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Yi Zhang,1,* Ansheng Xie,2,* Di Wang,2 Weiwei Deng2 1Department of Dermatology, the Affiliated Hospital of Inner Mongolia Medical University, Hohhot, People’s Republic of China; 2Dermatology Hospital of Southern Medical University, Zhou Guang, People’s Republic of China*These authors contributed equally to this workCorrespondence: Weiwei Deng; Di Wang, Email dengww@smu.edu.cn; 602619666@qq.comBackground: Skin cutaneous melanoma (SKCM) ranks among the most prevalent malignant tumors, highlighting the significance of identifying new research targets. In this study, our objective was to pinpoint pivotal genes implicated in SKCM pathogenesis and ascertain their potential as prognostic biomarkers.Methods: Leveraging data from 1809 normal skin samples and 471 SKCM samples, we identified differentially expressed genes (DEGs). Using a comprehensive suite of bioinformatic analyses, including weighted gene co-expression network analysis (WGCNA), we elucidated the functions of these DEGs and singled out hub genes. Cox analyses and overall survival analyses underscored that elevated expression of these genes correlated with more favorable prognoses.Results: Ultimately, we identified five genes (PLAC8, IL4I1, ZNF80, CCR8, CLEC4C) as novel prognostic markers for SKCM. Furthermore, multivariate Cox analyses pinpointed ZNF80 and CCR8 as independent prognostic biomarkers. Experimental validation targeting these genes revealed significant downregulation in melanoma cells, except for CCR8. Subsequent knockdown of IL4I1 promoted both the proliferation and inhibited the apoptosis of melanoma cells.Conclusion: In summary, our study identified a series of potential prognostic genes in melanoma and verified the functional role of IL4I1 among them.Keywords: skin cutaneous melanoma, prognostic biomarkers, IL4I1, ZNF80, CCR8

Zhihong Liu,1,2,* Xiaofang Liang,1,* Yu Zhang,1 Wenbo Deng,1 Yulin Wang,3 Zhangping Lu,2 Qianqian Liu,2 Lianhua Wei2 1School of Public Health, Gansu University of Traditional Chinese Medicine, Lanzhou, Gansu, People’s Republic of China; 2Department of Clinical Laboratory, Gansu Provincial Hospital, Lanzhou, Gansu, People’s Republic of China; 3Ningxia Medical University, Yinchuan, Ningxia, People’s Republic of China*These authors contributed equally to this workCorrespondence: Lianhua Wei, Email 107306723@qq.comAbstract: The development of antibiotic resistance complicates the treatment of infectious diseases and is a global public health threat. However, drug repurposing can address this resistance issue and reduce research and development costs. Niclosamide is a salicylanilide compound approved by the Food and Drug Administration (FDA), and it has been used clinically for treating parasitic infections for many years. Recent studies have shown that niclosamide can inhibit bacterial and fungus activity by affecting the quorum sensing system, biofilm formation, cell membrane potential, and other mechanisms. Here, we discuss recent advances in the antimicrobial applications of niclosamide and its derivatives to provide new perspectives in treating infectious diseases.Keywords: antimicrobial resistance, multi-drug resistance, niclosamide, a derivative, drug repurposing

Qiongdan Mai,* Weiming Lai,* Wenyu Deng, Junfei Guo, Yasha Luo, Ru Bai, Chunming Gu, Guanbin Luo, Rongjia Mai, Mingyong Luo Department of Clinical Laboratory, Guangdong Women and Children Hospital, Guangzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Mingyong Luo, Department of Clinical Laboratory, Guangdong Women and Children Hospital, NO. 521 Xingnan Road, Panyu District, Guangzhou, People’s Republic of China, Tel +86-15920356428, Email luo-my@163.comPurpose: Acute gastroenteritis caused by Salmonella spp. among children post a great threat for global public health. The increasing rate of drug-resistant Salmonella spp. has also become a challenging problem worldwide. In this study, the prevalence, serotypes, and antimicrobial characteristics of Salmonella isolated from children in Guangzhou, China, were investigated to provide supporting information for clinical treatment and prevention.Methods: Clinical data of children featured with gastroenteritis symptoms from 2018 to 2023 in Guangdong Women and Children Hospital were collected. The difference and fluctuation of antimicrobial resistance between serotypes and years were retrospectively analyzed.Results: A total of 1304 Salmonella isolates were cultural-confirmed. The overall positive rate of Salmonella isolated from stool samples was 22.0% (1304/5924). Salmonella infections occur mainly from June to September and the majority of infected children aged under 4 years. Serogroup B was the most common serogroup among Salmonella isolates (74.6%, 973/1304). The predominant serotypes of Salmonella isolates were Typhimurium (63.1%, 823/1304). Higher drug resistance rate of Salmonella spp. to ceftriaxone was observed in 2023. The drug resistance rates of Salmonella isolates to sulfamethoxazole/trimethoprim and ampicillin are at high level during the past 6 years. Notably, higher multi-drug resistance (MDR) rate was demonstrated in Salmonella Typhimurium compared with other serotypes.Conclusion: Salmonella Typhimurium was the most common serotype isolated from children in Guangzhou, China, and it may mainly account for the high drug resistance rate in Salmonella spp. to most of the antimicrobial profiles. For controlling the high drug resistance rate of Salmonella spp. continuous surveillance of drug resistance and appropriate use of antibiotics based on clinical and laboratory results are of great significance.Keywords: gastroenteritis, Salmonella, antimicrobial resistance, Guangzhou, China

Wenguang Deng, Zhiming Zeng, Qingyan Liu, Jingjing Deng, Liyu Wang, Hui Li, Yuenong Zhang The Anesthesiology Surgery Center of The Third Affiliated Hospital of Sun Yat-sen University-Yuedong Hospital, Guangdong, People’s Republic of ChinaCorrespondence: Yuenong Zhang, Email 36856665@qq.com

Yishan Duan,1,* Jing Ren,2,* Jing Wang,3,* Suyan Wang,4 Rui Zhang,1 Huohuo Zhang,1 Jinrui Hu,1 Wen Deng,1 Weimin Li,1,3,4 Bojiang Chen1,3 1Department of Respiratory and Critical Care Medicine, West China Hospital of Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China; 2The Integrated Care Management Center, West China Hospital of Sichuan University, Chengdu, Chengdu, Sichuan Province, 610041, People’s Republic of China; 3Precision Medicine Center, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China; 4Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan University, Chengdu, Sichuan Province, 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Bojiang Chen; Weimin Li, Email cjhcbj@outlook.com; weimin003@163.comPurpose: Early empiric antibiotics were prescribed to numerous patients during the Coronavirus disease 2019 (COVID-19) pandemic. However, the potential impact of empiric antibiotic therapy on the clinical outcomes of patients hospitalized with COVID-19 is yet unknown.Methods: In this retrospective cohort study, early antibiotics use cohort was defined as control group, which was compared with no antibiotic use and delayed antibiotic use cohorts for all-cause mortality during hospitalization. The 1:2 propensity score matched patient populations were further developed to adjust confounding factors. Survival curves were compared between different cohorts using a Log rank test to assess the early antibiotic effectiveness.Results: We included a total of 1472 COVID-19 hospitalized patients, of whom 87.4% (1287 patients) received early antibiotic prescriptions. In propensity-score-matched datasets, our analysis comprised 139 patients with non-antibiotic use (with 278 matched controls) and 27 patients with deferred-antibiotic use (with 54 matched controls). Patients with older ages, multiple comorbidities, severe and critical COVID-19 subtypes, higher serum infection indicators, and inflammatory indicators at admission were more likely to receive early antibiotic prescriptions. After adjusting confounding factors likely to influence the prognosis, there is no significant difference in all-cause mortality (HR=1.000(0.246– 4.060), p = 1.000) and ICU admission (HR=0.436(0.093– 2.04), p = 0.293), need for mechanical ventilation (HR=0.723(0.296– 1.763), p = 0.476) and tracheal intubation (HR=1.338(0.221– 8.103), p = 0.751) were observed between early antibiotics use cohort and non-antibiotic use cohort.Conclusion: Early antibiotics were frequently prescribed to patients in more severe disease condition at admission. However, early antibiotic treatment failed to demonstrate better clinical outcomes in hospitalized patients with COVID-19 in the propensity-score-matched cohorts.Keywords: Coronavirus disease 2019, COVID-19, early antibiotics use, bacterial co-infections, clinical outcomes

Yongqiang Xiao,1– 3,&ast; Wanqing Chen,4,&ast; Wei Deng,1,&ast; Guoqing Zhu,1 Jin Xie,1 Laihui Luo,1 Liucong Lin,1 Jiahao Tao,1 Zhigao Hu,1 Renfeng Shan1 1Department of General Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 2Department of General Surgery, Ganjiang New Area People’s Hospital, Nanchang, Jiangxi, People’s Republic of China; 3Department of General Surgery, Ganjiang New Area Hospital of the First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 4Department of Gastroenterology, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhigao Hu; Renfeng Shan, Department of General Surgery, the First Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 17, Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86-791-88692522, Email 854189568@qq.com; srf1978@126.comPurpose: This study aimed to assess the prognostic significance of alpha-fetoprotein (AFP) response in patients with unresectable hepatocellular carcinoma (u-HCC) who underwent hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab.Methods: A retrospective review was conducted on patients with u-HCC receiving treatment with HAIC combined with lenvatinib and camrelizumab. Early AFP response was defined as a > 20% decrease in AFP within 4 weeks, and AFP response as a > 75% decrease in AFP within 8 weeks. The correlation between early AFP response, AFP response, therapeutic response, overall survival (OS), and progression-free survival (PFS) was investigated.Results: The study included 63 patients. AFP responders exhibited superior objective response rates compared to AFP non-responders, as determined by RECIST v1.1 or mRECIST criteria (45.5 vs. 18.2%, p=0.014, or 81.8 vs. 48.5%, p=0.013). Furthermore, early AFP responders demonstrated prolonged OS (not reached vs. 8.0 months, p< 0.001) and PFS (13.3 vs. 3.0 months, p= 0.018) relative to early AFP non-responders. Similarly, AFP responders exhibited improved OS (not reached vs. 9.0 months, p< 0.001) and PFS (19.3 vs. 5.1 months, p=0.002) compared to AFP non-responders. Multivariate analysis results indicated that both early AFP response and AFP response independently predicted OS [hazard ratio (HR) 2.963, 95% confidence interval (CI) 1.333– 6.585, p=0.008, and HR 6.182, 95% CI 1.780– 21.466, p=0.004] and PFS (HR 2.186, 95% CI 1.107– 4.318, p=0.024, and HR 3.078, 95% CI 1.407– 6.730, p=0.005), serving as significant prognostic values.Conclusion: Early AFP response and AFP response serve as predictive biomarkers for the effectiveness of HAIC combined with lenvatinib and camrelizumab in patients with u-HCC.Keywords: unresectable hepatocellular carcinoma, alpha-fetoprotein, hepatic arterial infusion chemotherapy, lenvatinib, camrelizumab

Biao Hou,1– 3,&ast; Bo Li,4,&ast; Wanjun Deng,3,&ast; Bo Li,1,2 Bibo Ren,5 Chao Hu,3 Guowei Zhang,1,2 Fen Yang,6 Meimei Xiao,3 Songlin Xie,3 Denghui Xie1,2 1Department of Joint Surgery and Sports Medicine, Center for Orthopedic Surgery, Orthopedic Hospital of Guangdong Province, The Third Affiliated Hospital of Southern Medical University, Guangzhou, People’s Republic of China; 2Guangdong Provincial Key Laboratory of Bone and Joint Degeneration Diseases, Academy of Orthopedics, Guangzhou, Guangdong Province, People’s Republic of China; 3Department of Hand and Foot Microsurgery, The affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang, People’s Republic of China; 4Department of Radiology, West China Hospital, Sichuan University, Chengdu, People’s Republic of China; 5College of Biomass Science and Engineering, Sichuan University, Chengdu, People’s Republic of China; 6Department of Infectious Diseases, The Affiliated Nanhua Hospital, Hengyang Medical College, University of South China, Hengyang, Hunan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Denghui Xie; Songlin Xie, Email smuspine@163.com; xiesonglin0929@163.comPurpose: This research was to innovate a nanozyme-based therapeutic strategy that combines aggregation-induced emission (AIE) photosensitizers with copper nanozymes. This approach is designed to address the hypoxic conditions often found in bacterial infections and aims to boost the effectiveness of photodynamic therapy (PDT) by ensuring sufficient oxygen supply for reactive oxygen species (ROS) generation.Methods: Our approach involved the synthesis of dihydroxyl triphenyl vinyl pyridine (DHTPY)-Cu@zoledronic acid (ZOL) nanozyme particles. We initially synthesized DHTPY and then combined it with copper nanozymes to form the DHTPY-Cu@ZOL composite. The nanozyme’s size, morphology, and chemical properties were characterized using various techniques, including dynamic light scattering, transmission electron microscopy, and X-ray photoelectron spectroscopy. We conducted a series of in vitro and in vivo tests to evaluate the photodynamic, antibacterial, and wound-healing properties of the DHTPY-Cu@ZOL nanozymes, including their oxygen-generation capacity, ROS production, and antibacterial efficacy against methicillin-resistant Staphylococcus aureus (MRSA).Results: The DHTPY-Cu@ZOL exhibited proficient H2O2 scavenging and oxygen generation, crucial for enhancing PDT in oxygen-deprived infection environments. Our in vitro analysis revealed a notable antibacterial effect against MRSA, suggesting the nanozymes’ potential to disrupt bacterial cell membranes. Further, in vivo studies using a diabetic rat model with MRSA-infected wounds showed that DHTPY-Cu@ZOL markedly improved wound healing and reduced bacterial presence, underscoring its efficacy as a non-antibiotic approach for chronic infections.Conclusion: Our study suggests that DHTPY-Cu@ZOL is a highly promising approach for combating antibiotic-resistant microbial pathogens and biofilms. The biocompatibility and stability of these nanozyme particles, coupled with their improved PDT efficacy position them as a promising candidate for clinical applications.Keywords: copper nanozyme, aggregate induced emission, photodynamic antibacterial therapy, antimicrobial resistance, diabetic wound healing

