastasis, Ras/PI3K/Akt

Hui Rao,1 Xianfang Wang,2 Yu Luo,3 Liu Liang,1 Wei Ye,1 Xuemin Guo1 1Department of Laboratory Medicine, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 2Center for Cardiovascular Diseases, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of China; 3Department of Gynaecology, Meizhou People’s Hospital, Meizhou Academy of Medical Sciences, Meizhou, People’s Republic of ChinaCorrespondence: Xuemin Guo, Department of Laboratory Medicine, Meizhou People’s Hospital, No. 63 Huangtang Road, Meijiang District, Meizhou, People’s Republic of China, Email Guoxm12@126.comBackground: The role of aldehyde dehydrogenase 2 (ALDH2) in cardiovascular diseases has been gradually studied. However, it is unclear whether ALDH2 polymorphism is associated with the risk of early onset (onset age ≤ 55 years old in men and ≤ 65 years old in women) coronary artery stenosis (CAS). The association between ALDH2 single nucleotide polymorphism (SNP) rs671 and risk in patients with early onset CAS was investigated in this study.Methods: The study included 213 early onset CAS patients and 352 individuals without CAS were set as controls. The ALDH2 rs671 polymorphism was genotyped by polymerase chain reaction (PCR) - microarray. Differences in ALDH2 rs671 genotypes and alleles between patients and controls were compared. Multiple logistic regression analysis was performed after adjusting for gender, body mass index (BMI), smoking history, drinking history, and diabetes mellitus to assess the relationship between ALDH2 rs671 genotypes and early onset CAS risk.Results: The frequency of the ALDH2 rs671 G/G genotype was lower in the early onset CAS patients (43.7% vs 55.3%, p=0.007) than that in the controls. The frequency of the ALDH2 rs671 A allele was higher (32.9% vs 25.0%) than that in the controls (p=0.005). After adjusting for other confounding factors, multivariate logistic regression showed that ALDH2 rs671 A/A genotype (A/A vs G/G: odds ratio (OR) 2.508, 95% confidence interval (CI): 1.130– 5.569, p=0.024), overweight (BMI≥ 24.0 vs 18.5– 23.9: OR 5.047, 95% CI: 3.275– 7.777, p< 0.001), history of smoking (yes vs no: OR 2.813, 95% CI: 1.595– 4.961, p< 0.001), and diabetes mellitus (yes vs no: OR 2.191, 95% CI: 1.397– 3.437, p=0.001) were the independent risk factors of early onset CAS.Conclusion: In men ≤ 55 years old and women ≤ 65 years old, individuals with ALDH2 rs671 A/A genotype, overweight (BMI ≥ 24.0 kg/m2), smoking history, and diabetes mellitus increased risk of developing CAS.Keywords: aldehyde dehydrogenase 2, gene polymorphism, coronary artery stenosis, early onset

Mu-Gen Dai,1,2 Si-Yu Liu,2 Lin Zhu,3 Wen-Feng Lu,4 Gui-Lin Xie,5 Lei Liang,6 Jun-Wei Liu,6 Bin Ye1 1Department of Gastroenterology, The Fifth Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 2Department of Laboratory Medicine, The Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Zhejiang University Lishui Hospital, Lishui, Zhejiang, People’s Republic of China; 3Department of Gastroenterology, Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 4Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, People’s Republic of China; 5Department of Hepatobiliary Surgery, Affiliated Hospital of Shaoxing University, Shaoxing, Zhejiang Province, 312000, People’s Republic of China; 6General Surgery, Cancer Center, Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of ChinaCorrespondence: Jun-Wei Liu, General Surgery, Cancer Center, Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China, Email liujunwei@hmc.edu.cn Bin Ye, Department of Gastroenterology, The Fifth Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China, Email 408252097@qq.comBackground & Aims: To examine the association of the history of preoperative antiviral therapy (AVT) with the tumor recurrence and overall survival in HBV-related HCC patients undergoing curative-intent hepatectomy.Methods: Patients who underwent curative-intent hepatectomy for HBV-related HCC between 2014 and 2019 at 4 Chinese hospitals were analyzed. Patients were categorized as having undergone preoperative antiviral therapy (AVT) > 1 year or without antiviral therapy (non-AVT). Patient clinical features, short-term outcomes, overall survival (OS), and time-to-recurrence (TTR) were also compared. Multivariate Cox regression analysis was performed to identify the impact of preoperative AVT on the OS and TTR.Results: Among the 565 patients, 190 (33.6%) underwent continuous AVT > 1 year before surgery. Patients in the non-AVT group were more likely to have worse liver function and more advanced tumor pathological characteristics than those in the AVT group. Postoperative morbidity and mortality rates were comparable between the two groups. Multivariate analyses revealed that a preoperative HBV viral level ≥ 2000 IU/mL was independently associated with poorer TTR (hazard ratio, 1.328; 95% CI, 1.049– 1.682) and preoperative AVT was a protective factor for OS (hazard ratio, 0.691; 95% CI, 0.484– 0.986).Conclusion: A high preoperative HBV DNA level was an independent risk factor for tumor recurrence. Preoperative AVT > 1 year was associated with better OS and a reduced incidence of tumor recurrence by inhibiting the preoperative level of HBV DNA. Keywords: hepatectomy, hepatitis B virus, antiviral therapy, survival, recurrence

