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Xia Zhou,1 Wei Feng,1 Xiaolong Wang,2 Zejun Niu,1 Peng Wang,1 Li Yuan,1 Pei Wang1 1Department of Anesthesiology, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province,People’s Republic of China; 2Department of Emergency Surgery, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People’s Republic of ChinaCorrespondence: Pei Wang, Email wangpei@qdu.edu.cnPurpose: Anesthesia for metabolic–bariatric surgery is challenging due to the increased risk of opioid-related adverse events. The purpose of the investigation was to assess the feasibility and efficacy of multimodal opioid-free general anesthesia with transversus abdominis plane (TAP) block for laparoscopic sleeve gastrectomy in contrast with conventional opioid-based general anesthesia.Patients and Methods: Eighty patients who underwent laparoscopic sleeve gastrectomy and eventually 71 patients included in the analysis. They were randomly divided into an opioid-based anesthesia group (control group) with sufentanil or opioid-free anesthesia (OFA) group. Esketamine, dexmedetomidine, and TAP were as part of the OFA. Sevoflurane, dexamethasone, and muscle relaxants were administered intraoperatively to all patients. The primary outcome was antiemetic rescue within 24 hours after surgery. The secondary outcomes included pain scores, analgesic needs, extubation time, complications, the hemodynamic changes, and duration of hospital stay.Results: In contrast with the control group, the need for antiemetic rescue was significantly reduced (p= 0.035). Furthermore, the visual Analog Scale (VAS) for postoperative pain was considerably lower in the OFA group (p < 0.01) than it was in the control group. There was no significant difference in the need for analgesic rescue in both groups (p= 0.155). Extubation time and post-anesthesia care unit (PACU) stay duration were equal between the two groups (p =0.328 and p =0.54). At the end of the surgery and after extubation, hemodynamic changes was more pronounced in the OFA group (p =0.027) than the control group. The length of the hospital stay was significantly shorter compared with the control group (p =0.002).Conclusion: OFA with TAP results in a significant decrease in the need for antiemetic rescue, a lower level of pain after the surgery, and a shorter hospital stay in contrast with anesthesia based on opioids.Keywords: opioid-free, nerve block, esketamine, post-operative nausea and vomiting, bariatric surgery

Zhihui Jia,1 Zimin Niu,1 Jia Ji Wang,2,3 Jose Hernandez,4,5 Yu Ting Li,6,7 Harry HX Wang1,8,9 1School of Public Health, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 2School of Public Health, Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Centre for General Practice, The Seventh Affiliated Hospital, Southern Medical University, Foshan, People’s Republic of China; 4Faculty of Medicine and Health, EDU, Digital Education Holdings Ltd., Kalkara, Malta; 5Green Templeton College, University of Oxford, Oxford, UK; 6State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 7Guangdong Provincial Key Laboratory of Ophthalmology and Visual Science, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, People’s Republic of China; 8Department of General Practice, The Second Hospital of Hebei Medical University, Shijiazhuang, People’s Republic of China; 9JC School of Public Health and Primary Care, Faculty of Medicine, The Chinese University of Hong Kong, New Territories, Hong Kong SAR, People’s Republic of ChinaCorrespondence: Yu Ting Li, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, 510060, People’s Republic of China, Email liyuting3@mail.sysu.edu.cn Harry HX Wang, School of Public Health, Sun Yat-Sen University, Guangzhou, 510080, People’s Republic of China, Email haoxiangwang@163.com; haoxiangwang@cuhk.edu.hkBackground: Treatment burden is a patient-centred, dynamic concept. However, longitudinal data on the changing pattern of treatment burden among patients with one or more long-term conditions (LTCs) are relatively scanty. We aimed to explore the longitudinal trajectories of treatment burden and associated risk factors in a large, patient population in primary care settings.Methods: We analysed data from 5573 primary care patients with long-term conditions (LTCs) recruited using a multistage sampling method in Shenzhen, southern China. The treatment burden was assessed by the Mandarin Chinese version of the Treatment Burden Questionnaire (TBQ). We used latent class growth mixture modelling (LCGMM) to determine trajectories of treatment burden across four time points, ie, at baseline, and at 6, 12, and 18 months. Predictors of trajectory classes were explored using multivariable logistic regression analysis.Results: The mean TBQ scores of patients with a single LTC (n = 2756), 2 LTCs (n = 1871), 3 LTCs (n = 699), and ≥ 4 LTCs (n = 247) were 18.17, 20.28, 21.32, and 26.10, respectively, at baseline. LCGMM identified three discrete classes of treatment burden trajectories over time, ie, a high-increasing class, a low-stable class, and a high-decreasing class. When controlling for individual-level factors including age, education, monthly household income per head, smoking, alcohol consumption, and attendance in health education, patients who had a clinical diagnosis of 3 LTCs (adjusted odds ratio [aOR] = 1.49, 95% CI = 1.21– 1.86, P < 0.001) or ≥ 4 LTCs (aOR = 1.97, 95% CI = 1.44– 2.72, P < 0.001) were more likely to belong to the high-increasing class. Sensitivity analysis using propensity score methods obtained similar results.Conclusion: Our study revealed the presence of discrete patterns of treatment burden over time in Chinese primary care patients with LTCs, providing directions for tailored interventions to optimise disease management. Patients with 3 or more LTCs should receive close attention in healthcare delivery as they tend to experience a greater treatment burden.Keywords: longitudinal trajectories, treatment burden, long-term conditions, multimorbidity, risk factors

