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Background Nonalcoholic fatty liver disease (NAFLD) is a major chronic liver disorder worldwide, and there is no established treatment for this disease. We conducted a network meta-analysis (NMA) to compare existing treatments, which include four classes of antidiabetic drugs, and examined the optimum treatments for NAFLD. Aim To compare the effectiveness of different treatments for NAFLD. Methods An NMA was conducted using Stata 14.0 (Corporation LLC, College Station, United States) and R (X64 3.6.3 version) in this study. Eligible randomized controlled trials (RCTs) were searched in the PubMed, Cochrane Library, Embase, Medline and Web of Science databases from database inception to April 2021. Two researchers independently screened the available studies in strict accordance with inclusion and exclusion criteria. The Cochrane Risk of Bias tool was used to evaluate the risk of bias of the included studies. The variables with and without dimensional differences were calculated as the standardized mean difference and weighted mean difference, respectively. An inconsistency model and "node-splitting" technique were used to test for inconsistency. Funnel plots were used to evaluate publication bias. Results Twenty-two eligible RCTs involving 1377 participants were eventually included in our analysis. Data were pooled using a random-effects model. Our NMA results revealed that glucagon-like peptide-1 receptor agonists (GLP-1RAs) were the most effective treatment, yielding improvements in hepatic fat content (HFC), alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum γ-glutamyl transferase (GGT) and body weight [surface under the cumulative ranking curve (SUCRA) = 99.6%, 92.6%, 82.8%, 92.3% and 99.6%, respectively], while thiazolidinediones (TZDs) were the best intervention for reducing the NAFLD activity score (NAS; SUCRA = 98.9%). In addition, moderate performance was observed for the sodium glucose cotransporter-2 inhibitors groups (SUCRA = 25.1%, 66.2%, 63.5%, 58.2% and 71.9% for HFC, ALT, AST, GGT and body weight, respectively). However, metformin performed poorly according to most indicators (SUCRA = 54.5%, 0.3%, 19.5%, 33.7%, 57.7% and 44.3% for HFC, NAS, ALT, AST, GGT and body weight, respectively). Conclusion GLP-1RAs may be the optimum choice for most patients with NAFLD. However, TZDs are considered the most effective therapies in NAFLD patients with histological disease activity.

Yang Luo,1,* Min-Hao Yu,1,* Yi-Zhou Huang,1 Ran Jing,1 Jun Qin,1 Shao-Lan Qin,1 Jay N Shah,1,2 Ming Zhong1 1Department of Gastrointestinal Surgery, Renji Hospital, Jiao Tong University School of Medicine, Shanghai, 200127, People’s Republic of China; 2Department of Surgery, Patan Hospital, Patan Academy of Health Sciences, Lalitpur, Kathmandu, 44700, Nepal*These authors contributed equally to this workCorrespondence: Ming Zhong; Jay N Shah Email drzhongming@hotmail.com; drjaywufei@gmail.comBackground: Preservation of the left colic artery in low-tie (LT) of inferior mesenteric artery remains controversial compared to high-tie (HT) in the colon and rectal cancers, for lymph node dissection, anastomotic leakage, and oncological outcome. This cohort study aims to analyze short- and long-term outcomes of laparoscopic anterior resections in LT vs HT for rectal cancers.Methods: We analyzed a cohort of laparoscopic AR for RC from 2013 to 2016 at Renji Hospital, Shanghai, China. Short- and long-term outcome in LT vs HT group were compared for clinico-demographic characteristics, operative-time, lymph node dissection, short-term 30-day outcome, and long-term 3- and 5-year overall survival as well as disease-free survival. The x2, t-test, and logistic regressions analysis were used and p< 0.05 was considered significant.Results: The cohort consisted of 614 laparoscopic AR with LT (236) and HT (378). The clinicodemographic characteristics were comparable among the groups. The surgery took longer in LT. The yield of LND was similar. Leakage occurred in 12.21% (n=75). Leakage was fewer in LT than HT, 8.89% vs 14.28%, p=0.047. The postoperative severe complications were higher in HT. The 30-day mortality was nil. The long-term 3- and 5-year overall survival and disease-free survival were similar in LT and HT.Conclusion: The LT with preservation of left colic artery had similar lymph node yield, but lower leakage and complications than HT in laparoscopic anterior resections for rectal cancers. The long-term 3- and 5-year overall and disease-free survival were similar in the two groups.Keywords: anastomotic leakage, Clavien-Dindo complications, laparoscopic anterior resection, left colic artery, low-tie high-tie of the inferior mesenteric artery, rectal cancer

