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Fang Wang,1,&ast; Chang Jiang,2– 4,&ast; Wenzhuo He,2– 4,&ast; Heping Li,1 Gui-Fang Guo,2– 4 Lixia Xu1 1Department of Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong Province, People’s Republic of China; 2State Key Laboratory of Oncology in South China, The Sun Yat-Sen University Cancer Center Guangzhou, Guangzhou, Guangdong Province, People’s Republic of China; 3Collaborative Innovation Center for Cancer Medicine, The Sun Yat-Sen University Cancer Center, Guangzhou, Guangdong Province, People’s Republic of China; 4VIP Department, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Lixia Xu, Department of Oncology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong Province, People’s Republic of China, Email xulixia@mail.sysu.edu.cn Gui-Fang Guo, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, VIP Department, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong Province, People’s Republic of China, Email guogf@sysucc.org.cnPurpose: The response of patients with biliary tract carcinoma (BTC) to immunotherapy varies widely, and there is an urgent need for biological indicators. The predictive value of inflammation based score (IBS) for the efficacy of immunotherapy in patients with BTC remains unclear, as the evidence is inconsistent. This study aimed to comprehensively examine the predictive value of IBS in peripheral blood on the survival of BTC patients receiving immunotherapy.Patients and Methods: We retrospectively assessed 118 patients with advanced BTC who received anti-PD-1 therapy in the first or second line in two medical centers. The Kaplan-Meier, time-dependent ROC, and Harrell’s concordance index (C-index) were applied to analyze the predictive value of 13 reported peripheral blood IBS.Results: All 13 IBS were identified as significant prognostic factors for OS in univariate analysis. Pan-immune-inflammation value (PIV) (p=0.005), PILE (composed of PIV, lactate dehydrogenase and Eastern Cooperative Oncology Group performance status) (p=0.033), neutrophil-to-lymphocyte ratio (NLR) (p=0.003), platelet-to-lymphocyte ratio (PLR) (p< 0.001), lymphocyte-to-monocyte ratio (LMR) (p=0.006), systemic immune inflammation index (SII) (p=0.039), CRP-to-albumin ratio (CAR) (p=0.025), and Albumin-NLR (p=0.008) were identified as independent prognostic factors for OS in multivariate analysis. PIV and PILE scores were superior to other scores, according to time-dependent ROC curves, and their superiority became more pronounced after the 12-month time point. C-index analysis showed PIV (C-index 0.62, 95% CI: 0.55, 0.68) and PILE (C-index 0.62, 95% CI: 0.55, 0.70), both superior to other IBS.Conclusion: PIV and PILE scores are independent predictors of OS in patients with BTC after immunotherapy and are superior to other IBS. PIV and PILE may be able to help screen out patients with advanced BTC who are less likely to benefit from anti-PD-1 monotherapy. Due to the retrospective nature of this analysis, the predictive value of PIV and PILE require validation in further prospective studies.Keywords: biliary tract carcinoma, anti-PD-1 therapy, inflammation-based scores, pan-Immune-Inflammation Value, PILE

Menghan Yu,1 Xiaoshu Fu,1 Yanli Zhu,2 Miao Li,3 Min Wu,1 Entong Zhou,1 Hanwen Dong,1 Likun Wang,1 Ruoxi Wang,4 Fang Liu,2 Chunlai Jiang,1 Xiangwei Kong,5 Weiheng Su1,6 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 2People’s Hospital of Jiangyuan District, Baishan, Jilin Province, People’s Republic of China; 3Department of Neurosurgery, China-Japan Union Hospital, Jilin University, Changchun, People’s Republic of China; 4School of Public Health, Capital Medical University, Beijing, People’s Republic of China; 5Changchun University of Science and Technology, Changchun, People’s Republic of China; 6Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, School of Life Sciences, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Weiheng Su, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China, Email suweiheng@jlu.edu.cn Xiangwei Kong, Changchun University of Science and Technology, Changchun, People’s Republic of China, Email tenbpro@163.comPurpose: Tick-borne encephalitis virus (TBEV) infections result in severe central nervous system diseases in humans across Asia and Europe. In China, cases of tick-borne encephalitis are primarily caused by the Far East subtype of TBEV, which exhibits a distinct disease course compared to other extensively studied subtypes. However, there is limited knowledge regarding the nucleic acid and serological diagnostic characteristics of patients infected with the TBEV in China, which is the focus of investigation in the present study.Methods: This study established a TaqMan qPCR approach to detect TBEV RNA in the serum with optimal specificity, sensitivity, and precision. Using TaqMan qPCR and ELISA assay for TBEV IgM detection, serum samples from 63 hospitalized patients bitten by ticks in Northeast China were investigated for diagnostic characteristics.Results: Twenty-five patients were positive for viral RNA; nineteen patients were positive for IgM, and nine were positive for both viral RNA and IgM. Through comparative analysis, TBEV RNA copies were negatively correlated with the virus incubation period. IgM levels were positively correlated with the clinical symptom scores of patients. The severity of clinical symptoms and the length after the tick bite could be used to predict the IgM occurrence. Furthermore, IgM levels and viral RNA copies were not correlated in double-positive patients.Conclusion: Both nucleic acid and serological detection methods exhibited distinct windows for detecting TBEV infection, with some overlap, and were associated with specific correlated factors. This study provided novel insights into the diagnosis and course of TBEV-induced tick-borne encephalitis in China.Keywords: tick-borne encephalitis, TBE, tick-borne encephalitis virus, TBEV, TaqMan qPCR, IgM

Junhai Zhen,1 Chuan Liu,2 Jixiang Zhang,2 Fei Liao,2 Huabing Xie,1 Cheng Tan,2 Ping An,2 Zhongchun Liu,3 Changqing Jiang,4 Jie Shi,5 Kaichun Wu,6 Weiguo Dong2 1Department of General Practice, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, 430060, People’s Republic of China; 2Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei Province, 430060, People’s Republic of China; 3Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 4Department of Clinical Psychology, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, People’s Republic of China; 5Department of Medical Psychology, Chinese People’s Liberation Army Rocket Army Characteristic Medical Center, Beijing, 100032, People’s Republic of China; 6Department of Gastroenterology, Xijing Hospital, Air Force Medical University, Xi’an, 710032, People’s Republic of ChinaCorrespondence: Kaichun Wu, Department of Gastroenterology, Xijing Hospital, Air Force Medical University, Xi’an, 710032, People’s Republic of China, Tel/Fax +8629-84771600, Email kaicwu@fmmu.edu.cn Weiguo Dong, Department of Gastroenterology, Renmin Hospital of Wuhan University, 99 Zhangzhidong Road, Wuhan, Hubei Province, 430060, People’s Republic of China, Tel/Fax +8627-88041911, Email dongweiguo@whu.edu.cnPurpose: Impaired quality of life (QOL) is common in patients with inflammatory bowel disease (IBD). A tool to more quickly identify IBD patients at high risk of impaired QOL improves opportunities for earlier intervention and improves long-term prognosis. The purpose of this study was to use a machine learning (ML) approach to develop risk stratification models for evaluating IBD-related QOL impairments.Patients and Methods: An online questionnaire was used to collect clinical data on 2478 IBD patients from 42 hospitals distributed across 22 provinces in China from September 2021 to May 2022. Eight ML models used to predict the risk of IBD-related QOL impairments were developed and validated. Model performance was evaluated using a set of indexes and the best ML model was explained using a Local Interpretable Model-Agnostic Explanations (LIME) algorithm.Results: The support vector machine (SVM) classifier algorithm-based model outperformed other ML models with an area under the receiver operating characteristic curve (AUC) and an accuracy of 0.80 and 0.71, respectively. The feature importance calculated by the SVM classifier algorithm revealed that glucocorticoid use, anxiety, abdominal pain, sleep disorders, and more severe disease contributed to a higher risk of impaired QOL, while longer disease course and the use of biological agents and immunosuppressants were associated with a lower risk.Conclusion: An ML approach for assessing IBD-related QOL impairments is feasible and effective. This mechanism is a promising tool for gastroenterologists to identify IBD patients at high risk of impaired QOL.Keywords: clinical research, artificial intelligence, model development, clinical decision support system

Dongdong Li,1 Lijun Bian,1 Lili Cui,2 Jingying Zhou,1 Gaotian Li,1 Xiaoyan Zhao,1 Liao Xing,1 Jiaxing Cui,1 Bo Sun,1 Chunlai Jiang,1,3,4 Wei Kong,1,3,4 Yong Zhang,1,3,4 Yan Chen1,3,4 1National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 2Beijing Institute of Drug Metabolism, Beijing, People’s Republic of China; 3Key Laboratory for Molecular Enzymology and Engineering of Ministry of Education, School of Life Sciences, Jilin University, Changchun, People’s Republic of China; 4NMPA Key Laboratory of Humanized Animal Models for Evaluation of Vaccines and Cell Therapy Products, Jilin University, Changchun, People’s Republic of ChinaCorrespondence: Yan Chen; Yong Zhang, National Engineering Laboratory for AIDS Vaccine, School of Life Sciences, Jilin University, Changchun, 130012, People’s Republic of China, Tel +86-431-85167751, Fax +86-431-85167674, Email chen_yan0417@126.com; zhypharm@jlu.edu.cnPurpose: Heterologous immunization using different vaccine platforms has been demonstrated as an efficient strategy to enhance antigen-specific immune responses. In this study, we performed a head-to-head comparison of both humoral and cellular immune response induced by different prime-boost immunization regimens of mRNA vaccine and adjuvanted protein subunit vaccine against varicella-zoster virus (VZV) in middle-aged mice, aiming to get a better understanding of the influence of vaccination schedule on immune response.Methods: VZV glycoprotein (gE) mRNA was synthesized and encapsulated into SM-102-based lipid nanoparticles (LNPs). VZV-primed middle-aged C57BL/6 mice were then subjected to homologous and heterologous prime-boost immunization strategies using VZV gE mRNA vaccine (RNA-gE) and protein subunit vaccine (PS-gE). The antigen-specific antibodies were evaluated using enzyme-linked immunosorbent assay (ELISA) analysis. Additionally, cell-mediated immunity (CMI) was detected using ELISPOT assay and flow cytometry. Besides, in vivo safety profiles were also evaluated and compared.Results: The mRNA-loaded lipid nanoparticles had a hydrodynamic diameter of approximately 130 nm and a polydispersity index of 0.156. Total IgG antibody levels exhibited no significant differences among different immunization strategies. However, mice received 2×RNA-gE or RNA-gE>PS-gE showed a lower IgG1/IgG2c ratio than those received 2×PS-gE and PS-gE> RNA-gE. The CMI response induced by 2×RNA-gE or RNA-gE>PS-gE was significantly stronger than that induced by 2×PS-gE and PS-gE> RNA-gE. The safety evaluation indicated that both mRNA vaccine and protein vaccine induced a transient body weight loss in mice. Furthermore, the protein vaccine produced a notable inflammatory response at the injection sites, while the mRNA vaccine showed no observable inflammation.Conclusion: The heterologous prime-boost strategy has demonstrated that an mRNA-primed immunization regimen can induce a better cell-mediated immune response than a protein subunit-primed regimen in middle-aged mice. These findings provide valuable insights into the design and optimization of VZV vaccines with the potentials to broaden varicella vaccination strategies in the future.Keywords: varicella-zoster Virus, mRNA vaccine, glycoprotein E, lipid nanoparticles, heterologous prime-boost, cell-mediated immunity

Chun Wang, Xiaoqin Niu, Siwen Bao, Weifeng Shen, Chaoyue Jiang Department of Clinical Laboratory, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, People’s Republic of ChinaCorrespondence: Chaoyue Jiang, Department of Clinical Laboratory, The First Hospital of Jiaxing, The Affiliated Hospital of Jiaxing University, No. 1882, Zhonghuan South Road, Nanhu District, Jiaxing, Zhejiang, People’s Republic of China, Tel +86-15858826573, Email tg30328@163.comPurpose: To systematically assess the distribution and antimicrobial susceptibility of pathogens in wound infections, and analyze risk factors associated with multidrug resistance (MDR).Patients and Methods: Retrospectively analyzing Jiaxing-region medical records between January 2021 and December 2023, we identified a cohort of 461 wound infection patients. Cultures were grown on various agars, with bacteria identified via Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry. The antimicrobial susceptibility of the organisms were conducted by VITEK 2 system, Kirby-Bauer disk diffusion method and Epsilometer test. Statistical Package for the Social Sciences (SPSS) version 22 was used for statistical analysis. Multivariable logistic regression models were developed to pinpoint risk factors for multidrug-resistant organism (MDRO) infections and predict occurrences.Results: From 461 patients, 549 bacterial pathogens were isolated, predominantly consisting of Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Acinetobacter baumannii, Enterobacter cloacae, and Enterococcus faecalis. Vancomycin, linezolid, and tigecycline maintained their efficacy against Staphylococcus aureus and Enterococcus species, while Pseudomonas aeruginosa demonstrated sensitivity to aminoglycosides. Conversely, Escherichia coli exhibited high amoxicillin resistance (85.4%). More than half of the isolates were resistant to levofloxacin, ceftriaxone, cotrimoxazole, and gentamicin, with Acinetobacter baumannii strains showing considerable resistance (65.8– 68.4%) to advanced cephalosporins and carbapenems. Within this group, 58 MDROs were detected, primarily originating from Burn Plastic Surgery, Emergency, and Intensive Care Unit (ICU) departments. Multivariate logistic regression identified hyperglycemia, hypoalbuminemia, surgery, extended hospitalization, and exposure to multiple antibiotic classes as independent risk factors for MDRO wound infections. Based on these findings, a predictive model for MDRO occurrence in wounds was constructed, which had a sensitivity of 0.627, specificity of 0.933, and an Area Under the Curve (AUC) of 0.838.Conclusion: Staphylococcus aureus and Pseudomonas aeruginosa dominated in wound infections with differential antibiotic resistance. Independent risk factors included hyperglycemia, hypoalbuminemia, surgery, extended hospitalization, and polyantibiotic use. We urge prioritizing culture, susceptibility tests, and personalized antibiotic strategies to address MDRO risks and improve wound infection management specificity and efficacy.Keywords: antibiotic resistance, wound infection, pathogenic bacteria, risk factor, prediction model