Zuohu Niu,1,&ast; Jialiang Chen,2,&ast; Huijing Wang,3,&ast; Rongrui Wang,3,4 Hongye Peng,3 Shaojie Duan,5 Shukun Yao4 1Department of Infections, Beijing Hospital of Traditional Chinese Medicine, Capital Medical University, Beijing, People’s Republic of China; 2Center of Integrative Medicine, Beijing Ditan Hospital, Capital Medical University, Beijing, People’s Republic of China; 3Graduate School, Beijing University of Chinese Medicine, Beijing, People’s Republic of China; 4Department of Gastroenterology, China-Japan Friendship Hospital, Beijing, People’s Republic of China; 5Department of Geriatrics, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaojie Duan, Department of Geriatrics, Taizhou Central Hospital (Taizhou University Hospital), Taizhou, Zhejiang, People’s Republic of China, Email 1782802171@qq.com Shukun Yao, Department of Gastroenterology, China-Japan Friendship Hospital, No. 2 Yinghua East Street, Chaoyang District, Beijing, 100029, People’s Republic of China, Email shukunyao@126.comPurpose: It is unclear how the Chinese Visceral Adiposity Index (cVAI) relates to metabolic dysfunction-associated fatty liver disease (MAFLD) and alanine aminotransferase (ALT) in nonobese individuals. In this study, we evaluated the ability of the cVAI to predict MAFLD and elevated ALT in nonobese participants.Methods: This cross-sectional study recruited 541 nonobese subjects from March 2019 to January 2022 with the age range of 18– 80 years. Hepatic steatosis was diagnosed by ultrasound. Participants were divided into four groups according to cVAI quartiles. To assess the associations between cVAI and MAFLD and elevated ALT, multivariate logistic regression was used. Receiver operating characteristic (ROC) curves were generated to evaluate the ability of the cVAI to predict MAFLD and elevated ALT.Results: Compared to the group with the lowest cVAI, the group with the highest cVAI was positively associated with nonobese MAFLD [16.173 (4.082– 64.073), P < 0.001] and elevated ALT [8.463 (2.859– 25.049), P < 0.001]. The area under the ROC curve (AUC) of the cVAI was greater than that of WC, waist-to-height ratio, or BMI for predicting nonobese MAFLD in the male, female, > 38 and ≤ 38 years old subgroups (P < 0.05), respectively. In addition, the ability of the cVAI to predict MAFLD was better in females, young individuals, and individuals with a higher education level (P < 0.05). The cVAI also had good predictive ability for elevated ALT levels [0.655 (0.602– 0.708)], particularly in females, young people, and highly educated participants. Furthermore, the cVAI was strongly positively correlated with the liver fibrosis score (P < 0.05) and was also a strong indicator of concomitant metabolic syndrome in nonobese MAFLD patients [AUC = 0.688 (0.612– 0.763)].Conclusion: The cVAI was strongly related to nonobese MAFLD and elevated ALT. The cVAI may be a reliable and accessible predictor of nonobese MAFLD and elevated ALT.Keywords: Chinese visceral adiposity index, metabolic dysfunction-associated fatty liver disease, nonobese, Chinese, cross-sectional study

Xiaojing Li,1 Liwei Bai,2 Ziru Niu,3 Qiang Lu3 1Department of Obstetrics, First Hospital of Qinhuangdao, Qinhuangdao, Hebei, 066000, People’s Republic of China; 2Department of Obstetrics, Qinhuangdao Hospital for Maternal and Child Health, Qinhuangdao, Hebei, 066000, People’s Republic of China; 3Department of Endocrinology, First Hospital of Qinhuangdao, Qinhuangdao, Hebei, 066000, People’s Republic of ChinaCorrespondence: Qiang Lu, Department of Endocrinology, First Hospital of Qinhuangdao, Qinhuangdao, Hebei, 066000, People’s Republic of China, Tel +86-13933909066, Email 13933909066@126.comPurpose: The objective of this study was to explore whether neck circumference can serve as an early predictor of the risk of Gestational Diabetes (GDM).Patients and Methods: A total of 318 singleton pregnant women who underwent routine prenatal examinations at Qinhuangdao Maternal and Child Health Hospital from September 2017 to September 2020 were selected and categorized into the GDM group and the normal glucose tolerance group (NGT) based on the results of the oral glucose tolerance test (OGTT) conducted during the second trimester. The general information and laboratory test results were compared and analyzed. Inter-group comparison was conducted using the t-test, and multivariate logistic regression analysis was employed to analyze the independent risk factors of GDM. The predictive threshold of various indicators for GDM occurrence during pregnancy was determined using the subject’s work curve.Results: The GDM group exhibited significantly higher levels of pre-pregnancy weight, pre-pregnancy BMI, neck circumference, waist circumference, hip circumference, triglycerides (TG), uric acid (UA), TG/HDL-C ratio, and waist-hip ratio compared to the NGT group. Additionally, HDL cholesterol (HDL-C) levels were significantly lower in the GDM group, and blood glucose levels at each point of the OGTT were markedly higher compared to the NGT group (P< 0.05). Multivariate logistic regression analysis revealed that neck circumference (OR=1.239, P< 0.001) and early pregnancy TG (OR=1.842, P< 0.001) were independent risk factors for GDM. The receiver operating characteristic analysis demonstrated that the optimal critical value of neck circumference for predicting GDM was 32.6 cm, with a sensitivity of 50% and specificity of 74.3%.Conclusion: The neck circumference during early pregnancy was found to be related to GDM, and the predictive cutoff point of 32.6 cm for neck circumference could be employed as a simple index to predict GDM in early pregnancy.Keywords: neck circumference, gestational diabetes, obesity, predictive indicators

