Clear evidence indicates that cytokines, for instance, adipokines, hepatokines, inflammatory cytokines, myokines, and osteokines, contribute substantially to the development of abnormal glucose and lipid metabolism. Some cytokines play a positive role in metabolism action, while others have a negative metabolic role linking to the induction of metabolic dysfunction. The mechanisms involved are not fully understood, but are associated with lipid accumulation in organs and tissues, especially in the adipose and liver tissue, changes in energy metabolism, and inflammatory signals derived from various cell types, including immune cells. In this review, we describe the roles of certain cytokines in the regulation of metabolism and inter-organ signaling in regard to the pathophysiological aspects. Given the disease-related changes in circulating levels of relevant cytokines, these factors may serve as biomarkers for the early detection of metabolic disorders. Moreover, based on preclinical studies, certain cytokines that can induce improvements in glucose and lipid metabolism and immune response may emerge as novel targets of broader and more efficacious treatments and prevention of metabolic disease.

Aims Observational studies have suggested strong associations between sleep duration and many cardiovascular diseases (CVDs), but causal inferences have not been confirmed. We aimed to determine the causal associations between genetically predicted sleep duration and 12 CVDs using both linear and nonlinear Mendelian randomization (MR) designs. Methods and results Genetic variants associated with continuous, short (≤6 h) and long (≥9 h) sleep durations were used to examine the causal associations with 12 CVDs among 404 044 UK Biobank participants of White British ancestry. Linear MR analyses showed that genetically predicted sleep duration was negatively associated with arterial hypertension, atrial fibrillation, pulmonary embolism, and chronic ischaemic heart disease after correcting for multiple tests (P < 0.001). Nonlinear MR analyses demonstrated nonlinearity (L-shaped associations) between genetically predicted sleep duration and four CVDs, including arterial hypertension, chronic ischaemic heart disease, coronary artery disease, and myocardial infarction. Complementary analyses provided confirmative evidence of the adverse effects of genetically predicted short sleep duration on the risks of 5 out of the 12 CVDs, including arterial hypertension, pulmonary embolism, coronary artery disease, myocardial infarction, and chronic ischaemic heart disease (P < 0.001), and suggestive evidence for atrial fibrillation (P < 0.05). However, genetically predicted long sleep duration was not associated with any CVD. Conclusion This study suggests that genetically predicted short sleep duration is a potential causal risk factor of several CVDs, while genetically predicted long sleep duration is unlikely to be a causal risk factor for most CVDs.

Introduction Combining lenvatinib with a programmed cell death protein-1 (PD-1) inhibitor has been explored for the treatment of un-resectable hepatocellular carcinoma (uHCC). This study aimed to investigate the real-world efficacy of and prognostic factors for survival associated with lenvatinib plus PD-1 inhibitor treatment in a large cohort of Asian uHCC patients even the global LEAP-002 study failed to achieve the primary endpoints. Methods Patients with uHCC treated with lenvatinib and PD-1 inhibitors were included. The primary endpoints were overall survival (OS) and progression-free survival (PFS), and the secondary endpoints were the objective response rate (ORR) and adverse events (AEs). Prognostic factors for survival were also analyzed. Results A total of 378 uHCC patients from two medical centers in China were assessed retrospectively. The median patient age was 55 years, and 86.5% of patients were male. Hepatitis B virus (HBV) infection (89.9%) was the dominant etiology of uHCC. The median OS was 17.8 (95% confidence interval (CI) 14.0–21.6) months. The median PFS was 6.9 (95% CI 6.0–7.9) months. The best ORR and disease control rate (DCR) were 19.6% and 73.5%, respectively. In multivariate analysis, Child‒Pugh grade, Barcelona Clinic Liver Cancer stage, Eastern Cooperative Oncology Group performance status score, involved organs, tumor burden score, and combination with local therapy were independent prognostic factors for OS. A total of 100% and 57.9% of patients experienced all-grade and grade 3/4 treatment-emergent AEs, respectively. Conclusion This real-world study of lenvatinib plus PD-1 inhibitor treatment demonstrated long survival and considerable ORRs and DCRs in uHCC patients in China. The tolerability of combination therapy was acceptable but must be monitored closely.

ABSTRACT. In this study, we aimed to explore the associations between HLA-A\B\DRB1 polymorphisms and the risks of vulvar lichen sclerosus (VLS) or squamous cell hyperplasia of the vulva (SCHV) in Han Chinese women. We enrolled 76 Han Chinese women with VLS (Group A), 74 with SCHV (Group B), and 66 healthy women (control group) in this study. Polymerase chain reaction amplification with sequence specific primers (PCR-SSP) was used to determine HLA-A\B\DRB1 polymorphisms. Compared with the control group, HLA-A*11, -B*15, and -DRB1*12 were present at a higher frequency in groups A and B, while HLA-B*13 was present at a higher frequency in group A. Fewer women in group A carried HLA-A*31, -DRB1*01, and -DRB1*03 genotypes and fewer women in group B carried HLA-B*40 and -DRB1*03 genotypes. Significant differences were found between group B and the control group for HLA-A