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

Yafei Zhou,1,2 Rui Zhou,1,2 Wenjun Huang,1,2 Jie Wang,1,2 Congshan Jiang,1,2 Anmao Li,1,2 Christopher LH Huang,3 Yanmin Zhang1,2,4 1Key Laboratory of Precision Medicine to Pediatric Diseases of Shaanxi Province, Affiliated Children’s Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Shaanxi Institute for Pediatric Diseases, Affiliate Children’s Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Physiological Laboratory, University of Cambridge, Cambridge, UK; 4Department of Cardiology, Xi’an Children’s Hospital, Affiliated Children’s Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaCorrespondence: Yanmin Zhang, Key Laboratory of Precision Medicine to Pediatric Diseases of Shaanxi Province, Affiliate Children’s Hospital of Xi’an Jiaotong University, No. 69 Xi Ju Yuan Xiang, Xi’an, Shaanxi, 710000, People’s Republic of China, Tel +86 029-87692527, Fax +86 029-87692000, Email ymzh628@126.comBackground and Objectives: Gene expression, morphology, and electrophysiological combination are essential for assessing the dynamic development of human induced pluripotent stem cell-derived atrial- and ventricular-like cardiomyocytes (iPS-AM and iPS-VM, respectively).Methods: For iPS-AM/VM differentiation, we performed the small molecule-based temporal modulation of the retinoic acid and bone morphogenetic protein signaling pathways. We investigated the gene expression and morphology using immunofluorescence, quantitative real-time polymerase chain reaction, flow cytometry, and transmission electron microscopy as well as registered electrophysiological functions using a whole-cell patch clamp on days 20, 30, and 60 post-differentiations.Results: Pan-cardiomyocyte marker, including troponin T2 (TNNT2) and alpha-actinin-2 (ACTN2), expressions increased both in iPS-AMs and iPS-VMs. Similarly, the mRNA expression of both iPS-AM-specific markers, ie, natriuretic peptide A (NPPA), myosin light chain 7 (MYL7), and K+ channel Kir3.4 (KCNJ5), and iPS-VM-specific markers, ie, gap junction α-1 (GJA1), myosin light chain 2 (MYL2), and alpha-1-subunit of a voltage-dependent L-type calcium channel (CACNA1C), increased from 0 to 20 days, and then decreased from 30 to 60 days. Concerning morphology, cardiac troponin-T (cTnT) arrangement was progressively organized and developed from a disorderly myofibrillar distribution to an organized sarcomere pattern both in iPS-AMs and iPS-VMs. Mitochondrial numbers gradually increased and those of lipid droplets decreased during dynamic development. Regarding physiological function, the resting and action potential amplitudes remained statistically indifferent in both cell types, and the action potential duration was prolonged during the development.Conclusion: IPS-AMs/VMs displayed dynamic development concerning their gene expression, morphology, and electrophysiological function. The discoveries of this study could provide novel insights into heart development and encourage further research. Keywords: cardiomyocytes, induced pluripotent stem cells, dynamic development, gene expression, morphology, action potential

Jie Gao,1,&ast; Jie Dou,1,&ast; Hui-Hui Yang,1 Ruo-Ling Guo,1 Chao Jiang,1 Gary Tse,2– 4 Tong Liu,2 Jian-Wei Liu,5 Dong-Lei Luo6 1Chengde Medical University, Chengde, 067000, People’s Republic of China; 2Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular Disease, Department of Cardiology, Tianjin Institute of Cardiology, Second Hospital of Tianjin Medical University, Tianjin, 300211, People’s Republic of China; 3School of Nursing and Health Studies, Hong Kong Metropolitan University, Hong Kong, 999077, People’s Republic of China; 4Epidemiology Research Unit, Cardiovascular Analytics Group, PowerHealth Limited, Hong Kong, 999077, People’s Republic of China; 5Department of Cardiothoracic Interventional Vascular Surgery, Chengde Central Hospital/Second Clinical College of Chengde Medical University, Chengde, Hebei, 067000, People’s Republic of China; 6Department of Cardiology, Chengde Central Hospital / Second Clinical College of Chengde Medical University, Chengde, 067000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dong-Lei Luo, Department of Cardiology, Chengde Central Hospital / Second Clinical College of Chengde Medical University, Chengde, 067000, People’s Republic of China, Email dongleiluocn@aliyun.com Jian-Wei Liu, Department of Cardiothoracic Interventional Vascular Surgery, Chengde Central Hospital/Second Clinical College of Chengde Medical University, Chengde, Hebei, 067000, People’s Republic of China, Email Ljw2112@126.comPurpose: To investigate the clinical application value of diagonal earlobe crease (DELC) in patients with chest pain for the diagnosis of coronary heart disease (CHD) and to construct a risk model by multivariate logistic regression.Patients and Methods: Our trial enrolled prospectively and consecutively 706 chest pain patients with suspected CHD between January 2021 to June 2023 from Chengde Central Hospital. According to coronary angiography results, they were categorized into the CHD (n=457) and non-CHD groups (n=249).Results: The trial demonstrated a significant positive relationship between DELC and CHD. Independent risk factors were sex, age, hypertension, diabetes mellitus, LP (a), Cys C, and DELC, whilst HDL-C was a protective factor, for CHD. Patients with-DELC were older than those in the without-DELC arm (P< 0.001) and had a higher proportion of males than females (61.6% vs 50.0%, P=0.026). After multifactorial correction, independent risk factors for CHD included DELC (OR=1.660, 95% CI:1.153 to 2.388, P=0.006), age (OR=1.024, 95% CI:1.002 to 1.045, P=0.030), gender (OR=1.702, 95% CI:1.141 to 2.539, P=0.009), hypertension (OR=1.744, 95% CI:1.226 to 2.482, P=0.002), diabetes mellitus (OR=2.113, 95% CI:1.404 to 3.179, P< 0.001), LP(a) (OR=1.010, 95% CI:1.003 to 1.017, P=0.005), Cys C (OR=3.549, 95% CI:1.605 to 7.846, P=0.002). The Hosmer and Lemeshow (H-L) test (P=0.818) suggests a high goodness of fit, and the area under the ROC curve was calculated to be 0.721 (95% CI:0.682 to 0.760, P< 0.001), which demonstrates that the model has a superior diagnostic value for CHD.Conclusion: DELC is an independent risk factor for CHD after adjusting for sex, age, hypertension, diabetes mellitus, smoking index, LP (a), Cys C, and HDL-C. Our model can be used clinically for assessing the risk of CHD.Keywords: coronary heart disease, diagonal earlobe crease, coronary angiography, model

Yi Zhang,1,&ast; Xinrui Wang,1,&ast; Chong Huang,2 Hui Yang,1 Chunguo Jiang,3 Xiaojia Yu,1 Jun Hong,2 Yi Zhang,1 Yushu Wang,1 Rui Zhao,1 Zhuoling An,1 Zhaohui Tong3 1Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China; 2School of Pharmaceutical Sciences, Capital Medical University, Beijing, People’s Republic of China; 3Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhuoling An, Department of Pharmacy, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +00-86-010-85231362, Email anzhuoling@163.com Zhaohui Tong, Department of Respiratory and Critical Care Medicine, Beijing Institute of Respiratory Medicine, Beijing Chao-Yang Hospital, Capital Medical University, 8 Gongren Tiyuchang Nanlu, Chaoyang District, Beijing, 100020, People’s Republic of China, Tel +00-86-010-85231464, Email tongzhaohuicy@sina.comObjective: The efficacy of nirmatrelvir–ritonavir for hospitalized patients with COVID-19 has not been fully established.Methods: We conducted a retrospective analysis of hospitalized COVID– 19 patients with high risk for disease progression at Beijing Chaoyang Hospital from October 15, 2022, to March 31, 2023. Patients ≥ 18 years old who were hospitalized with COVID-19 within 5 days of symptom onset were included. Baseline data were obtained from the routine electronic health record database of the hospital information system. Outcomes were monitored at 28 days via electronic medical record reviews or telephone interviews.Results: We identified 1120 patients hospitalized with COVID-19 during the study period. After exclusions, 167 nirmatrelvir–ritonavir users and 132 controls were included. 28-day all-cause mortality rate was 12.0% (20/167) in the nirmatrelvir–ritonavir group, versus 22.7% (30/132) in the control group (unadjusted log-rank p = 0.010; HR = 0.49, 95% confidence interval [CI] = 0.28– 0.86, IPTW-adjusted HR = 0.58, 95% CI = 0.40– 0.86). The 28-day disease progression rates did not differ between the two groups (unadjusted HR = 0.59, 95% CI = 0.34– 1.02, IPTW-adjusted HR = 0.73, 95% CI = 0.50– 1.06). Nirmatrelvir–ritonavir significantly reduced all-cause mortality and disease progression within 28 days among patients aged ≥ 65 years without ≥ 2 vaccine doses.Conclusion: We found significantly reduced all-cause mortality in the nirmatrelvir–ritonavir group, particularly in elderly patients who were incompletely vaccinated. Future randomized controlled studies are needed to validate our findings.Keywords: nirmatrelvir–ritonavir, COVID-19, hospitalized

Jian Yu,1,2,&ast; Huan Xu,1,2,&ast; Jiaojiao Wei,1,2 Liangliang Niu,1,2 Haohao Zhu,1,3 Chunhui Jiang1,2 1Department of Ophthalmology and Visual Science, Eye, Ear, Nose and Throat Hospital, Shanghai Medical College of Fudan University, Shanghai, People’s Republic of China; 2Key Laboratory of Myopia of State Health Ministry and Key Laboratory of Visual Impairment and Restoration of Shanghai, Shanghai, People’s Republic of China; 3Department of Ophthalmology, Shanghai Fifth People’s Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunhui Jiang, Department of Ophthalmology and Vision Science, Eye and ENT Hospital, Fudan University, 83 Fenyang Road, Shanghai, 200031, People’s Republic of China, Email chhjiang70@163.com Haohao Zhu, Department of Ophthalmology, Shanghai Fifth People’s Hospital, Fudan University, 128 Ruili Road, Shanghai, 200240, People’s Republic of China, Tel +86-21-64308151, Fax +86-21-64300477, Email haohao700315@163.comBackground: Bacterial endophthalmitis is an acute progressive visual threatening disease and one of the most important causes of blindness worldwide. Current treatments are unsatisfactory due to the emergence of drug-resistant bacteria and the formation of biofilm.Purpose: The aim of our research was to construct a novel nano-delivery system with better antimicrobial and antibiofilm effects.Methods: This study developed a novel antibiotic nanoparticle delivery system (MXF@UiO-UBI-PEGTK), which is composed of (i) moxifloxacin (MXF)-loaded UiO-66 nanoparticle as the core, (ii) bacteria-targeting peptide ubiquicidin (UBI29-41) immobilized on UiO-66, and (iii) ROS-responsive poly (ethylene glycol)-thioketal (PEG-TK) as the surface shell. Then the important properties of the newly developed delivery system, including biocompatibility, toxicity, release percentage, thermal stability, ability of targeting bacteria, and synergistic antibacterial effects on bacterial biofilms and endophthalmitis, were evaluated.Results: In vitro, MXF@UiO-UBI-PEGTK exhibited significant antibiotic effects including the excellent antibiofilm property against Staphylococcus aureus, Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus at high levels of ROS. Moreover, MXF@UiO-UBI-PEGTK demonstrated outstanding efficacy in treating bacterial endophthalmitis in vivo.Conclusion: This novel nanoparticle delivery system with ROS-responsive and bacteria-targeted properties promotes the precise and effective release of drugs and has significant potential for clinical application of treating bacterial endophthalmitis. Keywords: endophthalmitis, nanoparticles, bacterial biofilms, ROS-responsive, moxifloxacin

Yinghong Li,1,&ast; Fanwu Wu,1,&ast; Jianbo Zhang,1 Ye Xu,1 Hong Chang,1 Yueyue Yu,1 Chunhua Jiang,1 Xiujuan Gao,1 Huijuan Liu,1 Zhen Chen,2 Chenxi Wu,1 Ji-An Li1,3 1Hebei Key Laboratory of Integrated Traditional Chinese and Western Medicine for Diabetes and Its Complications, College of Traditional Chinese Medicine, North China University of Science and Technology, Tangshan, People’s Republic of China; 2Oriental Herbs KFT, Budapest, Hungary; 3School of Public Health, North China University of Science and Technology, Tangshan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chenxi Wu; Ji-An Li, Tel +86-15930951086, Fax +86-03158805765, Email chenxi.wu@ncst.edu.cn; JianLi@ncst.edu.cnPurpose: Type 2 diabetes mellitus (T2DM) is associated with reduced insulin uptake and glucose metabolic capacity. Potentilla discolor Bunge (PDB) has been used to treat T2DM; however, the fundamental biological mechanisms remain unclear. This study aimed to understand the active ingredients, potential targets, and underlying mechanisms through which PDB treats T2DM.Methods: Components and action targets were predicted using network pharmacology and molecular docking analyses. PDB extracts were prepared and validated through pharmacological intervention in a Cg>InRK1409A diabetes Drosophila model. Network pharmacology and molecular docking analyses were used to identify the key components and core targets of PDB in the treatment of T2DM, which were subsequently verified in animal experiments.Results: Network pharmacology analysis revealed five effective compounds made up of 107 T2DM-related therapeutic targets and seven protein–protein interaction network core molecules. Molecular docking results showed that quercetin has a strong preference for interleukin-1 beta (IL1B), IL6, RAC-alpha serine/threonine-protein kinase 1 (AKT1), and cellular tumor antigen p53; kaempferol exhibited superior binding to tumor necrosis factor and AKT1; β-sitosterol demonstrated pronounced binding to Caspase-3 (CASP3). High-performance liquid chromatography data quantified quercetin, kaempferol, and β-sitosterol at proportions of 0.030%, 0.025%, and 0.076%, respectively. The animal experiments revealed that PDB had no effect on the development, viability, or fertility of Drosophila and it ameliorated glycolipid metabolism disorders in the diabetes Cg>InRK1409A fly. Furthermore, PDB improved the body size and weight of Drosophila, suggesting its potential to alleviate insulin resistance. Moreover, PDB improved Akt phosphorylation and suppressed CASP3 activity to improve insulin resistance in Drosophila with T2DM.Conclusion: Our findings suggest that PDB ameliorates diabetes metabolism disorders in the fly model by enhancing Akt activity and suppressing CASP3 expression. This will facilitate the development of key drug targets and a potential therapeutic strategy for the clinical treatment of T2DM and related metabolic diseases. Keywords: Potentilla discolor Bunge, T2DM, network pharmacology, molecular docking, Drosophila