The liquefaction of crop residues in the presence of ethylene glycol, ethylene carbonate, or polyethylene glycol using sulfuric acid as a catalyst was studied. For all experiments, the liquefaction was conducted at 160C and atmospheric pressure. The mass ratio of feedstock to liquefaction solvents used in all the experiments was 30:100. The results show that the acid catalyzed liquefaction process fit a pseudo-first-order kinetics model. Liquefaction yields of 80, 74, and 60% were obtained in 60 minutes of reaction when corn stover was liquefied with ethylene glycol, a mixture of polyethylene glycol and glycerol (9:1, w/w), and ethylene carbonate, respectively. When ethylene carbonate was used as solvent, the liquefaction yields of rice straw and wheat straw were 67% and 73%, respectively, which is lower than that of corn stover (80%). When a mixture of ethylene carbonate and ethylene glycol (8:2, w/w) was used as solvent, the liquefaction yields for corn stover, rice straw and wheat straw were 78, 68, and 70%, respectively.

Shitong Su,1,2 Lianjing Liang,1 Lin Lü,1 Mingfeng Li,3 Xiaoling Zhang,4 Yongmei Jin,5 Wei Wei,1 Zhi Wan6 1Department of Emergency Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Division of Head & Neck Tumor Multimodality Treatment, Cancer Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 3Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 4Department of Cardiology, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 5Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 6Rare Diseases Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Wei Wei, Chest Pain center, Department of Emergency Medicine, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Wuhou District, Chengdu, 610041, People’s Republic of China, Email ww8075@126.com Zhi Wan, Rare Diseases Center, West China Hospital, Sichuan University, No. 37, Guoxue Lane, Wuhou District, Chengdu, 610041, People’s Republic of China, Email 456wz@163.comAbstract: Loeffler endocarditis, eosinophilic endocarditis or eosinophilic endomyocardial disease are conditions associated with hypereosinophilia and they affect the heart function. Loeffler endocarditis is a rare endomyocardial disorder thought to be caused by eosinophilic damage. The disorder is characterized by inflammatory infiltration, formation of thrombus within cardiovascular system, and ultimately fibrosis of the afflicted area. It can lead to multiple severe complications, including thromboembolic disease, thickening of fibrous tissue in the endocardium of ventricles, valve involvement, apical obliteration, and various heart disorders. Although early clinical intervention can lead to remission, the underlying mechanisms of the disorder remain unresolved. In the present article, we summarise the existing literature concerning Loeffler endocarditis based on PubMed, Web of Science, and other medical databases to conduct an in-depth review of the epidemiology, etiology, pathophysiological mechanisms, staging, diagnosis, treatment and prognosis of Loeffler endocarditis. Meanwhile, we provide novel patients data and clinical figures of Loeffler endocarditis to supplement the understanding of this cardiac disorder. The findings presented in this article provide a basis for further studies and can be used to improve management of the disorder.Keywords: Loeffler endocarditis, hypereosinophilia, eosinophils damage