Zishuai Li,1– 3,&ast; Zihan Zhang,4,&ast; Letian Fang,1– 3,&ast; Jiayi Zhao,1– 3,&ast; Zheyun Niu,4 Hongsen Chen,1– 3 Guangwen Cao1– 3 1Key Laboratory of Biological Defense, Ministry of Education, Second Military Medical University, Shanghai, 200433, People’s Republic of China; 2Shanghai Key Laboratory of Medical Bioprotection, Second Military Medical University, Shanghai, 200433, People’s Republic of China; 3Department of Epidemiology, Second Military Medical University, Shanghai, 200433, People’s Republic of China; 4Department of Epidemiology, Tongji University School of Medicine Tongji University, Shanghai, 200120, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Guangwen Cao, Department of Epidemiology, Second Military Medical University, 800 Xiangyin Road, Shanghai, 200433, People’s Republic of China, Tel/Fax +86 21-8187-1060, Email gcao@smmu.edu.cnAbstract: Globally, primary liver cancer is the third leading cause of cancer death, and hepatocellular carcinoma (HCC) accounts for 75%– 95%. The tumor microenvironment (TME), composed of the extracellular matrix, helper cells, immune cells, cytokines, chemokines, and growth factors, promotes the immune escape, invasion, and metastasis of HCC. Tumor metastasis and postoperative recurrence are the main threats to the long-term prognosis of HCC. TME-related therapies are increasingly recognized as effective treatments. Molecular-targeted therapy, immunotherapy, and their combined therapy are the main approaches. Immunotherapy, represented by immune checkpoint inhibitors (ICIs), and targeted therapy, highlighted by tyrosine kinase inhibitors (TKIs), have greatly improved the prognosis of HCC. This review focuses on the TME compositions and emerging therapeutic approaches to TME in HCC. Keywords: hepatocellular carcinoma, tumor microenvironment, immunotherapy, targeted therapy

Fang-xue Gong,1 Xin Zhou,2 Zhao-he Niu,1 Yan Mao,1 Yong-mei Wang,1 Meng Lv,1 Xue-qiang Gao,1 Wen-jing Liu,1 Hai-bo Wang1 1Department of Breast Disease Center, The Affiliated Hospital of Qingdao University, Qingdao, Shandong Province, People’s Republic of China; 2Qingdao Medical College of Qingdao University, Qingdao, Shandong Province, People’s Republic of ChinaCorrespondence: Hai-bo Wang, Department of Breast Disease Center, The Affiliated Hospital of Qingdao University, No. 59 Haier Road, Laoshan District, Qingdao City, Shandong Province, People’s Republic of China, Tel +86 18661805787, Email hbwang66@126.comPurpose: Autologous fat grafting (AFG) is a technique that can improve the appearance of breasts in surgical patients. There are currently few studies on breast-conserving surgery (BCS) combined with immediate AFG, although we believe that it could achieve satisfactory effects. Therefore, the purpose of this study is to observe the effects of BCS combined with immediate AFG on oncologic safety, satisfaction and psychology of breast cancer patients.Patients and Methods: We retrospectively collected the data of 85 breast cancer patients from February 2018 to October 2018. After screening, 40 patients in AFG group (AG, BCS combined with immediate AFG) and 40 patients in control group (CG, BCS alone) were finally included in the study. The primary outcomes were the survival, tumor recurrence and metastasis, and BREAST-Q score of patients. The secondary outcomes were short and long-term complications, degree of depression and anxiety of patients.Results: A total of 80 patients were included in the analysis. There was no significant difference in the clinicopathological data between the two groups (P> 0.05). The average follow-up time of the two groups was 40.58± 2.630 and 40.28± 2.679 months. In the analysis of oncologic safety, no patients died in AG and 1 patient died in CG. In addition, there was no significant difference between the two groups in terms of the overall recurrence rate and the distribution of recurrence types (P> 0.05). As for satisfaction, the BREAST-Q score of AG was significantly higher than that of CG (57.85± 4.833 vs 51.93± 5.045, P< 0.001). In the secondary outcomes, there was no short-term complication specified in the study; in the long-term complications, the incidence of calcification in AG was not significantly higher than that in CG (P=0.065). In the analysis of depression and anxiety, there was no significant difference between the two groups (P> 0.05).Conclusion: BCS combined with immediate AFG can significantly improve patients’ satisfaction without increasing the risk of death and tumor recurrence. However, it does not seem to play a role in improving the conditions of depression and anxiety.Keywords: breast cancer, breast-conserving surgery, autologous fat grafting, oncologic safety, BREAST-Q, psychology