Peiqiu Zhu,1 Weiwei Deng2 1Department of Dermatology and Venereology, Beijing Jishuitan Hospital, Capital Medical University, Beijing, People’s Republic of China; 2Department of Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Weiwei Deng, Department of Dermatology, Dermatology Hospital of Southern Medical University, Guangzhou, People’s Republic of China, Tel +86 15622165048, Email 1601178683@qq.comBackground: Systemic sclerosis represents a persistent autoimmune disorder marked with fibrosis affecting both skin and other organs, which leads to a diminished quality of life and increased mortality. The affected skin provides a valuable opportunity to explore the pathogenesis of systemic sclerosis. Nevertheless, the roles of various cell populations within scleroderma remain intricate.Methods: We conducted a comprehensive reanalysis of recently published single-cell RNA-sequencing data from skin tissue cells in scleroderma. Through the utilization of Seurat, irGSEA, AUCell packages, and WGCNA analysis, we aimed to unveil crucial genes associated with the disease’s etiological factors. Our investigation involved the characterization of heterogeneous pathway activities in both healthy and SSc-affected skin. Furthermore, we employed immunofluorescence techniques to validate the expression patterns of hub genes and differentially expressed genes.Results: The Endothelial-to-Mesenchymal Transition (EndMT) pathway was upregulated in SSc skin. Notably, the M4 module within Endothelial cell subpopulation 1 exhibited a strong association with EndMT. Furthermore, we identified three overexpressed genes (APLNR, INS-IGF2, RGCC) that demonstrated a significant correlation with EndMT. Importantly, their expression levels were markedly higher in skin of individuals with SSc when compared to healthy controls.Conclusion: APLNR, INS-IGF2 and RGCC serve as potential key players in the pathogenesis of SSc skin through EndMT-dependent mechanisms.Keywords: systemic sclerosis skin, single cell RNA-sequencing analysis, the Endothelial to Mesencchymal Transition, EndMT, APLNR, INS-IGF2, RGCC

Ziyu Ren,1 Jiangchuan Long,1 Wenzhen Deng,1 Yuanyuan Jing,1 Jingwen Qiu,1 Wei Ren,2 Dongfang Liu1 1Department of Endocrinology and Metabolism, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China; 2Department of Endocrinology and Metabolism, The First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Wei Ren, Department of Endocrinology, The First Affiliated Hospital of Chongqing Medical University, No. 1. You-Yi Road, Yuzhong District, Chongqing, 400016, People’s Republic of China, Tel +86-23-89012755, Email renwei67@sina.com Dongfang Liu, Department of Endocrinology, The Second Affiliated Hospital of Chongqing Medical University, No. 74, Linjiang Road, Yuzhong District, Chongqing, 400010, People’s Republic of China, Tel +86-23-63832133, Email 300306@hospital.cqmu.edu.cn; ldf023023@qq.comBackground: In recent years, multiple observational studies have confirmed the association between sleep traits and various human physiopathological states. However, the causal relationship between sleep traits and hypothalamic-pituitary-target gland axis (HPTGA) function remains unknown.Methods: We obtained summary statistics on sleep traits (insomnia, chronotype, and sleep duration (long and short)) from the UK Biobank database. Data related to the HPTGA functions were obtained from the publicly available database. Subsequently, a two-sample Mendelian randomization (MR) analysis was performed to investigate the causal relationship between different sleep traits and the HPTGA function. Reverse MR analysis was conducted to examine the direction of causality.Results: The MR analysis results suggested that chronotype is associated with decreased levels of six hormones in HPTGA. Sleep duration was causally associated with decreased levels of free thyroxine and progesterone. Both long and short sleep durations are detrimental to the secretion of prolactin-releasing peptide, somatostatin, and plasma cortisol, while short sleep duration can promote progesterone secretion. After gender stratification, we found that female reproductive function is more susceptible to the influence of unfavorable sleep traits.Conclusion: Our MR analysis indicated a significant causal association between chronotype and suppressed gonadal function in healthy adult humans, with no apparent gender-specific effect. Extreme sleep durations were also found to be detrimental to the maintenance of normal HPTGA secretion function. Compared to males, gonadal function in the female cohort is more susceptible to extreme sleep habits. Subsequent observational studies are urgently needed to confirm the underlying mechanisms.Keywords: hypothalamo-hypophyseal-target gland axis, sleep traits, causal inference, Mendelian randomization

Wenying Deng,1,&ast; Zeyi Zhao,1,&ast; Tao Zou,2 Tongdong Kuang,3,&ast; Jing Wang1,&ast; 1School of Basic Medical Sciences, University of South China, Hengyang, Hunan Province, 421001, People’s Republic of China; 2Department of Cardiovascular Medicine, First Affiliated Hospital of University of South China, Hengyang, Hunan Province, 421001, People’s Republic of China; 3Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin, Guangxi Province, 541199, People’s Republic of China&ast;These authors contributed equally to this workThese authors contributed equally to this studyCorrespondence: Tongdong Kuang, Guangxi Key Laboratory of Diabetic Systems Medicine, Guilin Medical University, Guilin, 541199, People’s Republic of China, Email 594536067@qq.com Jing Wang, School of Basic Medical Sciences, University of South China, Hengyang, Hunan Province, 421001, People’s Republic of China, Tel +86 15200735915, Email 738212405@qq.comAbstract: Diabetes mellitus (DM) is a chronic metabolic disease characterized by elevated blood glucose levels, resulting in multi-organ dysfunction and various complications. Fusion proteins can form multifunctional complexes by combining the target proteins with partner proteins. It has significant advantages in improving the performance of the target proteins, extending their biological half-life, and enhancing patient drug compliance. Fusion protein-based drugs have emerged as promising new drugs in diabetes therapeutics. However, there has not been a systematic review of fusion protein-based drugs for diabetes therapeutics. Hence, we conducted a comprehensive review of published literature on diabetic fusion protein-based drugs for diabetes, with a primary focus on immunoglobulin G (IgG) fragment crystallizable (Fc) region, albumin, and transferrin (TF). This review aims to provide a reference for the subsequent development and clinical application of fusion protein-based drugs in diabetes therapeutics.Keywords: diabetes mellitus, fusion protein, Fc protein, glucagon-like peptide 1 receptor agonists, transferrin, albumin

Yongqiang Xiao,&ast; Guoqing Zhu,&ast; Jin Xie,&ast; Laihui Luo, Wei Deng, Liucong Lin, Jiahao Tao, Zhigao Hu, Renfeng Shan Department of General Surgery, the First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhigao Hu; Renfeng Shan, Department of General Surgery, the First Affiliated Hospital of Nanchang University, No. 17, Yongwaizheng Street, Nanchang, Jiangxi, 330006, People’s Republic of China, Tel/Fax +86-791-88692522, Email 854189568@qq.com; srf1978@126.comPurpose: This study aimed to assess the prognostic significance of the neutrophil-lymphocyte ratio (NLR) in patients with unresectable hepatocellular carcinoma (u-HCC) treated with hepatic artery infusion chemotherapy (HAIC) combined with lenvatinib and camrelizumab.Patients and Methods: We conducted a retrospective cohort study involving patients diagnosed with u-HCC who underwent HAIC combined with lenvatinib and camrelizumab. Patients were stratified into two cohorts using the median NLR as the cutoff point. We then assessed treatment response, overall survival (OS), progression-free survival (PFS), and adverse events in these patient groups.Results: Between October 2020 and April 2022, a total of 88 patients were enrolled in the study. The overall cohort exhibited a median PFS of 7.9 months, while the median OS was not reached, and a median NLR of 3.46. Notably, the group with NLR< 3.46 demonstrated significantly superior OS (not reached vs 9.6 months, p = 0.017) and PFS (18.3 vs 5.3 months, p = 0.0015) compared to the NLR≥ 3.46 group. Furthermore, multivariate analysis revealed that an alpha-fetoprotein (AFP) ≥ 400 ng/mL [hazard ratio (HR), 2.133; 95% confidence interval (CI), 1.102– 4.126; p = 0.024], Barcelona Clinical Hepatocellular Carcinoma (BCLC) stage C (HR, 2.319; 95% CI, 1.128– 4.764; p = 0.022), and NLR ≥ 3.46 (HR, 2.35; 95% CI, 1.239– 4.494; p = 0.009) were identified as independent risk factors for OS. Additionally, multivariate analysis demonstrated that AFP ≥ 400 ng/mL, BCLC stage C, and NLR ≥ 3.46 were independent negative factors of PFS.Conclusion: NLR can be associated with outcomes in patients with u-HCC treated with HAIC combined with lenvatinib and camrelizumab.Keywords: unresectable hepatocellular carcinoma, neutrophil-to-lymphocyte ratio, hepatic arterial infusion chemotherapy, lenvatinib, camrelizumab

Yuting Yang,1,&ast; Hao Wang,1,&ast; Wen Sha,2 Xiaoqin Guo,3 Wei Deng,1 Jingyi Wang,1 Chaowei Fu1 1School of Public Health; NHC Key Laboratory of Health Technology Assessment, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Municipal Center for Health Promotion, Shanghai, People’s Republic of China; 3Songjiang District Center for Health Promotion, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chaowei Fu; Jingyi Wang, School of Public Health; NHC Key Laboratory of Health Technology Assessment, Fudan University, 446-2 Zhaojiabang Road, Shanghai, 200032, People’s Republic of China, Tel/Fax +86 21 3356 3933 ; +86 21 6416 9553, Email fcw@fudan.edu.cn; jingyi_wang@fudan.edu.cnPurpose: Digital interventions for adolescent mental health are emerging in high-income countries, but have faced challenges and are scarce in China. This study investigated the effect of a short video-based mental health intervention on depressive symptoms in Chinese adolescents.Methods: A three-arm cluster randomized controlled trial was conducted in four junior high schools in Shanghai from December 2020 to December 2021 with the measurement at baseline, 6 months after study entry, and 12 months. Outcomes were collected by self-completed questionnaires administered by teachers masked to allocation. The primary outcome was depressive symptoms assessed by the Depression Self-Rating Scale for Children (DSRSC). Mixed effects models were used to compare psychologist-led intervention (n=428 students) and teacher-led intervention (n=385) including six short video-based sessions to usual school provision (n=751).Results: Using intention-to-treat analyses, psychologist-led intervention showed more reduction in depressive symptoms compared to usual school provision at 6 months (coefficient − 1.00, 95% CI − 1.94 to − 0.05), but not at 12 months. Using per-protocol analyses among participants who watched at least three video episodes, both psychologist-led (− 1.14, − 2.20 to − 0.09) and teacher-led intervention (− 1.23, − 2.45 to − 0.02) reduced depressive symptoms compared to usual school provision at 6 months, and the effect of teacher-led intervention persisted at 12 months (− 1.58, − 3.13 to − 0.03). Further exploration found that compared with urban students, the between-group differences for depressive symptoms in rural students were more significant (p< 0.05 for interaction) and the effects were maintained at 12 months.Conclusion: The short video-based mental health intervention showed potential to reduce depressive symptoms among Chinese adolescents, and the effects were more significant if the minimum video viewing frequency was reached.Keywords: short video-based intervention, adolescents, mental health, depressive symptoms, randomized controlled trial

Wei Deng,1,2 Yanhua Lu,1,2 Ping Hu,1,2 Qingqing Zhang,1,2 Shuangyan Li,1,2 Dong Yang,1,2 Ning Zhao,1,2 Kejian Qian,1,2 Fen Liu1,2 1Department of Critical Medicine, The First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of China; 2Medical Innovation Center, First Affiliated Hospital of Nanchang University, Nanchang, People’s Republic of ChinaCorrespondence: Fen Liu, Email liufen9934@163.comBackground: Acute lung injury (ALI) is associated with a high mortality rate; however, the underlying molecular mechanisms are poorly understood. The purpose of this study was to investigate the expression profile and related networks of long noncoding RNAs (lncRNAs), microRNAs (miRNAs), and mRNAs in lung tissue exosomes obtained from sepsis-induced ALI.Methods: A mouse model of sepsis was established using the cecal ligation and puncture method. RNA sequencing was performed using lung tissue exosomes obtained from mice in the sham and CLP groups. Hematoxylin-eosin staining, Western blotting, immunofluorescence, quantitative real-time polymerase chain reaction, and nanoparticle tracking analysis were performed to identify relevant phenotypes, and bioinformatic algorithms were used to evaluate competitive endogenous RNA (ceRNA) networks.Results: Thirty lncRNA-miRNA-mRNA interactions were identified, including two upregulated lncRNAs, 30 upregulated miRNAs, and two downregulated miRNAs. Based on the expression levels of differentially expressed mRNAs(DEmRNAs), differentially expressed LncRNAs(DELncRNAs), and differentially expressed miRNAs(DEmiRNAs), 30 ceRNA networks were constructed.Conclusion: Our study revealed, for the first time, the expression profiles of lncRNA, miRNA, and mRNA in exosomes isolated from the lungs of mice with sepsis-induced ALI, and the exosome co-expression network and ceRNA network related to ALI in sepsis.Keywords: sepsis, acute lung injury, inflammation, lung tissue exosomes, ceRNA networks