Lina Yu,1,&ast; Zidan Xu,1,&ast; Guanxiong Zhu,1,&ast; Liting Zeng,1 Zeyu Zhang,1 Yang Yu,2 Siran Wang,1 Xin Zhang,3 Na Zhou,3 Lu Liang1,4 1Department of Preventive Dentistry, School and Hospital of Stomatology, Guangdong Engineering Research Center of Oral Restoration and Reconstruction & Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Department of Sports and Health, Guangzhou Sport University, Guangzhou, People’s Republic of China; 3State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wailong, Taipa, Macau, People’s Republic of China; 4Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lina Yu; Lu Liang, Email yulina@gzhmu.edu.cn; lliangaa@gzhmu.edu.cnBackground: The photodynamic therapy (PDT) showed promising potential in treating tongue squamous cell carcinoma (TSCC). The Food and Drug Administration approved Verteporfin (Ver) is a powerful alternative in this field for its penetrating power and high production of reactive oxygen species (ROS). However, its applications in the treatment of TSCC are still rare.Methods: Ver was loaded onto Poly (lactic-co-glycolic acid) (PLGA) nanoparticles, followed by the modification with RGD peptide as the ligand. The nanostructured was named as RPV. In vitro assessments were conducted to evaluate the cytotoxicity of RPV through the Live/Dead assay analysis and Cell Counting Kit-8 (CCK-8) assay. Using the reactive oxygen species assay kit, the potential for inducing targeted tumor cell death upon laser irradiation by promoting ROS production was investigated. In vivo experiments involved with the biological distribution of RPV, the administration with RPV followed by laser irradiation, and the measurement of the tumor volumes. Immunohistochemical analysis was used to detect the Ki-67 expression, and apoptosis induced by RPV-treated group. Systemic toxicity was evaluated through hematoxylin-eosin staining and blood routine analysis. Real-time monitoring was employed to track RPV accumulation at tumor sites.Results: The in vitro assessments demonstrated the low cytotoxicity of RPV and indicated its potential for targeted killing TSCC cells under laser irradiation. In vivo experiments revealed significant tumor growth inhibition with RPV treatment and laser irradiation. Immunohistochemical analysis showed a notable decrease in Ki-67 expression, suggesting the effective suppression of cell proliferation, and TUNEL assay indicated the increased apoptosis in the RPV-treated group. Pathological examination and blood routine analysis revealed no significant systemic toxicity. Real-time monitoring exhibited selective accumulation of RPV at tumor sites.Conclusion: The findings collectively suggest that RPV holds promise as a safe and effective therapeutic strategy for TSCC, offering a combination of targeted drug delivery with photodynamic therapy.Keywords: photodynamic therapy, verteporfin, RGD sequence, tumor-specific drug delivery

Lin Feng,1 Jiachen Li,1 Zhenbei Qian,2 Chenglong Li,3,4 Darui Gao,3,4 Yongqian Wang,3,4 Wuxiang Xie,3,4 Yutong Cai,5 Zhaohui Tong,2 Lirong Liang1 1Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Heart and Vascular Health Research Center, Peking University Clinical Research Institute, Peking University First Hospital, Beijing, People’s Republic of China; 4Key Laboratory of Epidemiology of Major Diseases (Peking University), Ministry of Education, Beijing, People’s Republic of China; 5Centre for Environmental Health and Sustainability, Department of Health Sciences, University of Leicester, Leicester, UKCorrespondence: Lirong Liang, Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China, Email llrcruie@163.comPurpose: Patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD) exhibit heterogeneous responses to corticosteroid treatment. We aimed to determine whether combining eosinophil levels with other routine clinical indicators can enhance the predictability of corticosteroid treatment outcomes and to come up with a scoring system.Patients and Methods: Consecutive patients admitted with AECOPD receiving corticosteroid treatment between July 2013 and March 2022 at Beijing Chao-Yang Hospital were retrospectively analyzed. Data on patients’ demographics, smoking status, hospitalization for AECOPD in the previous year, comorbidities, blood laboratory tests, in-hospital treatment and clinical outcomes were collected. Least absolute shrinkage and selection operator (LASSO) regression and backward logistic regression were used for predictor selection, and predictive nomograms were developed. The discrimination and calibration of the nomograms were assessed using the area under the receiver operating curve (AUC) and calibration plots. Internal validation was performed using the 500-bootstrap method, and clinical utility was evaluated using decision curve analysis (DCA).Results: Among the 3254 patients included, 804 (24.7%) had treatment failure. A nomogram of eosinophils, platelets, C-reactive protein (CRP), low density lipoprotein cholesterol, prognostic nutritional index (PNI), hospitalization for AECOPD in the previous year, ischemic heart diseases and chronic hepatic disease was developed to predict treatment failure for patients with a smoking history. For patients without a smoking history, a nomogram of CRP, PNI, ischemic heart diseases and chronic hepatic disease was developed. Although the AUCs of these two nomograms were only 0.644 and 0.647 respectively, they were significantly superior to predictions based solely on blood eosinophil levels.Conclusion: We developed easy-to-use comprehensive nomograms utilizing readily available clinical biomarkers related to inflammation, nutrition and immunity, offering modestly enhanced predictive value for treatment outcomes in corticosteroid-treated patients with AECOPD. Further investigations into novel biomarkers and additional patient data are imperative to optimize the predictive performance.Keywords: chronic obstructive pulmonary disease, glucocorticoids, prediction model, least absolute shrinkage and selection operator