Min Wang,1,2,&ast; Dongyue Wang,1,&ast; Jingzhi Zuo,3 Tianyu Liu,4 Zheng Niu,5 Juan Xie,1 Dunyi Qi2 1Department of Anesthesiology, Jinshan Hospital of Fudan University, Shanghai, People’s Republic of China; 2Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China; 3Emergency Department, Yichang Central People’s Hospital, Yichang, Hubei, People’s Republic of China; 4Department of Anesthesiology, Peking University People’s Hospital, Beijing, People’s Republic of China; 5Department of Anesthesiology, Zhangjiagang First People’s Hospital, Zhangjiagang, Jiangsu, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Dunyi Qi, Department of Anesthesiology, Affiliated Hospital of Xuzhou Medical University, Xuzhou, Jiangsu, People’s Republic of China, Email qdy6808@163.comPurpose: Prophylactic intravenous nalbuphine was administered to observe its median effective dose (ED50) in reducing pain after undergoing laparoscopic total hysterectomy. To investigate the effect of different doses of nalbuphine on postoperative analgesia and adverse reactions in patients.Patients and Methods: The 120 patients undergoing laparoscopic total hysterectomy were divided into 6 groups: group C (control) and group P (5 different doses of nalbuphine) with 20 patients per group. The doses of nalbuphine in group P were in an equally proportional series (groups P1, P2, P3, P4, and P5 received doses of 0.280, 0.200, 0.140, 0.100, and 0.070 mg/kg, respectively), diluted to 20 mL with saline and administered 5 min before the induction of anesthesia. A similar volume (20 mL) of saline was administered to group C 5 min before the induction of anesthesia. The numeric rating scale (NRS) of patients during awakening and after surgery, the number of postoperative salvage analgesia, and the occurrence of postoperative adverse effects were recorded.Results: The ED50 (95% confidence interval (CI)) of nalbuphine in preventing pain during the awakening period in patients calculated using the point-slope method was 0.125 (0.108, 0.145) mg/kg. NRS scores differed among the 6 groups at 30 min and 1 h after extubation (P < 0.001; P < 0.001). Pairwise comparisons between groups revealed that, at 30 min after extubation, compared with group P1, the NRS scores of groups P4, P5, and C were higher (P = 0.001, P < 0.001, P < 0.001); compared with group P2, groups P5 and C had higher NRS scores (P = 0.011, P = 0.001). At 1 h after extubation, the NRS scores of groups P1 and P2 were lower than that of group P4 (P = 0.046, P = 0.036). Compared with the control, only the group P1 had a lower cough score (P = 0.009) and there were no differences in the other groups. There were no differences in sedation score at 10 min after extubation, the incidence of adverse events at 24 h postoperatively, or the number of remedial analgesics at 24 h postoperatively (P > 0.05).Conclusion: The ED50 (95% CI) of nalbuphine as a prophylactic in reducing pain during recovery was 0.125 (0.108, 0.145) mg/kg. Compared with the control, nalbuphine at doses of 0.140, 0.200, and 0.280 mg/kg prevented pain during the awakening period. Among these doses, 0.280 mg/kg was determined to be the best, the occurrence of cough was less during extubation and the postoperative analgesic effect was good. However, it is necessary to pay attention to the occurrence of adverse reactions.Keywords: gynecology, laparoscopy, preventive analgesia, nalbuphine, ED50

Tianyu Liu,1,&ast; Wenju Chang,1,2,&ast; Hao Wang,3,&ast; Qi Lin,1,2,&ast; Ye Wei,1,2 Wentao Tang,1 Yu Liu,1 Yijiao Chen,1 Zhengchuan Niu,1 Yudong Jiang,1 Li Ren,1,2 Jianmin Xu1,2 1Colorectal Cancer Center, Department of General Surgery, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 2Shanghai Engineering Research Center of Colorectal Cancer Minimally Invasive Technology, Shanghai, People’s Republic of China; 3Department of Thoracic Surgery; Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Jianmin Xu; Li RenColorectal Cancer Center, Department of General Surgery, Zhongshan Hospital, Fudan University, 180 Fenglin Road, Shanghai, 200032, People’s Republic of ChinaTel/Fax +86-21-64041990Email xujmin@aliyun.com; ren.li@zs-hospital.sh.cnPurpose: This study aimed to evaluate the role of anatomical resection (AR) in lung metastasectomy (LM) of colorectal cancer (CRC) and to investigate clinically relevant prognostic factors.Patients and Methods: The medical records of 350 consecutive patients who underwent LM of CRC from 2011 to 2019 were reviewed. The patients were designated into AR group (lobectomy and segmentectomy), and non-anatomical resection (NAR) group (wedge resection), respectively. Kaplan–Meier method was used to analyze disease-free survival (DFS), pulmonary-specific disease-free survival (PDFS) and overall survival (OS). Cox proportional hazards regression model was performed to analyze the factors associated with DFS, PDFS and OS.Results: A total of 92 (31.2%) patients were enrolled in AR group and 203 (68.8%) in non-anatomical resection (NAR) group. AR significantly improved the 3-year DFS (64.1% vs 46.8%, HR 0.587, 95% CI 0.397– 0.867, P = 0.007) and PDFS (75.0% vs 60.1%, HR 0.565, 95% CI 0.356– 0.899, P = 0.016) compared with NAR. However, the extent of resection did not significantly impact the 3-year OS (AR 92.4% vs NAR 85.7%, HR 0.511, 95% CI 0.224– 1.165, P = 0.110). In multivariate analysis, AR was identified as a protective factor for DFS (HR 0.576, 95% CI 0.356– 0.934, P = 0.025) and PDFS (HR 0.631, 95% CI 0.409– 0.973, P = 0.037). Preoperative abnormal CA19-9 was identified as the only prognostic factor for OS.Conclusion: AR was superior to NAR for DFS and PDFS after LM from CRC.Keywords: pulmonary metastasis, lobectomy, wedge resection, prognosis