Xiaodan Wang,1,&ast; Weiping Deng,1,&ast; Jiehui Zhao,2,&ast; Yongchao Guo,3 Haifang Lai,4 Yueliang Hu,5 Wenyan Kang,1 Yong Li,6– 8 Junli Zuo5 1Department of Neurology and Institute of Neurology, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 2Department of General Practice, Daning Community Health Service Center, Shanghai, 200072, People’s Republic of China; 3Department of Nutrition, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 4Department of Rehabilitation Medicine Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 5Department of Geriatrics, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 6Department of Pulmonary and Critical Care Medicine, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, People’s Republic of China; 7Institute of Respiratory Disease, Shanghai Jiaotong University School of Medicine, Shanghai, People’s Republic of China; 8Shanghai Key Laboratory of Emergency Prevention, Diagnosis and Treatment of Respiratory Infectious Disease, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Junli Zuo; Yong Li, Email zjl12616@rjh.com.cn; bangliyong@163.comBackground: Nutrition is an important prevention in old patients with COVID-19. However, in China, there are few studies on the correlation between nutrition and COVID-19.Methods: A total of 148 hospitalized COVID-19 (65.7 ± 16.0 [range: from 21 to 101] years old) patients were enrolled in this study. The information of demographic, biochemical results, vaccination doses, types of COVID-19, PCR test negative conversion time, and scores of Mini Nutritional Assessment Short Form (MNA-SF) for evaluating nutritional status were recorded. We first explored the relationships between MNA-SF performance and the severities of COVID-19 in the groups with non-vaccinated, vaccinated, and all the patients using multivariable ordinal logistic regression. Further, we explored the relationships between performance of MNA-SF and the time of negative conversion of PCR in the groups with non-vaccinated, vaccinated, and all the patients using COX proportional hazards survival regression.Results: Group of patients with malnutrition or at risk of malnutrition group was associated with older of the age, those who had not been vaccinated, in fewer people who were asymptomatic type and in more people who showed longer of the negative conversion time of PCR, lower of the BMI, and the lower of the hemoglobin level. Each additional increase of one point of MNA-SF was associated with a 17% decrease in the odds of a worse type of COVID-19 in all patients, and the significant result exists in non-vaccinated patients. One point increase of MNA-SF was associated with increased 11% of hazard ratios of turning negative of PCR and well-nourished group was associated with increased 46% of hazard ratio of turning negative of PCR.Conclusion: Higher nutrition is associated with less severity of COVID-19, especially in the non-vaccinated group. Higher nutrition is also associated with shorter time of turning negative of PCR in non-ICU COVID-19 patients.Keywords: COVID-19, nutrition, MNA-SF, vaccination

Ruoshan Wu,1 Longjun Jing,1,2 Yang Liu,3 Huilin Wang,3,4 Lin Xie,5 Wu Deng6 1School of Physical Education, Hunan University of Science and Technology, Xiangtan, 411201, People’s Republic of China; 2China Athletics College, Beijing Sport University, Beijing, 100084, People’s Republic of China; 3School of Business, Hunan University of Science and Technology, Xiangtan, 411201, People’s Republic of China; 4Faculty of Economics, Chulalongkorn University, Bangkok, 10330, Thailand; 5School of Physical Fitness of Guangzhou Sport University, Guangzhou, 510000, People’s Republic of China; 6School of Physical Education, Shenzhen University, Shenzhen, 518000, People’s Republic of ChinaCorrespondence: Huilin Wang, Email 15897325733@163.comPurpose: Despite the Advances in sports training methods and medicine, they have not reduced the recurrence rate of athletes’ injuries significantly, and obligatory exercise may be an important reason for their re-injury. The purpose of this study was to investigate the effects of mindfulness on obligatory exercise behavior, self-criticism, and competitive state anxiety in athletes recovering from injury, and explain their interactions.Patients and Methods: The study adopted the snowball and convenience sampling methods. From November to December 2022, a total of 265 high-level sports players in South China were selected, and ultimately, 208 valid data samples were obtained. Maximum likelihood estimation was used to analyze the data and test the hypotheses proposed using 5000 bootstrap samples to test the mediating effects of the structural equation model.Results: The results demonstrated that there were positive correlations between self-criticism and obligatory exercise (standardized coefficients = 0.38, p < 0.001), as well as competitive state anxiety and self-criticism (standardized coefficients = 0.45, p < 0.001). Mindfulness and obligatory exercise were correlated negatively (standardized coefficients = − 0.31, p < 0.001), but there was no significant relation between competitive state anxiety and obligatory exercise (standardized coefficients = 0.05, p > 0.01). Self-criticism and competitive state anxiety mediated mindfulness’s positive effects on obligatory exercise in part (standardized indirect effect = − 0.16, p < 0.01), and this explanatory power was higher than in any previous study (R2 = 0.37).Conclusion: The irrational beliefs in Activating events–Beliefs–Consequence (ABC) theory play an important role in explaining athletes’ obligatory exercise, and mindfulness has a positive effect on reducing obligatory exercise behavior.Keywords: obligatory exercise, mindfulness, cognitive behavioral therapy, ABC theory, sports reinjury

Wusheng Deng,1,&ast; Yun Jiang,2,&ast; Jiaoxia Qin,1,&ast; Gang Chen,3,&ast; Yongjie Lv,1 Yanmei Lei,1 Jing Luo,1 Kangkang Hong,1 Bing Huang,1 Luhai Qin,4 Xiujia Tang,1 Liumei Ye,1 Yuhai Dang,1 Chao Wang,1 Feiyang Long,1 Ke Wang,1 Jinliang Kong1 1Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Shaoyang University, Shaoyang, Hunan, People’s Republic of China; 3Department of Pathology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 4Department of Pulmonology, Hechi Traditional Chinese Medicine Hospital, Hechi, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jinliang Kong; Ke Wang, Department of Respiratory and Critical Care Medicine, The First Affiliated Hospital of Guangxi Medical University, No. 6 Shuangyong Road, Nanning, 530021, People’s Republic of China, Email kjl071@163.com; keewang@hotmail.comBackground: Aspergillus fumigatus is an opportunistic fungal pathogen, which is commonly found in lungs and rarely causes infections in mediastinum. Mediastinal Aspergillus abscess is a serious infectious condition, and is characterized by difficult diagnosis due to its clinical manifestations being nonspecific.Case Presentation: Here, we report a case of a mediastinal Aspergillus fumigatus abscess in an immunocompetent patient. The patient was a 45-year-old woman who presented with a 20-day history of sore throat without any underlying diseases. Chest computed tomography (CT) showed a mass in the anterior superior mediastinum. Metagenomic next-generation sequencing (mNGS) identified Aspergillus fumigatus sequences in endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) tissue, indicating the mediastinal Aspergillus fumigatus infection of this patient. The following mediastinal biopsy histological analysis and tissue fungi culture also suggested Aspergillus fumigatus infection, confirming the mNGS detection. The patient was diagnosed with mediastinal aspergillosis caused by Aspergillus fumigatus. After timely voriconazole treatment, the patient was discharged with good condition.Conclusion: Our study presented a rare case with mediastinal Aspergillus fumigatus abscess in an immunocompetent patient. As a new clinical diagnostic method, mNGS could assist timely diagnosis and precise treatment of Aspergillus infection.Keywords: mediastinal abscess, Aspergillus fumigatus, metagenomic next-generation sequencing, diagnosis, case report

Laihui Luo,1,&ast; Yongzhu He,1,&ast; Guoqing Zhu,1,&ast; Yongqiang Xiao,1 Shengjiang Song,1 Xian Ge,2 Tao Wang,3 Jin Xie,1 Wei Deng,1 Zhigao Hu,1 Renfeng Shan1 1Department of General Surgery, The First Affiliated Hospital of Nanchang, Nanchang, People’s Republic of China; 2Department of Pathology, The First Affiliated Hospital of Nanchang, Nanchang, People’s Republic of China; 3Department of Day Surgery Ward, The First Affiliated Hospital of Nanchang, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Renfeng Shan, Department of General Surgery, The First Affiliated Hospital of Nanchang University, 17 Yong Wai Zheng Street, Nanchang, 330006, People’s Republic of China, Tel +86 0791-88692522, Email srf1978@126.comPurpose: Conversion therapy gives some patients with initially unresectable hepatocellular carcinoma (HCC) access to surgery. The purpose of this study was to evaluate the safety and efficacy of hepatectomy after conversion therapy and how it differed from those who undergoing direct hepatectomy.Patients and Methods: From January 2018 to April 2022, 745 patients underwent hepatectomy for HCC were enrolled. Among them, 41 patients of unresectable HCC underwent hepatectomy after conversion therapy. A demographically and clinically comparable cohort was created from the remaining patients in a 1:1 ratio using propensity score matching.Results: The median duration of conversion therapy was 108 (42– 298) days, 8 patients achieved complete response (CR) and 33 achieved partial response (PR). Conversion therapy resulted in some degree of myelosuppression, but liver function index remained good. Compared with the direct hepatectomy group, the conversion group had more blood loss (600 mL vs 400 mL, p=0.015), longer operative time (270 min vs 240 min, p=0.02), higher blood transfusion rates, and longer hospital stay (8 days vs 11 days, p< 0.001). Patients in the conversion group had significantly more complications of any grade (82.9% vs 51.2%, p=0.002) and grade 3/4 (26.8% vs 4.9%, p=0.013), and 6 patients developed post-hepatectomy liver failure (PHLF). There were no deaths in either group. All patients achieved R0 resection, 6 (6/41, 14.6%) achieved pathological complete response (pCR), 14 achieved major pathologic responses (MPR). During a median follow-up of 12.8 months, 14 patients in the conversion group experienced recurrence or metastasis, no deaths.Conclusion: Hepatectomy after conversion therapy was more difficult than direct hepatectomy, but accurate preoperative assessment could ensure the safety of the surgery. The damage of liver function after conversion therapy was more severe than expected, PHLF should be prevented and treated. Hepatectomy was effective and necessary, postoperative pathological examination could provide guidance for adjuvant therapy.Keywords: hepatocellular carcinoma, conversion therapy, hepatectomy, post-hepatectomy liver failure, pathological complete response

Jing Li,&ast; Hong Gao,&ast; Yue Xiong,&ast; Ling Wang, Haojie Zhang, Fumei He, Jingxin Zhao, Shuna Liu, Liqian Gao, Ying Guo, Wenbin Deng School of Pharmaceutical Sciences (Shenzhen), Shenzhen Campus of Sun Yat-Sen University, Shenzhen, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ying Guo; Wenbin Deng, Email guoying1226@hotmail.com; dengwb5@mail.sysu.edu.cnBackground: Wound healing of skin is a complicated process. Cutaneous innervation and neurotrophic factors could participate in multiple stages of wound healing. Neurotrophic factors are mainly produced and released by neurons and neural stem cells (NSCs) which could be obtained in large quantities from human-induced pluripotent stem cells (iPSCs) in vitro. However, the potential wound healing effects of NSC secretions, such as exosomes, are unexplored yet.Methods: NSCs-derived exosomes (NSC-exo) and iPSCs-derived exosomes (iPSC-exo) were isolated from the cell culture supernatants by centrifugation, and then quantified and characterized. The effects of these exosomes on the migration of human dermal fibroblasts (HDF) cells and the tube formation of human umbilical vein endothelial cells (HUVECs) were investigated in vitro. And the in vivo wound healing effect of these exosomes were tested on the mouse skin trauma model. Therefore, a dipeptide/hyaluronic acid (Nap-FF/HA) composite hydrogel was used to encapsulate the exosomes as a sustained release carrier. Histological observations were performed to evaluate the wound healing effect of exosomes. Furthermore, the non-labeling proteomic analysis was performed to explore the possible mechanisms of NSC-exo on wound healing.Results: We obtained extracellular vesicles in a bowl-like structure with membranes which meet the general standards of exosomes. NSC-exo showed promotion effect on the migration of HDF cells and the tube formation of HUVECs in vitro. In a mouse skin injury model, NSC-exo enhanced the wound healing and the Nap-FF/HA hydrogel that contained exosomes did so with less drug frequency by sustaining release of exosomes. Further proteomic analysis demonstrated that the carried neurotrophic factors and immunity-related proteins in NSC-exo may play a functional role in wound healing.Conclusion: NSC-exo may enhance wound healing via neurotrophic factors and immunomodulation.Graphical Abstract: Keywords: wound healing, neural stem cells, exosomes, proteomic analysis

Zeyu Xie, Sensen Yang, Weishang Deng, Jinjian Li, Jisheng Chen Key Specialty of Clinical Pharmacy, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaCorrespondence: Jisheng Chen, Key Specialty of Clinical Pharmacy, the First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, 510080, People’s Republic of China, Tel +86+20-87622305, Fax +86+20-61321967, Email cjslym@163.comPurpose: The effect and safety of Semaglutide and Liraglutide on weight loss in people with obesity or overweight were evaluated by a Network Meta-Analysis system to provide an evidence-based reference for clinical treatment.Methods: Computer searched PubMed, Embase, and Cochrane Library databases to collect Liraglutide and Semaglutide injection monotherapy RCTs until April 2022, using Stata 16 software for Network Meta-Analysis.Results: Twenty-three RCTs study with 11,545 patients and 4 interventions (semaglutide 2.4mg, semaglutide 1.0mg, liraglutide 3.0mg and liraglutide 1.8 mg) were finally included. In terms of efficacy, semaglutide 2.4mg (− 12.47 kg) had the best weight loss, followed by liraglutide 3.0mg (− 5.24 kg), semaglutide 1.0mg (− 3.74 kg) and liraglutide 1.8mg (− 3.29 kg). In terms of decreased HbA1c, semaglutide 2.4mg (MD=− 1.48%, 95% CI [− 1.93, − 1.04]), semaglutide 1.0mg (MD=− 1.36%, 95% CI [− 1.72, − 1.01]), liraglutide 1.8mg (MD=− 1.23%, 95%Cl [− 1.66, − 0.80]) more effective than placebo. In terms of safety, the total incidence of adverse events was semaglutide 2.4mg > liraglutide 3.0mg > liraglutide 1.8mg > semaglutide 1.0mg compare to placebo, the incidence of serious adverse events was liraglutide 3.0mg > liraglutide 1.8mg > semaglutide 2.4mg > semaglutide 1.0mg, the incidence of hypoglycemic events was semaglutide 2.4mg > liraglutide 3.0mg > semaglutide 1.0mg > liraglutide 1.8mg.Conclusion: This meta-analysis indicates that all GLP-1RAs were more efficacious than placebo in people with obesity or overweight on efficacy. Semaglutide 2.4mg has an absolute advantage in weight loss and decreased HbA1c, but the incidence of total adverse events is also the highest and can cause hypoglycemia. In addition, although liraglutide 3.0mg was less effective than semaglutide 2.4mg, serious adverse events were still the most elevated.Keywords: glucagon-like peptide-1 receptor agonists, weight loss, systematic review, liraglutide, semaglutide