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

Lina Yu,1,&ast; Guanxiong Zhu,1,&ast; Zeyu Zhang,1,&ast; Zidan Xu,1 Weijie Peng,1,2 Liting Zeng,1 Yang Yu,3 Siran Wang,1 Zhongxiao Lin,1,2,4 Xin Zhang,4 Na Zhou,4 Lingmin Zhang,1,2 Lu Liang1,2 1Department of Preventive Dentistry, Affiliated Stomatology Hospital of Guangzhou Medical University, Guangdong Engineering Research Center of Oral Restoration and Reconstruction, Guangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative Medicine, Guangzhou, 510182, People’s Republic of China; 2Guangzhou Municipal and Guangdong Provincial Key Laboratory of Molecular Target & Clinical Pharmacology, the State & NMPA Key Laboratory of Respiratory Disease, School of Pharmaceutical Sciences & the Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China; 3Department of Sports and Health, Guangzhou Sport University, Guangzhou, People’s Republic of China; 4State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wailong, Taipa, Macau, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lingmin Zhang; Lu Liang, Email zhanglm@gzhmu.edu.cn; lliangaa@gzhmu.edu.cnBackground: Photodynamic therapy (PDT) has emerged as a promising strategy for oral cancer treatment. Verteporfin is a powerful photosensitizer and widely used in the treatment of macular degeneration. However, rare work has reported its potential in the treatment of oral cancer.Methods: In this study, we introduce an innovative approach of nano-photosensitizer based on Verteporfin, which was prepared by utilizing macrophage membrane to coat Verteporfin-loaded zeolitic imidazolate framework 8 (ZIF-8) for effective photodynamic therapy against oral cancer. Nanoparticle characteristics were assessed including size, zeta potential, and PDI. Cellular uptake studies were conducted using CAL-27 cells. Furthermore, inhibitory effects in both in vitro and in vivo settings were observed, ensuring biosafety. Assessment of anticancer efficacy involved tumor volume measurement, histological analyses, and immunohistochemical staining.Results: In vitro experiments indicated that the nano-photosensitizer showed efficient cellular uptake in the oral cancer cells. Upon the laser irradiation, the nano-photosensitizer induced the generation of reactive oxygen species (ROS), leading to cancer cell apoptosis. The in vivo experiments indicated that the coating with cell membranes enhanced the circulation time of nano-photosensitizer. Moreover, the specificity of the nano-photosensitizer to the cancer cells was also improved by the cell membrane-camouflaged structure in the tumor-bearing mouse model, which inhibited the tumor growth significantly by the photodynamic effect in the presence of laser irradiation.Conclusion: Overall, our findings demonstrate the potential of macrophage membrane-coated ZIF-8-based nanoparticles loaded with Verteporfin for effective photodynamic therapy in oral cancer treatment. This nano-system holds promise for synergistic cancer therapy by combining the cytotoxic effects of PDT with the activation of the immune system, providing a novel therapeutic strategy for combating cancer.Keywords: photodynamic therapy, verteporfin, oral cancer, macrophages, zeolitic imidazolate framework 8

Yuyi Chen,1 Xuemei Zhao,1 Lin Liang,1 Pengchao Tian,1 Jiayu Feng,1 Liyan Huang,1 Boping Huang,1 Yihang Wu,1 Jing Wang,1 Jingyuan Guan,1 Xinqing Li,1 Jian Zhang,1,2 Yuhui Zhang1 1Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China; 2Key Laboratory of Clinical Research for Cardiovascular Medications, National Health Committee, Beijing, People’s Republic of ChinaCorrespondence: Yuhui Zhang, Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China, Tel +8615901314243, Email yuhuizhangjoy@163.com Jian Zhang, Heart Failure Center, State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, People’s Republic of China, Tel +8613911102015, Email fwzhangjian62@126.comObjective: To identify biomarkers with independent prognostic value and investigate the prognostic value of multiple biomarkers in combination in patients hospitalized with heart failure.Methods: A total of 884 consecutive patients hospitalized with heart failure from 2015 to 2017 were enrolled. Twelve biomarkers were measured on admission, and the relationships between biomarkers and outcomes were assessed.Results: During the median follow-up of 913 days, 291 patients (32.9%) suffered from primary endpoint events. Soluble suppression of tumorigenicity-2 (sST2) (per log [unit] increase, adjusted HR [95% CI]: 1.39 [1.13,1.72], P = 0.002) and big endothelin-1 (big ET-1) (per log [unit] increase, adjusted HR [95% CI]: 1.56 [1.23,1.97], P < 0.001) remained independent predictors of primary endpoint event after adjusting for other predictors including N-terminal pro-B-type natriuretic peptide (NT-proBNP) and high-sensitivity cardiac troponin T (hs-cTnT). Both sST2 (C-statistic: 0.810 vs 0.801, P = 0.005, and 0.832 vs 0.826, P = 0.024, respectively) and big ET-1 (C-statistic: 0.829 vs 0.801, P = 0.001, and 0.843 vs 0.826, P < 0.001, respectively) significantly improved the predictive value for primary endpoint event at 1 year and 3 years. However, only big ET-1 (C-statistic: 0.852 vs 0.846, P = 0.014) significantly improved the predictive value at 3 months when added to clinical predictors and known biomarkers. According to the number of elevated biomarkers (including NT-proBNP, hs-cTnT, sST2, and big ET-1), patients with three or more elevated biomarkers had a higher risk of primary endpoint event compared to those with two elevated biomarkers (P = 0.001), as well as in patients with two elevated biomarkers compared to those with one elevated biomarker (P = 0.004). However, the risk of primary endpoint event was comparable between patients with one elevated biomarker and those with no elevated biomarker (P = 0.582).Conclusion: Multiple biomarkers in combination could provide a better prognostic value than a single biomarker. sST2 and big ET-1 could act as alternatives of multi-biomarkers strategies for prognosis evaluation beyond NT-proBNP and hs-cTnT in patients hospitalized with heart failure.Keywords: heart failure, prognostic value, multiple biomarkers, sST2, big ET-1

