BACKGROUND:Overactive osteoclasts disrupt bone homeostasis and play a bad role in the pathological mechanisms of related skeletal diseases,such as osteoporosis,fragility fractures,and osteoarthritis.Studies have confirmed that ellagic acid and ellagtannin have the potential to inhibit osteoclast differentiation.As their natural metabolites,urolithin A has antioxidant,anti-inflammatory,anti-proliferative and anti-cancer effects,but its effect on osteoclast differentiation and its underlying molecular mechanisms remain unclear. OBJECTIVE:To explore the effect of urolithin A on osteoclast differentiation induced by receptor activator for nuclear factor-κB ligand and its mechanism. METHODS:Mouse mononuclear macrophage leukemia cells(RAW264.7)that grew stably were cultured in vitro.Toxicity of urolithin A(0,0.1,0.5,1.5,2.5 μmol/L)to RAW264.7 cells were detected by cytotoxic MTS assay to screen out the safe concentration.Different concentrations of urolithin A were used again to intervene with receptor activator for nuclear factor-κB ligand-induced differentiation of RAW264.7 cells in vitro.Then,tartrate-resistant acid phosphatase staining and F-actin ring and nucleus staining were performed to observe its effect on the formation and function of osteoclasts.Finally,the expressions of urolithin A on upstream and downstream genes and proteins in the MAPK signaling pathway were observed by western blot and RT-qPCR assays. RESULTS AND CONCLUSION:Urolithin A inhibited osteoclast differentiation and F-actin ring formation in a concentration-dependent manner and 2.5 μmol/L had the strongest inhibitory effect.Urolithin A inhibited the mRNA expression of Nfatc1,Ctsk,Mmp9 and Atp6v0d2 and the protein synthesis of Nfatc1 and Ctsk,related to osteoclast formation and bone resorption.Urolithin A inhibited the activity of osteoclasts by downregulating the phosphorylation of p38 protein to inhibit the mitogen-activated protein kinase signaling pathway.

Objective:To systematically evaluate the effects of insulin combined with metformin in the treatment of gestational diabetes mellitus(GDM)on maternal and neonatal outcomes in China,in order to provide evidence-based medical recommendations for clinical treatment.Methods:The Chinese Academic Database(CNKI),VIP Database,and Wanfang Database were searched from the establishment of the database to April 2022 for randomized controlled trials(RCTs)of insulin combined with metformin versus insulin alone in the treatment of GDM to observe the adverse outcomes for neonates.The Cochrane Collaboration was used for quality evaluation and Review Manager 5.4 software was utilized for meta-analysis.Results:A total of 51 studies were included in the meta-analysis,including 4 916 GDM patients,with 2 460 cases in the combined treatment group and 2 456 cases in insulin alone group.The meta-analysis results revealed significant reductions in rates of cesarean section(OR=0.32,95%CI:0.26-0.39),preterm birth(OR=0.26,95%CI:0.20-0.34),polyhydramnios(OR=0.27,95%CI:0.20-0.36),gestational hypertension(OR=0.25,95%CI:0.18-0.35),neonatal jaundice(OR=0.25,95%CI:0.19-0.32),neonatal hypoglycemia(OR=0.33,95%CI:0.25-0.45),macrosomia(OR=0.23,95%CI:0.17-0.30),and neonatal respiratory distress(OR=0.23,95%CI:0.16-0.34)in the combined treatment group than those in the control group(P＜0.01).Conclusions:For patients with GDM,insulin combined with metformin is significantly more effective than insulin alone in reducing the incidence of maternal and neonatal complications.This combination therapy results in improved outcomes for both mothers and infants.