Dong-Mei Cai,1,&ast; Fan-Biao Mei,1,&ast; Chao-Jun Zhang,1 San-Chun An,1 Rui-Bo Lv,1 Guan-Hua Ren,1 Chan-Chan Xiao,1 Long Long,1,2 Tian-Ren Huang,1,2 Wei Deng1,2 1Department of Experimental Research, Guangxi Medical University Cancer Hospital, Nanning, Guangxi, 530021, People’s Republic of China; 2Guangxi Cancer Molecular Medicine Engineering Research Center, Nanning, Guangxi, 530021, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wei Deng; Tianren Huang, Department of Experimental Research, Guangxi Medical University Cancer Hospital, No. 71, Hedi Road, Nanning, Guangxi, 530021, People’s Republic of China, Email dengwei@gxmu.edu.cn; tianrenhuang@sina.comBackground: Microcystin-LR (MC-LR) and hepatitis B virus (HBV) are associated with hepatocellular carcinoma (HCC). However, the concentrations of MC-LR in drinking water and the synergistic effect of MC-LR and HBV on hepatocellular carcinogenesis through their disturbance of redox balance have not been fully elucidated.Methods: We measured the MC-LR concentrations in 168 drinking water samples of areas with a high incidence of HCC. The relationships between MC-LR and both redox status and liver diseases in 177 local residents were analyzed. The hepatoma cell line HepG2 transfected with C-terminal truncated hepatitis B virus X gene (Ct-HBX) were treated with MC-LR. Reactive oxygen species (ROS), superoxide dismutase (SOD), glutathione (GSH) and malondialdehyde (MDA) were measured. Cell proliferation, migration, invasion, and apoptosis were assessed with cell activity assays, scratch and transwell assays, and flow cytometry, respectively. The mRNA and protein expression-related redox status genes were analyzed with qPCR and Western blotting.Results: The average concentration of MC-LR in well water, river water and reservoir water were 57.55 ng/L, 76.74 ng/L and 132.86 ng/L respectively, and the differences were statistically significant (P < 0.05). The MC-LR levels in drinking water were correlated with liver health status, including hepatitis, clonorchiasis, glutamic pyruvic transaminase abnormalities and hepatitis B surface antigen carriage (all P values < 0.05). The serum MDA increased in subjects who drank reservoir water and were infected with HBV (P < 0.05). In the cell experiment, ROS increased when Ct-HBX-transfected HepG2 cells were treated with MC-LR, followed by a decrease in SOD and GSH and an increase in MDA. MC-LR combined with Ct-HBX promoted the proliferation, migration and invasion of HepG2 cells, upregulated the mRNA and protein expression of MAOA gene, and downregulated UCP2 and GPX1 genes.Conclusion: MC-LR and HBV may synergistically affect redox status and play an important role in hepatocarcinoma genesis.Keywords: hepatocellular carcinoma, microcystins-LR, hepatitis B virus X gene, redox balance

Zeyu Xie, Jinjian Li, Sensen Yang, Weishang Deng, Jisheng Chen Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, People’s Republic of ChinaCorrespondence: Jisheng Chen, Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangdong, 510080, People’s Republic of China, Tel +86 20-87622305, Fax +86 20-61321967, Email cjslym@163.comPurpose: According to the requirements of the “Quick Guide for Drug Evaluation and Selection in Chinese Medical Institutions”, this health technology assessment provides an evidence-based basis for drug selection and rational clinical use of glucagon-like peptide-1 receptor agonist drugs in medical institutions.Methods: We consult the drug instructions, clinical treatment guidelines and search relevant documents in databases such as China national knowledge infrastructure, Wanfang, PubMed, and government websites such as National Medical Products Administration, Food and Drug Administration, European Medicines Agency, and Pharmaceuticals and Medical Devices Agency to collect and sort out the relevant information of the indications, pharmacological effects, guideline recommendations, drug prices and other information of glucagon-like peptide-1 receptor agonists, using a percentile system systematically evaluate the five dimensions of glucagon-like peptide-1 receptor agonists in terms of pharmaceutical properties, efficacy, safety, economy, and other attributes.Results: The final scores of the evaluation results from high to low are semaglutide (71.00 points), dulaglutide (68.75 points), liraglutide (67.50 points), exenatide (67.00 points), lixisenatide (63.50 points), polyethylene glycol loxenatide (58.00 points) and benaglutide (49.00 points).Conclusion: In clinical practice, semaglutide and dulaglutide are the top two drugs that can be used as recommended drugs. This health technology assessment can provide an evidence-based basis for hospital selection and rational use of glucagon-like peptide-1 receptor agonists. Clinicians can rationally choose and use drugs according to the patient’s conditions and needs.Keywords: glucagon-like peptide-1 receptor agonist, hospital-based health technology assessment, drug selection and evaluation

Ru Chen,1,2,&ast; Bing Hu,1,&ast; Ming Jiang,1,&ast; Wen Deng,1 Ping Zheng,3 Bin Fu1,4 1Department of Urology, the First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, People’s Republic of China; 2Department of Urology, The First Hospital of Putian City, Putian, Fujian, People’s Republic of China; 3Department of Urology, Shangrao municipal Hospital, Shangrao, 334000, Jiangxi Province, People’s Republic of China; 4Jiangxi Institute of Urology, Nanchang City, Jiangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Fu, Email urofbin@163.comObjective: The minichromosome maintenance (MCM) complex (MCM2, MCM3, MCM4, MCM5, MCM6, and MCM7), which regulates DNA replication and cell cycle progression, is essential for the development and progression of multiple tumors, but their role in bladder cancer development remains unclear. In the present study, the biological role and clinical significance of the MCM complex in bladder cancer were systematically elucidated.Materials and Methods: We analyzed DNA mutations, mRNA expression and protein levels, protein–protein interaction (PPI) networks, functional enrichment, prognostic value of MCM2/3/4/5/6/7 in bladder urothelial carcinoma (BLC) and the connections between the immune cell infiltration and the overall survival of BLC patients with the MCM expression levels using Oncomine, Gene Expression Profiling Interactive Analysis (GEPIA), the Cancer Genome Atlas database (TCGA), Human Protein Atlas, UALCAN, STRING, cBioPortal, TIMER and GSCALite databases.Results: The outcomes showed that the mRNA expression level of each member of the MCM complex was significantly correlated with histologic grade and tumor histology in BLC patients. Moreover, survival analysis showed that MCM/2/3/4/5/6/7 mRNA expressions were significantly associated with prognosis in patients with bladder cancer. Moreover, we experimentally validated the overexpression of the MCM2-7 complex in the BLC. Based on functional enrichment and PPI network analysis, the MCM complex might promote the progression of bladder cancer by activating DNA replication and accelerating cell cycle progression. In addition, MCM2/3/4/5/6/7 genes were also significantly associated with tumor immune cells infiltration and the drug sensitivity in BLC.Conclusion: Our study suggests that the MCM complex especially MCM2/4/6/7 might be potential molecular therapeutic targets for BLC treatment and might be useful biomarkers for diagnosis and prognosis.Keywords: bladder cancer, minichromosome maintenance complex, bioinformatics, potential biomarkers

Xiao-Feng Cheng,&ast; Zhen-Hao Zeng,&ast; Wen Deng, Yi-Fu Liu, Xiao-Chen Zhou, Cheng Zhang, Gong-Xian Wang Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang City, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Gong-Xian Wang, Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang City, 330000, Jiangxi Province, People’s Republic of China, Email wanggx-mr@126.comBackground: The aim of this study was to identify novel genetic features of Hunner’s lesion interstitial cystitis (HIC) via comprehensive analysis of the Gene Expression Omnibus (GEO) database.Methods: The GSE11783 and GSE28242 datasets were downloaded from GEO for further analysis. Differentially expressed genes (DEGs) were identified and analyzed for functional annotation. The diagnostic markers for HIC were screened and validated using the least absolute shrinkage and selection operator (LASSO) logistic regression and support vector machine recursive feature elimination (SVM-RFE) algorithms. Finally, the cell-type identification by estimating relative subsets of RNA transcripts (CIBERSORT) algorithm was adopted to investigate the correlation between immune cell infiltration and diagnostic markers in HIC.Results: A total of 7837 DEGs were identified in GSE11783 and 1583 DEGs in GSE28242. Venn diagrams were used to obtain 16 overlapping upregulated and 67 overlapping downregulated DEGs separately. The LASSO logistic model and SVM-RFE algorithm were used to identify 6 genes including KRT20, SLFN11, CD86, ITGA4, PLAC8, and BTN3A3 from DEGs as diagnostic markers for HIC. Their diagnostic potential in HIC and bladder pain syndrome/interstitial cystitis (BPS/IC) were acceptable. PLAC8 exhibited the best diagnostic performance in BPS/IC with an area under the curve of 0.916. The results of immune infiltration involving GSE11783 revealed that the plasma cell ratio (p = 0.017), activated memory CD4+ T cells (p = 0.009), activated dendritic cells (p = 0.01), eosinophils (p = 0.004), and neutrophils (p = 0.03) were significantly higher in HIC than in normal samples, in contrast to resting mast cells (p = 0.022). A positive correlation existed between diagnostic markers and infiltrating immune cells.Conclusion: KRT20, SLFN11, CD86, ITGA4, PLAC8, and BTN3A3 represent novel and potent diagnostic markers for HIC. They also exhibit certain diagnostic potential in BPS/IC. Immune cell infiltration might play a key role in the pathogenesis and progression of BPS/IC.Keywords: interstitial cystitis, Hunner’s lesion, immune cells, diagnostic marker, Gene Expression Omnibus

Xiaoyan Jiang,1,&ast; Fang Deng,1,2,&ast; Shunli Rui,1 Yu Ma,1 Min Wang,1 Bo Deng,1 Hongyan Wang,1 Chenzhen Du,1 Bing Chen,2 Xiuhua Yang,3 Johnson Boey,4 David G Armstrong,5 Wuquan Deng,1 Xiaodong Duan6 1Department of Endocrinology, Chongqing University Central Hospital, School of Medicine Chongqing University, Chongqing, 400014, People’s Republic of China; 2Department of Endocrinology, Chongqing Southwest Hospital, Chongqing, 400038, People’s Republic of China; 3Department of Lower Extremity Surgery, NO.1 Orthopedics Hospital of Chengdu, Chengdu City, 610000, Sichuan, People’s Republic of China; 4Department of Podiatry, National University Hospital, 169608, Singapore; 5Department of Surgery, Keck School of Medicine of University of Southern California, Los Angeles, CA, 90033, USA; 6Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Wuquan Deng, Department of Endocrinology, Chongqing University Central Hospital, School of Medicine Chongqing University, No. 1 Jiankang Road, Yuzhong District, Chongqing, 400014, People’s Republic of China, Tel +86 23 63692185, Email wuquandeng@cqu.edu.cn Xiaodong Duan, Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China, Email duanxiaodong2032@sina.comObjective: Falls often occur in patients with diabetic neuropathy due to biomechanical alternation. The implication of diabetic peripheral neuropathy (DPN) on gait and balance remains poorly understood.Methods: A total of 11 dynamic gait, balance and electrophysiological parameters were evaluated in 176 participants. The biomechanical parameters were compared between groups.Results: Stride length and stride velocity were significantly lower in all subgroups of DPN compared with healthy subjects (p< 0.05). Stance phase and double support phase were significantly higher, but swing phase were significantly lower across all subgroups of DPN than healthy subjects (p< 0.05). Under eyes-open standing, the ML and AP range parameters of CoM sway, ankle sway and hip sway, CoM sway index, ankle swing index in both subclinical and confirmed DPN patients were all significantly higher compared to healthy subjects (p< 0.05). Under eyes-closed standing, AP range parameters of CoM sway in subclinical DPN and confirmed DPN patients were significantly higher than healthy subjects (p< 0.05). The hip sway areas in diabetics were significantly higher compared to healthy subjects (p< 0.05).Conclusion: The abnormal biomechanical parameters existed in the early stages of patients with DPN. The static balance under eyes-open and eye-closed condition is maintained by ankle joint compensation strategy and hip joint protection strategy. An early evaluation and better risk management is essential for diabetic patients with a history of more than 5 years even without DPN clinical symptoms and signs.Clinical Trial Registration Number: No. ChiCTR1800019179, www.chictr.org.cn.Keywords: gait, balance, diabetic peripheral neuropathy, risk assessment, wearable biomechanical system

Ru Chen,1,2,&ast; Zhicheng Zhang,1,&ast; Bing Hu,1,&ast; Ming Jiang,1,&ast; Ping Zheng,3 Wen Deng,1 Bin Fu,1,4 Ting Sun1,4 1Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang City, 330000, Jiangxi Province, People’s Republic of China; 2Department of Urology, The First Hospital of Putian City, Putian, 350001, Fujian, People’s Republic of China; 3Department of Urology, Shangrao municipal Hospital, Shangrao, 334000, Jiangxi Province, People’s Republic of China; 4Jiangxi Institute of Urology, Nanchang City, 330000, Jiangxi Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Fu; Ting Sun, Email urofbin@163.com; 361439919033@email.ncu.edu.cnBackground: Multiple studies have identified that E2F transcriptions act as important regulators for the tumorigenesis and progression of several human cancers. However, little is known about the function of E2Fs in clear cell renal cell carcinoma (ccRCC).Methods: We firstly investigated the expression levels, genetic alteration, and biological function of E2Fs in patients with ccRCC and the connections between the immune cell infiltration and the overall survivals of ccRCC patients with the E2Fs expression levels based on UALCAN, The Cancer Genome Atlas database, Gene Expression Profiling Interactive Analysis, TIMER, STRING, GSCALite and cBioPortal databases.Results: Results revealed that the expression levels of E2F1/2/3/4/6/7/8 were markedly upregulated in patients with ccRCC, while the expression of E2F5 displayed an opposite trend. We also experimentally validated the overexpression of E2F3/4/7 in human ccRCC tissues and ccRCC cell lines. Furthermore, the high E2F1/2/3/4/7/8 expression levels were clearly associated with worse pathological characteristics of ccRCC, including high pathological stage, poor molecular subtypes and high tumor grade. Meanwhile, high expression levels of E2F1/2/4/7/8 were evidently associated with worse overall survivals (OSs) and progression-free survivals (PFSs) of patients harboring ccRCC. Univariate and multivariate analyses illustrated that the expressions of E2F4/5/7 were independent factors associated with the OSs and PFSs of patients with ccRCC. Meanwhile, the mutations in E2Fs were also significantly related to poor OSs and PFSs of patients with ccRCC. Mechanically, the E2Fs genes synergistically promoted the progression of ccRCC by accelerating the cell cycle and inhibiting DNA damage response and apoptosis after performing the protein structure, functional enrichment, and PPI network analyses. In addition, E2Fs genes were also significantly associated with tumor immune cells infiltration and the drug sensitivity in ccRCC.Conclusion: As a result, E2F4/7 were highly expressed in ccRCC and significantly associated with worse pathological characteristics of ccRCC, including high pathological stage, poor molecular subtypes and high tumor grade, tumor immune cell infiltration, and drug sensitivity, consequently translating into poor OSs and PFSs of patients with ccRCC. Our results indicated that E2F4/7 could be potential biomarkers and therapeutic targets of ccRCC patients.Keywords: clear cell renal cell carcinoma, E2Fs, prognosis, UALCAN, GEPIA