Ya-Ming Xie,1 Wenfeng Lu,2 Jian Cheng,1 Mugen Dai,3 Si-Yu Liu,4 Dong-Dong Wang,1 Tian-Wei Fu,1 Tai-Wei Ye,1 Jun-Wei Liu,1 Cheng-Wu Zhang,1 Dong-Sheng Huang,1 Lei Liang1 1Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, General Surgery, Cancer Center, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou, Zhejiang, People’s Republic of China; 2Department of Hepatobiliary Surgery, Eastern Hepatobiliary Surgery Hospital, Second Military Medical University (Navy Medical University), Shanghai, People’s Republic of China; 3Department of Gastroenterology, The Fifth Affiliated Hospital of Wenzhou Medical University, Wenzhou, Zhejiang Province, People’s Republic of China; 4Department of Laboratory Medicine, The Key Laboratory of Imaging Diagnosis and Minimally Invasive Interventional Research of Zhejiang Province, Zhejiang University Lishui Hospital, Lishui, Zhejiang, People’s Republic of ChinaCorrespondence: Lei Liang; Dong-Sheng Huang, Department of Hepatobiliary & Pancreatic Surgery and Minimally Invasive Surgery, General Surgery, Cancer Center, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang, 310014, People’s Republic of China, Email liangl1992@hotmail.com; huangdshz88@hotmail.comBackground: Nutritional and inflammatory status has been reported to be associated with the prognosis of hepatocellular carcinoma (HCC), but many studies did not include all biomarkers simultaneously. The present study aimed to determine the impact of Naples prognostic score (NPS) on the long-term survival in patients undergoing hepatectomy for HCC.Methods: Patients with HCC after curative resection were eligible. Then, all patients were stratified into three groups according to the NPS. Clinical features and survival outcomes were compared among the three groups. Independent prognostic factors were determined by COX analysis. The time dependent receiver operating characteristic (ROC) curves were used to compare prognostic performance with other immunonutrition scoring systems.Results: A total of 476 patients were enrolled eventually. Baseline characteristics showed that patients with higher NPS had a higher proportion of poor liver function and advanced tumor features. Accordingly, Kaplan-Meier survival curves showed that patients with higher NPS had a lower rate of overall survival (OS) and recurrence-free survival (RFS). Multivariable COX analysis demonstrated that NPS was an independent risk factor of OS (NPS group 2 vs 1: HR=1.958, 95% CI: 1.038– 3.369, p = 0.038; NPS group 3 vs 1: HR=2.608, 95% CI: 1.358– 5.008, p=0.004, respectively) and RFS (NPS group 2 vs 1: HR=2.014, 95% CI: 1.299-2-3.124, p=0.002; NPS group 3 vs 1: HR=2.002, 95% CI: 1.262– 3.175, p=0.003, respectively). The time-dependent ROC curve showed that NPS was superior to other models in prognostic performance and discriminatory power for long-term survival (median AUC 0.675, 95% CI: 0.586– 0.712, P < 0.05).Conclusion: The NPS is a simple tool strongly associated with long-term survival in patients undergoing curative hepatectomy for HCC.Keywords: hepatocellular carcinoma, Naples prognostic score, nutritional indicator, inflammatory indicator, prognostic performance