Objectives:To explore the spatial distribution characteristics, trend changes, and spatial clustering of esophageal cancer among residents in China at the county (city, district) scale, a spatial epidemiological approach was used, with the aim of providing localized evidence for the prevention and treatment of esophageal cancer in China.Methods:The data source was the incidence (crude rate) and mortality (crude rate) of esophageal cancer from 2005 to 2016 in the 2008-2019 edition of China Cancer Registration Annual Report published by the National Cancer Center. The Joinpoint model was used for time trend analysis. The tumor registration area in 2016 was selected as the study area for spatial feature analysis, with a total of 487 counties (cities and districts), covering 27.6% of the national population. Spatial autocorrelation analysis was performed to reveal spatial distribution characteristics by using Arcgis 10.6 software, and spatial scanning statistics was used to analyze spatial clustering characteristics by using SaTScan 9.5 software. The log-likelihood ratio ( LLR) and relative risk ( RR) were calculated in different windows, and the region with the largest LLR value represented the most likely cluster. Results:From 2005 to 2016, the incidence and mortality rate of esophageal cancer in China showed a trend of increasing at first and then decreasing. The incidence and mortality rate of esophageal cancer in 2016 were characterized by spatial positive correlation. High incidence and high mortality were mainly concentrated in the areas through which the Huaihe River flowed. The primary clusters (taking high incidence rate as an example LLR=6 374.41, RR=2.37, P＜0.001) were mainly distributed in Jiangsu, Anhui and Shandong in eastern China and eastern Henan and southern Hebei in central China, and secondary clusters (taking high incidence rate as an example LLR=1 971.19, RR=1.91, P＜0.001) in Gansu, Ningxia Hui Autonomous Region, Shaanxi, Sichuan and other central and western regions. Conclusions:The incidence and mortality of esophageal cancer in China have decreased since 2010. The disease burden of esophageal cancer has obvious spatial differences, and measures should be taken according to local conditions in high-risk cluster areas such as the Huaihe River basin.

Objectives:To explore the spatial distribution characteristics, trend changes, and spatial clustering of esophageal cancer among residents in China at the county (city, district) scale, a spatial epidemiological approach was used, with the aim of providing localized evidence for the prevention and treatment of esophageal cancer in China.Methods:The data source was the incidence (crude rate) and mortality (crude rate) of esophageal cancer from 2005 to 2016 in the 2008-2019 edition of China Cancer Registration Annual Report published by the National Cancer Center. The Joinpoint model was used for time trend analysis. The tumor registration area in 2016 was selected as the study area for spatial feature analysis, with a total of 487 counties (cities and districts), covering 27.6% of the national population. Spatial autocorrelation analysis was performed to reveal spatial distribution characteristics by using Arcgis 10.6 software, and spatial scanning statistics was used to analyze spatial clustering characteristics by using SaTScan 9.5 software. The log-likelihood ratio ( LLR) and relative risk ( RR) were calculated in different windows, and the region with the largest LLR value represented the most likely cluster. Results:From 2005 to 2016, the incidence and mortality rate of esophageal cancer in China showed a trend of increasing at first and then decreasing. The incidence and mortality rate of esophageal cancer in 2016 were characterized by spatial positive correlation. High incidence and high mortality were mainly concentrated in the areas through which the Huaihe River flowed. The primary clusters (taking high incidence rate as an example LLR=6 374.41, RR=2.37, P＜0.001) were mainly distributed in Jiangsu, Anhui and Shandong in eastern China and eastern Henan and southern Hebei in central China, and secondary clusters (taking high incidence rate as an example LLR=1 971.19, RR=1.91, P＜0.001) in Gansu, Ningxia Hui Autonomous Region, Shaanxi, Sichuan and other central and western regions. Conclusions:The incidence and mortality of esophageal cancer in China have decreased since 2010. The disease burden of esophageal cancer has obvious spatial differences, and measures should be taken according to local conditions in high-risk cluster areas such as the Huaihe River basin.