Peiqiu Zhu,1– 5 Weiwei Deng,1– 5 Jin Yu,1– 5 Shuxia Yang1– 5 1Department of Dermatology and Venereology, Peking University First Hospital, Beijing, People’s Republic of China; 2Research Center for Medical Mycology, Peking University, Beijing, People’s Republic of China; 3Beijing Key Laboratory of Molecular Diagnosis on Dermatoses, Beijing, People’s Republic of China; 4National Clinical Research Center for Skin and Immune Diseases, Beijing, People’s Republic of China; 5NMPA Key Laboratory for Quality Control and Evaluation of Cosmetics, Beijing, People’s Republic of ChinaCorrespondence: Shuxia Yang; Jin Yu, Tel +86 83573103 ; +86 83573075, Email yangshuxia@bjmu.edu.cn; yujin676@126.comBackground: Thyroxine is important to maintain the normal operation of the body. Both clinical and experimental results show thyroxine is closely related to hair growth, the mechanism of which is not fully understood.Purpose: Investigate the effect of thyroxine receptor agonist, TDM10842, for dorsal hair growth in C3H mice and explore its underlying mechanism.Methods: Depilated mice were applied with the TDM10842, vehicle of this drug and without any materials on dorsal skin. RNA‐sequencing (RNA‐seq) was employed to identify the change in gene expression of skin tissues. Quantitative real-time PCR (rt-PCR) and immunoblotting were conducted to validate key differentially expressed genes (DEGs) between different groups.Results: The TDM group showed early induction of anagen. 857, 782, and 276 differentially expressed genes were identified between 3 groups. As a critical DEG in group TDM, Pclaf was positively related to the motivation of Wnt/beta-catenin and Hedgehog signaling pathways, with a high expression of Ki67 and cyclinD1.Conclusion: TDM10842 accelerates the anagen entrance and the potential mechanism might be the activation of Wnt/beta-catenin and Hedgehog pathways. Pclaf serves as a critical molecule involved in pathway activation, and cyclinD1 is an important effector protein downstream of the pathways.Keywords: thyroid hormone receptor, C3H mice, hair cycle, Pclaf, Wnt/beta-catenin pathway, Hedgehog pathway

Xi Zhang,1,&ast; Hongyan Wang,1,&ast; Chenzhen Du,1 Xiaoyun Fan,2 Long Cui,3 Heming Chen,4 Fang Deng,5 Qiang Tong,6 Min He,7 Mei Yang,8 Xingrong Tan,9 Lin Li,10 Zerong Liang,11 Yaqin Chen,12 Deqing Chen,13 David G Armstrong,14 Wuquan Deng1 1Department of Endocrinology, Chongqing University Central Hospital, Chongqing University, Chongqing, People’s Republic of China; 2Department of Endocrinology, Hospital for Occupational Diseases of Chongqing, Chongqing, People’s Republic of China; 3Department of Endocrinology, Armed Police Hospital of Chongqing, Chongqing, People’s Republic of China; 4Department of Endocrinology, Ankang Central Hospital, Ankang, Shaanxi, People’s Republic of China; 5Department of Endocrinology, Chongqing Southwest Hospital, Chongqing, People’s Republic of China; 6Department of Endocrinology, Chongqing Xinqiao Hospital, Chongqing, People’s Republic of China; 7Department of Endocrinology, The People’s Hospital of Shapingba District, Chongqing, People’s Republic of China; 8Department of Endocrinology, The First People’s Hospital of Chongqing Liangjiang New Area, Chongqing, People’s Republic of China; 9Department of Endocrinology, The 9th People’s Hospital of Chongqing, Chongqing, People’s Republic of China; 10Department of Endocrinology, Zhejiang University School of Medicine Sir Run Run Shaw Hospital, Hangzhou, People’s Republic of China; 11Department of Endocrinology, Chongqing Red Cross Hospital, People’s Hospital of Jiangbei District, Chongqing, 400020, People’s Republic of China; 12Department of Endocrinology, The People’s Hospital of Shizhu, Chongqing, People’s Republic of China; 13Department of Endocrinology, The People’s Hospital of Rongchang, Chongqing, People’s Republic of China; 14Department of Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA&ast;These authors contributed equally to this workCorrespondence: Wuquan Deng Email wuquandeng@cqu.edu.cnBackground: Recurrence of high-risk diabetic feet, after wound, healing is a common challenge among diabetic patients. Continuous use of an offloading device significantly prevents recurrence of high-risk diabetic feet, although patient adherence is imperative to ensuring this therapy’s clinical efficacy. In this study, we explored clinical outcomes of patients with a high-risk diabetic foot who had been prescribed with custom-molded offloading footwear under different adherence conditions.Methods: A total of 48 patients (17 females and 31 males) with high-risk diabetic feet, who had been with prescribed offloading footwear in 13 medical centers across 4 cities, were enrolled in the current study. The patients were assigned into either continuous offloading therapy (COT, n = 31) or interrupted offloading therapy (IOT, n = 17) groups, according to their adherence to the therapy. All patients were followed up monthly, and differences in recurrence, amputation, and deaths between the groups were analyzed at 4 months after therapy.Results: Forty-eight patients met our inclusion criteria and were therefore included in the final analysis. Among them, 31 were stratified into the COT group and adhered to offloading therapy throughout the study period, whereas 17 were grouped as IOT and exhibited interrupted adherence to offloading therapy. We found statistically significant differences in recurrence rates (0 vs 38.46%, p < 0.01), amputation (0 vs 11.76%, p < 0.01), and deaths (0% vs 5.88%, p < 0.01) between the groups during follow-up.Conclusion: Patients’ adherence is imperative to efficacy of custom-molded offloading footwear during treatment of high-risk diabetic foot. Further studies are needed to elucidate the role of improved design of the offloading device and the need for enhanced patient education for improved adherence.Keywords: custom-molded offloading footwear, high-risk diabetic foot, patient adherence

Shuyi Li,1 Mengke Niu,2 Wenying Deng,1 Ning Li,1 Chen Wei,1 Chi Zhang,1 Suxia Luo1 1Department of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou, 450008, Henan Province, People’s Republic of China; 2Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, Hubei Province, People’s Republic of ChinaCorrespondence: Suxia LuoDepartment of Medical Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, No. 127 Dongming Road, Zhengzhou, 450008, Henan Province, People’s Republic of ChinaTel +86 371 65587805Email zlyyluosuxia0361@zzu.edu.cnBackground: Primary hepatic neuroendocrine carcinoma (PHNEC) is a rare liver tumor, and there is no clear therapeutic recommendation for patients with advanced PHNEC. This study aims to compare the efficacy of platinum-based chemotherapy (etoposide combined with cisplatin/carboplatin, EP/EC) and transcatheter arterial chemoembolization (TACE) in patients with advanced PHNEC, and to evaluate the relevant prognostic factors.Patients and Methods: The clinical data of 41 patients with advanced PHNEC from June 2014 to October 2019 were retrospectively reviewed.Results: At a median follow-up time of 13.9 months, the median overall survival (OS) was 14.8 months in the EP/EC group and 12.2 months in the TACE group (P = 0.040). The median progression-free survival (PFS) was 4.4 months and 2.7 months in the EP/EC group and the TACE group, respectively (P = 0.005). No significant differences in the overall response rate and disease control rate were observed between the EP/EC group and the TACE group (26.1% vs 11.1%, P = 0.429; 73.9% vs 44.4%, P = 0.055, respectively). A univariate analysis indicated that the Eastern Cooperative Oncology Group performance status (ECOG PS), Ki-67, tumor number, and treatment options were prognostic factors for OS. A multivariate analysis further showed that ECOG PS (P < 0.001), Ki-67 (P = 0.003), and treatment options (P = 0.022) were independent prognostic factors for OS.Conclusion: Ki-67, ECOG PS, and treatment options were the independent prognostic factors for OS in patients with advanced PHNEC. EP/EC may be a better choice for patients with advanced PHNEC.Keywords: chemotherapy, transcatheter arterial chemoembolization, hepatic neuroendocrine carcinoma, prognosis

Wen Deng,1,&ast; Gongxian Wang,1,&ast; Huanhuan Deng,2,&ast; Yan Yan,3,&ast; Ke Zhu,1,&ast; Ru Chen,1,4 Xiaoqiang Liu,1 Luyao Chen,1 Tao Zeng,2 Bin Fu1 1Department of Urology, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, People’s Republic of China; 2Department of Urology, The Second Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, People’s Republic of China; 3Department of Nephrology, The First Affiliated Hospital of Nanchang University, Nanchang City, Jiangxi Province, People’s Republic of China; 4Department of Urology, The First Hospital of Putian City, Putian City, Fujian Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Bin Fu; Tao Zeng Tel + 86 13879103861; +86 18779101830Fax +86 0791-88698102; +86 0791-86120120Email urofbin@163.com; taozeng40709@sina.comPurpose: This study aimed to evaluate the functions of critical N6-methyladenosine (m6A)-related long non-coding RNAs (lncRNAs) and their correlations with immunotherapeutic targets in clear cell renal cell carcinoma (ccRCC).Methods: m6A-related lncRNAs were analyzed using the dataset from The Cancer Genome Atlas database via Pearson correlation analysis. Then, their prognostic functions in patients with ccRCC were determined via univariate Cox analysis. A prognostic m6A-related lncRNA signature (MRLS) in ccRCC was established using the least absolute shrinkage and selection operator (LASSO) Cox regression model. In addition, the correlations between these prognostic m6A-related lncRNAs with immune checkpoints were further evaluated in clinical samples.Results: MRLS was established by the LASSO Cox regression model on the basis of seven prognostic m6A-related lncRNAs. The risk score for each patient was calculated using the MRLS model, and the patients were further stratified into high- and low-risk subgroups. The MRLS model was validated with a robust prognostic ability by the stratification analysis. On the basis of age, grade, stage, and risk score, a nomogram was developed with a strong reliability in forecasting the overall survival percentages of the patients with ccRCC. Moreover, seven prognostic m6A-related lncRNAs enrolled in the MRLS model were found to be correlated with various immunotherapeutic targets, namely, PD-1, PD-L1, CTLA4, and LAG3, and the expression levels of which in the high-risk subgroup were significantly higher than those in the low-risk subgroup. The significant correlations between LINC00342 and the aforementioned immunotherapeutic targets were also confirmed in clinical samples.Conclusion: In this study, seven m6A-related lncRNAs were identified as potential biomarkers for forecasting the prognosis of patients with ccRCC and evaluating the efficacy of immunotherapy for these patients. Furthermore, a prognostic and predictive MRLS model with a high reliability was constructed to predict the overall survival probability of patients with ccRCC.Keywords: immunotherapy, N6-methyladenosine modification, long non-coding RNA, renal cell carcinoma, prognosis

Xiaonan Zhang,1,&ast; Huimin Fang,1,&ast; Zhigang Zeng,1 Kaijun Zhang,1 Zhanyi Lin,1,2 Gang Deng,1 Weiping Deng,1 Lichang Guan,1 Xuebiao Wei,1 Xinyi Li,2 Lei Jiang,1– 3 Lishu Xu1– 3 1Guangdong Provincial Geriatrics Institute, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, Guangzhou, 510080, People’s Republic of China; 2School of Medicine, South China University of Technology, Guangzhou, 510641, People’s Republic of China; 3The Second School of Clinical Medicine, Southern Medical University, Guangzhou, 510515, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lei Jiang; Lishu Xu Tel +86-20-83827812; +86-20-13660032429Email jianglei@smu.edu.cn; xulishu70@163.comPurpose: Gastric cancer is a common tumor type associated with nutritional and immune status. The aim of the current study was to investigate the prognostic value of a preoperative prognostic nutritional index (PNI), composed of nutritional factors and immune factors in elderly patients undergoing gastric cancer surgery.Patients and Methods: A total of 454 patients undergoing gastric cancer surgery were divided into two groups based on preoperative PNI scores: ≤ 45.1 (n = 307) and > 45.1 (n = 147). Survival analysis was performed using the Kaplan–Meier method and Log rank tests. Univariate and multivariate analyses were conducted to identify independent prognostic factors using a Cox proportional hazards model.Results: According to the X-tile program, the optimal cutoff value for predicting overall survival (OS) with the PNI was 45.1. The receiver operating characteristic analysis revealed that PNI exhibited 70.6% sensitivity and 56.5% speci&filig;city for predicting death during long-term follow-up. The cumulative incidence of postoperative 4-year mortality indicated that the risk of death increased significantly for PNI ≤ 45.1. In multivariate analysis, preoperative PNI was a significant independent predictor of mortality. In the age-stratified subgroup analysis, preoperative PNI was more sensitive for the old elderly subgroup than for the young elderly subgroup.Conclusion: Preoperative PNI is a sensitive and specific prognostic predictor among elderly patients undergoing gastric cancer surgery.Keywords: elderly patients, gastric cancer, prognostic nutritional index, radical gastrectomy