Zhixin Liu,1,2,&ast; Huanyu Zhang,1 Nan Wang,1,&ast; Yajie Feng,1,&ast; Junping Liu,1 Lin Wu,1 Zhaoyue Liu,1 Xinru Liu,1 Libo Liang,1 Jie Liu,3 Qunhong Wu,1 Chaojie Liu4 1Department of Social Medicine, School of Health Management, Harbin Medical University, Harbin, People’s Republic of China; 2Department of Health Policy and Management, School of Public Health, Peking University, Beijing, People’s Republic of China; 3Intensive Care Unit, The 2nd Affiliated Hospital of Harbin Medical University, Harbin, People’s Republic of China; 4Department of Public Health, School of Psychology and Public Health, La Trobe University, Melbourne, VIC, Australia&ast;These authors contributed equally to this workCorrespondence: Libo Liang; Jie Liu, Email llbhit@163.com; liujie21814@126.comBackground: This study aimed to test the mediating role of anxiety and insomnia in the association between fear of infection and fatigue.Methods: A cross-sectional questionnaire survey was conducted on the nurses deployed to Heihe. A serial multiple mediation model was established to determine the role of anxiety and insomnia in the association between fear of infection and fatigue.Findings: Over half (53.0%) of the study participants reported experiencing fear of infection despite stringent personal protection measures. The scores of anxiety (11.87± 5.19), insomnia (16.33± 5.95), and fatigue (45.94± 12.93) were moderately correlated, with a Pearson correlation coefficient ranging from 0.501 to 0.579. Anxiety, either alone or in combination with insomnia, mediated the association between fear of infection and fatigue.Conclusion: The findings suggest that anxiety and insomnia play a mediating role in the relationship between fear of infection and fatigue. These results emphasize the importance of implementing targeted mental health interventions and work arrangements to address the well-being of healthcare professionals.Keywords: fear of infection, anxiety, insomnia, fatigue, COVID-19

Shuai Shao,1,&ast; Zhijin Zhang,1,&ast; Lin Feng,2 Lirong Liang,2 Zhaohui Tong1 1Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China; 2Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhaohui Tong, Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, NO. 8, Gong Ti South Road, Chao-Yang District, Beijing, 100020, People’s Republic of China, Email tongzhaohuicy@sina.comPurpose: To discover potential inflammatory biomarkers, which can compare favorably with traditional biomarkers, and their best cut-offs at first admission to predict clinical outcomes (short-term and long-term) and the risk of readmission among acute exacerbations of chronic obstructive pulmonary disease (AECOPD) patients.Patients and Methods: Novel inflammatory biomarkers (such as the neutrophil–lymphocyte ratio [NLR], platelet–lymphocyte ratio [PLR], etc.) were compared with traditional biomarkers by Pearson’s correlation test. Logistic regression analysis and receiver operating characteristic (ROC) curves were applied to judge the accuracy of these novel biomarkers to predict in-hospital mortality.Results: Surviving AECOPD patients had lower NLR, PLR, and lymphocyte-to-monocyte ratios than non-survival patients (all P < 0.001). According to Pearson’s correlation test, there was a linear correlation between novel and traditional biomarkers (all P < 0.05). In terms of a single biomarker, the AUC value of NLR was the largest, which was not inferior to C-reactive protein (Z-P = 0.064), and superior to erythrocyte sedimentation rate (Z-P = 0.002) and other novel single inflammatory biomarkers (all Z-P < 0.05). The mortality of patients with NLR ≥ 4.43 was 2.308-fold higher than that of patients with NLR < 4.43. After dividing patients into a higher or lower NLR group, pooled results showed that patients with NLR ≥ 4.43 had a higher rate of treatment failure, intensive care unit admission, longer hospital length of stay, one-year mortality after the index hospitalization, and overall mortality than patients with NLR < 4.43 (all P < 0.001). Patients with NLR ≥ 4.43 were associated with higher and earlier first readmission due to AECOPD than patients with lower NLR.Conclusion: NLR was the best to forecast the clinical prognosis and readmission risk among AECOPD patients, which was not inferior to CRP, and the best cut-off value of NLR was 4.43.Keywords: acute exacerbations of chronic obstructive pulmonary disease, neutrophil–lymphocyte ratio, mortality, inflammatory biomarkers, readmission rate, treatment failure rate