Kai Guo,1 Lijuan Qiu,1 Yufen Xu,2 Xiaoqiong Gu,2 Linyuan Zhang,3 Kun Lin,3 Xiaohuan Wang,1 Shanshan Song,1 Yu Liu,1 Zijian Niu,1 Shuxuan Ma1 1Department of Transfusion Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health, Beijing, People’s Republic of China; 2Department of Clinical Biological Resource Bank, Guangzhou Institute of Pediatrics, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of China; 3Department of Clinical Lab, Guangzhou Women and Children’s Medical Center, Guangzhou Medical University, Guangzhou, People’s Republic of ChinaCorrespondence: Shuxuan MaDepartment of Transfusion Medicine, Beijing Children’s Hospital, Capital Medical University, National Center for Children’s Health No. 56 Nan Lishi Road, Xi Cheng District, Beijing, 100045, People’s Republic of ChinaTel +86 10 59616422Email masxfwyy@sina.comBackground: Kawasaki disease (KD) is a multisystem vasculitis in infants and young children and involved in the NOD-like receptor family, pyrin domain-containing 3 (NLRP3) inflammasome activation. Genetic factors may increase the risk of KD. To assess the association between rs7248320 in long noncoding RNA (lncRNA) AC008392.1 located in the upstream region of CARD8 and the risk of KD, a case–control study was conducted in the Han Chinese population.Methods: This study genotyped the polymorphism rs7248320 in the lncRNA AC008392.1 gene using the TaqMan real-time polymerase chain reaction assay. The genetic contribution of rs7248320 was evaluated using odds ratios (ORs) and 95% confidence intervals (CIs) using unconditional logistic regression analysis. The association between rs7248320 and KD susceptibility was analyzed by performing a hospital-based case–control study including 559 KD patients and 1055 non-KD controls.Results: In this study, a significant relationship between rs7248320 and KD risk was observed in the genotype/allele frequency distribution. The rs7248320 polymorphism was associated with a significantly decreased risk of KD after adjustment for age and sex (AG vs AA: adjusted OR = 0.80, 95% CI: 0.64– 0.99, P = 0.0421; GG vs AA: adjusted OR = 0.71, 95% CI: 0.51– 1.00, P = 0.0492; AG/GG vs AA: adjusted OR = 0.78, 95% CI: 0.63– 0.96, P = 0.0186). Moreover, the rs7248320 G allele also exhibited a decreased risk for KD (adjusted OR = 0.83, 95% CI: 0.72– 0.97, P = 0.0193) compared with the A allele. In the stratification analysis, compared to the rs7248320 AA genotype, AG/GG genotypes were more protective for males (OR = 0.71, 95% CI: 0.55– 0.93, P = 0.0122).Conclusion: This study suggests for the first time that the lncRNA AC008392.1 rs7248320 polymorphism may be involved in KD susceptibility in the Han Chinese population.Keywords: Kawasaki disease, rs7248320, AC008392.1, CARD8, lncRNA, single-nucleotide polymorphism

Wenfei Xue1 1, Xiaopeng Zhang2 2, Zhancong Niu3 3, Zhifei Xin2 2, Hua Zhang2 2, Qingtao Zhao1 12 2, Jie He2 2, Zhonghui Hu2 2, Guochen Duan1 1 1Study Office of Thoracic Surgery, Hebei Medical University, Shijiazhuang, 050017, People’s Republic of China; 2Department of Thoracic Surgery, Hebei General Hospital, Shijiazhuang, 050000, People’s Republic of China; 3Department of Infectious Diseases, Hebei General Hospital, Shijiazhuang, 050000, People’s Republic of ChinaCorrespondence: Guochen DuanStudy Office of Thoracic Surgery, Hebei Medical University, No. 361, Zhongshan East Road, Changan District, Shijiazhuang, 050017, People’s Republic of ChinaTel +86 13513380703Email duanguoc@126.comBackground: The object of the study was to elucidate the relationship between the neutrophil–lymphocyte ratio (NLR) and the growth of pulmonary ground-glass opacity (GGO) in stage IA lung adenocarcinoma.Methods: All patients with GGO following surgical procedures were enrolled, with the time of follow-up and the variation tendency of GGO recorded. Meanwhile, laboratory parameters, age, gender, smoking history, histology, tumor size, and stage were recorded. Logistic regression was used to evaluate the value of NLR and the cutoff value was calculated by SPSS 22.0.Results: In the whole cohort, 30 cases of growing GGO and 43 cases of stable GGO undergoing surgical procedures were diagnosed as lung adenocarcinoma. There was significant statistical difference between the two groups. Multivariable analysis showed that NLR could predict the GGOs with growth (odds ratio 5.198, 95% confidence interval (95%CI: 1.583– 14.581, P=0.002). Receiver operating characteristics analysis for NLR showed the optimal cutoff value of 2.38, with a sensitivity of 60.0% and specificity of 81.4%.Conclusion: Our study demonstrated that the NLR appeared to have value as a promising clinical predictor of GGOs with growth. Further studies are needed to confirm this conclusion.Keywords: neutrophil–lymphocyte ratio, ground-glass opacity, early lung adenocarcinoma

