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Nonsyndromic cleft lip with or without a cleft palate (NSCL/P) is among the most common human congenital birth defects and imposes a substantial physical and financial burden on affected individuals. Here, we conduct a case-control-based GWAS followed by two rounds of replication; we include six independent cohorts from China to elucidate the genetic architecture of NSCL/P in Chinese populations. Using this combined analysis, we identify a new locus at 16p13.3 associated with NSCL/P: rs8049367 between CREBBP and ADCY9 (odds ratio ¼ 0.74, P ¼ 8.98 Â 10 À 12 ). We confirm that the reported loci at 1q32.2, 10q25.3, 17p13.1 and 20q12 are also involved in NSCL/P development in Chinese populations. Our results provide additional evidence that the rs2235371-related haplotype at 1q32.2 could play a more important role than the previously identified causal variant rs642961 in Chinese populations. These findings provide information on the genetic basis and mechanisms of NSCL/P.

Osteoporosis is a progressive skeletal disease characterized by decreased bone mass and degraded bone microstructure, which leads to increased bone fragility and risks of bone fracture. Osteoporosis is generally age related and has become a major disease of the world. Uncovering the molecular mechanisms underlying osteoporosis and developing effective prevention and therapy methods has great significance for human health. Mesenchymal stem cells (MSCs) are multipotent cells capable of differentiating into osteoblasts, adipocytes, or chondrocytes, and have become the favorite source of cell-based therapy. Evidence shows that during osteoporosis, a shift of the cell differentiation of MSCs to adipocytes rather than osteoblasts partly contributes to osteoporosis. Thus, uncovering the molecular mechanisms of the osteoblast or adipocyte differentiation of MSCs will provide more understanding of MSCs and perhaps new methods of osteoporosis treatment. The MSCs have been applied to both preclinical and clinical studies in osteoporosis treatment. Here, we review the recent advances in understanding the molecular mechanisms regulating osteoblast differentiation and adipocyte differentiation of MSCs and highlight the therapeutic application studies of MSCs in osteoporosis treatment. This will provide researchers with new insights into the development and treatment of osteoporosis.

Compared with placebo, dapagliflozin 5 and 10 mg demonstrated clinically and statistically significant improvements in HbA1c levels after 24 weeks of treatment. Dose-dependent, statistically significant reductions in fasting plasma glucose, postprandial glucose, and weight were also observed for both doses compared with placebo. AEs and serious AEs were balanced across groups, with low rates of hypoglycemia and no increase in renal events. Genital infections and urinary tract infections were more common with dapagliflozin. Dapagliflozin as monotherapy in these drug-naive Asian patients was well tolerated, significantly improving glycemic control with the additional benefit of weight loss.

The Arabidopsis ethylene receptor gene ETR1 and two related genes, ERS1 and ETR2, were identified previously. These three genes encode proteins homologous to the two-component regulators that are widely used for environment sensing in bacteria. Mutations in these genes confer ethylene insensitivity to wild-type plants. Here, we identified two Arabidopsis genes, EIN4 and ERS2, by cross-hybridizing them with ETR2. Sequence analysis showed that they are more closely related to ETR2 than they are to ETR1 or ERS1. EIN4 previously was isolated as a dominant ethylene-insensitive mutant. ERS2 also conferred dominant ethylene insensitivity when certain mutations were introduced into it. Double mutant analysis indicated that ERS2, similar to ETR1, ETR2, ERS1, and EIN4, acts upstream of CTR1. Therefore, EIN4 and ERS2, along with ETR1, ETR2, and ERS1, are members of the ethylene receptor-related gene family of Arabidopsis. RNA expression patterns of members of this gene family suggest that they might have distinct as well as redundant functions in ethylene perception.

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To determine incidence and clinically relevant risk factors for diabetic amputation in a large cohort study of diabetic foot ulceration patients in China, we investigated a total of 669 diabetic foot ulceration patients, who were assessed at baseline for demographic information, medical and social history, peripheral neuropathy screening, periphery artery disease screening, assessment of nutritional status and diabetic control, physical examination including foot deformity in 15 Grade III-A hospitals. Of the 669 patients, 435 were male and 201 were female, with the mean age being 64.0 years. Of all patients, 110 had neuropathic ulcers, 122 had ischemic ulcers, 276 had neuroischemic ulcers, and 12 cases were unclassified. Wagner classification showed 61 cases were grade I, 216 cases grade II, 159 cases grade III, 137 cases grade IV, and 7 cases grade V. The overall amputation rate among diabetic foot patients was 19.03%, and major and minor amputation rates were 2.14% and 16.88%, respectively. By univariate analysis, statistically significant differences were found in smoking, rest pain, ulcer history, revascularization history, amputation history, gangrene, infection, Wagner grades, duration of diabetes, and postprandial blood glucose, aldehyde, total protein, globulin, albumin, white blood cell (WBC), hemoglobin, HbA1c, ulcer property, body mass index, as well as creatinine. Binary logistic regression model showed that increased WBC (odds ratio 1.25) and ulcer history (odds ratio 6.8) were associated with increased risks from diabetic foot ulcer to major amputation; increased duration of diabetes (odds ratio 1.004), WBC (odds ratio 1.102), infection (odds ratio 2.323), foot deformity (odds ratio 1.973), revascularization history (odds ratio 2.662), and decreased postprandial blood sugar (odds ratio 0.94) were associated with increased risks from diabetic foot ulcer to minor amputation. It is of great importance to give better management to diabetic patients at early stages. Following a diagnosis of DFU more intensive surveillance and aggressive care may improve outcome.

SummaryPrivate-sector organizations play a critical role in shaping the food environments of individuals and populations. However, there is currently very limited independent monitoring of private-sector actions related to food environments. This paper reviews previous efforts to monitor the private sector in this area, and outlines a proposed approach to monitor private-sector policies and practices related to food environments, and their influence on obesity and non-communicable disease (NCD) prevention. A step-wise approach to data collection is recommended, in which the first ('minimal') step is the collation of publicly available food and nutrition-related policies of selected private-sector organizations. The second ('expanded') step assesses the nutritional composition of each organization's products, their promotions to children, their labelling practices, and the accessibility, availability and affordability of their products. The third ('optimal') step includes data on other commercial activities that may influence food environments, such as political lobbying and corporate philanthropy. The proposed approach will be further developed and piloted in countries of varying size and income levels. There is potential for this approach to enable national and international benchmarking of private-sector policies and practices, and to inform efforts to hold the private sector to account for their role in obesity and NCD prevention.