Bo Deng,1,* Yi Yuan,1,* Miao Zhong,1,* Rui Ren,1 Wuquan Deng,1 Xiaodong Duan2 1Department of Endocrinology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing, 400014, People’s Republic of China; 2Department of Rehabilitation, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Xiaodong Duan Email duanxiaodong2032@sina.comAim: The relationship between thyroid status and metabolic factors was investigated as well as iodine nutrition in the general population and among the elderly population.Methods: We performed a cross-sectional survey of 2483 subjects to assess the status of national iodine nutrition and incidence of thyroid disease. The general and elderly populations were divided into normal thyroid function (NTF) and subclinical hypothyroidism (SCH) groups. The anthropometric parameters and biochemical indicators were then analyzed.Results: Overall, 327 participants were diagnosed with thyroid diseases, 73 (22.32%) of whom were 65 years or older. For the general population, compared with the NTF group, individuals in the SCH group were older, presented with higher systolic blood pressure, fasting blood glucose, serum cholesterol, and urinary iodine concentration (all p< 0.05) but lower blood uric acid (UA) (p< 0.05). Linear regression analysis further revealed that age and triglyceride (TG) serum levels positively correlated with serum thyroid-stimulating hormone (TSH) levels. Multiple regression analyses revealed that age, TG, waist circumference (WC), and body mass index were independent predictors for abnormal TSH serum levels. For the elderly population, compared with NTF group, individuals in the SCH group were substantially older (p< 0.05) but presented with lower UA (p< 0.05). Pearson linear regression analysis revealed a positive correlation between age (p=0.003) as well as TG levels (p< 0.001) and serum TSH levels. In contrast, WC (p=0.003) was negatively related to TSH serum levels. Further multiple regression analysis revealed that age, TG, WC and heart rate were independent predictors of blood TSH.Conclusion: The large-scale national study of iodine nutrition, thyroid disease has shown a vital relationship between metabolic indicators and serum TSH levels. Age and metabolic diseases increase the likelihood of developing thyroid diseases, both the general population and among the elderly.Keywords: thyroid function, metabolic status, aging

Peiyan Ni,1– 3 Manli Liu,1– 3 Dequan Wang,1– 3 Yang Tian,1– 3 Liansheng Zhao,1– 3 Jinxue Wei,1– 3 Xueli Yu,1– 3 Xueyu Qi,1– 3 Xiaojing Li,1– 3 Hua Yu,1– 3 Rongjun Ni,1– 3 Xiaohong Ma,1– 3 Wei Deng,1– 3 Wanjun Guo,1– 3 Qiang Wang,1– 3 Tao Li1– 4 1The Psychiatric Laboratory, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 2Mental Health Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 3Huaxi Brain Research Center, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of China; 4Guangdong-Hong Kong-Macao Greater Bay Area Center for Brain Science and Brain-Inspired Intelligence, Guangzhou, People’s Republic of ChinaCorrespondence: Tao LiThe Psychiatric Laboratory, West China Hospital, Sichuan University, 28 Dian Xin Nan Road, Chengdu, Sichuan, 610041, People’s Republic of ChinaTel/Fax +86-28-85423561Email litaohx@scu.edu.cnIntroduction: Schizophrenia, bipolar disorder (BD), and major depressive disorder are three common mental disorders. Although their diagnosis and treatment differ, they partially overlap.Methods: To explore the similarities and characteristics of these three psychiatric diseases, an intelligence quotient (IQ) assessment was performed to evaluate cognitive deficits. Relative catechol-O-methyltransferase (COMT) expression in peripheral blood mononuclear cells was examined in all three groups compared with healthy controls (HCs).Results: The results indicated that patients with any of the three psychiatric diseases presented IQ deficits, and that the first-episode schizophrenia (FES) group had even lower cognitive function than the other two groups. The relative COMT expression decreased in the FES group and increased in the BD group compared with the HC group. The correlation analysis of COMT expression level and IQ scores showed a positive correlation between relative COMT expression and full-scale IQ in the HC group. However, this correlation disappeared in all three psychiatric diseases studied.Conclusion: In conclusion, this cross-disease strategy provided important clues to explain lower IQ scores and dysregulated COMT expression among three common mental illnesses.Keywords: first-episode schizophrenia, FES, bipolar disorder, BD, first-episode major depressive disorder, MDD, catechol-O-methyltransferase, COMT, intelligence quotient, IQ

Solubility of CO2 in molten Li2CO3-LiCl was measured by a pressure differential method, and the enthalpy change of the solution was calculated on that basis. The relationships between the solubility and the enthalpy change, and the temperature and the composition of the melts were discussed. The results showed that when the temperature was 873–923 K and the Li2CO3 content was 10–50 mol%, the solubility of CO2 increased with decreasing temperature and/or increasing Li2CO3 content. The maximum solubility was 3.965 × 10−7gCO2/gmelt at 873 K when the content of Li2CO3 was 50 mol%. The solution of CO2 was exothermic. With increasing temperature and Li2CO3 content, more enthalpy was needed for CO2 solution.

Zhengping Li,* Xiaozhong Yuan,* Wei Deng Department of Anesthesiology and Pain Medicine, The Affiliated Hospital of Jiaxing University, Jiaxing, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei Deng Email dengwei1992868@163.comBackground: Positive-pressure ventilation (PPV) delivered via a facemask during anesthesia induction can result in gastric content being inhaled into the lungs. We hypothesized that the real-time ultrasound left paratracheal esophagus monitoring could more effectively reduce air entry into the stomach than real-time ultrasound monitoring of the gastric antrum (GA).Methods: Patients were divided into two groups: study (S; n=30) and control (C; n=30) groups. During the induction of general anesthesia, mask ventilation adopts a pressure control mode. The initial ventilation pressure of both groups was 15 cmH2O. Before anesthesia induction, an ultrasonic probe was used to monitor the cross-sectional area (CSA) of the GA and the presence of gas in the stomach. During and after anesthesia induction, group S used a high-frequency ultrasound probe to observe the entry of air from the left paratracheal esophagus into the GA. The ventilation pressure was gradually reduced over time until no esophageal air was found. In group C, the ventilatory pressure was set maintained at 15 cmH2O and the CSA of the GA and air intake were monitored using an ultrasonic probe.Results: Before and after PPV, the CSA of the GA in group S decreased (P< 0.001), whereas the CSA in group C increased (P=0.002). The GA CSA in group C after PPV was larger than in group S after PPV (P=0.002). The proportion of patients who experienced intragastric air intake in group S (23.3%) was significantly lower than that in group C (66.7) (P=0.001).Conclusion: Compared with ultrasound monitoring of the GA, real-time ultrasound detection of LPEOAE into the GA during anesthesia induction was more effective, more sensitive, significantly reduced the prevalence of intragastric air intake, and provided sufficient tidal volume and oxygen for patients.Keywords: left paratracheal esophagus, anesthesia, ultrasonography, gastric antrum

Yi Liang,1 Lv Lv,2 Liang He,1 Wei Deng,3 Cai Chen,1 Jingjuan Li1 1Department of Anesthesiology, The Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of China; 2Emergency Department, The Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of China; 3Department of Anesthesiology, The First Hospital of Jiaxing (Affiliated Hospital of Jiaxing University), Jiaxing, People’s Republic of ChinaCorrespondence: Liang HeDepartment of Anesthesiology, The Affiliated Hospital of Guilin Medical University, Lequn Road 15#, Guilin 541001, People’s Republic of ChinaTel +8613659633168Email jimyliang@hotmail.comBackground and Objectives: Patients with femoral neck fractures often suffer severe pain. This randomized controlled clinical study compared the effect of femoral nerve block (FNB) and fascia iliaca compartment block (FICB) in this population.Patients and Methods: Forty-six patients were randomly assigned to one of the two groups: FNB group (femoral nerve block, n=23) or FICB group (fascia iliaca compartment block, n=23). Before positioning for spinal anesthesia, patients received FNB with 15 mL of 0.5% ropivacaine or FICB with 40 mL of 0.5% ropivacaine. Pain was evaluated using a visual analogue scale (VAS) at rest and during hip flexion after admission to the operation room; at 3, 5, 8, and 10 min after analgesia intervention; and during positioning for spinal anesthesia. Positioning was attempted after 10 min of analgesia intervention in each group. Time required to perform spinal anesthesia, quality of positioning, and patient satisfaction were documented.Results: The VAS scores in the FNB group were significantly lower than those in FICB group at 3 and 5 min after analgesia intervention (P=0.000). However, there were no significant differences in VAS between groups at 8 or 10 min or during positioning.Conclusion: FNB and FICB produce similar analgesic effects in patients with femoral neck fractures, but FNB has a more rapid onset of pain relief.Keywords: femoral neck fracture, femoral nerve block, fascia iliaca compartment block, analgesia

Zaibing Li,1,2,* Jingyu Li,1,* Liyan Liu,1 Wenyi Deng,3 Qingrong Liu,4 Ruofan Liu,4 Wen Zhang,3 Zaiqing He,5 Lei Fan,6 Yingzhuo Yang,7 Yun Duan,7 Huifang Hou,1 Xinyuan Wang,1 Zhimei Yang,1 Xiaoying Wang,1 Shanze Chen,1 Yi Wang,1 Ning Huang,1 Junli Chen1 1Department of Pathophysiology, West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, People’s Republic of China; 2Department of Pathophysiology, School of Basic Medical Science, Southwest Medical University, Luzhou, Sichuan 646000, People’s Republic of China; 3West China Medical School, Sichuan University, Chengdu 610041, People’s Republic of China; 4West China School of Basic Medical Sciences & Forensic Medicine, Sichuan University, Chengdu 610041, People’s Republic of China; 5Department of Pathology, Nuclear of Industry 416 Hospital, Chengdu, Sichuan 610051, People’s Republic of China; 6Department of Occupational Medicine, Nuclear of Industry 416 Hospital, Chengdu, Sichuan 610051, People’s Republic of China; 7Department of Nuclear Medicine, Sichuan Cancer Hospital, Chengdu 610041, People’s Republic of China*These authors contributed equally to this workCorrespondence: Junli Chen; Ning Huang Email chenjunlinsf@163.com; ninghuangcjl@163.comBackground: α2A-adrenoceptor (AR) is a potential target for the treatment of degenerative diseases of the central nervous system, and α2A-AR agonists are effective drugs for this condition. However, the lack of high selectivity for α2A-AR subtype of traditional drugs greatly limits their clinic usage.Methods: A series of homobivalent 4-aminoquinolines conjugated by two 4-aminoquinoline moieties via varying alkane linker length (C2-C12) were characterized for their affinities for each α2-AR subtype. Subsequently, docking, molecular dynamics and mutagenesis were applied to uncover the molecular mechanism.Results: Most 4-aminoquinolines (4-aminoquinoline monomer, C2-C6, C8-C10) were selective for α2A-AR over α2B- and α2C-ARs. Besides, the affinities are of similar linker length-dependence for each α2-AR subtype. Among all the compounds tested, C10 has the highest affinity for α2A-AR (pKi=− 7.45± 0.62), which is 12-fold and 60-fold selective over α2B-AR and α2C-AR, respectively. Docking and molecular dynamics suggest that C10 simultaneously interacts with orthosteric and “allosteric” sites of the α2A-AR. The mutation of F205 decreases the affinity by 2-fold. The potential allosteric residues include S90, N93, E94 and W99.Conclusion: The specificity of C10 for the α2A-AR and the potential orthosteric and allosteric binding sites proposed in this study provide valuable guidance for the development of novel α2A-AR subtype selective compounds.Keywords: alpha2-adrenoceptor, selectivity, linker length, allosteric modulation

Xiaoyan Jiang,1,* Ning Li,1,* Yi Yuan,1 Cheng Yang,1 Yan Chen,1 Yu Ma,1 Jianbai Wang,2 Dingyuan Du,2 Johnson Boey,3 David G Armstrong,4 Wuquan Deng1 1Department of Endocrinology and Nephrology, Diabetic Foot Center, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, People’s Republic of China; 2Department of Traumatology, Diabetic Foot Center, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, People’s Republic of China; 3Department of Podiatry, National University Hospital, Singapore; 4Keck School of Medicine of University of Southern California, Los Angeles, CA, USA*These authors contributed equally to this workCorrespondence: Wuquan DengDepartment of Endocrinology and Nephrology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, No. 1 Jiankang Road, Chongqing 400014, People’s Republic of ChinaTel +86 23 63692186Email wuquandeng@gmail.comAbstract: Biomechanical changes caused by structural foot deformities predispose patients to plantar ulceration. Plantar ulcer recurrence often leads to osteomyelitis, which is more commonly observed in patients with diabetes. Once the infection of diabetic foot ulcer (DFU) spreads and is complicated by osteomyelitis, treatment becomes more complicated and difficult. Osteomyelitis treatment remains challenging because of low drug concentration within the tissue caused by poor circulation and inadequate localized nutrition. Moreover, tissues around plantar ulcers are fewer and are thin, making the formation of granulation tissues difficult due to elevated plantar pressure. Furthermore, the skin around the wound is excessively keratinized, and the epidermis is hard to regenerate. Meanwhile, skin grafting at that site is often not successful due to poor blood circulation. Therefore, it is technically challenging to manage diabetic pressure plantar ulcer with osteomyelitis and prevent its recurrence. Here, we present a case of chronic DFU complicated by osteomyelitis due to foot deformity. The ulcer was successfully healed using advanced wound repair technology comprising of surgical bone resection, vancomycin-loaded bone cement implant, negative-pressure wound therapy, and autologous platelet-rich gel. Subsequently, preventive foot care with custom-made offloading footwear was prescribed. The plantar ulcer did not recur and improvement in biomechanical parameters was observed after the intervention. This case represents an effective and comprehensive management strategy for limb salvage and prevention in patients with complicated foot conditions.Keywords: diabetic foot ulcer, osteomyelitis, antibiotic-loaded bone cement, autologous platelet-rich gel, negative-pressure wound therapy, offloading footwear

