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Meijuan Liu, Kun Zhang, Linjie Wang, Hongbo Yang, Kemin Yan, Hui Pan, Huijuan Zhu, Fengying Gong Key Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, People’s Republic of ChinaCorrespondence: Fengying Gong; Huijuan ZhuKey Laboratory of Endocrinology of National Health Commission, Department of Endocrinology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, 1# Shuaifuyuan, Wangfujing, Beijing 100730, People’s Republic of ChinaTel +86 10 69155100Fax +86 10 69155073Email fygong@sina.com; shengxin2004@163.comIntroduction: To explore serum zinc-α 2-glycoprotein (ZAG) and adiponectin in metabolically healthy non-obese (MHNO), metabolically healthy obesity (MHO), metabolically abnormal obesity (MAO) and metabolically abnormal diabetic obese (MADO) subjects and the relationship with metabolically phenotypes of obesity.Methods: Two hundred twenty-five subjects including 32 with MHNO, 40 with MHO, 104 with MAO and 49 with MADO were enrolled. Baseline clinical data and biochemical variables were collected. Serum ZAG and adiponectin levels were measured by enzyme-linked immunosorbent assay (ELISA) kits. Metabolically healthy (< 3 metabolic abnormalities) or abnormal (≥ 3 metabolic abnormalities) subjects were classified based on the National Cholesterol Education Program–Adult Treatment Panel III (NCEP/ATP III) criteria. Obesity (body mass index ≥ 28 kg/m2) was recommended by China Obesity Task Force.Results: Serum ZAG levels were higher in the MHO group, but were progressively lower in MAO and MADO groups (P all< 0.05). In all subjects, total cholesterol, 2-hour postprandial blood glucose and homeostasis model assessment of adiponectin were independent variables to serum ZAG levels. Compared with subjects in the highest tertile of ZAG, the odds ratio (OR) of metabolically abnormal risks of subjects in the lowest and median tertiles of ZAG were higher both in a univariate and three adjustment models (P all< 0.05). Serum ZAG could discriminate the metabolically abnormal phenotype with receiver operating characteristic (ROC) curve area of 0.622 (95% CI, 0.539– 0.706, P< 0.05). Combination of ZAG and adiponectin had improved diagnosis value accuracy, with ROC curve area of 0.703 (95% CI, 0.629– 0.776, P< 0.05), and 62.7% sensitivity and 73.6% specificity.Conclusion: Serum ZAG levels were higher in MHO subjects, but lower in MAO and MADO subjects. The decreased serum ZAG levels were closely related to the metabolically abnormal phenotype of obese patients. Serum ZAG, especially the combination with adiponectin might be the potential diagnostic biomarkers for metabolically abnormal obese patients.Keywords: zinc-α 2-glycoprotein, ZAG, metabolically healthy non-obese, MHNO, metabolically healthy obese, MHO, metabolically abnormal obese, MAO, metabolically abnormal diabetic obese, MADO

Background. Autism spectrum disorder (ASD) is a highly heterogeneous neurodevelopmental disorder with complex pathogenesis. Currently, the pathogenesis of ASD is not fully understood. Moreover, current treatments do not effectively alleviate the primary symptoms of ASD social disorder (SCDA). Jiawei Yinhuo Tang (JWYHT) is an improved version of the classic prescription Yinhuo Tang. Although this medication has been shown to improve social behavior in ASD patients, the mechanism by which it works remains unknown. Methods. In this study, network pharmacology bioinformatics analysis was used to identify the key targets, biological functions, and signal pathways of JWYHT in SCDA. Then, molecular docking and molecular dynamic simulation were used to validate the activity and stability of the active ingredient and the target protein during the binding process. Results. The analysis identified 157 key targets and 9 core targets of JWYHT (including proto-oncogene (FOS), caspase 3 (CASP3), mitogen-activated protein kinase-3 (MAPK3), interleukin-6 (IL6), mitogen-activated protein kinase-1 (MAPK1), tumor necrosis factor (TNF), mitogen-activated protein kinase-8 (MAPK8), AKT serine/threonine kinase 1 (AKT1), and 5-hydroxytryptamine receptor 1B (5HT1B)) in SCDA. In addition, the Kyoto Encyclopedia of Gene and Genome results, as well as the staggering network analyses, revealed 20 biological processes and 20 signal pathways targeted by JWYHT in SCDA. Finally, molecular docking analysis was used to determine the binding activity of the main active components of JWYHT to the key targets. The binding activity and stability of methyl arachidonate and MAPK8 were demonstrated using molecular dynamics simulation. Conclusion. This study demonstrates that JWYHT regulates neuronal development, synaptic transmission, intestinal and cerebral inflammatory response, and other processes in SCDA.

Additional file 1. Physical symptoms relatedto side effects of dopamine agonist drugs.

Cells and tissues in the human body are subjected to mechanical forces of varying degrees, such as tension or pressure. During tumorigenesis, physical factors, especially mechanical factors, are involved in tumor development. As lung tissue is influenced by movements associated with breathing, it is constantly subjected to cyclical stretching and retraction; therefore, lung cancer cells and lung cancer-associated fibroblasts (CAFs) are constantly exposed to mechanical load. Thus, to better explore the mechanisms involved in lung cancer progression, it is necessary to consider factors involved in cell mechanics, which may provide a more comprehensive analysis of tumorigenesis. The purpose of this review is: 1) to provide an overview of the anatomy and tissue characteristics of the lung and the presence of mechanical stimulation; 2) to summarize the role of mechanical stretching in the progression of lung cancer; and 3) to describe the relationship between mechanical stretching and the lung cancer microenvironment, especially CAFs.

Objectives. Both glucagon-like peptide-1 receptor agonists (GLP-1RAs) and metformin (MET) have markedly antiobesity effects in overweight/obese polycystic ovary syndrome (PCOS) patients. However, there was no literature to compare the antiobesity effects of these two medicines. Therefore, a systematic review and meta-analysis were conducted in our present study to evaluate the antiobesity effects of GLP-1RAs either as monotherapy or combined with MET in comparison with MET alone in overweight/obese PCOS patients. Methods. All randomized controlled trials (RCTs) which reported the efficacy of GLP-1RAs and MET in overweight/obese PCOS patients in Medline (from Pubmed), Embase, Cochrane Central Register of Controlled Trials, Web of Science, and Scopus databases were independently searched by two reviewers. The random-effect model was used to pool data extracted from the included literature. The weighted mean difference (WMD) and 95% confidence interval (CI) were used to present the meta-analysis results (PROSPERO registration number: CRD42020173199). Results. A total of eight eligible RCTs were finally enrolled in our meta-analysis from the 587 retrieved literature. The results showed that GLP-1RAs alone or combined with MET was associated with a greater weight loss (N = 318, WMD = −2.61, 95% CI: −3.51 to −1.72, P≤0.001, I2 = 77.5%), more obvious reduction of waist circumference (N = 276, WMD = −3.46, 95% CI: −4.36 to −2.56, P≤0.001, I2 = 0.0%), and body mass index (BMI) (N = 318, WMD = −0.93, 95% CI: −1.60 to −0.26, P=0.007, I2 = 84.9%) in overweight/obese PCOS patients when compared with MET alone. Further sensitivity analysis demonstrated that the meta-analysis results of the efficacy differences in terms of body weight, waist circumference, and BMI were relatively stable and reliable. Conclusion. Our meta-analysis demonstrated that the antiobesity effect of GLP-1RAs alone or combined with MET was superior to MET alone in terms of weight loss, the reduction of waist circumference, and BMI. More large-scale, high-quality RCTs are needed to further confirm these results in PCOS patients.