Jiachen Li,1 Lirong Liang,1 Lin Feng,1 Siyu Cao,2 Yutong Samuel Cai,3 Xiaobo Li,4 Zhenbei Qian,2 Christopher E Brightling,5 Zhaohui Tong2 1Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Centre for Environmental Health and Sustainability, Department of Population Health Sciences, University of Leicester, Leicester, UK; 4Beijing Key Laboratory of Environmental Toxicology, School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 5Institute for Lung Health, NIHR Leicester Biomedical Research Centre, University of Leicester, Leicester, UKCorrespondence: Lirong Liang, Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, No. 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86 010-85231547, Email llrcruie@163.comPurpose: Blood eosinophil is a promising biomarker for phenotyping patients with acute exacerbation of COPD (AECOPD). We aimed to evaluate the prognostic value of eosinophil on short- and long-term outcomes stratified by corticosteroid treatment among AECOPD inpatients.Patients and Methods: In this retrospective cohort study, we included patients hospitalized for AECOPD from July 2013 to June 2021 in Beijing, China. Clinical data were collected from electronic medical records. The blood eosinophil count was measured within 24h after admission. Eosinophilic AECOPD was defined as having an eosinophil percentage ≥ 2%. The study outcomes were length of stay (LOS), treatment failure, and AECOPD readmission risk within 3 years of discharge. Multivariable models were used to analyze the associations between blood eosinophil count and outcomes stratified by corticosteroid treatment during hospitalization.Results: A total of 2406 AECOPD patients were included. The median LOS of AECOPD patients was 10 (interquartile range: 8– 14) days. The eosinophil percentage was negatively associated with LOS (P-trend=0.014). Compared with the non-eosinophilic AECOPD group, the eosinophilic group had a 58% lower risk of treatment failure (OR=0.42, 95% CI: 0.20– 0.89) in patients treated with systemic corticosteroids, but no association was observed in those treated with inhaled corticosteroids (ICS) only (OR=0.95, 95% CI: 0.60– 1.52). The eosinophilic group had an increased risk of 90-day re-admission in patients treated with ICS only (HR=1.51, 95% CI: 1.00– 2.29), but not in patients treated with systemic corticosteroids during hospitalization (HR=0.67, 95% CI: 0.39– 1.15). No statistically significant results were found for 180-day, 1-year, or 3-year readmission risk.Conclusion: Elevated blood eosinophils in AECOPD were associated with shorter length of stay and improved response to treatment with systemic corticosteroids, but not inhaled corticosteroids. Our study suggested that a therapeutic approach of using systemic corticosteroid may benefit patients present with eosinophilic AECOPD.Keywords: chronic obstructive pulmonary disease, eosinophilic inflammation, glucocorticoids, interaction

Chunhui Shu,1,&ast; Jiaqiang Zhou,2,&ast; Hongqiong Yu,1 Weijing Fu,1 Jiayi Shen,1 Linchun Liang,3 Lisi Zheng,4 Lin Mao,5 Xuyan Fu,4 Tao Lv,4,6 Yunbo Chen4 1Department of Laboratory Medicine, Ningbo Mingzhou Hospital, Ningbo, People’s Republic of China; 2Department of Neurosurgery, Ningbo Mingzhou Hospital, Ningbo, People’s Republic of China; 3Department of Oncology, Ningbo Mingzhou Hospital, Ningbo, People’s Republic of China; 4State 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, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 5Department of Rehabilitation Medicine, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China; 6Jinan Microecological Biomedicine Shandong Laboratory, Jinan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Tao Lv; Yunbo Chen, State 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, First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, People’s Republic of China, Tel/Fax +86 571-87236756, Email xifan_lvtao@163.com; chenyunbo@aliyun.comBackground: Clostridioides difficile is an important pathogen causing approximately 20– 30% of the cases-with antibiotic-associated diarrhea and 90% of those with Pseudomembranous enteritis. However, limited surveillance of C. difficile infections (CDI) in China is done at present, especially in terms of multi-hospital epidemiological reports.Methods: Between June 2020 and November 2020, we conducted a prospective study addressing antimicrobial susceptibility profiles and genomic epidemiology of C. difficile strains isolated from inpatients with diarrhea in seven tertiary hospitals in the same city.Results: In total, 177 strains of toxin-producing C. difficile were isolated, and the dominant toxin gene profiles were tcdA+tcdB+ (84.2%, 149/177) and tcdA-tcdB+ (15.8%, 28/177). Furthermore, 130 isolates were successfully analyzed for antimicrobial susceptibility phenotype in which the rates of resistance to clindamycin, erythromycin, levofloxacin, and moxifloxacin were higher than to other antibiotics. All strains were susceptible to metronidazole and vancomycin. Fluoroquinolone-associated mutations (such as gyrA) were the most frequently found ones in the analyzed genomes. Moreover, 24 different sequence types (STs) were identified in the 130 isolates, and the most prevalent types were ST3 (26.2%, 34/130) followed by ST54 (16.9%, 22/130) and ST2 (10%, 13/130). The so-called highly virulent strain ribotyping 027 (B1/NAP1/ST1) was not identified. In addition, we also compared single nucleotide polymorphisms (SNPs) among the isolates and carried out genomic epidemiological studies on the isolates. We found that ST3 and ST54 could cause transmission in both intra- and inter-hospital settings.Conclusion: Although it is the so-called hypervirulent epidemic strain, ribotyping 027 (ST1), was not detected. ST3 and ST54 can be transmitted through different hospitals. Therefore, it is necessary to conduct further molecular epidemiological monitoring of C. difficile and screening of patients admitted to key departments.Keywords: Clostridioides difficile infection, genomic analysis, toxin gene, antibiotic resistance, transmission