Wei Deng,1,* Dan Fu,2,* Liang He3 1Department of Anesthesiology, The First Hospital of Jiaxing (Affiliated Hospital of Jiaxing University), Jiaxing, People’s Republic of China; 2Department of Paediatrics, Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of China; 3Department of Anesthesiology, Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liang HeDepartment of Anesthesiology, Affiliated Hospital of Guilin Medical University, Guilin, People’s Republic of ChinaEmail jimyliang@hotmail.comBackground: Pectoral nerve block type I (PECS I Block) and type II (PECS II Block) with ropivacaine are relatively new analgesic methods for breast-cancer surgery. We evaluated the safety and efficacy of different concentrations of ropivacaine given in the same volume for the PECS II Block in patients undergoing modified radical mastectomy (MRM).Patients and Methods: One hundred and twenty women undergoing elective MRM who met inclusion criteria were divided randomly into four groups of 30: control group without PECS II Block and R0.2%, R0.3%, and R0.4% groups, who received general anesthesia plus the PECS II Block with ropivacaine at 0.2%, 0.3%, and 0.4%, respectively, in a volume of 40 mL.Results: The postoperative numerical rating scale (NRS) pain score at rest and active was significantly higher in the control group than that in the three ropivacaine groups (P< 0.05 for all), and the postoperative NRS score in the R0.3% group and R0.4% group at 12, 24, and 48 h postoperatively were significantly lower than that in the R0.2% group (P< 0.05 for all); there was no significant difference between the R0.3% group and R0.4% group. The time when pain was first felt after MRM, the total number of complaints during 3, 6, 12, 24, and 48 h after MRM, and the total analgesic requirement (tramadol consumption) during the first 24 h postoperatively in the R0.3% group and R0.4% group were significantly lower than those in the control group and R0.2% group (P< 0.05 for all); there was no significant difference between the R0.3% group and R0.4% group.Conclusion: A dose of 0.3% ropivacaine was the optimal concentration for a PECS II Block for patients undergoing MRM because it provided efficacious analgesia during and > 48 h after MRM. Increasing the ropivacaine concentration did not improve the analgesia of the PECS II Block significantly.Keywords: modified radical mastectomy, pectoral nerve block, postoperative analgesia

Wenhao Man,* Huajun Lin,* Zhao Liu, Lei Jin, Jin Wang, Jun Zhang, Zhigang Bai, Hongwei Yao, Zhongtao Zhang, Wei Deng Department of General Surgery, Beijing Friendship Hospital, Capital Medical University and National Clinical Research Center for Digestive Diseases, Beijing 100050, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei DengDepartment of General Surgery, Beijing Friendship Hospital, Capital Medical University, No. 95 Yongan Road, Xicheng District, Beijing 100050, People’s Republic of ChinaTel +86 134 2613 6152Email dengweiwei@126.comPurpose: We aimed to investigate the value of inflammation-based prognostic scores for predicting early complications after radical surgery for colorectal carcinoma.Methods: We retrospectively analyzed data of 154 patients who underwent elective resection of colorectal carcinoma between January 2017 and December 2018 at Beijing Friendship Hospital. Univariate, multivariate, and receiver operating characteristic curve analyses were conducted. As inflammation indices, we evaluated the preoperative modified Glasgow Prognostic Score (GPS), as well as the C-reactive protein/albumin ratio (CAR), postoperative GPS, and C-reactive protein levels on postoperative day 3 (POD3).Results: Within 30 days postoperatively, complications occurred in 80 patients (51.9%). And high levels of preoperative mGPS (P=0.002), preoperative CAR (P=0.019), POD3 CAR (P< 0.001) and POD3 poGPS (P< 0.001) can significantly affect postoperative complications after surgery for colorectal cancer, with CRP on POD3 (odds ratio, 1.015; 95% confidence interval, 1.006– 1.024; P=0.001) as independent risk factors. Among all inflammation-based indicators, POD3 CAR had the highest area under the curve (0.711) and positive predictive value (83.2%). Higher CAR (≥ 2.6) on POD3 was associated with a higher rate of complications (92.9% vs 36.6%, P< 0.001), especially of infectious nature (54.8% vs 16.1%, P< 0.001).Conclusion: CAR≥ 2.6 on POD3 reflects sustained systemic inflammation and represents a useful predictor of complications after surgery for colorectal carcinoma, facilitating early detection, timely intervention, and enhanced recovery.Keywords: C-reactive protein, albumin, Glasgow Prognostic Score, colorectal carcinoma, surgery, postoperative complications, risk prediction

Song Cao,1,2 Jie Yuan,1,2 Dexing Zhang,1 Song Wen,1 Jie Wang,1 Ying Li,1 Wenwen Deng3 1Department of Pain Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, People’s Republic of China; 2Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Zunyi 563003, People’s Republic of China; 3Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, People’s Republic of ChinaCorrespondence: Ying LiDepartment of Pain Medicine, Affiliated Hospital of Zunyi Medical University, 149 Dalian Street, Zunyi 563000, People’s Republic of ChinaEmail zyliying1219-0321@163.comWenwen DengDepartment of Cardiology, Affiliated Hospital of Zunyi Medical University, 149 Dalian Street, Zunyi 563000, People’s Republic of ChinaEmail 912395627@qq.comBackground: Mechanisms of neuropathic pain are not fully understood. Molecular changes in spinal dorsal horn take part in the initiation and development of neuropathic pain.Methods: To detect the transcriptome changes in the dorsal spinal cord of neuropathic pain rat, sciatic nerve chronic constriction injury (CCI) rats were used. Then, the CCI ipsilateral dorsal spinal cords of lumbar L3-L5 segments were collected at 14th day post-CCI and subjected to microRNA and long non-coding RNA (lncRNA)/mRNA microarray. To evaluate functions of differential mRNAs, bioinformatics methods including gene ontology (GO) and KEGG pathway analysis were conducted for significantly up- and downregulated mRNAs.Results: MicroRNA microarrays showed that 13 microRNAs were differently expressed between CCI and sham-operated rats (fold change ≥ 2.0). Six of them were upregulated, and the other seven were downregulated in CCI group. MicroRNA-1b overexpressed 18.7 times after CCI. LncRNA/mRNA microarray detected 876 lncRNAs with significant differential expression (fold change ≥ 2.0). Among them, 339 were significantly upregulated, and 537 were downregulated in CCI group. Sixteen of them differentially expressed more than 10 times and the lncRNA XR_356687 overexpressed as high as 53 times. In addition, 950 mRNAs were differentially expressed (fold change ≥ 2.0), including 405 upregulated and 545 downregulated in CCI group. Ten of these mRNAs with changed expressions of more than 10 times. The Hspa1b (encodes heat shock protein 70) overexpressed 24 times in CCI rats. Gene ontology analysis revealed that hundreds of differentially expressed mRNAs involved in the biological processes, cellular component, and molecular function. In addition, these genes significantly enriched into 32 KEGG pathways, including the TNF, FoxO, cytokine–cytokine receptor interaction, and calcium signaling pathways.Conclusion: Neuropathic pain induced comprehensive changes of transcription profile in the dorsal spinal cord. These differentially expressed transcripts in spinal cord could be potential targets in defeating neuropathic pain.Keywords: neuropathic pain, peripheral nerve injury, microRNA, long non-coding RNA, mRNA, pathways, spinal dorsal horn, chronic constriction injury

Song Cao,1,2 Dexin Zhang,1 Jie Yuan,1,2 Chengxi Liu,2 Wenjing Zhou,2 Lin Zhang,2 Shouyang Yu,2 Bangyong Qin,1 Ying Li,1 Wenwen Deng3 1Department of Pain Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, People’s Republic of China; 2Guizhou Key Laboratory of Anesthesia and Organ Protection, Zunyi Medical University, Zunyi 563003, People’s Republic of China; 3Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, People’s Republic of ChinaCorrespondence: Song CaoDepartment of Pain Medicine, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, People’s Republic of ChinaTel +8618212170434 Email caosong4321@163.com Wenwen Deng Department of Cardiology, Affiliated Hospital of Zunyi Medical University, Zunyi 563000, People’s Republic of ChinaTel +8615085064354Email 912395627@qq.comAbstract: Mechanisms of postherpetic neuralgia (PHN) are still not clear. Transcripts such as microRNA (miRNA) and circular RNA (circRNA) in the affected skin may take part in the initiation and development of this neuropathic pain; however, their expression profiles in skins of PHN patients have not been reported. The PHN affected skin and the mirror skin were collected and subjected to miRNA and circRNA microarray, and expression profiles were comparatively analyzed. There were 317 differently expressed miRNAs in PHN affected skin compared with mirror skin (fold change ≥2.0), and 13 of them showed fold change >10 in the PHN skin. Only one circRNA, hsa_circRNA_405463 showed fold change >2 in PHN skin, however, 31 circRNAs with fold change ≥1.5. To evaluate functions of differential miRNAs, their target mRNAs were predicted and bioinformatics analyses including gene ontology, Kyoto Encyclopedia of Genes and Genomes pathway were conducted. Target mRNAs significantly (P

Rui Ren,1,2 Yu Ma,2 Fang Deng,1 Tao Li,1 Hongyan Wang,2 Jing Wei,3 Xiaoyan Jiang,2 Min He,1 Mingyuan Tian,4 Dongfang Liu,4 Bing Chen,1 Wuquan Deng1,21Department of Endocrinology and Nephrology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing, People’s Republic of China; 2Department of Endocrinology, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China; 3Department of Endocrinology, General Hospital of Xinjiang Military Region, PLA, Urumqi, People’s Republic of China; 4Department of Endocrinology, The Second Affiliated Hospital, Chongqing Medical University, Chongqing, People’s Republic of ChinaCorrespondence: Wuquan DengDepartment of Endocrinology and Nephrology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, No. 1 Jiankang Road, Yuzhong District, Chongqing, People’s Republic of ChinaTel +86 236 369 2185Email wuquandeng@gmail.comBackground: Whether a relationship exists between various metabolic factors and thyroid-stimulating hormone (TSH) levels in euthyroid persons remains unknown. This study aims to explore the relationship between TSH levels and metabolic factors in euthyroid individuals.Methods: A total of 2,663 subjects were enrolled from a nationwide population-based cross-sectional survey of iodine nutrition, thyroid disease and diabetes in China (2014–2017). Euthyroid individuals were divided into four groups according to quartiles of TSH levels: group A (n=305, 0.3–1.3 mIU/L), group B (n=829, 1.3–2.2 mIU/L), group C (n=673, 2.2–3.2 mIU/L) and group D (n=349, 3.2–4.2 mIU/L). Anthropometric parameters, biochemical indicators and TSH levels were determined.Results: A total of 2,156 euthyroid subjects with serum TSH levels within the normal range accounted for 86.8% of the sample. The systolic blood pressure (SBP) in group D was significantly higher than that in the other three groups. Group C displayed significantly lower thyroid peroxidase antibody (TPOAb) levels than the other three groups. Group C also had lower anti-thyroglobulin antibody (TgAb) levels than groups A and D, whereas the TgAb levels in group B were only lower than those in group A. Spearman’s or Pearson’s linear regression analysis showed that SBP (r=0.054; P=0.013) was positively correlated with TSH, but cholesterol (TC) (r=−0.043, P=0.047) was negatively correlated with TSH. Multiple stepwise regression analysis revealed that SBP, the urinary iodine concentration (UIC), waist circumference (WC), body mass index (BMI), TC, triglycerides (TGs) and low-density lipoprotein cholesterol (LDL-C) were independent predictors of serum TSH levels.Conclusion: This large population-based study demonstrates a significant interaction between metabolic factors and TSH levels. An adverse weight status, high blood pressure levels, blood lipid metabolism disorder and excessive iodine intake may be early manifestations of thyroid disease in euthyroid subjects.Keywords: thyroid-stimulating hormone, metabolic syndrome, iodine nutrition, euthyroid state

Yayun Chen,1,2 Xiao Yang,1,2 Xiaorong Qin,3 Qin Yang,3 Huanhuan Fan,1,2 Jun Li,4 Xiuli Song,1,2 Shuang Xu,4 Wanjun Guo,1,2 Wei Deng,1,2 Qiang Wang,1,2 Tao Li,1,2 Xiaohong Ma1,21Mental Health Center and Psychiatric Laboratory, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 2Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 3Community Mental Health Prevention Department, The Severe Mental Health Disorder System of Chengdu, Chengdu, Sichuan, People’s Republic of China; 4Department of Geriatric Psychiatry, Sichuan Province Recover Veterans Hospital, Chongzhou, Sichuan, People’s Republic of ChinaBackground: Research on antipsychotics and early mortality in schizophrenia has arisen from Western countries and results show that mortality from natural causes is obviously increased in schizophrenia. China, differs largely from Western countries in health and social welfare systems, and Asian patients are more susceptible to side-effects and might require less antipsychotics than their Western counterparts. We, therefore, investigated the association between antipsychotic use and increased mortality from natural causes among patients with schizophrenia in China.Methods: We conducted a population-based nested case–control study using patients’ hardcopy archives obtained from the Severe Mental Health Disorder Systems of Chengdu between January 1, 2006 and December 31, 2013. We identified all schizophrenic patients aged 18–65 years who died of natural causes in 2013 (N=157), and their age- and gender-matched controls (N=444).Results: Antipsychotic use was more frequent in controls than in cases (59.9% vs 32.5%). Risk of death decreased significantly in those receiving antipsychotic monotherapy (adjusted odds ratio=0.27, 95% CI=0.16–0.46) and antipsychotic polypharmacy (adjusted odds ratio=0.29, 95% CI=0.12–0.70) than antipsychotic-free patients. Compared with monotherapy, antipsychotic-free treatment was associated with prominently increased mortality (adjusted odds ratio=3.64, 95% CI=2.18–6.08). When stratified by age and gender, the results remained unchanged.Conclusion: Antipsychotic monotherapy significantly decreased mortality from natural causes in schizophrenic patients while antipsychotic polypharmacy did not contribute to the excess mortality and deserves further clarification. We need to improve the physical health of schizophrenic patients and promote health education among community mental health staff and primary caregivers.Keywords: antipsychotics, polypharmacy, mortality, odds ratio, schizophrenia