Chunxia Jiang,1– 4,&ast; Xiumei Ma,1– 4,&ast; Jiao Chen,2– 5,&ast; Yan Zeng,1– 4 Man Guo,2– 4 Xiaozhen Tan,2– 4 Yuping Wang,1,6 Peng Wang,1 Pijun Yan,2– 4 Yi Lei,1– 4 Yang Long,2– 4 Betty Yuen Kwan Law,1 Yong Xu1– 4 1Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao, People’s Republic of China; 2Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 3Metabolic Vascular Disease Key Laboratory of Sichuan Province, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 4Sichuan Clinical Research Center for Nephropathy, The Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan, People’s Republic of China; 5Department of Endocrinology, The Third’s Hospital of Mianyang, Sichuan Mental Health Center, Mianyang, Sichuan, People’s Republic of China; 6Department of Breast, Thyroid and Vascular Surgery, Traditional Chinese Medicine Hospital Affiliated to Southwest Medical University, Luzhou, Sichuan, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Betty Yuen Kwan Law, Dr. Neher’s Biophysics Laboratory for Innovative Drug Discovery, State Key Laboratory of Quality Research in Chinese Medicine, Faculty of Chinese Medicine, Macau University of Science and Technology, Macao, 999078, People’s Republic of China, Email yklaw@must.edu.mo Yong Xu, Department of Endocrinology and Metabolism, The Affiliated Hospital of Southwest Medical University, Luzhou, 646000, People’s Republic of China, Email xywyll@swmu.edu.cnPurpose: To establish nomograms integrating serum lactate levels and traditional risk factors for predicting diabetic kidney disease (DKD) in type 2 diabetes mellitus (T2DM) patients.Patients and methods: A total of 570 T2DM patients and 100 healthy subjects were enrolled. T2DM patients were categorized into normal and high lactate groups. Univariate and multivariate logistic regression analyses were employed to identify independent predictors for DKD. Then, nomograms for predicting DKD were established, and the model performance was evaluated using the area under the receiver operating characteristic curve (AUC), calibration, and decision curve analysis (DCA).Results: T2DM patients exhibited higher lactate levels compared to those in healthy subjects. Glucose, platelet, uric acid, creatinine, and hypertension were independent factors for DKD in T2DM patients with normal lactate levels, while diabetes duration, creatinine, total cholesterol, and hypertension were indicators in high lactate levels group (P< 0.05). The AUC values were 0.834 (95% CI, 0.776 to 0.891) and 0.741 (95% CI, 0.688 to 0.795) for nomograms in both normal lactate and high lactate groups, respectively. The calibration curve demonstrated excellent agreement of fit. Furthermore, the DCA revealed that the threshold probability and highest Net Yield were 17– 99% and 0.36, and 24– 99% and 0.24 for the models in normal lactate and high lactate groups, respectively.Conclusion: The serum lactate level-based nomogram models, combined with traditional risk factors, offer an effective tool for predicting DKD probability in T2DM patients. This approach holds promise for early risk assessment and tailored intervention strategies.Keywords: serum lactate, diabetic kidney disease, nomograms, prediction model, risk factors

Chunhui Jiang,1– 3 Jiani Chen,1– 3 Tong Sun,2,3 Jiaqin Xu,2,3 Hongguo Zhu,2,3 Jiaxi Chen1– 3 1School of Basic Medical Sciences & Forensic Medicine, Hangzhou Medical College, Hangzhou, People’s Republic of China; 2Clinical Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, Linhai, People’s Republic of China; 3Department of Laboratory Medicine, Enze Hospital, Taizhou Enze Medical Center (Group), Taizhou, People’s Republic of ChinaCorrespondence: Jiaxi Chen, Clinical Laboratory, Taizhou Hospital of Zhejiang Province Affiliated to Wenzhou Medical University, 150 Ximen Street, Linhai, Zhejiang Province, 317000, People’s Republic of China, Tel +86-13606652901, Email chenjx@enzemed.comPurpose: The pathogenesis of T cell subsets in sepsis during the body’s resistance to infection is currently unknown. We aimed to investigate the dynamics and molecular mechanisms of T cells during the development of sepsis.Patients and Methods: Perform single-cell data analysis on peripheral blood mononuclear cells (PBMCs) specimen samples from seven healthy controls, five early-stage sepsis patients, and four late sepsis patients, and the atlas were mapped and analyzed using reference mapping to identify the T cell subpopulations specific to early sepsis. Expression network upstream to investigate the changes of regulatory transcription factors and pathways by pySCENIC.Results: Twenty-two CD4+ T-cell subpopulations and 10 CD8+ T-cell subpopulations were identified by mapping analysis. At the early stage of sepsis, we observed altered ratios of multiple immune cells in PBMCs. Three cell types CD4 Tn cells, CD8 (GZMK+ early Tem), and CD8 (ZNF683+CXCR6− Tm) showed an upward trend (p < 0.05) in the early stages of sepsis compared to normal and returned to normal levels after two weeks. In addition, we found the presence of four sepsis-specific transcription factors (MXI1, CHD1, ARID5A, KLF9) in these three types of cells, which were validated in two external datasets. The differentially expressed genes in CD4 Tn cells, CD8 (GZMK+ early Tem), and CD8 (ZNF683+CXCR6− Tm) cells between the healthy group and the early-stage sepsis group are commonly enriched in the allograft rejection pathway. In addition, it was found that CD8 cells exhibit a trend towards differentiation into CD8 Temra cells in sepsis.Conclusion: We successfully depicted the dynamic changes of T cell subsets during sepsis onset and progression, which provides important clues for an in-depth understanding of T cells’ function and regulatory mechanisms during sepsis pathogenesis.Keywords: scRNA-seq, pySCENIC, GRN, reference mapping

Xiaodi Yan,1,2 Peng Xia,3 Hanwen Tong,4 Chen Lan,1,2 Qian Wang,1,2 Yujie Zhou,5,&ast; Huaijun Zhu,6 Chenxiao Jiang6,&ast; 1Department of Pharmacy, Nanjing Drum Tower Hospital, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, People’s Republic of China; 2School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Pharmacy, Nanjing Drum Tower Hospital, School of Pharmacy, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China; 4Department of Emergency Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 5Department of Respiratory Critical Care Medicine, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China; 6Department of Pharmacy, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chenxiao Jiang; Yujie Zhou, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Zhongshan Road No. 321, Nanjing, Jiangsu, People’s Republic of China, Tel +86 177 6173 2923 ; +86 137 0140 9863, Email sharejcx@163.com; yujiezhoum@163.comBackground: Acute ischemic stroke (AIS) in patients with atrial fibrillation (AF) carries a substantial risk of mortality, emphasizing the need for effective risk assessment and timely interventions. This study aimed to develop and validate a practical dynamic nomogram for predicting 3-month mortality in AIS patients with AF.Methods: AIS patients with AF were enrolled and randomly divided into training and validation cohorts. The nomogram was developed based on independent risk factors identified by multivariate logistic regression analysis. The prediction performance of the nomogram was evaluated using the area under the receiver operating characteristic curve (AUC-ROC), calibration plots, decision curve analysis (DCA), and Kaplan-Meier survival analysis.Results: A total of 412 patients with AIS and AF entered final analysis, 288 patients in the training cohort and 124 patients in the validation cohort. The nomogram was developed using age, baseline National Institutes of Health Stroke Scale score, early introduction of novel oral anticoagulants, and pneumonia as independent risk factors. The nomogram exhibited good discrimination both in the training cohort (AUC, 0.851; 95% CI, 0.802– 0.899) and the validation cohort (AUC, 0.811; 95% CI, 0.706– 0.916). The calibration plots, DCA and Kaplan-Meier survival analysis demonstrated that the nomogram was well calibrated and clinically useful, effectively distinguishing the 3-month survival status of patients with AIS and AF, respectively. The dynamic nomogram can be obtained at the website: https://yanxiaodi.shinyapps.io/3-monthmortality/.Conclusion: The dynamic nomogram represents the first predictive model for 3-month mortality and may contribute to managing the mortality risk of patients with AIS and AF.Keywords: dynamic nomogram, mortality, acute ischemic stroke, atrial fibrillation

Nongnong Yang,1,&ast; Haiyan Ma,1,2 Mengyi Huang,1,&ast; Esther Yuet Ying Lau,3– 5 Daniel Yee Tak Fong,6 Meng Wang,7 Pengqiao Wang,1 Siyi Xu,8 Jiale Xu,1 Chen Jiang,1 Yi Luo,9 Runtang Meng1,2,&ast; 1School of Public Health, Hangzhou Normal University, Hangzhou, Zhejiang, People’s Republic of China; 2Engineering Research Center of Mobile Health Management System, Ministry of Education, Hangzhou, Zhejiang, People’s Republic of China; 3Sleep Laboratory, Department of Psychology, The Education University of Hong Kong, Hong Kong, People’s Republic of China; 4Centre for Psychosocial Health, The Education University of Hong Kong, Hong Kong, People’s Republic of China; 5Centre for Religious and Spirituality Education, The Education University of Hong Kong, Hong Kong, People’s Republic of China; 6School of Nursing, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong, People’s Republic of China; 7Ophthalmology Center, Ningbo Yinzhou No.2 Hospital, Ningbo, Zhejiang, People’s Republic of China; 8School of Nursing, Hangzhou Normal University, Hangzhou, Zhejiang, People’s Republic of China; 9School of Nursing, Ningbo College of Health Sciences, Ningbo, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Runtang Meng; Haiyan Ma, School of Public Health, Hangzhou Normal University, No. 2318, Yuhangtang Road, Yuhang District, Hangzhou, Zhejiang, 311121, People’s Republic of China, Email mengruntang@hznu.edu.cn; mahaiyan@hznu.edu.cnPurpose: The World Health Organization-Five Well-Being Index (WHO-5) is widely used to assess subjective well-being. Nevertheless, measurement invariance and optimal cutoff point of the WHO-5 have not been examined in Chinese samples. We aimed to assess measurement properties of the Chinese version of the WHO-5 (WHO-5-C) among healthcare students.Patients and Methods: A two-wave longitudinal assessment was conducted among 343 Chinese healthcare students from September to November 2022. Measurement properties of the WHO-5-C were assessed through structural validity using confirmatory factor analysis (CFA), measurement invariance using multigroup CFA (MGCFA) and longitudinal CFA (LCFA), convergent validity using correlation analysis with the Self-Rated Health Questionnaire (SRHQ) and Patient Health Questionnaire-4 (PHQ-4), reliability using internal consistency and test–retest reliability, and optimal cutoff point using receiver operating characteristic (ROC) analysis.Results: The WHO-5-C demonstrated satisfactory structural validity with comparative fit index (CFI) of 0.968 at baseline and 0.980 at follow-up, and adequate measurement invariance in different sociodemographic variables at baseline (gender, age, major, home location, being only child, monthly household income, part-time job, physical exercise, hobby, frequency of visiting home, and stress coping strategy) (CFI changes [ΔCFI] = − 0.009– 0.003) and over a week (ΔCFI = − 0.006– 0.000). The WHO-5-C also had good internal consistency (Cronbach’s α = 0.907– 0.934; McDonald’s ω = 0.908– 0.935) and test–retest reliability (intraclass correlation coefficient [ICC] = 0.803). Convergent validity was supported by moderate correlations of the WHO-5-C with the SRHQ and PHQ-4. The optimal cutoff point of the WHO-5-C was found to be 50, with an area under the ROC curve of 0.882 at baseline data, with sensitivity of 0.803 and specificity of 0.762 at follow-up.Conclusion: The WHO-5-C demonstrated adequate measurement properties, especially concerning cross-sectional and longitudinal measurement invariance, with a recommended optimal cutoff point of ≥ 50 for assessing adequate level of psychological well-being in healthcare students.Keywords: WHO-5 Well-Being Index, subjective well-being, measurement properties, diagnostic performance, observational longitudinal design, healthcare students

Gang Chen,1– 3 Lei Li,2,4 Taipeng Sun,1– 3 Chenguang Jiang,1,2 Wei Xu,1,2 Suzhen Chen,1,2 Changchun Hu,1 Yingying Yue,1,2 Tianyu Wang,1,2 Wenhao Jiang,1,2 Yonggui Yuan1,2 1Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 2Institute of Psychosomatics, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China; 3Department of Medical Psychology, Huai’an NO 3 People’s Hospital, Huaian, People’s Republic of China; 4Department of Sleep Medicine, The Fourth People’s Hospital of Lianyungang, Lianyungang, People’s Republic of ChinaCorrespondence: Wenhao Jiang; Yonggui Yuan, Department of Psychosomatics and Psychiatry, ZhongDa Hospital, School of Medicine, Southeast University, No. 87 Dingjiaqiao, Gulou District, Nanjing, Jiangsu, 210009, People’s Republic of China, Tel +86-25-83285124, Email wjiang43@outlook.com; yygylh2000@sina.comBackground: Depression is a heritable brain disorder. Laminin genes were recently identified to affect the brain’s overall thickness through neurogenesis, differentiation, and migration in depression. This study aims to explore the effects of the LAMA2’s single nucleotide polymorphisms (SNP), a subunit gene of laminin, on the detected brain regions of patients with major depressive disorder (MDD).Methods: The study included 89 patients with MDD and 60 healthy controls with T1-weighted structural magnetic resonance imaging and blood samples for genotyping. The interactions between LAMA2 gene SNPs and diagnosis as well as duration of illness (DOI) were explored on brain measures controlled for age, gender, and site.Results: The right transverse temporal gyrus and right parahippocampal gyrus showed reduced thickness in MDD. Almost all seven LAMA2 SNPs showed significant interactions with diagnosis on both gyrus (corrected p < 0.05 or trending). In MDD, rs6569604, rs2229848, rs2229849, rs2229850, and rs2784895 interacted with DOI on the right transverse temporal gyrus (corrected p < 0.05), but not the right parahippocampal gyrus.Conclusion: The thickness of the right transverse temporal gyrus in patients with MDD may be affected by LAMA2 gene and DOI.Keywords: major depressive disorder, right transverse temporal gyrus, LAMA2, interaction

Zhi-Hao Zhao, Chao Jiang, Qing-Yuan Wu, Guo-Yue Lv, Meng Wang Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, the First Hospital of Jilin University, Changchun, Jilin Province, People’s Republic of ChinaCorrespondence: Meng Wang, Department of Hepatobiliary and Pancreatic Surgery, General Surgery Center, the First Hospital of Jilin University, 71 Xinmin Street, Changchun, Jilin Province, People’s Republic of China, Tel +86 13578767515, Email wmdoctor@jlu.edu.cnPurpose: Acute liver failure (ALF) is a severe complication of spontaneous ruptured hepatocellular carcinoma (SRHCC) that requires accurate prediction for effective treatment strategies. We aimed to develop a predictive nomogram to estimate the risk of ALF in patients with SRHCC undergoing treatment.Patients and Methods: We performed a retrospective analysis of historical data from 284 patients diagnosed with SRHCC at the First Hospital of Jilin University over the past decade. Variables were selected through univariate and multivariate logistic regression analyses, and a predictive nomogram was constructed. We evaluated its predictive accuracy against the Child-Pugh Score, R.MELD, and ALBI by assessing discrimination, calibration, and net clinical benefit.Results: Among the 284 patients, 65 developed ALF. The risk factors identified for model development included largest tumor size (LTS), platelet counts, prolonged prothrombin time, and elevated serum α-fetoprotein levels. The nomogram exhibited high accuracy in predicting ALF risk with a C-index of 0.91 (0.87– 0.95). The Delong test showed a significant difference between the nomogram and the other three models (p< 0.05). The calibration curve for the nomogram fit well, and the decision curve analysis revealed superior net benefit. The optimal cut-off point for the nomogram was determined to be 40, yielding sensitivity, specificity, positive predictive value, and negative predictive value of 83.10%, 87.20%, 65.90% and 94.60%, respectively.Conclusion: The nomogram we developed provides an optimized tool for predicting ALF in SRHCC patients. Its application can help determine individual patient’s risk of ALF, enabling more rational and personalized treatment strategies.Keywords: predict, transcatheter arterial chemoembolization, hepatectomy, prognosis, α-fetoprotein