The osteogenic potential of mesenchymal stromal cells (MSCs) varies among different tissue sources. Strontium enhances the osteogenic differentiation of bone marrow-derived MSCs (BM-MSCs), but whether it exerts similar effects on placental decidual basalis-derived MSCs (PDB-MSCs) remains unknown. Here, we compared the influence of strontium on the proliferation and osteogenic differentiation of human PDB- and BM-MSCs in vitro. We found that 1 mM and 10 mM strontium, but not 0.1 mM strontium, evidently promoted the proliferation of human PDB- and BM-MSCs. These doses of strontium showed a comparable alkaline phosphatase activity in both cell types, but their osteogenic gene expressions were promoted in a dose-dependent manner. Strontium at doses of 0.1 mM and 1 mM elevated several osteogenic gene expressions of PDB-MSCs, but not those of BM-MSCs at an early stage. Nevertheless, they failed to enhance the mineralization of either cell type. By contrast, 10 mM strontium facilitated the osteogenic gene expression as well as the mineralization of human PDB- and BM-MSCs. Collectively, this study demonstrated that human PDB- and BM-MSCs shared a great similarity in response to strontium, which promoted their proliferation and osteogenic differentiation in a dose-dependent manner.

Human multipotent stem cell-based therapies have shown remarkable potential in regenerative medicine and tissue engineering applications due to their abilities of self-renewal and differentiation into multiple adult cell types under appropriate conditions. Presently, human multipotent stem cells can be isolated from different sources, but variation among their basic biology can result in suboptimal selection of seed cells in preclinical and clinical research. Thus, the goal of this study was to compare the biological characteristics of multipotent stem cells isolated from human bone marrow, placental decidua basalis, and urine, respectively. First, we found that urine-derived stem cells (USCs) displayed different morphologies compared with other stem cell types. USCs and placenta decidua basalis-derived mesenchymal stem cells (PDB-MSCs) had superior proliferation ability in contrast to bone marrow-derived mesenchymal stem cells (BMSCs); these cells grew to have the highest colony-forming unit (CFU) counts. In phenotypic analysis using flow cytometry, similarity among all stem cell marker expression was found, excluding CD29 and CD105. Regarding stem cell differentiation capability, USCs were observed to have better adipogenic and endothelial abilities as well as vascularization potential compared to BMSCs and PDB-MSCs. As for osteogenic and chondrogenic induction, BMSCs were superior to all three stem cell types. Future therapeutic indications and clinical applications of BMSCs, PDB-MSCs, and USCs should be based on their characteristics, such as growth kinetics and differentiation capabilities.

Large articular cartilage defects remain an immense challenge in the field of regenerative medicine because of their poor intrinsic repair capacity. Currently, the available medical interventions can relieve clinical symptoms to some extent, but fail to repair the cartilaginous injuries with authentic hyaline cartilage. There has been a surge of interest in developing cell-based therapies, focused particularly on the use of mesenchymal stem/progenitor cells with or without scaffolds. Mesenchymal stem/progenitor cells are promising graft cells for tissue regeneration, but the most suitable source of cells for cartilage repair remains controversial. The tissue origin of mesenchymal stem/progenitor cells notably influences the biological properties and therapeutic potential. It is well known that mesenchymal stem/progenitor cells derived from synovial joint tissues exhibit superior chondrogenic ability compared with those derived from non-joint tissues; thus, these cell populations are considered ideal sources for cartilage regeneration. In addition to the progress in research and promising preclinical results, many important research questions must be answered before widespread success in cartilage regeneration is achieved. This review outlines the biology of stem/progenitor cells derived from the articular cartilage, the synovial membrane, and the synovial fluid, including their tissue distribution, function and biological characteristics. Furthermore, preclinical and clinical trials focusing on their applications for cartilage regeneration are summarized, and future research perspectives are discussed.