Rongli Cui,* Zhiqiang Song,* Baojun Suo, Xueli Tian, Yan Xue, Lingmei Meng, Zhanyue Niu, Zhu Jin, Hejun Zhang, Liya Zhou Department of Gastroenterology, Peking University Third Hospital, Beijing, 100191, People’s Republic of China*These authors contributed equally to this workCorrespondence: Liya ZhouDepartment of Gastroenterology, Peking University Third Hospital, 49 Road Garden, Haidian District, Beijing, 100191, People’s Republic of ChinaTel +86-13911827827Fax +86-10-82265021Email zhouliya123456@163.comBackground: It has not been fully confirmed whether the detection of Helicobacter pylori resistance gene mutation can replace antibiotic drug sensitivity test to guide the clinical individualized treatment. Therefore, we have studied this aspect and discussed the application value of antibiotic sensitivity gene test.Materials and Methods: The biopsy specimen of gastric mucosa from the patients examined by endoscopy and positive for rapid urease test were collected continuously for histopathological analysis, H. pylori culture, antibiotic drug sensitivity test (E-test drug sensitivity test), and antibiotic sensitivity gene test (high-throughput nucleotide sequencing). The participants received triple plus bismuth solution eradication treatment (esomeprazole 20 mg, amoxicillin 1000 mg, clarithromycin 500 mg, and bismuth potassium citrate 220 mg, twice daily for 14 days) for follow-up, and the eradication effect was determined.Results: The 551/602 subjects, who met the inclusion criteria, were subjected to culture for H. pylori and antibiotic drug sensitivity determination; among them 506 were cultured successfully. The results showed that the resistance rates of H. pylori were 38.9% for clarithromycin and 31.0% for levofloxacin. In 489 H. pylori strains, the mutations were detected in clarithromycin and levofloxacin resistance genes, indicating the genotype resistance. The resistance genes of clarithromycin and levofloxacin were consistent with phenotype resistance with respect to sensitivity (81.2% and 69.7% for clarithromycin and levofloxacin, respectively) and specificity (88.9% and 93.7% for clarithromycin and levofloxacin, respectively). The eradication rate of H. pylori in the clarithromycin-resistant group was significantly lower than that in the sensitive group (ITT: 52.1% vs 85.0%, P < 0.001).Conclusion: A correlation was established between the resistance genes of clarithromycin and levofloxacin and their phenotypic resistance and clinical efficacy. The detection of H. pylori resistance genes has a good clinical application prospect.Keywords: Helicobacter pylori, drug resistance, clarithromycin, levofloxacin, mutation, high-throughput nucleotide sequencing

Rong Shi, Birong Wu, Zheyun Niu, Hui Sun, Fan Hu School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Fan HuSchool of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaTel/Fax +862151322466Email Joyking2003@163.comIntroduction: This study aimed to study risk factors for coronary heart disease (CHD) in type 2 diabetes mellitus (T2DM) patients and establish a clinical prediction model.Research Design and Methods: A total of 3402 T2DM patients were diagnosed by clinical doctors and recorded in the electronic medical record system (EMRS) of six Community Health Center Hospitals from 2015 to 2017, including the communities of Huamu, Jinyang, Yinhang, Siping, Sanlin and Daqiao. From September 2018 to September 2019, 3361 patients (41 patients were missing) were investigated using a questionnaire, physical examination, and biochemical index test. After excluding the uncompleted data, 3214 participants were included in the study and randomly divided into a training set (n = 2252) and a validation set (n = 962) at a ratio of 3:1. Through lead absolute shrinkage and selection operator (LASSO) regression analysis and logistic regression analysis of the training set, risk factors were determined and included in a nomogram. The C-index, receiver operating characteristic (ROC) curve, calibration plot and decision curve analysis (DCA) were used to validate the distinction, calibration and clinical practicality of the model.Results: Age, T2DM duration, hypertension (HTN), hyperuricaemia (HUA), body mass index (BMI), glycosylated haemoglobin A1c (HbA1c), high-density lipoprotein (HDL-C) and low-density lipoprotein (LDL-C) were significant factors in this study. The C-index was 0.750 (0.724– 0.776) based on the training set and 0.767 (0.726– 0.808) based on the validation set. Through ROC analysis, the set area was 0.750 for the training set and 0.755 for the validation set. The calibration test indicated that the S:P of the prediction model was 0.982 in the training set and 0.499 in the validation set. The decision curve analysis showed that the threshold probability of the model was 16– 69% in the training set and 16– 73% in the validation set.Conclusion: Based on community surveys and data analysis, a prediction model of CHD in T2DM patients was established.Keywords: prediction model, coronary heart disease, type 2 diabetes mellitus

Rong Shi, Zheyun Niu, Birong Wu, Fan Hu School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Fan Hu Tel/Fax +86 2151322466Email joyking2003@163.comPurpose: The study aimed to identify diseases that exhibit significant differences between hyperuricaemia (HUA) and non-hyperuricaemia (NHUA) groups and analyse the risk factors for HUA based on the related diseases in type 2 diabetes mellitus (T2DM).Methods: A total of 3264 T2DM patients were investigated from 2013 to 2017 in the Jinyang and Sanlin communities by obtaining basic data from the electronic medical record system (EMRS). From September 2018 to July 2019, 3000 patients (264 patients were missing during follow-up) were investigated with questionnaires, physical examinations and biochemical index tests. After removing missing values, 2899 patients were divided into HUA and NHUA groups. The chi-square test was used to identify diseases with differences. Using Lasso analysis and logistic regression analysis, risk factors for HUA based on the related diseases were obtained. The C-index, receiver operating characteristic (ROC) curve and calibration plot were used to validate the discrimination and accuracy of the factors.Results: The chi-square test showed that there were significant differences in coronary heart disease (CHD) and diabetic nephropathy (DN) between the HUA group and the NHUA group. Through Lasso regression, glycosylated haemoglobin A1c (HbA1c), triglyceride (TG), blood urea nitrogen (BUN) and serum creatinine (SCR) were screened in the CHD group. Body mass index (BMI), HbA1c, total cholesterol (TC), TG, BUN, SCR and urine microalbumin (UMA) were screened in the DN group. The P-value of all the variables was less than 0.05. Through the C-index, calibration, and ROC curve analyses, these risk factors had medium accuracy.Conclusion: HUA was significantly related to CHD and DN. The level of UA was correlated with HbA1c, TG, BUN, and SCR based on CHD. The level of UA was associated with BMI, HbA1c, TC, TG, BUN, SCR, and UMA based on DN.Keywords: hyperuricaemia, complications, risk factors, type 2 diabetes mellitus