Zhiyong Han, Dan Wang, Chuanyun Jiang, Yuliang Zhang School of Business Administration, Anhui University of Finance and Economics, Bengbu, People’s Republic of ChinaCorrespondence: Yuliang Zhang, School of Business Administration, Anhui University of Finance and Economics, 962, Caoshan Road, Bengbu, 233030, People’s Republic of China, Email zyl_1203@163.comPurpose: The COVID-19 pandemic has dramatically affected all aspects of people’s lives and work, negatively impacting personal well-being and job satisfaction. Based on the conservation of resources theory, this study examines the relationship of organizational adaptive practices (OAP) responding to COVID-19 and psychological resilience (PR) with employee job satisfaction (JS) while incorporating the mediating role of emotional exhaustion (EE).Methods: We surveyed 340 employees from China through an online questionnaire, which was used under convenience sampling and finally recovered a valid sample size of 314. We used SPSS and AMOS to analyze the correlation and hypothesis testing of the collected data through structural equation modelling (SEM) and bootstrapping.Results: Both OAP and PR facilitate JS and inhibit employee EE. EE negatively predicted employee JS. EE mediated both the relationship between OAP and subordinate JS and the relationship between PR and subordinate JS.Conclusion: The study provides a new perspective on increasing JS during the COVID-19 pandemic, thereby expanding the scope of the antecedents of employee JS in crisis situations. It also reveals the mediating role of EE and deepens the research on the mechanism by which OAP and PR affect individuals, providing practical guidance for organizations to improve employee satisfaction in sudden public crisis situations.Keywords: COVID-19, organizational adaptive practices, psychological resilience, job satisfaction, emotional exhaustion

Chen Jiang,1,2,&ast; Meijuan Peng,1,2,&ast; Ziyu Dai,1,2 Qiong Chen1,2 1Department of Geriatrics, Respiratory Medicine, Xiangya Hospital, Central South University, Changsha, 410008, China; 2National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, 410008, China&ast;These authors contributed equally to this workCorrespondence: Qiong Chen, National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, No. 87, Xiangya Road, Kaifu District, Changsha, Hunan, 410008, China, Email qiongch@163.comObjective: It has been observed that local and systemic disorders of lipid metabolism occur during the development of chronic obstructive pulmonary disease (COPD), but no specific mechanism has yet been identified.Methods: The mRNA microarray dataset GSE76925 of COPD patients was downloaded from the Gene Expression Omnibus database and screened for differentially expressed genes (DEGs). Lipid metabolism-related genes (LMRGs) were extracted from the Kyoto Encyclopedia of Genes and Genomes database and Molecular Signature Database. The DEGs were intersected with LMRGs to obtain differentially expressed lipid metabolism-related genes (DeLMRGs). GO enrichment analysis and KEGG pathway analysis were performed on DeLMRGs, and protein-protein interaction networks were constructed and screened to identify hub genes. The GSE8581 validation set and further ELISA experiments were used to validate key DeLMRG expression.Results: Differential analysis of dataset GSE76925 identified 587 DEGs, of which 62 genes were up-regulated and 525 were down-regulated. Taking the intersection of 587 DEGs with 1102 LMRGs, 20 DeLMRGs were obtained, including 1 up-regulated gene and 19 down-regulated genes. 10 hub genes were screened by cytohubba plugin, including 9 down-regulated genes PLA2G4A, HPGDS, LEP, PTGES3, LEPR, PLA2G2D, MED21, SPTLC1 and BCHE, as well as the only up-regulated gene PLA2G7. Validation of the identified 10 DeLMRGs using the validation set GSE8581 revealed that BCHE and PLA2G7 expression levels differed between the two groups. We further constructed the ceRNA network of BCHE and PLA2G7. Cell experiments also showed that PLA2G7 expression was up-regulated and BCHE expression was down-regulated in CSE-treated RAW264.7 and THP-1 cells.Conclusion: Based on a comprehensive bioinformatic analysis of lipid metabolism genes, we identified BCHE and PLA2G7 as potentially significant biomarkers of COPD. These biomarkers may represent promising targets for COPD diagnosis and treatment.Keywords: COPD, lipid metabolism, bioinformatics, BHCE, PLA2G7

Yingxian Luo, Qiong Wu, Runtang Meng, Fuzhi Lian, Chen Jiang, Meiyu Hu, Yaxin Wang, Haiyan Ma School of Public Health, Hangzhou Normal University, Hangzhou, People’s Republic of ChinaCorrespondence: Haiyan Ma, School of Public Health, Hangzhou Normal University, No. 2318, Yuhangtang Road, Yuhang District, Hangzhou, Zhejiang, 311121, People’s Republic of China, Email mahaiyan@hznu.edu.cnObjective: To evaluate the associations between serum uric acid (SUA) levels and estimated glomerular filtration rate (eGFR) and chronic kidney disease (CKD), with a focus on gender differences, and variations among women pre-and post-menopausal stages.Design: A retrospective cohort study.Setting: A large community-based survey was conducted every two years from 2010 to 2018 in Hangzhou, Zhejiang Province, Southeastern China.Participants: 10,218 participants (40 years or above) without CKD at baseline who underwent three physical examinations were enrolled. CKD was defined as an eGFR of less than 60 mL/min/1.73m2.Methods: Participants with SUA levels were divided into four groups (Q1-Q4) based on baseline SUA quartiles. The Q1 was the reference. By stratifying participants by gender, the relationships between SUA levels and eGFR were investigated using the generalized additive mixture model. The associations of SUA and the risk of incident CKD were examined using multivariate logistic regression models in the generalized estimating equation.Results: After adjusting for confounding variables, a nonlinear association between SUA and eGFR was observed in females, while an approximately linear relationship was observed in males, suggesting that elevated SUA levels are associated with renal function decline. Furthermore, the highest quartile of SUA was associated with a 2.16-fold (95% CI: 1.31– 3.58) increased risk of CKD in males and a 2.76-fold (95% CI: 1.59– 4.78) increased risk in females, compared with the lowest quartile. And the spline curves demonstrated a U-shaped pattern, suggesting a potential threshold effect of SUA on the risk of CKD. Additionally, Subgroup analyses revealed significant associations between elevated SUA levels with CKD in postmenopausal women, but not in premenopausal women.Conclusion: Elevated SUA levels are associated with an increased risk of CKD development and renal function decline in middle-aged and elderly individuals, particularly in postmenopausal women.Keywords: uric acid, estimated glomerular filtration rate, chronic kidney disease, Chinese cohort

Xiaofei Hao,1,&ast; Yuying Jia,2,&ast; Jie Chen,2 Chuan Zou,1 Cuinan Jiang3 1Department of General Medicine, Chengdu Fifth People’s Hospital, Chengdu, Sichuan, 611130, People’s Republic of China; 2Department of Outpatient, The General Hospital of Western Theater Command, Chengdu, Sichuan, 610083, People’s Republic of China; 3Department of General Surgery, The Third People’s Hospital of Chengdu & The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, 610031, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Cuinan Jiang, Department of General Surgery, The Third People’s Hospital of Chengdu & The Affiliated Hospital of Southwest Jiaotong University, Chengdu, Sichuan, 610031, People’s Republic of China, Email 591670443@qq.comBackground: Subthreshold depression (StD) is considered to be the “precursor” stage of major depressive disorder (MDD), which could cause higher risk of suicide, disease burden and functional impairment. There have been various non-pharmacological interventions for StD. However, the comparison of their effectiveness still lacks sufficient evidence. We performed a systematic review and network meta-analysis to evaluate and rank the efficacy of multiple non-pharmacological interventions targeting StD.Methods: We conducted a thorough search across various databases including PubMed, Medline, Embase, Web of Science and PsycINFO from inception to December 2022. All included studies were randomized controlled trials (RCTs) of non-pharmacological interventions for patients with StD compared with control group (CG). Several universal scales for measuring depression severity were used as efficacy outcomes. The surface under the cumulative ranking curve (SUCRA) was used to separately rank each intervention using the “Stata 17.0” software.Results: A total of thirty-six trials were included, involving twenty-eight interventions and 7417 participants. The research found that most non-pharmacological interventions were superior to controls for StD. In each outcome evaluation by different scales for measuring depression, psychotherapy always ranked first in terms of treatment effectiveness, especially Problem-solving Therapy (PST), Behavioral Activation Therapy (BAT), Cognitive Behavioral Therapy (CBT)/Internet-based CBT (I-CBT)/Telephone-based CBT (T-CBT). Since different groups could not be directly compared, the total optimal intervention could not be determined.Conclusion: Here, we show that psychotherapy may be the better choice for the treatment of StD. This study provides some evidence on StD management selection for clinical workers. However, to establish its intervention effect more conclusively, the content, format and operators of psychotherapy still require extensive exploration to conduct more effective, convenient and cost-effective implementation in primary healthcare. Notably, further research is also urgently needed to find the biological and neural mechanisms of StD by examining whether psychotherapy alters neuroplasticity in patients with StD.Keywords: subthreshold depression, non-pharmacological intervention, efficacy, comparison, network meta-analysis, systematic review

Yan Sun,1,&ast; Jiayu Song,2,&ast; Xue Lan,1 Fei Ma,2 Mingyu Jiang,3 Chunming Jiang1,2 1Department of Neonatology, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China; 2Department of Neonatology, Zhuhai Women and Children’s Hospital, Zhuhai, Guangdong, 519060, People’s Republic of China; 3Department of Pediatrics, The First Affiliated Hospital of Harbin Medical University, Harbin, Heilongjiang, 150001, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunming Jiang, Department of Neonatology, The First Affiliated Hospital of Harbin Medical University, 23 Youzheng Street, Nangang District, Harbin, Heilongjiang, 150001, People’s Republic of China, Tel +86-13303601657, Fax +86 0451-53670428, Email chunming0451@163.comPurpose: The calcium-sensing receptor (CaSR) acts as a major modulator of tissue responses related to calcium homeostasis and expresses highly in the mammalian intestine. Endotoxemia tends to impair intestinal barrier function and poses significant obstacles in clinical treatment. This work is designed to decipher whether CaSR can protect lipopolysaccharide (LPS)-induced intestinal barrier dysfunction in neonatal rats by targeting intestinal metabolites.Patient and Methods: In this study, we utilized gas chromatography (GC) combined with liquid chromatography-mass spectrometry (LC-MS) to quantitatively analyze SCFAs and metabolites in fecal samples of 24 neonatal rats with LPS induced endotoxemia.Results: Our results showed that CaSR alleviated endotoxin damage to the intestinal tight junction structure and upregulated the levels of butyric acid, propionic acid, valeric acid, and isovaleric acid in short-chain fatty acids (SCFAs). Non-targeted metabolomics analysis indicated that CaSR improved intestinal metabolic disorders by regulating glycerophospholipid metabolism, α-linolenic acid metabolism, as well as sphingolipids metabolism.Conclusion: CaSR can alter intestinal microbiota metabolites, especially SCFAs, and improve intestinal barrier damage in neonatal rat endotoxemia.Keywords: calcium-sensing receptor, lipopolysaccharide, endotoxemia, short chain fatty acids, metabolomics

Xuefang Liu,&ast; Suyan Li,&ast; Jingni Xiong, Dandan Chen, Chan Jiang, Liankun Zeng, Youyan Qiu,&ast; Bi-Wen Xia&ast; Department of Endocrine Medicine, The Fourth Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Youyan Qiu; Bi-Wen Xia, Department of Endocrine Medicine, The Fourth Affiliated Hospital of Guangzhou Medical University, No. 1 Guangming East Road, Zengjiang Street, Zengcheng District, Guangzhou City, Guangdong, 511330, People’s Republic of China, Tel +86-020-62287186, Email qyy20112014@163.com; biwenxia1550@163.comBackground: Thyroxine binding globulin (TBG) deficiency is a rare thyroid disease, mostly caused by genetic mutations and acquired by X-linked recessive inheritance. The clinical features of children with TBG deficiency and their family members were summarised and the Serpina7 gene mutation was analysed, providing a reference for the differentiation of TBG deficiency.Methods: Thyroid function was detected in TBG deficient patients, and genetic analysis was performed using polymerase chain reaction (PCR) and direct DNA sequencing to detect the characteristics of TBG mutants. Using “thyroxine binding globulin, gene and mutation” as keywords, PubMed (biomedical literature database), Web of Science and other databases were searched for relevant studies to collect and summarise relevant information.Results: The TBG (14.7 μg/mL), 70% triiodothyronine (T3) (< 0.3 nmol/L), total T3 (Tr3) (< 0.05 ng/mL) and thyroxine (T4) (14.72 nmol/L) values were lower than normal, while the thyrotropin (TSH) (2.33 uIU/mL), free T3 (FT3) (1.62 pmol/L), and free T4 (FT4) (11.39 pmol/L) values were normal. These values indicate a TBG partially deficient phenotype. Using PCR amplification and direct sequencing of the target gene, a missense mutation in exon 4 of the Serpina7 gene was found in the patient and the father, and the nucleic acid variant was C.909 (exon 4) g > T; the patient was heterozygous and the father was hemizygous. The literature search retrieved a total of 45 studies, most of which were related to mutations in the Serpina7 gene. The mutation locations included exons, introns, enhancers and promoters, with exons the predominant location. A total of 49 variants of the Serpina7 gene were identified.Conclusion: Serpina7 C.909G (P.L303F) is a mutation acquired from the father by X-linked recessive inheritance. The main clinical features of TBG deficiency patients are low serum T4, T3 and TBG levels, normal TSH, FT3 and FT4 levels, and no clinical manifestations.Keywords: thyroxine-binding globulin, deficiency, genes, mutation