Yuan Huang,1 Lu Liang,2 Yong-Xiang Zhao,3 Bi-Hui Yao,2 Rui-Min Zhang,3 Lei Song,2 Zhong-Tao Zhang1 1Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing, 100050, People’s Republic of China; 2Department of General Surgery, Baotou Central Hospital, Baotou, 014000, People’s Republic of Chin; 3Department of Pediatrics and Urology Surgery, Baotou No.4 Hospital, Baotou, 014000, People’s Republic of ChinaCorrespondence: Zhong-Tao Zhang, Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, No. 95 Yongan Road, Xicheng District, Beijing, 100050, People’s Republic of China, Tel +8613801060364, Email zhangzht@ccmu.edu.cnObjective: Gastric cancer is one of the most common malignancies worldwide; however, its overall mortality has not improved significantly over the last decade. Chemoresistance plays a critical role in this issue. This study aimed to clarify the role and mechanism of runt-related transcription factor 2 (RUNX2) in platinum-based chemotherapy resistance.Methods: First, a drug-resistant model of gastric cancer cells was established to evaluate the relative expression level of the RUNX2 as a potential biomarker of chemotherapy resistance. Next, exogenous silencing was conducted to study whether RUNX2 could reverse drug resistance and understand the underlying mechanisms. Simultaneously, the correlation between the clinical outcomes of 40 patients after chemotherapy and the RUNX2 expression levels in tumor samples was analyzed.Results: We discovered that RUNX2 was significantly expressed in drug-resistant gastric cancer cells and tissues; it was also reversibly resistant to transformation treatment by exogenous RUNX2 silencing. It is confirmed that RUNX2 negatively regulates the apoptosis pathway of the p53 to reduce the chemotherapeutic effects of gastric cancer.Conclusion: RUNX2 is a possible target for platinum-based chemotherapy resistance.Keywords: gastric cancer, RUNX2, platinum, chemotherapy resistance

Zhiqiang Liu,1,&ast; Xiaoli Gao,1,&ast; Lirong Liang,2 Xuan Zhou,1 Xiaozhe Han,3 Ting Yang,4– 7 Kewu Huang,8 Yingxiang Lin,8 Shu Deng,9 Zuomin Wang,1 Chen Wang4– 7,10 1Department of Stomatology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Clinical Epidemiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Department of Oral Science and Translational Research, Nova Southeastern University College of Dental Medicine, Fort Lauderdale, FL, USA; 4Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 5National Clinical Research Center for Respiratory Diseases, Beijing, People’s Republic of China; 6Institute of Respiratory Medicine, Peking Union Medical College, Beijing, People’s Republic of China; 7Department of Respiratory Medicine, Capital Medical University, Beijing, People’s Republic of China; 8Beijing Key Laboratory of Respiratory and Pulmonary Circulation Disorders, Department of Pulmonary and Critical Care Medicine, Beijing Chao-Yang Hospital, Beijing, People’s Republic of China; 9Department of Immunology and Infectious Diseases, The Forsyth Institute, Harvard School of Dental Medicine Affiliate, Cambridge, MA, USA; 10WHO Collaborating Centre for Tobacco Cessation and Respiratory Diseases Prevention, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zuomin Wang, Department of Stomatology, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongti South Road, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +86 10 85231492, Email wzuomin@sina.cn Chen Wang, Department of Pulmonary and Critical Care Medicine, Center of Respiratory Medicine, China-Japan Friendship Hospital, 2 Yinghuayuan Dongjie, Chaoyang District, Beijing, 100029, People’s Republic of China, Tel +86 10 65105565, Email wangchen@pumc.edu.cnPurpose: There is insufficient information about the prevalence and risk factors of gastroesophageal reflux disease (GERD) in the Chinese adult population. We aimed to assess the prevalence and identify the risk factors of GERD in China.Methods: We collected data from a nationally representative sample (50,991 subjects) of Chinese adults from a large nation-wide cross-sectional survey. GERD was diagnosed by a standardized Chinese-language GERD questionnaire with a score of ≥ 8. The demographic characteristics, comorbidities and periodontal factors of all participants were collected.Results: Fifty-thousands-one-hundred-eighty-three participants were finally included in this study. The overall prevalence of GERD was 5.6% (95% CI, 5.4– 5.8%) among the general Chinese population aged 20 years or older. Women, smokers, and people with older age, BMI ≥ 25.0 kg/m2, urban residence, lower education level or comorbidities were more prevalent with GERD (p < 0.001). Symptoms of severe periodontitis (OR = 1.40, 95% CI 1.28– 1.52, p < 0.001) and lower frequency of tooth brushing (OR = 2.01, 95% CI 1.76– 2.29, p < 0.001) were significantly associated with risk of GERD.Conclusion: Symptom-based GERD is highly prevalent in the Chinese population. Overweight and smoking are major preventable risk factors for GERD. Periodontal factors are novel potential risk factors for GERD and should be given more attention in GERD prevention.Keywords: gastroesophageal reflux disease, prevalence, risk factor, periodontitis, epidemiology