Hongmei Liu,1– 3,* Yamin Yao,1,3,* Hongbo Liu,4,* Yanmin Peng,1,3,* Juanjuan Ren,2,3 Xiaohui Wu,1,3 Ruizhi Mao,1,3 Jie Zhao,1,3 Yuncheng Zhu,1,3 Zhiang Niu,1,3 Tao Yang,1,3 Xiujia Sun,2,3 Ping Jiang,2,3 Chen Zhang,1– 3 Yiru Fang1– 3,5 1Division of Mood Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 2Laboratory of Biochemistry and Pharmacology, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 3Shanghai Key Laboratory of Psychotic Disorders, Shanghai Mental Health Center, Shanghai Jiao Tong University School of Medicine, Shanghai, People’s Republic of China; 4Department of Blood Transfusion, Loudi Center Hospital, Loudi, People’s Republic of China; 5CAS Center for Excellence in Brain Science and Intelligence Technology, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yiru Fang; Chen Zhang Email yirufang@aliyun.com; zhangchen645@163.comBackground: The phospholipase A2 Group 6 (PLA2G6, also known as PLA2, PARK14, and iPLA2) gene encodes a group VIA calcium-independent phospholipase A2. Genetic polymorphism of PLA2G6 has been indicated to be involved in conferring susceptibility for Parkinson’s disease (PD), whereas conclusive results have not been obtained. Thus, we intended to conduct a systematic review to determine if PLA2G6 genetic variation confers a greater susceptibility to PD.Methods: All case-control studies that investigated the association of the PLA2G6 polymorphisms with the risk of PD published before 15 July 2018 were included. The literature was comprehensively searched and identified in five English databases (EBSCO, Pubmed, OVID, EMBASE and ISI Web of Knowledge) and four Chinese databases (Wanfang database, Chinese Biomedical Literature Database, China Academic Journals Database and VIP database). We performed analyses of study characteristics, heterogeneity, and forest plot in analyses analogous to dominant, codominant and additive models with the pooled odds ratio (OR) in fixed- or random-effects models as the measure of association.Results: A total of 664 potentially relevant studies were retrieved with the initial search, of which eight studies fulfilled the inclusion criteria, and included 2,779 PD patients and 3,291 control participants,. Among all the reported 27 genetic variants, 15 single nucleotide polymorphisms (SNPs) were present only in patients, and only five available SNPs (rs2267369, rs140758033, c.1959T>A (Gly653Gly), rs76718524, rs199935023) were pooled in the meta-analysis. However, there was no evidence for a significant association between the five SNPs and PD risk in dominant, codominant and allele models, suggesting a lack of association between PLA2G6 genetic variation and PD susceptibility.Conclusion: The present study assessed the association of PLA2G6 genetic polymorphism with the risk PD, and the result strongly demonstrates that PLA2G6 polymorphism is not associated with PD susceptibility.Keywords: Parkinson’s disease, PD, PLA2G6, systematic review

Rong Shi, Zheyun Niu, Birong Wu, Taotao Zhang, Dujie Cai, Hui Sun, Yuhong Hu, Ruohui Mo, Fan Hu School of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaCorrespondence: Fan HuSchool of Public Health, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of ChinaTel +8613585828140Fax +862151322466Email joyking2003@163.comPurpose: This study aimed to develop a diabetic nephropathy (DN) or diabetic retinopathy (DR) incidence risk nomogram in China’s population with type 2 diabetes mellitus (T2DM) based on a community-based sample.Methods: We carried out questionnaire evaluations, physical examinations and biochemical tests among 4219 T2DM patients in Shanghai. According to the incidence of DN and DR, 4219 patients in our study were divided into groups of T2DM patients with DN or DR, patients with both, and patients without any complications. We successively used least absolute shrinkage and selection operator regression analysis and logistic regression analysis to optimize the feature selection for DN and DR. To ensure the accuracy of the results, we carried out multivariable logistic regression analysis of the above significant risk factors on the sample data for both DN and DR. The selected features were included to establish a prediction model. The C-index, calibration plot, curve analysis and internal validation were used to validate the distinction, calibration, and clinical practicality of the model.Results: The predictors in the prediction model included disease course, body mass index (BMI), total triglycerides (TGs), systolic blood pressure (SBP), postprandial blood glucose (PBG), haemoglobin A1C (HbA1c) and blood urea nitrogen (BUN). The model displayed moderate predictive power with a C-index of 0.807 and an area under the receiver operating characteristic curve of 0.807. In internal verification, the C-index reached 0.804. The risk threshold was 16– 75% according to the analysis of the decision curve, and the nomogram could be applied in clinical practice.Conclusion: This DN or DR incidence risk nomogram incorporating disease course, BMI, TGs, SBP, PBG, HbA1c and BUN can be used to predict DN or DR incidence risk in T2DM patients. The research team has developed an online app based on a clinical prediction model incorporating risk factors for rapid and simple prediction.Keywords: diabetic nephropathy, diabetic retinopathy, predictors, nomogram, type 2 diabetes mellitus

The recent progress in the studies of nuclear charge-exchange excitations with localized covariant density functional theory is briefly presented, by taking the fine structure of spin-dipole excitations in 16O as an example. It is shown that the constraints introduced by the Fock terms of the relativistic Hartree-Fock scheme into the particle-hole residual interactions are straightforward and robust.