Kun Qiao,1,&ast; Cheng Luo,2,&ast; Rong Huang,3,4 Jingfeng Xiang,5 You Pan,3,4 Shiyuan Zhang,1 Cong Jiang,1 Shuaijie Ding,6 Huawei Yang,3,4 Yuanxi Huang,1 Shipeng Ning3,4 1Department of Breast Surgery, Harbin Medical University Cancer Hospital, Harbin, 150081, People’s Republic of China; 2Department of Anesthesiology, The Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region, Nanning, 530000, People’s Republic of China; 3Guangxi Medical University Cancer Hospital, Nanning, 530000, People’s Republic of China; 4Key Laboratory of Breast Cancer Diagnosis and Treatment Research of Guangxi Department of Education, Nanning, 530000, People’s Republic of China; 5Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, People’s Republic of China; 6Department of Gastrointestinal Surgery & Department of Geriatrics, Shenzhen People’s Hospital (The Second Clinical Medical College, Jinan University, The First Affiliated Hospital, Southern University of Science and Technology), Shenzhen, Guangdong, 518020, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shipeng Ning; Yuanxi Huang, Email nspdoctor@163.com; rxwk@163.comIntroduction: Sonodynamic therapy (SDT) as an emerging tumor treatment gained wide attention. However, tumor vascular destruction and oxygen depletion in SDT process may lead to further hypoxia. This may lead to enhanced glycolysis, lactate accumulation, and immunosuppression.Methods: A glycolysis inhibitor (3PO) loaded and PEG modified black phosphorus nanosheets (BO) is constructed for potent starvation therapy and efficient immune activation.Results: Under ultrasound irradiation, the BO can produce ROS to destroy tumors and tumor blood vessels and lead to further hypoxia and nutrients block. Then, the released 3PO inhibits tumor glycolysis and prevents the hypoxia-induced glycolysis and lactate accumulation. Both SDT and 3PO can cut off the source of lactic acid, as well as achieve antitumor starvation therapy through the blockade of the adenosine triphosphate (ATP) supply. In addition, the combination of starvation treatment and SDT further facilitates dendritic cells (DC) maturation, promotes antigen presentation by DCs, and eventually propagates the antitumor immunity and inhibition of abscopal tumor growth.Conclusion: This is the first time that combines SDT with inhibition of glycolysis, achieving admirable tumor treatment and decreasing adverse events caused by SDT process and that has caused good immune activation. Our system provides a new idea for the future design of anti-tumor nanomedicines.Keywords: sonodynamic therapy, glycolysis inhibitor, black phosphorus nanosheets, starvation therapy, immune activation

Xiangnan Qiu,1 Changchen Jiang,1 Shenghua Jing,1 Aomei Li,1 Xiangdong Sun,1 Zetian Shen2 1Department of Radiation Oncology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, 210002, People’s Republic of China; 2Department of Radiation Oncology, The Fourth Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu, 210031, People’s Republic of ChinaCorrespondence: Zetian Shen; Xiangdong Sun, Email sztflk@163.com; sxdflk@163.comPurpose: The standard treatment regimen of preoperative chemoradiotherapy (CRT) for locally advanced rectal cancer (LARC) is still controversial. The purpose of this study was to analyze the efficacy and safety of preoperative intensive CRT in our institution.Methods: A retrospective data collection and analysis of 181 LARC patients receiving oxaliplatin (85%) of standard doses in capecitabine-based preoperative CRT and two additional cycle of neoadjuvant chemotherapy between the end of concurrent CRT and surgery.Results: The compliance of the preoperative CRT was satisfactory with 99.4%patients completed radiotherapy and 97.19%patients completed all 2 cycles of concurrent chemotherapy. Except for 20 patients diagnosed clinical complete remission (cCR) managed according to watch and wait strategy, 160 patients received R0 radical surgery. The pathological complete response (pCR) rate was 23.75% (38/160) and tumor regression grade (TRG) 0/1 was 40% (72/180). In terms of tumor downstaging, 89 (55.63%) had T downstaging while 115 (71.88%) had N downstaging. The 1-overall survival (OS),2-OS,3-OS and 5-OS were 98.7%, 96.5%, 91.4% and 81.5%, respectively. The total rate of sphincter preservation was 86.25% (138/160) and the rate of patients with low rectal cancer was 73.0% (54/74) without affecting local control rates and survival rates. Both acute adverse reactions to preoperative CRT and postoperative complications were tolerable and controllable.Conclusion: In this retrospective study, preoperative intensive CRT of patients with LARC achieved satisfied disease control and survival outcomes and well acquired the sphincter retention rate in recent years in our institution. On the basis of these findings, a Phase III study to definitively test the intensified preoperative CRT strategy is warranted.Keywords: rectal cancer, preoperative chemoradiotherapy, overall survival, disease control

Rong Yu,1,&ast; Chuan Liu,1,&ast; Jixiang Zhang,1,&ast; Jiao Li,1,&ast; Shan Tian,2 Fugui Ding,1 Zhengru Liu,3 Ting Wang,4 Zhongchun Liu,5 Changqing Jiang,6 Jie Shi,7 Kaichun Wu,8 Weiguo Dong1 1Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 2Department of Infectious Diseases, Union Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430000, People’s Republic of China; 3Department of Gastroenterology, First Affiliated Hospital of Kunming Medical University, Kunming, 650032, People’s Republic of China; 4Department of Gastroenterology, First Affiliated Hospital of Hainan Medical College, Haikou, 570102, People’s Republic of China; 5Department of Psychiatry, Renmin Hospital of Wuhan University, Wuhan, 430060, People’s Republic of China; 6Department of Clinical Psychology, Beijing Anding Hospital, Capital Medical University, Beijing, 100088, People’s Republic of China; 7Department of Medical Psychology, Chinese People’s Liberation Army Rocket Army Characteristic Medical Center, Beijing, 100088, People’s Republic of China; 8Department of Gastroenterology, Xijing Hospital, Air Force Medical University, Xi’an, 710032, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Weiguo Dong, Department of Gastroenterology, Renmin Hospital of Wuhan University, No. 99 Zhangzhidong Road, Wuhan, Hubei Province, 430060, People’s Republic of China, Tel +86 027-88041911, Email dongweiguo@whu.edu.cn Kaichun Wu, Department of Gastroenterology, Xijing Hospital, Air Force Medical University, No. 127 West Changle Road, Xi’an, Shaanxi Province, 710032, People’s Republic of China, Tel +86 029-84771600, Email kaicwu@fmmu.edu.cnObjective: To explore the correlation between disease activity and anxiety, depression, sleep quality, and quality of life in patients with inflammatory bowel disease (IBD).Methods: The disease activity of IBD patients was evaluated by 66 gastroenterologists from 42 hospitals in 22 provinces in China from September 2021 to May 2022. Anxiety, depression, sleep quality and quality of life of IBD patients were investigated and statistically analyzed by different scales, including Generalized Anxiety Disorder 7-item Scale (GAD-7), Patient Health Questionnaire-9 (PHQ-9), Pittsburgh Sleep Quality Index (PSQI), and Inflammatory Bowel Disease Quality-of-Life Questionnaire (IBD-Q).Results: A total of 2478 IBD patients were included, of which 1532 (61.8%) were in active stage and 946 (38.2%) were in remission. The proportions of active IBD with anxiety, depression, sleep disturbance, and poor quality of life were 29.5%, 29.7%, 71.1%, and 50.1%, respectively, while the proportions of remission IBD with anxiety, depression, sleep disturbance, and poor quality of life were 19.1%, 24.4%, 69.3%, and 17.4%, respectively. IBD patients who also had anxiety, depression, sleep disturbances and poor quality of life had 80 cases (8.46%) in remission and 114 cases (7.44%) in active stage, with 54 cases (9.18%) in mild activity, 51 cases (6.95%) in moderate activity and 9 cases (4.49%) in severe activity. IBD patients with different disease activity levels differed in GAD-7 scores, PHQ-9 scores, PSQI scores, and IBD-Q scores (all P< 0.001). In IBD patients, anxiety, depression, and sleep disturbance, which interact with each other, can further aggravate their disease activity (all P< 0.001).Conclusion: Anxiety, depression, sleep disturbances, and quality of life are strongly correlated with disease activity in IBD patients, and IBD patients with psychological disturbances are most often in the active stage and have a poor quality of life.Keywords: inflammatory bowel disease, disease activity, anxiety, depression, sleep quality, quality of life, survey

Chunxiang Jiang,1,2 Siqi Cai,1,2 Lijuan Zhang1,2 1Paul. C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen, People’s Republic of China; 2University of Chinese Academy of Sciences, Beijing, People’s Republic of ChinaCorrespondence: Lijuan Zhang, Paul. C. Lauterbur Research Center for Biomedical Imaging, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, 1068 Xueyuan Avenue, Shenzhen University Town, Shenzhen, 518055, People’s Republic of China, Tel +86 0755 86392247, Fax +86 0755 86392299, Email lj.zhang@siat.ac.cnPurpose: Functional magnetic resonance imaging (fMRI) has been widely adopted to investigate the neural activity in gray matter (GM) in the field of sleep research, but the neural activity in white matter (WM) has received much less attention. The current study set out to test our hypothesis that WM functional abnormality is associated with poor sleep quality.Participants and Methods: K-means clustering analysis was performed on 78 healthy adults drawn from the Human Connectome Project dataset to extract stable WM functional networks (WM-FNs) and GM-FNs. The differences in functional connectivity within WM-FNs and between WM- and GM-FNs, as well as the power spectrum between good sleep quality group (Pittsburgh Sleep Quality Index (PSQI) < 6, daytime dysfunction = 0) and poor sleep quality group (PSQI > 6, daytime dysfunction > 0) were examined between groups with good and poor sleep quality. Additionally, linear relationships between sleep quality and altered functional characteristics of WM-FNs were evaluated.Results: Functional connectivity between middle and superficial WM-FNs, short- and long-range functional connectivity between WM- and GM-FNs were decreased in poor sleepers and negatively correlated with PSQI score. The mean amplitudes of right sensorimotor WM networks at whole, high and low frequency bands were higher in poor sleepers and were positively correlated with PSQI score.Conclusion: WM functional abnormality is associated with poor sleep quality. The neurobiological mechanisms that underlie the functional alterations of WM-FNs in poor sleepers need to be investigated in future studies.Keywords: human connectome project, sleep quality, white matter, functional connectivity, functional magnetic resonance imaging

Yao Liu,1– 3 Jinqing Liu,1– 3 Lei Fu,1– 3 Chuan Jiang,1– 3 Shifang Peng1– 3 1Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 2Key Laboratory of Viral Hepatitis of Hunan Province, Xiangya Hospital, Central South University, Changsha, People’s Republic of China; 3National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, People’s Republic of ChinaCorrespondence: Shifang Peng, Department of Infectious Diseases, Xiangya Hospital, Central South University, Changsha, People’s Republic of China, Email sfp1988@csu.edu.cnObjective: Despite its high case-fatality risk, pyogenic liver abscess (PLA) lacks clear management guidelines in patients with negative microbial cultures. Our aim was to evaluate differences in clinical characteristics between patients with culture-negative liver abscess (CNLA) and those with culture-positive liver abscess (CPLA), and identify differences in the main causative pathogen.Methods: In this study, we retrospectively collected medical records of PLA patients admitted to a teaching hospital from January 2010 to December 2019.Results: In total, 324 PLA patients were enrolled in this study. Of these, 202 (62.3%) cases were confirmed cultural positive, including 109 patients (54%) and 20 (9.9%) patients infected with Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E.coli), respectively. Patients in the CPLA group were older (p=0.029) and had higher prevalence of abscesses larger than 5 cm in diameter (p = 0.003), gas-forming rate (p = 0.016), and percutaneous drainage (p < 0.001) compared with CNLA group. Patients with CPLA had significantly longer hospitalizations than those with CNLA (p = 0.010). Nevertheless, there was no significant difference in in-hospital mortality between the two groups (p = 0.415). Compared with patients with E. coli, those with K. pneumoniae had higher incidence of diabetes mellitus (p = 0.041), solitary abscess (p < 0.001), localization in the right hepatic lobe (p = 0.033), abscess size larger than 5 cm (p < 0.001) and percutaneous drainage (p = 0.002), but mortality was not significantly different (p = 1.000).Conclusion: No significant difference in in-hospital mortality was found between patients with CNLA and those with CPLA group. However, clinical characteristics and management were different between the main causative pathogens, including K. pneumoniae and E. coli.Keywords: PLA, culture negative, culture positive, Klebsiella pneumoniae, Escherichia coli

Cheng Ma,1– 4,&ast; Yin Cao,1,&ast; Guang Zhang,1– 3,&ast; Jiannan Qiu,2 Yan Zhou,1 Peng Wang,2 Shuo Wang,2 Dongliang Yan,1 Ding Ma,2 Chunping Jiang,1– 3 Zhongxia Wang1– 3 1Department of Hepatobiliary Surgery, Drum Tower Clinical College of Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Hepatobiliary Surgery, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, People’s Republic of China; 3Department of Tissue Engineering, Jinan Microecological Biomedicine Shandong Laboratory, Jinan, People’s Republic of China; 4Department of Gastrointestinal Surgery, Xuzhou Central Hospital, Xuzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongxia Wang; Chunping Jiang, Email freud_t@126.com; chunpingjiang@163.comBackground: The prediction of prognosis of hepatocellular carcinoma (HCC) is of great significance in improving disease outcome and optimizing clinical management, while reliable prognostic indicators are lacking. This study was conducted to develop readily-to-use nomograms for prognosis prediction of HCC after hepatectomy.Materials and Methods: Data of eligible patients were collected and analyzed retrospectively. Independent prognostic factors were identified by Cox regression, and nomograms for the prediction of disease-free survival (DFS) and overall survival (OS) were developed. The performance of the nomograms was evaluated by receiver operating characteristics (ROC) curves, C-indexes and calibration curves and was verified by the validation cohort. The predictive value of the nomograms was also compared with the 8th edition of American Joint Committee on Cancer (AJCC) Tumor-Node-Metastasis (TNM) and the Barcelona Clinic Liver Cancer (BCLC) staging systems.Results: In total, 599 patients were enrolled in the analysis: 420 in the training cohort and 179 in the validation cohort. The optimal cut-off value of Gamma-Glutamyl Transpeptidase-to-Lymphocyte Ratio (GLR) was 19.5. GLR contributed significantly to the nomograms with good predictive power. In ROC analyses, the areas under curve (AUCs) of the nomograms for 1-, 3- and 5-year DFS and OS prediction were 0.758, 0.756, 0.734 and 0.810, 0.799, 0.758, respectively. The C-indexes of the DFS nomogram were 0.697 (95% CI 0.665– 0.729) in the training cohort and 0.710 (95% CI 0.664– 0.756) in the validation cohort. For OS prediction, the C-indexes were 0.741 (95% CI 0.704– 0.778) and 0.758 (95% CI 0.705– 0.811) in the training and validation cohorts, respectively. The calibration curves demonstrated satisfactory agreement between nomogram predictions and actual observations. The nomograms demonstrated superior predictive performance to the TNM and the BCLC staging systems.Conclusion: Our novel nomograms showed adequate performance in the prediction of HCC prognosis after hepatectomy, which may facilitate the risk stratification and individualized management of HCC patients.Keywords: hepatocellular carcinoma, nomogram, gamma-glutamyl transferase, lymphocyte, hepatectomy

