Recent studies have demonstrated the stimulatory effects of adiponectin on bone formation, but the mechanism underlying these effects remains unclear. The Wnt/β-catenin pathway, one of the most important pathways in osteogenesis, has rarely been associated with the osteogenic effects of adiponectin in previous studies. The present study was designed to investigate the effects of adiponectin on bone mesenchymal stem cell (BMSC) osteogenic differentiation and bone formation through the Wnt/β-catenin pathway. We detected adiponectin receptor expression in BMSCs, constructed a recombinant adenovirus containing the human adiponectin gene, and then used the adenovirus to transfect BMSCs in vitro or injected the adenovirus into bone defect areas in animal models. Wnt/β-catenin pathway and osteogenesis were detected by real-time PCR, western blotting, immunofluorescence, HE staining and micro-CT. In both our in vivo and in vitro experiments, we detected higher gene and protein expression levels of the Wnt/β-catenin pathway-related factors β-catenin and cyclinD1 in adiponectin transgenic BMSCs and rats. Similar results were noted regarding the gene and protein expression levels of osteogenesis-related genes. In addition, more new bone formation was observed in the adiponectin-treated groups. Our results indicate that adiponectin could facilitate BMSC osteogenic differentiation and osteogenesis, and the Wnt/β-catenin pathway was involved in the osteogenic effect of adiponectin.

Background and objectives Metabolic acidosis is associated with progression of CKD and has significant adverse effects on muscle and bone. A systematic review and meta-analysis was conducted to evaluate the benefits and risks of metabolic acidosis treatment with oral alkali supplementation or a reduction of dietary acid intake in those with CKD. Design, setting, participants, & measurements MEDLINE, Embase, and Cochrane CENTRAL were searched for relevant trials in patients with stage 3-5 CKD and metabolic acidosis (,22 mEq/L) or low-normal serum bicarbonate (22-24 mEq/L). Data were pooled in a meta-analysis with results expressed as weighted mean difference for continuous outcomes and relative risk for categorical outcomes with 95% confidence intervals (95% CIs), using a random effects model. Study quality and strength of evidence were assessed using Cochrane risk of bias and the Grading of Recommendations Assessment, Development and Evaluation criteria. Results Fourteen clinical trials were included (n=1394 participants). Treatment of metabolic acidosis with oral alkali supplementation or a reduction of dietary acid intake increased serum bicarbonate levels (14 studies, 1378 patients, mean difference 3.33 mEq/L, 95% CI, 2.37 to 4.29) and resulted in a slower decline in eGFR (13 studies, 1329 patients, mean difference 23.28 ml/min per 1.73 m 2 , 95% CI, 24.42 to 22.14; moderate certainty) and a reduction in urinary albumin excretion (very-low certainty), along with a reduction in the risk of progression to ESKD (relative risk, 0.32; 95% CI, 0.18 to 0.56; low certainty). Oral alkali supplementation was associated with worsening hypertension or the requirement for increased antihypertensive therapy (very-low certainty). Conclusions Low-to-moderate certainty evidence suggest that oral alkali supplementation or a reduction in dietary acid intake may slow the rate of kidney function decline and potentially reduce the risk of ESKD in patients with CKD and metabolic acidosis.

A thorough interrogation of the immune landscape is crucial for immunotherapy strategy selection and prediction of clinical responses in non-small-cell lung cancer (NSCLC) patients. Single-cell RNA sequencing (scRNA-seq) techniques have prompted the opportunity to dissect the distinct immune signatures between lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), the two major subtypes of NSCLC. Here, we performed scRNA-seq on 72,475 immune cells from 40 samples of tumor and matched adjacent normal tissues spanning 19 NSCLC patients, and drew a systematic immune cell transcriptome atlas. Joint analyses of the distinct cellular compositions, differentially expressed genes (DEGs), cell–cell interactions, pseudotime trajectory, transcriptomic factors and prognostic factors based on The Cancer Genome Atlas (TCGA), revealed the central roles of cytotoxic and effector T and NK cells and the distinct functional macrophages (Mφ) subtypes in the immune microenvironment heterogeneity between LUAD and LUSC. The dominant subtype of Mφ was FABP4-Mφ in LUAD and SPP1-Mφ in LUSC. Importantly, we identified a novel lymphocyte-related Mφ cluster, which we named SELENOP-Mφ, and further established its antitumor role in both types, especially in LUAD. Our comprehensive depiction of the immune heterogeneity and definition of Mφ clusters could help design personalized treatment for lung cancer patients in clinical practice.

Background: Lung cancer is the leading cause of cancer-related deaths worldwide and the prognosis remains poor. The recent introduction of the immune checkpoint inhibitor (ICI), or plus chemotherapy, both resulted in the survival benefit for patients with advanced non-small-cell lung cancer (NSCLC), but it remains unanswered which is superior. The current study aimed to estimate the comparative efficacy and safety of ICI-chemotherapy versus ICI-monotherapy in advanced NSCLC.Methods: Studies were identified by searching PubMed, Embase, and Cochrane library. The randomized controlled trials (RCTs) that ICI monotherapy or ICI plus chemotherapy compared with chemotherapy in NSCLC were included with available primary endpoints of progression-free survival (PFS), overall survival (OS), objective response rate, or treatment-related adverse events. A fixed-effect or random-effects model was adopted depending on between-study heterogeneity.Results: A total of 20 RCTs involving 12,025 patients with NSCLC were included. Both ICI-monotherapy and ICI-chemotherapy resulted in significantly prolonged survival compared to chemotherapy and the former led to significantly longer PFS. The magnitude of survival benefits appeared to be greatest among those treated with pembrolizumab plus platinum-based chemotherapy (OS, 0.56; PFS, 0.54). Additionally, OS and PFS advantages of ICI therapies were observed in patients with NSCLC with low or high programmed cell death 1 ligand 1 (PD-L1) expression level, but not in intermediate PD-L1 TPS.Conclusions: Pembrolizumab plus platinum-based chemotherapy was recommended as the optimal first-line therapy for advanced patients with NSCLC.

Objective: To investigate the correlation between periodontal disease and breast cancer.Materials and Methods: PubMed and China National Knowledge Infrastructure (CNKI) databases were searched up to February 8, 2018 for observational studies examining the association between periodontal disease and breast cancer. Study selection was conducted according to predesigned eligibility criteria, and two authors independently extracted data from included studies. Meta-analysis was performed using the Comprehensive Meta-Analysis v2 software and risk estimates were calculated as relative risks (RRs) with corresponding 95% confidence intervals (CIs).Results: A total of 11 study were included. Meta-analysis indicated that periodontal disease significantly increased the risk of breast cancer by 1.22-fold (RR = 1.22, 95% CI = 1.06–1.40). Amongst participants with periodontal patients and a history of periodontal therapy, the risk of developing breast cancer was not significant (RR = 1.23; 95% CI = 0.95–1.60). The association results between periodontal diseases and breast cancer were found to be robust, as evident in the leave-one-out sensitivity analysis.Conclusions: Periodontal disease may be a potential risk factor for the development of breast cancer among women, and thus effective periodontal therapy may present as a valuable preventive measure against breast cancer.