The covariant density functional theory (CDFT) with a few number of parameters allows a very successful description of the properties of nuclei all over the nuclear chart. The recent progress on the application of the CDFT as well as its extensions for a series of interesting and hot topics in nuclear structure and nuclear astrophysics are summarized. In particular, the newly proposed point-coupling parametrization PC-PK1 and the application of the CDFT to the single particle level of the radioactive neutron-rich doubly magic nucleus 132Sn, the deformed halo in nuclei, and the β decay life-time of neutron rich nuclei are discussed in details.

Multimetallic nanowires with long-range atomic ordering hold the promise of unique physicochemical properties in many applications. Here we demonstrate the synthesis and study the stability of Cu3Au intermetallic nanowires. The synthesis is achieved by using Cu@Au core-shell nanowires as precursors. With appropriate Cu/Au stoichiometry, the Cu@Au core-shell nanowires are transformed into fully ordered Cu3Au nanowires under thermal annealing. Thermally-driven atom diffusion accounts for this transformation as revealed by X-ray diffraction and electron microscopy studies. The twin boundaries abundant in the Cu@Au core-shell nanowires facilitate the ordering process. The resulting Cu3Au intermetallic nanowires have uniform and accurate atomic positioning in the crystal lattice, which enhances the nobility of Cu. No obvious copper oxides are observed in fully ordered Cu3Au nanowires after annealing in air at 200 °C, a temperature that is much higher than those observed in Cu@Au core-shell and pure Cu nanowires. This work opens up an opportunity for further research into the development and applications of intermetallic nanowires. [Figure not available: see fulltext.].

Liquid water transport in perforated gas diffusion layers (GDLs)is numerically investigated using a three-dimensional (3D)two-phase volume of fluid (VOF)model and a stochastic reconstruction model of GDL microstructures. Different perforation depths and diameters are investigated, in comparison with the GDL without perforation. It is found that perforation can considerably reduce the liquid water level inside a GDL. The perforation diameter (D = 100 μm)and the depth (H = 100 μm)show pronounced effect. In addition, two different perforation locations, i.e. the GDL center and the liquid water break-through point, are investigated. Results show that the latter perforation location works more efficiently. Moreover, the perforation perimeter wettability is studied, and it is found that a hydrophilic region around the perforation further reduces the water saturation. Finally, the oxygen transport in the partially-saturated GDL is studied using an oxygen diffusion model. Results indicate that perforation reduces the oxygen diffusion resistance in GDLs and improves the oxygen concentration at the GDL bottom up to 101% (D = 100 μm and H = 100 μm).

The cross flow in the under-land gas diffusion layer (GDL) between 2 adjacent channels plays an important role on water transport in proton exchange membrane fuel cell. A 3-dimensional (3D) two-phase model that is based on volume of fluid is developed to study the liquid water-air cross flow within the GDL between 2 adjacent channels. By considering the detailed GDL microstructures, various types of air-water cross flows are investigated by 3D numerical simulation. Liquid water at 4 locations is studied, including droplets at the GDL surface and liquid at the GDL-catalyst layer interface. It is found that the water droplet at the higher-pressure channel corner is easier to be removed by cross flow compared with droplets at other locations. Large pressure difference Δp facilitates the faster water removal from the higher-pressure channel. The contact angle of the GDL fiber is the key parameter that determines the cross flow of the droplet in the higher-pressure channel. It is observed that the droplet in the higher-pressure channel is difficult to flow through the hydrophobic GDL. Numerical simulations are also performed to investigate the water emerging process from different pores of the GDL bottom. It is found that the amount of liquid water removed by cross flow mainly depends on the pore's location, and the water under the land is removed entirely into the lower-pressure channel by cross flow.

This paper proposes a three-dimensional (3D) volume of fluid (VOF) study to investigate two-phase flow in the gas diffusion layer (GDL) of proton exchange membrane (PEM) fuel cells and liquid water distribution. A stochastic model was adopted to reconstruct the 3D microstructures of Toray carbon papers and incorporate the experimentally-determined varying porosity. The VOF predictions were compared with the water profiles obtained by the X-ray tomographic microscopy (XTM) and the Leverett correlation. It was found local water profiles are similar in the sample’s sub-regions under the pressure difference p = 1000 Pa between the two GDL surfaces, but may vary significantly under p = 6000 Pa. The water-air interfaces inside the GDL structure were presented to show water distribution and breakthrough.

In this study, the effective oxygen diffusivity in the dry or partially-saturated gas diffusion layer (GDL) is numerically investigated by an oxygen diffusion model in GDLs reconstructed by a stochastic method. The predicted effective diffusivity in dry GDLs is compared with various diffusivity models from literatures. Reasonable agreements with other models were obtained. The effect of the PTFE loading in the dry Toray carbon paper is also investigated and compared with recent experimental data. It is found that the effective diffusivity becomes lower under higher PTFE loading due to the decreased pore volume, as expected. The relative effective oxygen diffusivity in partially-saturated GDLs is calculated using the two-phase volume of fluid (VOF) model and an oxygen diffusion model. The effects of different local water profiles and porosity distribution on the effective oxygen diffusivity in both the through-plane (TP) and in-plane (IP) directions are investigated and compared with a lattice Boltzmann model and experimental data. The present results are in good agreement with other studies. It is found that local water profile has significant impacts on the effective diffusivity in partially-saturated GDLs and the diffusivity in the TP direction is more sensitive to the water distribution than the IP direction.