Miao Li,1,2 Jiazhao Zhang,3 Chenguang Jiang,2,4 Jun Wang,2 Ruhong Sun,5 Shayu Jin,5 Ning Zhang,1,&ast; Zhenhe Zhou2,&ast; 1Department of Psychology, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China; 2Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, People’s Republic of China; 3Grade 2019 Class 6, Basic Medicine College of Jinzhou Medical University, Jinzhou, People’s Republic of China; 4Department of Psychosomatics and Psychiatry, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China; 5Department of Psychiatry, Nanjing Medical University Graduate School, Nanjing, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Ning Zhang, Department of Psychology, Nanjing Brain Hospital Affiliated to Nanjing Medical University, Nanjing, People’s Republic of China, Tel +86-13601588630, Email zn6360@126.com Zhenhe Zhou, Department of Psychiatry, The Affiliated Wuxi Mental Health Center of Jiangnan University, Wuxi Central Rehabilitation Hospital, Wuxi, People’s Republic of China, Tel +86-13358118986, Email zhouzh@njmu.edu.cnPurpose: Deficits in facial emotional intensity recognition have been associated with social cognition in patients with major depression. The study examined multiple event-related potential (ERP) components in patients with major depression and investigated the relationships between ERPs, social cognition, and clinical features.Participants and Methods: Thirty-one patients met DSM-IV diagnosis of depression and 31 healthy participants completed the emotion intensity recognition task (EIRT), while ERPs were recorded. Data on ERP components (P100, N170, P200, and P300) were analyzed.Results: The behavioral results showed that patients with major depression performed worse on EIRT, including all six categories of emotions (sadness, disgust, happiness, surprise, anger, and fear), compared to healthy participants. The ERP results showed that patients with major depression exhibited higher P100 amplitudes for sad and happy faces than healthy participants; P300 amplitudes induced by sad and surprise faces were also higher than in healthy participants, mainly in the central and temporal lobes. A positive correlation was found between sadness intensity scores and P100 amplitudes in patients with major depression.Conclusion: Patients with major depression are biased in their identification of facial expressions indicating emotional intensity. Specifically, they have emotional biases in the early and late stages of cognitive processing, mainly in the form of sensitivity to sad stimuli. It may lead to a persistent rumination of sadness that is detrimental to the remission of depression. Additionally, patients with major depression devote different amounts of cognitive resources for different intensities of sad faces during the preconscious stage of cognitive processing. The more intense their perception of sadness, the more cognitive resources they devote. Therefore, the assessment of the intensity of facial expressions is an important research topic, with clinical implications on social cognitive function in patients with major depression.Keywords: major depression, event-related potentials, emotional intensity recognition, social cognition, emotional tasks

Yuting Yang,1,&ast; Jin Zhao,2,&ast; Chunmeng Jiang,1 Yue Zhang,1 Mei Han,1 Hui Liu1 1Department of Gastroenterology, Second Hospital of Dalian Medical University, Dalian, Liaoning, 116000, People’s Republic of China; 2Department of Pulmonary and Critical Care Medicine, Air Force Medical Center, PLA, Beijing, 100000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Hui Liu; Mei Han, Department of Gastroenterology, Second Hospital of Dalian Medical University, 467 Zhongshan Road, Shahekou Region, Dalian, Liaoning, 116000, People’s Republic of China, Email liuhuidoctor@dmu.edu.cn; hanmei@dmu.edu.cnAbstract: WKYMVm (Trp-Lys-Tyr-Met-Val-D-Met) is a synthetic hexapeptide identified as a potent agonist of FPRs. FPRs are widely expressed on the cell membrane of immune cells. Therefore, WKYMVm participates in the regulation of immune cells by activating FPRs, and plays a therapeutic role in infections, tumors, autoimmune diseases and so on. WKYMVm can promote the chemotactic migration, increase the bactericidal activity of neutrophils and monocytes. WKYMVm also regulates the number and polarization of macrophages, affects the maturation of DCs and the differentiation of T cells, and promotes the activation and chemotaxis of NK cells. These functions make WKYMVm a candidate drug for immunotherapy. In this paper, we summarize the regulatory effects and underlying mechanisms of WKYMVm on six immune cells (neutrophils, monocytes, macrophages, DCs, T cells and NK cells) to increase comprehensive understanding and promote further research on WKYMVm.Keywords: WKYMVm, FPRs, immune cells, chemotaxis, polarization

Chen Jiang,1,&ast; Stefanos Mastrotheodoros,2,3 Yihong Zhu,4,&ast; You Yang,5 Souheil Hallit,6– 8 Bing Zhao,4 Yuping Fan,1 Mengyi Huang,1 Cen Chen,1 Haiyan Ma,1,9 Runtang Meng1,9,&ast; 1School of Public Health, Hangzhou Normal University, Hangzhou, People’s Republic of China; 2Department of Psychology, University of Crete, Rethymno, Greece; 3Department of Youth and Family, Utrecht University, Utrecht, the Netherlands; 4The Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, People’s Republic of China; 5School of Nursing, Hangzhou Normal University, Hangzhou, People’s Republic of China; 6School of Medicine and Medical Sciences, Holy Spirit University of Kaslik, Jounieh, Lebanon; 7Applied Science Research Center, Applied Science Private University, Amman, Jordan; 8Research Department, Psychiatric Hospital of the Cross, Jal Eddib, Lebanon; 9Engineering Research Center of Mobile Health Management System, Ministry of Education, Hangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Runtang Meng; Haiyan Ma, School of Public Health, Hangzhou Normal University, No. 2318, Yuhangtang Road, Yuhang District, Hangzhou, Zhejiang, 311121, People’s Republic of China, Email mengruntang@hznu.edu.cn; mahaiyan@hznu.edu.cnPurpose: Stress may relate to an increased risk of psychological and physical disorders. Thus, a brief and efficient measurement instrument for researchers to measure stress is essentially needed.Participants and Methods: To assess measurement properties of the validated Chinese version of the Perceived Stress Questionnaire-13 (PSQ-C-13), we conducted a two-wave longitudinal study from September to December, 2021 with a convenient sample of medical students.Results: A two-factor (constraint and imbalance) structure showed good fit indices (Comparative Fit Index [CFI] = 0.972, Tucker-Lewis Index [TLI] = 0.966, Root Mean Square Error of Approximation [RMSEA] = 0.062). Spearman correlations with the Chinese Perceived Stress Scale-10 illustrated that convergent validity of the PSQ-C-13 was relatively satisfactory (r = 0.678 [baseline], 0.753 [follow-up]). Measurement invariance was supported across subgroups (gender, age, home location, single-child status, monthly households’ income, and part-time status) and time points. Internal consistency was sound (Cronbach’s α = 0.908 [baseline], 0.922 [follow-up]; McDonald’s ω = 0.909 [baseline], 0.923 [follow-up]). Stability between time points was good (Intraclass Correlation Coefficient = 0.834).Conclusion: The two factors of the PSQ-C-13 including constraint and imbalance may adequately measure the level of stress on participants. The PSQ-C-13 is a convenient and efficient instrument that contains valid and reliable psychometric properties.Keywords: Perceived Stress Questionnaire, longitudinal survey, medical students, psychometrics

Fang Wang,1,&ast; Feng-Hua Wang,2,3,&ast; Kaiyu Sun,4,&ast; Chang Jiang,2,5 Sui Peng,6 Li-Xia Xu,1 Ming Kuang,7 Gui-Fang Guo,2,5,8 Shu-Ling Chen9 1Department of Oncology, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2State Key Laboratory of Oncology in South China, The Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 3Department of Oncology, The Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 4Department of Gastrointestinal Surgery, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 5Collaborative Innovation Center for Cancer Medicine, The Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 6Institute of Precision Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China; 7Department of Liver Surgery, Center of Hepato-Pancreato-Biliary Surgery, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, People’s Republic of China; 8VIP Department, Sun Yat-sen University Cancer Center, Guangzhou, People’s Republic of China; 9Institute of Diagnostic and Interventional Ultrasound, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shu-Ling Chen; Gui-Fang Guo, Email chenshling@mail.sysu.edu.cn; guogf@sysucc.org.cnIntroduction: Advanced biliary tract carcinoma (BTC) has a poor prognosis and few treatment options. We compared the efficacy of the PD-1 monoclonal antibody (PD-1-mAb) combined regimens with the standard chemotherapy in the first-line and second-line treatment of advanced BTC.Methods: We retrospectively assessed the patients with advanced BTC, who received treatment at the First Affiliated Hospital of Sun Yat-Sen University and the Sun Yat-Sen University Cancer Center. The patients were treated with PD-1-mAb combined regimens or standard chemotherapy at the first line or treated with PD-1-mAb combined regimens or systematic therapy at the second line. Further subgroup analyses were assessed to identify superior regimens.Results: This study included 210 patients. The first-line PD-1-mAb combination group (n = 83) achieved longer median PFS (mPFS) (7.3 vs 5.3 months, p=0.001) and median OS (mOS) (15.6 vs 11.4 months, p=0.002) than the first-line standard chemotherapy group (n=76). Similarly, the second-line PD-1-mAb combination group (n=50) yielded longer mPFS (6.1 vs 2.6 months, p< 0.001) and mOS (11.7 vs 7.2 months, p=0.008) than the second-line systematic therapy group (n=51). Subgroup analyses showed that the PD-1-mAb combined with TKI group achieved better mPFS than the chemotherapy group whether in the first-line (HR = 0.468, p=0.005) or the second-line setting (HR = 0.45, p=0.009), but did not achieve superiority in mOS (both p> 0.05). Compared with the chemotherapy group, the PD-1-mAb combined with chemotherapy group achieved longer mOS (HR = 0.53, p=0.023) in the first-line setting and longer mPFS in the second-line setting (HR = 0.54, p=0.044).Conclusion: The PD-1-mAb combination therapy is superior to the standard chemotherapy in advanced or unresectable BTC, whether as a first-line or second-line treatment. Among the combination therapy, both the PD-1-mAb combined with TKI and combined with standard chemotherapy were promising options for advanced BTC patients.Keywords: biliary tract carcinoma, PD-1-mAb, PD-1 plus anti-angiogenesis TKI, PD-1 plus chemotherapy, the first-line chemotherapy, the second-line chemotherapy

Wei-dong Jin,1 Jun-qin Mao,2 Jie Liu,2 Gang Liang,2 Chao Jiang,2 Zhi-min Sheng2 1Department of Anesthesiology, Jinhua Maternity and Child Health Care Hospital, Jinhua, People’s Republic of China; 2Department of Anesthesiology, Wenling Maternity and Child Health Care Hospital, Taizhou, People’s Republic of ChinaCorrespondence: Zhi-min Sheng, Department of Anesthesiology, Wenling Maternity and Child Health Care Hospital, 102, Xiabao Road, Chengdong Street, Taizhou, 317500, People’s Republic of China, Tel +86-576-86168030, Email 2191200789@zju.edu.cnBackground: Although the optimal infusion dose of norepinephrine combined with crystalloid coload for preventing spinal anesthesia-induced hypotension (SAIH) for cesarean delivery has been established, the infusion regimen of norepinephrine combined with colloid coload has not been fully quantified. The objective of this study was to compare and determine the median effective dose (ED50) and 90% effective dose (ED90) of norepinephrine infusion combined with crystalloid coload versus colloid coload for preventing SAIH during cesarean delivery.Methods: Two hundred parturients were randomly assigned to receive norepinephrine infusion at 0.02, 0.04, 0.06, 0.08, or 0.10 μg/kg/min in combination with 10 mL/kg crystalloid coload or colloid coload to prevent SAIH. The study period was defined as the interval from the commencement of intrathecal injection to delivery of the neonate. The primary outcome was non-occurrence of hypotension, defined as systolic blood pressure (SBP) less than 80% of the baseline before delivery. The ED50 and ED90 of norepinephrine infusion dose were determined using probit regression analysis. By calculating the 95% confidence intervals (CIs) of relative median potency to determine whether the prophylactic infusion of norepinephrine requirement was different between the two groups.Results: The derived ED50 and ED90 of norepinephrine infusion combined with crystalloid coload were 0.030 (95% CIs 0.020 to 0.038) and 0.097 (95% CIs 0.072 to 0.157) μg/kg/min, respectively. The ED50 and ED90 of norepinephrine infusion combined with colloid coload were 0.021 (95% CIs 0.013 to 0.029) and 0.070 (95% CIs 0.053 to 0.107) μg/kg/min, respectively. The estimate of relative median potency for norepinephrine between the two groups was 1.37 (95% CIs 0.94 to 2.23).Conclusion: Under the conditions of this study, 10 mL/kg colloid coload reduced the dose of prophylactic norepinephrine infusion by approximately 30% in parturients during spinal anesthesia for cesarean delivery compared with the crystalloid coload.Keywords: norepinephrine, hypotension, the dose–response relationship, crystalloid, colloid, ED50, ED90

Xingyu Chang,1,&ast; Yuchen Kang,2,&ast; Yuxuan Yang,1,&ast; Yajie Chen,1 Yanyu Shen,1 Chenjun Jiang,1 Yi Shen3 1The First Clinical Medical College, Lanzhou University, Lanzhou, People’s Republic of China; 2The Second Clinical Medical College, Lanzhou University, Lanzhou, People’s Republic of China; 3Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Yi Shen, Department of Orthopaedics, The Second Xiangya Hospital of Central South University, Changsha, People’s Republic of China, Tel +86-13517490910, Email shenyiak487@163.comAbstract: Osteoarthritis (OA) is one of the most common chronic joint diseases and is gradually becoming the main cause of disability and joint pain in the elderly worldwide. Pyroptosis is a regulated programmed cell death triggered by inflammasomes. It leads to cell swelling, lysis, and bioactive molecule secretion. Studies found that the damaged chondrocytes in OA joints had morphological characteristics of pyroptosis, and the cytokines associated with pyroptosis in synovial fluid increased, indicating that pyroptosis may have certain impacts on the pathological progression of OA. This review briefly summarizes the molecular mechanisms of pyroptosis and the epidemiology and pathogenesis of OA. Furthermore, we discussed the role of pyroptosis in articular cartilage and synovium during OA and reviewed the progress of pyroptosis-related molecules in the targeted therapy of OA joints, hoping to provide feasible directions for the diversified treatment of OA.Keywords: pyroptosis, osteoarthritis, articular cartilage, synovium, NLRP3 inflammasome, GSDMD

Li Wang,1,&ast; Yu-Ling Zhang,2,&ast; Chang Jiang,1,&ast; Fang-Fang Duan,1 Zhong-Yu Yuan,1 Jia-Jia Huang,1 Xi-Wen Bi1 1Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-Sen University Cancer Center, Guangzhou, People’s Republic of China; 2Department of Endocrinology, Jiangxi Provincial People’s Hospital, Nanchang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Xi-Wen Bi; Jia-Jia Huang, Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People’s Republic of China, Email bixw@sysucc.org.cn; huangjiaj@sysucc.org.cnBackground: The value of the lymphocyte-to-C-reactive protein (CRP) ratio (LCR) in early breast cancer (BC) is unclear. We explored the correlation between the LCR and survival of patients with early BC and established effective LCR-based prognostic signatures for predicting prognosis.Methods: In this retrospective study, we randomized 623 patients with early-stage BC diagnosed in December 2010 to October 2012 at the Sun Yat-sen University Cancer Center to training and verification datasets. The median follow-up of all patients was 109 months. The survival differences were calculated by Kaplan–Meier method using the Log rank test. For overall survival (OS) and disease-free survival (DFS), the independent factors in the training dataset were identified using univariate and multivariate Cox analyses, in which two-tailed P-values < 0.05 were considered statistically significant. Based on this, we respectively constructed novel signatures for survival prediction and validated the efficiency of signatures through the concordance index (C-index), calibration and receiver operating characteristic (ROC) curves in both datasets.Results: The LCR, lymphatic vessel invasion (LVI), progesterone receptor (PR) status, and Ki67 index were independent prognostic factors of OS. And the LCR and LVI are associated to DFS too. High LCR was associated with better OS and DFS. We constructed the prediction signatures based on those independent prognostic factors and calculated the risk scores. Patients in the training dataset with higher risk scores had significantly worse prognosis (P < 0.001). The signature had excellent discrimination capacity, with an OS C-index of 0.785 [95% confidence interval (CI): 0.713– 0.857] and 0.750 (95% CI: 0.669– 0.832) in the training and verification datasets, respectively. The time–ROC curves also suggest accurate prediction by the signature.Conclusion: The LCR was a significant prognostic predictor of OS and DFS in early BC. The LCR-based prognostic signatures could be a useful tool for individualized therapeutic guidance.Keywords: survival, nomogram, early breast cancer, LCR