Objective:To develop a deep transfer learning method for the differential diagnosis of osteonecrosis of the femoral head (ONFH) with other common hip diseases using anteroposterior hip radiographs.Methods:Patients suffering from ONFH, DDH, and other hip diseases including primary hip osteoarthritis, non-infectious inflammatory hip disease, and femoral neck fracture treated in the First Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2018 to December 2020 were enrolled in the study. A clinical data set containing anteroposterior hip radiographs of the eligible patients was created. Data augmentation by rotating and flipping images was performed to enlarge the data set, then the data set was divided equally into a training data set and a testing data set. The ResNet-152, a deep neural network model, was used in the study, but the original Batch Normalization was replaced with Transferable Normalization to construct a novel deep transfer learning model. The model was trained to distinguish ONFH and DDH from other common hip diseases using anteroposterior hip radiographs on the training data set and its classification performance was evaluated on the testing data set.Results:The clinical data set was comprised of anteroposterior hip radiographs of 1024 hips, including 542 with ONFH, 296 with DDH, and 186 with other common hip diseases (56 hips with primary osteoarthritis, 85 hips with non-infectious inflammatory osteoarthritis, 45 hips with femoral neck fracture). After data augmentation, the size of the data set multiplied to 6144. The model was trained 100 050 times in each task. Accuracy was used as the representative parameter to evaluate the performance of the model. In the binary classification task to identify ONFH, the best accuracy was 95.80%. As for the multi-classification task for classification of ONFH and DDH from other hip diseases, the best accuracy was 91.40%. The plateau of the model was observed in each task after 50 000 times of training. The mean accuracy in plateaus was 95.35% (95% CI: 95.33%, 95.37%), and 90.85% (95% CI: 90.82%, 90.87%), respectively. Conclusion:The present study proves the encouraging performance of a deep transfer learning method for the first-visit classification of ONFH, DDH, and other hip diseases using the convenient and economical anteroposterior hip radiographs.

Objective:To investigate the relationship between smoking status and the onset age of stomach cancer patients and estimate the patients’ direct medical cost burden of stomach cancer due to smoking in Anhui province.Methods:The information about the primary stomach cancer patients and their direct treatment expenditures in 10 cancer-registered areas in Anhui were collected in 2017. The association between smoking status and the age of onset of stomach cancer patients was analyzed by univariate regression and multivariate logistic regression models. The median and smoking-attributed risk method was used to describe the direct treatment expenditure of stomach cancer patients in Anhui due to smoking.Results:A total of 736 patients with stomach cancer were analyzed in this study. Univariate regression analysis showed that rural household registration ( t=2.091, P=0.037), smoking ( t=-2.357, P=0.001 9) and alcohol consumption ( t=-2.036, P=0.042) were related to the age of onset of stomach cancer. After adjusting for gender, alcohol consumption, body mass index and household registration type, the risk of early stomach cancer in people who quitted smoking cessation was lower than that in smokers ( OR=0.36, 95 %CI: 0.17-0.75). The total direct medical cost burden of 736 newly diagnosed stomach cancer patients was 6.939 6 million RMB. The direct medical expenditure in stomach cancer patients who had smoking behavior was higher than that in stomach cancer patients who quitted smoking and never smoked. Conclusions:Smoking is one of the risk factors for the earlier onset of stomach cancer in Anhui. It is necessary to strengthen tobacco control to reduce the economic burden of patients with stomach cancer.

Objective:To explore the effects of WeChat-based health education on management of hypertensive outpatients under medical consortium.Methods:Totally 180 hypertensive patients who attended the Multidisciplinary Clinics of Beijing Anzhen Hospital, Capital Medical University, and Datun Community Health Service Center from communities under our medical consortium from November 2018 to April 2019 were selected and divided into the observation group ( n=91) and the control group ( n=89) according to the visit time. Patients in the control group received routine health education, while patients in the observation group received WeChat-based health education under medical consortium for 6 months. The self-management ability (using Hypertension Patients Behavior Rating Scale, HPSMBRS) , treatment compliance (using Therapeutic Adherence Scale for Hypertensive Patients, TASHP) , the 24 h average systolic and diastolic blood pressure, the average systolic and diastolic blood pressure at daytime, and the average systolic blood pressure and diastolic blood pressure at night were compared between the two groups. Results:After the intervention, the diet management, medication management, disease monitoring, exercise management, work and rest and emotional management scores of the observation group were higher than those of the control group, and the differences were statistically significant ( P<0.05) . After the intervention, the medication-taking behavior, bad medication-taking behavior, daily activity management behavior and tobacco and alcohol addiction scores were higher than those of the control group, and the differences were statistically significant ( P<0.05) . After the intervention, the 24 h average systolic and diastolic blood pressure, average systolic and diastolic blood pressure at daytime and average systolic and diastolic blood pressure at night decreased in the observation group, and the differences were statistically significant compared with the control group ( P<0.05) . Conclusions:The WeChat platform under medical consortium provides standardized, consistent, continuous and effective health education, which can improve the self-management ability and treatment compliance of hypertensive outpatients, and can effectively control blood pressure levels. It shows sound effects in clinical use.