Min Wang,1,2 Jinxue Wei,1,2 Xiao Yang,1,2 Peiyan Ni,1,2 Yingcheng Wang,1,2 Liansheng Zhao,1,2 Wei Deng,1,2 Wanjun Guo,1,2 Qiang Wang,1,2 Tao Li,1,2 Xiaohong Ma1,21Mental Health Center and Psychiatric Laboratory, West China Hospital of Sichuan University, Chengdu, People’s Republic of China; 2Huaxi Brain Research Center, West China Hospital of Sichuan University, Chengdu, People’s Republic of ChinaPurpose: Major depression disorder (MDD) was associated with inflammatory processes, but association results of inflammatory syndrome and MDD were inconsistent. To provide more evidence, we measured the plasma levels of IL-1β, IL-6, interferon (INT)-α2, INT-γ, and tumor necrosis factor (TNF)-α in patients having MDD and explored correlations between the five proinflammatory cytokines and specific depressive symptoms.Patients and methods: Plasma concentrations of IL-1β, IL-6, INT-α2, INT-γ, and TNF-α were measured using ELISA for 44 MDD patients and 54 healthy controls. Patients with MDD were assessed on the 17-item Hamilton Depression Rating Scale (HAMD-17), and a total score and five syndrome scores were acquired.Results: IL-6 levels in depressed patients were significantly elevated than in healthy controls, but no significant differences were observed in the levels of INF-α2, INF-γ, IL-1β, or TNF-α. In addition, correlation analysis revealed that sleep disturbances positively correlated with IL-6. Although there was no significant difference between the two groups in the levels of INF-α2, a significant positive correlation between IFN-α2 and retardation was observed.Conclusion: Elevated IL-6 levels were observed in MDD patients and IL-6 may correlate with sleep disturbances.Keywords: major depression disorder, inflammation, cytokine, interleukin-6, sleep disturbances

Meng-Xin Tian,1,2,* Liu-Ping Luo,3,4,* Wei-Ren Liu,1,2,* Wei Deng,5 Jia-Cheng Yin,1,2 Lei Jin,1,2 Xi-Fei Jiang,1,2 Yu-Fu Zhou,1,2 Wei-Feng Qu,1,2 Zheng Tang,1,2 Han Wang,1,2 Chen-Yang Tao,1,2 Yuan Fang,1,2 Shuang-Jian Qiu,1,2 Jian Zhou,1–2,6 Jing-Feng Liu,3,4 Jia Fan,1–2,6 Ying-Hong Shi1,21Department of Liver Surgery, Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Key Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, People’s Republic of China; 3Department of Hepatobiliary Surgery, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 4The United Innovation of Mengchao Hepatobiliary Technology Key Laboratory of Fujian Province, Mengchao Hepatobiliary Hospital of Fujian Medical University, Fuzhou, Fujian, People’s Republic of China; 5Department of Health Statistics and Social Medicine, Key Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, People‘s Republic of China; 6Institutes of Biomedical Sciences, Fudan University, Shanghai, People‘s Republic of China*These authors contributed equally to this work Purpose: To develop and validate a decision aid to help make individualized estimates of tumor recurrence for patients with resected combined hepatocellular cholangiocarcinoma (CHC).Patients and methods: Risk factors of recurrence were identified in the derivation cohort of 208 patients who underwent liver resection between 1995 and 2014 at Zhongshan Hospital to develop a prediction score. The model was subsequently validated in an external cohort of 101 CHC patients using the C concordance statistic and net reclassification index (NRI).Results: On multivariate analysis, five independent predictors associated with tumor recurrence were identified, including sex, γ-glutamyl transferase, macrovascular invasion, hilar lymphoid metastasis and adjuvant transcatheter arterial chemoembolization. The prediction score was constructed using these 5 variables, with scores ranging from 0 to 5. A patient with a score of 0 had a predicted 1- and 5-year recurrence risk of 11.1% and 22.2%, respectively. In the validation cohort, the NRIs of prediction score vs American Joint Committee on Cancer 7th, TNM staging system at 1-year and 5-year were 0.185 (95% CI, 0.090–0.279, P

Jing Xie,1 Ning Li,1 Xiaoyan Jiang,1 Liyin Chai,1 Jian-Jun Chen,2 Wuquan Deng11Department of Endocrinology and Nephrology, Chongqing University Central Hospital, Chongqing Emergency Medical Center, Chongqing 400014, People’s Republic of China; 2Institute of Life Sciences, Chongqing Medical University, Chongqing 400016, People’s Republic of ChinaBackground: Consistent evidence is still lacking on which one, glimepiride plus metformin or repaglinide plus metformin, is better in treating type 2 diabetes mellitus (T2DM). Therefore, this study was conducted to compare the short-term efficacy and safety of these two methods in treating T2DM.Methods: The literature research dating up to August 2018 was conducted in the electronic databases. The randomized controlled trials (RCTs) comparing the short-term (treatment period ≤12 weeks) efficacy and safety of these two methods in treating patients with T2DM were included. No language limitation was used in this study. The decreased hemoglobin A1c (HbA1c), fasting plasma glucose (FPG), and 2h plasma glucose (2hPG) levels were used as the primary outcome to assess the efficacy, and the adverse events and hypoglycemia were used as the secondary outcome to assess the safety.Results: In total, 11 RCTs composed of 844 T2DM patients were included. The results showed that there were no significant differences in decreasing HbA1c and FPG levels between the two methods, but the estimated standardized mean differences favored the repaglinide plus metformin. Meanwhile, the repaglinide plus metformin was significantly more effective in decreasing 2hPG levels than glimepiride plus metformin. In addition, fewer patients reported adverse events and experienced hypoglycemia in the repaglinide plus metformin group.Conclusion: These results indicated that the repaglinide plus metformin might have some advantages over glimepiride plus metformin in the short-term treatment of patients with T2DM, and should be further explored.Keywords: repaglinide, glimepiride, metformin, diabetes

Meng Liu, Yukai Huang, Zhengping Huang, Qidang Huang, Xin Guo, Yunqing Wang, Weiming Deng, Zhixiang Huang, Tianwang LiDepartment of Rheumatology and Immunology, Guangdong Second Provincial General Hospital, Guangzhou, Guangdong, People’s Republic of ChinaPurpose: We assessed the prevalence of metabolic syndrome (MetS) and associated factors in mainland Chinese patients with ankylosing spondylitis (AS).Patients and methods: A retrospective study was conducted in 117 AS patients and 117 age- and sex-matched healthy controls. Parameters of MetS based on the criteria established by the Chinese Diabetes Society in 2013 were tabulated. Demographic features, laboratory data, and clinical characteristics were also collected. Independent factors correlated with MetS in AS patients were identified by backward stepwise multivariate analysis.Results: The prevalence of MetS was higher in AS patients than in healthy controls (P= 0.026). AS patients also had higher blood pressure and fasting serum glucose levels, but generally lower serum lipid levels. AS patients with and without MetS had no distinct differences in disease duration, medication usage, disease activity, or biomarkers of inflammation. Multivariable logistic regression analysis showed that hyperuricemia (odds ratio [OR] = 2.385, 95% confidence interval [95% CI] = 1.019–5.582, P= 0.045) and high body mass index (BMI, OR = 5.165; 95% CI = 1.935–13.787, P=0.001) were independent factors for MetS in AS patients.Conclusion: Chinese AS patients living in the mainland have an increased risk of developing MetS. Hyperuricemia and high BMI are predictors of MetS in AS patients.Keywords: ankylosing spondylitis, metabolic syndrome, prevalence, hyperuricemia

Tao Li,1 Yu Ma,2 Min Wang,1 Tao Wang,3 Jing Wei,4 Rui Ren,1 Min He,1 Guixue Wang,2 Johnson Boey,5 David G Armstrong,6 Wuquan Deng,2 Bing Chen1 1Department of Endocrinology, Southwest Hospital, Army Medical University, Chongqing, People’s Republic of China; 2Department of Endocrinology and Nephrology, Key Laboratory for Biorheological Science and Technology of Ministry of Education, Chongqing University, Affiliated Central Hospital of Chongqing University, Chongqing, People’s Republic of China; 3Institute of Combined Injury, State Key Laboratory of Trauma, Burn and Combined Injury, Army Medical University, Chongqing, People’s Republic of China; 4Department of Endocrinology, General Hospital of Xinjiang Military Region, The Chinese People’s Liberation Army, Urumqi, People’s Republic of China; 5Department of Podiatry, Singapore General Hospital, Singapore; 6Southwestern Academic Limb Salvage Alliance (SALSA), Department of Surgery, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USA Aim: This study was designed to examine the potential mechanism underlying these roles of platelet-rich plasma in treating diabetic foot ulcers (DFUs). Methods: Staphylococcus aureus and HaCaT were co-cultured under high glucose conditions to serve as an in vitro model for infected cells in DFUs. Platelet-rich gel (PRG) or extract liquid of platelet-rich gel (EPG) were used to interfere with the model to observe the growth of HaCaT cells and S. aureus, and the effect of miR-21 changes in HaCaT cells on PDCD4, NF-κB activity and related inflammatory factors. Results: Incubation of HaCaT cells with S. aureus promoted the decline of cell proliferation. Under this condition, the level of PDCD4 and the activity of NF-κB were increased in HaCaT cells with concomitant increased of IL-6, TNF-α and decreased IL-10, TGF-β1 in cultured supernatant. Both of PRG and EPG exhibited specific anti-S. aureus activity where they protect HaCaT cells from bacterial damage and promote cell proliferation. Meanwhile, EPG was observed to increase intracellular miRNA-21 while reduce PDCD4 expression and inhibit NF-κB activity to suppress the inflammation in HaCaT cells. Conclusion: This in vitro model provides a valuable tool for study of wound healing in the treatment of DFUs. Our results suggest that miRNA-21 may regulate the expression of NF-κB through PDCD4 where it plays an anti-inflammatory role and promote proliferation in infected DFUs treated by PRP. These findings could provide novel therapeutic targets for refractory wounds. Keywords: platelet-rich plasma, antibacterial, anti-inflammatory, cell proliferation-promoting, diabetic infected wound

Sandhya Clement,1,2,* Wenjie Chen,1,* Wei Deng,1,2 Ewa M Goldys1,2 1Australian Research Council Centre of Excellence for Nanoscale BioPhotonics (CNBP), Department of Physics and Astronomy, Macquarie University, Sydney, NSW, Australia; 2The Graduate School of Biomedical Engineering, University of New South Wales, Sydney, NSW, Australia *These authors contributed equally to this work Introduction: The depth limitation of conventional photodynamic therapy (PDT) with visible electromagnetic radiation represents a challenge for the treatment of deep-seated tumors. Materials and methods: To overcome this issue, we developed an X-ray-induced PDT system where poly(lactide-co-glycolide) (PLGA) polymeric nanoparticles (NPs) incorporating a photosensitizer (PS), verteporfin (VP), were triggered by 6 MeV X-ray radiation to generate cytotoxic singlet oxygen. The X-ray radiation used in this study allows this system to breakthrough the PDT depth barrier due to excellent penetration of 6 MeV X-ray radiation through biological tissue. In addition, the conjugation of our NPs with folic acid moieties enables specific targeting of HCT116 cancer cells that overexpress the folate receptors. We carried out physiochemical characterization of PLGA NPs, such as size distribution, zeta potential, morphology and in vitro release of VP. Cellular uptake activity and cell-killing effect of these NPs were also evaluated. Results and discussion: Our results indicate that our nanoconstructs triggered by 6 MeV X-ray radiation yield enhanced PDT efficacy compared with the radiation alone. We attributed the X-ray-induced singlet oxygen generation from the PS, VP, to photoexcitation by Cherenkov radiation and/or reactive oxygen species generation facilitated by energetic secondary electrons produced in the tissue. Conclusion: The cytotoxic effect caused by VP offers the possibility of enhancing the radiation therapy commonly prescribed for the treatment of cancer by simultaneous PDT. Keywords: PLGA nanoparticles, verteporfin, singlet oxygen generation, photodynamic therapy, X-ray PDT, folic acid targeting

Yaqi Wang,1,2,* Lifeng Yang,1,2,* Menglong Zhou,1,2 Lijun Shen,1,2 Jing Zhang,1,2 Weijuan Deng,1,2 Liping Liang,1,2 Ran Hu,1,2 Wang Yang,1,2 Ye Yao,1,2 Zhen Zhang1,2 1Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, People’s Republic of China; 2Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, People’s Republic of China *These authors contributed equally to this work Purpose: To investigate whether young patients exhibit different characteristics and survival according to tumor location and stage using data from the Surveillance, Epidemiology, and End Results (SEER) database.Patients and methods: Young patients (20–49 years old) with stage I–III colon cancers were identified from the SEER program from 1990 to 2014. Kaplan–Meier survival analysis and Cox proportional hazards regression were used to analyze the data. Subset analyses were also done among different age and stage subgroups.Results: Of 8197 patients, 3709 (45.2%) had right-sided colon cancers (RCCs). Patients with RCCs were more likely to be male, to be younger, and to have more poorly differentiated and more advanced tumors. The Kaplan–Meier survival curves and univariate survival models revealed that left-sided colon cancers (LCCs) had lower mortality for all stages combined and stage III, but higher mortality for stage II, compared with right-sided tumors. However, multivariate Cox regression models showed no significant survival differences by location for all patients (adjusted hazard ratio [HR], 0.95; 95% confidence interval [CI], 0.86–1.05; P=0.34) or for stage I (adjusted HR, 1.47; 95% CI, 0.82–2.63; P=0.20). Stage II left-sided cancers had higher mortality (adjusted HR, 1.24; 95% CI, 1.00–1.54; P=0.048), whereas stage III left-sided cancers had lower mortality (adjusted HR, 0.86; 95% CI, 0.77–0.97; P=0.01). For 20- to 39-year-old patients, a significant difference was only found in stage II disease, with a higher mortality for left-sided tumors (adjusted HR, 1.82; 95% CI, 1.12–2.97; P=0.02). However, for 40- to 49-year-old patients, a significant difference was only found in stage III disease, with a lower mortality for left-sided tumors (adjusted HR, 0.83; 95% CI, 0.72–0.95; P=0.008).Conclusion: In patients younger than 50 years, there were no significant differences in mortality between RCCs and LCCs for all stages combined after adjusting for multiple clinicopathological features. However, RCCs had lower mortality in stage II (especially in 20- to 39-year-old patients) and higher mortality in stage III (especially in 40- to 49-year-old patients). Keywords: young patients, survival, right-sided colon cancers, left-sided colon cancers, stages, SEER