Chunyu Duan,1 Fan Feng,1 Lijuan Liu,1 Fang Qu,1 Zhiye Yang,2 Hui Zhang,2 Chunguang Jiang1 1Pediatric Ophthalmology, Aier Eye Hospital Group, Kunming Air Eye Hospital, Kunming, Yunnan, 650200, People’s Republic of China; 2Physical Examination Center, Kunming Army Special Service Rehabilitation Center, Kunming, Yunnan, 650000, People’s Republic of ChinaCorrespondence: Chunguang Jiang, Pediatric Ophthalmology, Kunming Aier Eye Hospital, No. 687 Huancheng South Road, Guandu District, Kunming City, Yunnan Province, 650200, People’s Republic of China, Tel + 86-15912177272, Email Chunguangjiang@outlook.comPurpose: To analyze the factors influencing the progression of myopia in adolescents receiving orthokeratology.Methods: This prospective cohort study collected the data of 378 myopia patients receiving orthokeratology. The follow-up time was 12 months ranging from December 2015 to December 2019. The group-based trajectory modeling (GBTM) was used to identify similar developmental trajectories in the levels of uncorrected visual acuity and changes of axial length elongation. Univariate and multivariate logistic regression analyses were conducted to explore the influencing factors of myopia development in patients wearing orthokeratology.Results: There was no factor having effect on visual acuity (left) and visual acuity (right) in different trajectories (all P> 0.05). The corneal curvature K1 (left) (OR=0.382, 95% CI: 0.188– 0.776), corneal curvature K2 (left) (OR=0.362, 95% CI: 0.187– 0.699), degree of spherical refraction (left) (OR=0.139, 95% CI: 0.082– 0.235) and spherical equivalent (left) (OR=7.276, 95% CI: 3.724– 14.215) were factors associated with the changes of axial length elongation (left). The corneal curvature K1 (right) (OR=0.260, 95% CI: 0.116– 0.585), corneal curvature K2 (left) (OR=0.272, 95% CI: 0.121– 0.610) and degree of spherical refraction (right) (OR=0.129, 95% CI: 0.068– 0.244) were correlated with the changes of axial length elongation (right). All P< 0.05.Conclusion: Orthokeratology is a promising method for controlling the progression of myopia. The corneal curvature, degree of spherical refraction and spherical equivalent were factors influencing the changes of axial length elongation in myopia patients wearing orthokeratology. The findings might give a reference for the application of orthokeratology in clinic.Keywords: group-based trajectory modeling, myopia, orthokeratology, factors

Ruoyu Zhang,1,&ast; Chen Sun,1,&ast; Xuemei Chen,1 Yunze Han,1 Weidong Zang,1 Chao Jiang,2 Junmin Wang,1 Jian Wang1 1Department of Human Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan Province, 450001, People’s Republic of China; 2Department of Neurology, The Fifth Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan Province, 450052, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jian Wang; Junmin Wang, Department of Anatomy, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, Henan, People’s Republic of China, Email jianwang2020@outlook.com; wangjunmin@zzu.edu.cnAbstract: The COVID-19 pandemic has caused devastating loss of life and a healthcare crisis worldwide. SARS-CoV-2 is the causative pathogen of COVID-19 and is transmitted mainly through the respiratory tract, where the virus infects host cells by binding to the ACE2 receptor. SARS-CoV-2 infection is associated with acute pneumonia, but neuropsychiatric symptoms and different brain injuries are also present. The possible routes by which SARS-CoV-2 invades the brain are unclear, as are the mechanisms underlying brain injuries with the resultant neuropsychiatric symptoms in patients with COVID-19. Ferroptosis is a unique iron-dependent form of non-apoptotic cell death, characterized by lipid peroxidation with high levels of glutathione consumption. Ferroptosis plays a primary role in various acute and chronic brain diseases, but to date, ferroptosis in COVID-19-related brain injuries has not been explored. This review discusses the mechanisms of ferroptosis and recent evidence suggesting a potential pathogenic role for ferroptosis in COVID-19-related brain injury. Furthermore, the possible routes through which SARS-CoV-2 could invade the brain are also discussed. Discoveries in these areas will open possibilities for treatment strategies to prevent or reduce brain-related complications of COVID-19.Keywords: brain injuries, cell death, COVID-19, ferroptosis, iron, neuropsychiatric symptoms

Jianting Long,1,&ast; Baoxian Liu,2,&ast; Zhijia Yao,1 Huiwen Weng,1 Heping Li,1 Chunlin Jiang,3,4 Shi Fang5 1Department of Medicinal Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 2Department of Medical Ultrasound, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China; 3Department of General Surgery, Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510799, People’s Republic of China; 4Guangzhou Key Laboratory of Enhanced Recovery After Abdominal Surgery, Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510799, People’s Republic of China; 5Department of Clinical Nutrition, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, 510080, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Chunlin Jiang, Email fangshi@mail.sysu.edu.cnPurpose: miR-500a-3p has been extensively reported to be implicated in the development and progression in several human cancer types. This study aimed to investigate the diagnostic and prognostic significance of miR-500a-3p as a biomarker in hepatocellular carcinoma (HCC).Methods: miR-500a-3p expression was evaluated by in situ hybridization (ISH) and real-time PCR in 10 adjacent normal tissues (ANT), 21 liver fibrosis tissues, and 110 HCC tissues. Statistical analysis was used to investigate the correlation of miR-500a-3p expression with clinicopathological features in HCC patients. Kaplan–Meier survival analysis was performed to evaluate the prognostic significance of miR-500a-3p in overall survival and recurrence-free survival in HCC patients.Results: In this study, we found that expression levels of miR-500a-3p were enhanced in HCC tissues. High miR-500a-3p levels were positively correlated with multiple clinicopathological features, including advanced clinical stage, distant metastatic status, increased AFP levels and poor tumor differentiation degree. More importantly, high miR-500a-3p levels predicted poor overall survival and early recurrence in HCC patients. Finally, a strong and positive correlation of miR-500a-3p mRNA expression with ISH staining scores was observed in clinical HCC tissues.Conclusion: Our findings suggest that miR-500a-3p might be used as a novel biomarker to facilitate early diagnosis and predict prognosis in HCC patients.Keywords: miR-500a-3p, diagnosis and prognosis, biomarker, hepatocellular carcinoma

Xin Hua,1,&ast; Fangfang Duan,1,&ast; Wenyu Zhai,2,&ast; Chenge Song,1 Chang Jiang,1 Li Wang,1 Jiajia Huang,1 Huanxin Lin,3 Zhongyu Yuan1 1Department of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 2Department of Thoracic Surgery, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China; 3Department of Radiotherapy, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Zhongyu YuanDepartment of Medical Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of China, Email yuanzhy@sysucc.org.cnHuanxin LinDepartment of Radiotherapy, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, Guangdong, 510060, People’s Republic of China, Email linhx@sysucc.org.cnPurpose: We attempted to explore the prognostic value of baseline inflammatory and nutritional biomarkers at diagnosis in patients with early-stage breast cancer and develop a novel scoring system, the inflammatory-nutritional prognostic score (INPS).Patients and Methods: We collected clinicopathological and baseline laboratory data of 1259 patients with early-stage breast cancer between December 2010 and November 2012 from Sun Yat-sen University Cancer Center. Eligible patients were randomly divided into training and validation cohorts (n = 883 and 376, respectively) in a 7:3 ratio. We selected the most valuable biomarkers to develop INPS by the least absolute shrinkage and selection operator (LASSO) Cox regression model. A prognostic nomogram incorporating INPS and other independent clinicopathological factors was developed based on the stepwise multivariate Cox regression method. Then, we used the concordance index (C-index), calibration plot, and time-dependent receiver operating characteristic (ROC) analysis to evaluate the prognostic performance and predictive accuracy of the predictive nomogram.Results: Four inflammatory-nutritional biomarkers, including neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), prognostic nutritional index (PNI), and albumin-alkaline phosphatase ratio (AAPR), were selected using the LASSO Cox analysis to construct INPS, which remained an independent prognostic indicator per the multivariate Cox regression analysis. Patients were stratified into low- and high-INPS groups based on the cutoff INPS determined by the maximally selected rank statistics. The prognostic model for overall survival consisting of INPS and other independent clinicopathological indicators showed excellent discrimination with C-indexes of 0.825 (95% confidence interval [CI]: 0.786– 0.864) and 0.740 (95% CI: 0.657– 0.822) in the training and validation cohorts, respectively. The time-dependent ROC curves showed a higher predictive accuracy of our prognostic nomogram than that of traditional tumor-node-metastasis staging.Conclusion: Baseline INPS is an independent indicator of OS in patients with early-stage breast cancer. The INPS-based prognostic nomogram could be used as a practical tool for individualized prognostic predictions.Keywords: early-stage breast cancer, LASSO Cox analysis, inflammatory-nutritional biomarker, prognostic nomograms, overall survival

Yan Xu,1 Mao Ye,1 Ying Hong,1 Yi Kang,2 Yue Li,1 Xiao Xiao,1 Li Zhou,1 Chunling Jiang1 1Department of Anesthesiology, West China Hospital, Sichuan University & The Research Units of West China (2018RU012), Chinese Academy of Medical Sciences, Chengdu, 610041, People’s Republic of China; 2Department of Anesthesiology and Translational Neuroscience Center, Laboratory of Anesthesia and Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, 610041, People’s Republic of ChinaCorrespondence: Chunling JiangDepartment of Anesthesiology, West China Hospital, Sichuan University & The Research Units of West China (2018RU012), Chinese Academy of Medical Sciences, Chengdu, 610041, People’s Republic of ChinaTel/Fax +86-28-8542-3593Email jiangchunling@scu.edu.cnPurpose: Many patients develop severe and persistent pain after hepatectomy delaying postoperative rehabilitation. Studies have suggested that intravenous lidocaine infusion relieved postoperative pain and improved overall postoperative outcomes. However, its efficacy on hepatectomy is still masked, due to the postoperative metabolic change of lidocaine by the liver. We hypothesized that intravenous lidocaine infusion in the perioperative period would lead to postoperative pain reduction and improve the overall patient experience.Study Design and Methods: In this prospective double-blind, randomized controlled design trial, 260 adults scheduled for hepatectomy will be allocated to the lidocaine and the placebo groups. The lidocaine group will be administered lidocaine intravenously during intraoperative period and 72 postoperative hours; the placebo group will be administered normal saline at the same volume, infusion rate, and timing. The primary outcome is the incidence of moderate-severe pain (numeric rating scale ≥ 4) during movement at 24 hours after surgery. The secondary outcomes include the incidence of moderate-severe pain at 24 hours after surgery at rest, the incidence of moderate-severe pain at 48 and 72 hours after surgery at rest and during movement, the cumulative morphine consumption at 24, 48 and 72 hours postoperatively, bowel function recovery, the incidence of postoperative nausea and vomiting, the incidence of postoperative pulmonary complications, the length of hospital stay, levels of inflammatory factors and patient satisfaction scores.Discussion: This is the first prospective trial to shed light on the efficacy of intraoperative period and 72 postoperative hours intravenous lidocaine on postoperative pain and recovery after hepatectomy. The findings will provide a new strategy of perioperative pain management for hepatectomy.Keywords: intravenous lidocaine, hepatectomy, postoperative pain, recovery

Chao Jiang,1,2,&ast; Si Yin,1,&ast; Jianmin Wei,3,&ast; Weigong Zhao,1 Xiaohui Wang,1,2 Yongyuan Zhang,1,2 Dingjun Hao,2 Heng Du1 1Department of Orthopaedics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 2Department of Spine Surgery, Honghui Hospital, Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of China; 3Department of Spine Surgery, Baoji City Hospital of Traditional Chinese Medicine, Baoji, Shaanxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Heng DuDepartment of Orthopaedics, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, Shaanxi, People’s Republic of ChinaEmail drdu18@126.comObjective: The purpose of this study was to introduce and evaluate the early clinical outcomes of the full-endoscopic posterior lumbar interbody fusion (Endo-PLIF) technique with epidural anesthesia (EA) for single-segment lumbar degenerative diseases.Methods: In this retrospective case series study, we explored the feasibility and effectiveness of the Endo-PLIF with EA for single-segment lumbar degenerative diseases. Between March 2018 and January 2019, a series of 24 patients with single-segment lumbar degenerative diseases underwent Endo-PLIF surgery and were followed up for a minimum of 12 months (15.21± 2.27 months). Clinical outcomes including visual analog scale (VAS) scores for back and leg pain, Oswestry Disability Index (ODI) scores, and the Short Form-36 health survey questionnaire (SF-36) were evaluated preoperatively, and postoperatively at 3 days and at 3, 6, and 12-months.Results: All patients underwent successful single-segment Endo-PLIF surgery. The mean operation time was 209.17± 39.49 min, and average amount of bleeding was 43.33± 14.87 mL. The VAS for lower extremity pain and back pain significantly improved at 3 days, and at 3, 6, 12 months compared with preoperative, respectively. The ODI scores decreased from 42.04± 3.96 to 12.75± 2.71 (P< 0.001) at preoperative and 12 months postoperatively, respectively. The SF-36 Physical Component Scores (PCS) improved from 34.96± 4.63 preoperatively to 52.08± 6.05 (P< 0.001) at 12 months postoperatively. Additionally, the SF-36 Mental Component Scores (MCS) improved from 39.38± 5.70 at preoperative to 53.13± 5.97 (P< 0.001) at 12 months postoperatively. Two patients experienced dysesthesia, and one patient had a wound infection.Conclusion: Endo-PLIF with EA is a feasible and valuable technique for the treatment of single-segment lumbar degenerative diseases in selected patients.Keywords: full-endoscopic posterior lumbar interbody fusion, lumbar degenerative disease, lumbar fusion, clinical outcome