Genetic mutations in triggering receptor expressed on myeloid cells 2 (TREM2) have been linked to a variety of neurodegenerative diseases including Alzheimer’s disease, amyotrophic lateral sclerosis, frontotemporal dementia and Parkinson’s disease. In the brain, TREM2 is highly expressed on the cell surface of microglia, where it can transduce signals to regulate microglial functions such as phagocytosis. To date, mechanisms underlying intracellular trafficking of TREM2 remain elusive. Mutations in the presenilin 1 (PS1) catalytic subunit of the γ-secretase complex have been associated with increased generation of the amyloidogenic Aβ (amyloid-β) 42 peptide through cleavage of the Aβ precursor amyloid precursor protein. Here we found that TREM2 interacts with PS1 in a manner independent of γ-secretase activity. Mutations in TREM2 alter its subcellular localization and affects its interaction with PS1. Upregulation of PS1 reduces, whereas downregulation of PS1 increases, steady-state levels of cell surface TREM2. Furthermore, PS1 overexpression results in attenuated phagocytic uptake of Aβ by microglia, which is reversed by TREM2 overexpression. Our data indicate a novel role for PS1 in regulating TREM2 intracellular trafficking and pathophysiological function.

BACKGROUND:Estrogen signaling pathway for interaction between aromatase and estrogen-related receptor may exist in bone marrow mesenchymal stem cel s, which is used for regulating biological activity of bone marrow mesenchymal stem cel s. OBJECTIVE:To observe the expression of aromatase and estrogen-related receptors in adult bone marrow mesenchymal stem cel s during osteogenic differentiation. METHODS:Bone marrow mesenchymal stem cel s were respectively cultured in low-glucose DMEM medium (control group) and osteogenic induction medium (induction group). Cel proliferation and calcium deposition were determined by MTT assay and alizarin red staining, respectively. The expression of aromatase, estrogen receptorα, estrogen receptorβ, and estrogen-related receptorαduring osteogenic differentiation were determined by real-time PCR and western blot analysis. Estradiol levels in supernatants and lysates were detected by ELISA method. RESULTS AND CONCLUSION:In the induction group, the proliferation ability of bone marrow mesenchymal stem cel s was the strongest at 72 hours of culture;while there were a great amount of calcium nodules formed at 21 days of culture. Results from PCR and western blot assay showed that the expression of aromatase and estrogen receptorαwas improved in the induction group, but the expression of estrogen-related receptorαwas inhibited. There was no difference in the expression of estrogen receptorβbetween the two groups. ELISA results indicated that the level of estradiol in the supernatant of induction group was the highest. These findings indicate that aromatase, estrogen receptorα, estrogen receptorβand estrogen-related receptorαare al involved in osteogenesis of bone marrow mesenchymal stem cel s. Moreover, estradiol can be synthesized and secreted in bone marrow mesenchymal stem cel s, and most likely, promote the osteogenic differentiation of bone marrow mesenchymal stem cel s by related receptor pathway.

Our primary health care institution began to implement national essential medicine system in 2009. In past fi ve years, the goal of national essential medicine system has been initially achieved. For examples, medicine price is steadily reducing, the quality of medical services is improving and residents' satisfaction is substantial increasing every year. However, at the same time, we also found some urgent problems needed to be solved. For examples, the range of national essential medicine is limited, which is difficult to guarantee the quality of essential medication. In addition, how to compensate the primary health care institution is still a question.
China ; Health Services Needs and Demand ; Primary Health Care ; organization & administration