Fan Wu,1,2,&ast; Changbin Jiang,1,&ast; Yumin Zhou,1,2,&ast; Youlan Zheng,1,&ast; Heshen Tian,1 Haiqing Li,1 Zhishan Deng,1 Ningning Zhao,1 Huai Chen,3 Pixin Ran1,2 1National Center for Respiratory Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China; 2Guangzhou Laboratory, Bio-island, Guangzhou, People’s Republic of China; 3Department of Radiology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pixin RanNational Center for Respiratory Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, People’s Republic of ChinaTel +86 20 83205187Fax +86 20-81340482Email pxran@gzhmu.edu.cnBackground: It has been found that the degree of terminal bronchiole destruction is associated with the severity of COPD. However, total airway count (TAC) of CT-visible and its relationship with COPD lung function severity and pulmonary function decline remains controversial. The present study aimed to determine whether TAC is significantly reduced in early-stage COPD (GOLD stage I–II) compared with healthy control subjects and whether TAC is associated with annual decline in pulmonary function in Chinese patients with early-stage COPD.Methods: A total of 176 participants were enrolled in this study, of which 139 participants had undergone at least two spirometry measurements within 7 years (average 5.5 [standard deviation 0.8] years) after baseline data acquisition. CT-visible TAC was measured by summing all airway segments using semi-automated software. Average lumen diameter, average inner area, emphysema index, air trapping, and inspiratory Pi10 were also measured. Multivariable linear analysis was performed to evaluate variables that were significantly related to pulmonary function parameters and to evaluate the correlation between TAC and annual decline in longitudinal pulmonary function.Results: Compared with healthy control subjects, CT-visible TAC was significantly reduced by 51% in GOLD II and by 31% in GOLD I after adjustment. TAC had the greatest impact on pre-bronchodilator FEV1, pre-bronchodilator FVC, post-bronchodilator FEV1, and post-bronchodilator FEV1/FVC (both p< 0.001) among all CT indicators measured. TAC has the best correlation with inspiratory Pi10 (ρ=− 0.751, p< 0.001), an evaluation indicator of the degree of airway remodeling. TAC was independently associated with annual decline in pre-bronchodilator FEV1 (p=0.023), post-bronchodilator FEV1 (p=0.018), and post-bronchodilator FEV1/FVC (p< 0.001).Conclusion: This finding suggests that CT-visible TAC may be an evaluation indicator of the degree of airway remodeling, and was diminished in greater COPD lung function severity, and independently associated with disease progression. Early-stage COPD patients have already occurred lung structural changes and early intervention may be needed to ameliorate the progression of disease.Clinical Trial Registration: ChiCTR-OO-14004264.Keywords: chronic obstructive pulmonary disease, COPD, computed tomography, total airway count, TAC

Chunteng Jiang,1,2 Santuan Xie,1 Guang Yang,3 Ningning Wang3 1Department of Internal Medicine, The Affiliated Zhongshan Hospital of Dalian University, Dalian, Liaoning, People’s Republic of China; 2Department of Cardiology and Pneumology, University Medical Center of Göttingen, Georg-August-University of Göttingen, Göttingen, Lower Saxony, Germany; 3Department of Food Nutrition and Safety, School of Public Health, Dalian Medical University, Dalian, Liaoning, People’s Republic of ChinaCorrespondence: Guang Yang; Ningning Wang Email yg290@163.com; zkxwnn@dmu.edu.cnAbstract: Inflammation is an intricate biological response of body tissues to detrimental stimuli. Cardiovascular disease (CVD) is the leading cause of death worldwide, and inflammation is well documented to play a role in the development of CVD, especially atherosclerosis (AS). Emerging evidence suggests that activation of the NOD-like receptor (NLR) family and the pyridine-containing domain 3 (NLRP3) inflammasome is instrumental in inflammation and may result in AS. The NLRP3 inflammasome acts as a molecular platform that triggers the activation of caspase-1 and the cleavage of pro-interleukin (IL)-1β, pro-IL-18, and gasdermin D (GSDMD). The cleaved GSDMD forms pores in the cell membrane and initiates pyroptosis, inducing cell death and the discharge of intracellular pro-inflammatory factors. Hence, the NLRP3 inflammasome is a promising target for anti-inflammatory therapy against AS. In this review, we systematically summarized the current understanding of the activation mechanism of NLRP3 inflammasome, and the pathological changes in AS involving NLRP3. We also discussed potential therapeutic strategies targeting NLRP3 inflammasome to combat AS.Keywords: cardiovascular disease, atherosclerosis, NLRP3 inflammasome, mechanisms, therapeutic strategies

Xiaoying Chao,1,&ast; Weiran Dai,1,&ast; Shuo Li,1 Chenyang Jiang,1 Zhiyuan Jiang,2 Guoqiang Zhong1 1Department of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China; 2Hypertension Division, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guoqiang ZhongDepartment of Cardiology, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of ChinaTel +86 13978635329Email drguoqiang@sina.comZhiyuan JiangHypertension Division, The First Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi, 530021, People’s Republic of ChinaTel +86 13597006702Email drjzy123@sina.comBackground: Circular RNA (circRNA) has been receiving increased attention in the research of atrial fibrillation (AF). Our study aims to find potential circRNAs and identify the circRNA-miRNA-mRNA regulatory network in AF based on bioinformatics analysis.Methods: GSE129409 was retrieved from the Gene Expression Omnibus (GEO) database, and we used R software to analyze the differentially expressed circRNAs (DECs). Subsequently, we used several bioinformatics methods to obtain the target miRNAs and the target genes. Next, we performed Gene Ontology (GO) classification and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the target genes. Then, we used Cytoscape 3.8.2 software to visualize and construct the circRNA-miRNA-mRNA regulatory network, the protein–protein interaction (PPI) network, and the autophagy-related genes network.Results: We identified a total of 21 DECs, including 6 upregulated DECs and 15 downregulated DECs. After further analysis, we obtained a circRNA-miRNA-mRNA regulatory network consisting of 11 DECs, 9 target miRNAs and 410 target genes, and a PPI network. Finally, the potential novel genes of autophagy in AF were revealed by bioinformatics analysis.Conclusion: This study could explore the potential role of circRNA, autophagy-related genes and construct the circRNA-miRNA-mRNA regulation network in AF.Keywords: circular RNA, bioinformatics analysis, ceRNA, autophagy, atrial fibrillation

Yang Bai,1,&ast; Fei Guan,1,&ast; Feifan Zhu,1 Chunjie Jiang,1 XiaoXiao Xu,1 Fang Zheng,2 Wenqi Liu,1 Jiahui Lei1 1Department of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China; 2Department of Immunology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jiahui LeiDepartment of Pathogen Biology, School of Basic Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People’s Republic of ChinaTel +86-13329722645Fax +86-27-83691246Email leijiahui@hotmail.comPurpose: Schistosoma japonicum-infected IL-33 and ST2 gene deficiency (IL-33−/− and ST2−/−, respectively) mice were used to explore the role of the IL-33/ST2 axis in liver pathology targeting regulatory T cells (Treg)/T helper 17 cells (Th17).Materials and Methods: Each mouse was infected percutaneously with 20 S. japonicum cercariae. Hepatic mass index (HMI), liver egg granulomas, hepatic fibrosis biomarkers and serum levels of alanine aminotransferase (ALT) were investigated. Treg and Th17 frequency was determined by flow cytometry. Expressions of Foxp3, ST2, TGF-β 1, IL-10, RORγt, and IL-17A were measured via quantitative real-time polymerase chain reaction (qRT-PCR). Concentrations of TGF-β 1, IL-10 and IL-17A were tested with ELISA. In vitro experiments, mRNA expressions of Foxp3, TGF-β 1, IL-10, Atg5, Beclin-1 and p62 associated with polarization of Treg by recombinant mouse IL-33 (rmIL-33) were detected by qRT-PCR.Results: An increased expression of IL-33/ST2 was shown in S. japonicum-infected mice. Deficiency of IL-33 or ST2 gene led to an aggravated liver pathology, which was evidenced by elevated hepatic granuloma volume, HMI and ALT levels and fibrosis, which was demonstrated by increased hepatic collagen deposition in the infected mice. Injection of rmIL-33 into the infected IL-33−/− mice strongly abrogated the liver pathology and fibrosis, whereas no detectable effect with injecting rmIL-33 into the infected ST2−/− mice. Furthermore, depletion of the IL-33/ST2 axis inhibited Treg, accompanied by increased Th17. rmIL-33 treatment upregulated Treg and downregulated Th17 in the infected IL-33−/− mice, while no effect in the infected ST2−/− mice. rmIL-33 led to elevated expressions of Atg5, Beclin-1 and inhibited expression of p62 in expansion of Treg.Conclusion: The IL-33/ST2 axis plays a protective role in S. japonicum infected mice, which is closely related to increasing Treg responses as well as suppressing Th17 responses. Expansion of Treg by IL-33 may be associated with its regulation of autophagy.Keywords: IL-33, ST2, liver pathology, fibrosis, Treg, Th17, autophagy

Fuqiang Liu,1– 4 Feng Han,4,5 Xiaoli Liu,4,5 Lina Yang,4,5 Caixia Jiang,4,5 Chen Cui,1– 4 Fang Yuan,1– 4 Xin Zhang,1– 4 Lei Gong,1– 4 Xinguo Hou,1– 4 Yuan Liu,1– 4 Li Chen1– 4 1Department of Endocrinology, Qilu Hospital of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 2Institute of Endocrine and Metabolic Diseases of Shandong University, Jinan, Shandong, 250012, People’s Republic of China; 3Key Laboratory of Endocrine and Metabolic Diseases, Shandong Province Medicine & Health, Jinan, Shandong, 250012, People’s Republic of China; 4Jinan Clinical Research Center for Endocrine and Metabolic Diseases, Jinan, Shandong, 250012, People’s Republic of China; 5Department of Endocrinology, Zhangqiu District People’s Hospital, Jinan, 250200, People’s Republic of ChinaCorrespondence: Yuan Liu; Li Chen Email liuyuan198735@163.com; chenli3@medmail.com.cnBackground: To investigate the correlation between serum interleukin-17A (IL-17A) levels and diabetic retinopathy (DR) in elderly individuals with type 2 diabetes mellitus (T2DM).Methods: The study included 194 elderly patients (94 males and 100 females) with T2DM. Digital retinal photography as well as fundus fluorescein angiography was employed to distinguish between nonproliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR). In addition, multiple logistic regression analysis was conducted to determine the correlation between serum IL-17A levels and DR status.Results: The average age of the study cohort was 69.14 ± 6.33 years, of which 52.08% were male. The study participants with the highest IL-17A (Q4) levels had higher TC, DBP, and low-density lipoprotein cholesterol (LDL-C) values than those the other groups. Analysis using unadjusted and adjusted linear regression revealed that the effect size of 1.09 for DR in the unadjusted model indicates that IL-17A is associated with an increase of 1.09 in DR (mmol/L) (β 1.09, 95% confidence interval (CI) 1.03, 1.16). Using the minimum-adjusted model (the model 2), as IL-17A increased, DR was higher by 1.11 (β 1.11, 95% CI 1.04, 1.18). With the fully adjusted model (the model 3), for each additional IL-17A increase, DR was higher by 1.15 (β 1.15, 95% CI 1.06, 1.24).Conclusion: Serum IL-17A levels are apparently positively correlated to DR in Chinese elderly individuals with T2DM.Keywords: interleukin-17A, diabetic retinopathy, type 2 diabetes mellitus

Jinglong Chen,1,2,&ast; Changbin Jiang,1,&ast; Youlan Zheng,1,&ast; Dongxing Zhao,1,&ast; Fan Wu,1 Zhuxiang Zhao,3 Jun Zhao,2 Qing Li,2 Bing Li,4 Gongyong Peng,1 Yumin Zhou,1 Pixin Ran1 1National Center for Respiratory Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of China; 2Department of Geriatrics, National Clinical Key Specialty, Guangzhou First People’s Hospital, South China University of Technology, Guangzhou, 510180, People’s Republic of China; 3The Pulmonary Medicine, Guangzhou First People’s Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, People’s Republic of China; 4GMU-GIBH Joint School of Life Sciences, Guangzhou Medical University, Guangzhou, 511436, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Pixin RanNational Center for Respiratory Medicine, State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People’s Republic of ChinaEmail pxran@gzhmu.edu.cnBackground and Objective: To determine the effects of BSE (biomass smoke exposure) on pulmonary and non-pulmonary changes in patients with COPD compared with normal individuals.Methods: Using a cohort, we recruited 16 healthy individuals with BSE (BSE normal), 19 patients with BSE+COPD, 13 healthy individuals with cigarette smoke exposure (CSE normal), 25 patients with CSE+COPD, and 25 healthy controls. Patients with GOLD stage I and II COPD were included. Baseline data (demographic data, BSE or CSE, lung function, and CT findings) and follow-up lung function data were collected. CT parameters of emphysema, pulmonary small vessels, airway remodeling, pectoralis muscles, and erector spinae muscle were measured.Results: Individuals with BSE were mainly women (32/35, 91.43%). Compared with the CSE+COPD group, the BSE+COPD group demonstrated slower lung function decline, increased lower lung emphysema, narrower airway lumen dimensions and increased airway wall thickening in the moderate and small airways (all P< 0.05). Compared with healthy controls, the CSE normal and BSE normal groups exhibited significant reductions in pulmonary small vessel area and obvious airway remodeling in small airways (P< 0.05). Compared with the BSE normal group, the BSE+COPD group showed significantly more severe emphysema and airway remodeling, as well as reduced left pectoralis major muscle area (all P< 0.05).Conclusion: Healthy individuals with BSE had reduced pulmonary small vessel area and evidence of airway remodeling; patients with BSE and COPD showed more severe emphysema, airway remodeling, and reductions in pectoralis major muscle area.Clinical Trial Registration: ChiCTR-OO-14004264.Keywords: biomass smoke, chronic obstructive pulmonary disease, computed tomography, pulmonary function

Yilan Jin,&ast; Xiaorong Li,&ast; Caihong Jiang,&ast; Jun Zhao, Guang Liu, Hui Li, Gaowa Jin, Quanfu Li Department of Medical Oncology, Ordos Central Hospital, Ordos, 017000, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Quanfu Li; Gaowa JinDepartment of Medical Oncology, Ordos Central Hospital, 23th Yinjihuoluo Western Road, Ordos, 017000, People’s Republic of ChinaTel +86 0477-8363279Fax +86 0477-8363158Email li_qfedu@163.com; jingw145@126.comAbstract: The occurrence and severity of chemotherapy-induced nausea and vomiting (CINV) are influenced by many factors; this includes therapeutic factors, such as the dose, administration mode, and chemotherapeutic agent emetogenicity, as well as patient-related risk factors, such as the gender, age, alcohol consumption history, and anxiety level. However, these factors cannot fully explain the individual CINV differences. In recent years, the correlation between gene polymorphism and CINV has been a hot research topic; the present paper reviews current research on CINV-related gene polymorphisms, and the results indicate that the use of gene polymorphism for the optimization of CINV efficacy is of important clinical significance.Keywords: chemotherapy-induced nausea and vomiting, gene polymorphisms, prevention and treatment, antiemetic