AIM:Bone morphogenetic protein 7(BMP7)reduces the expression of Yes-related protein 1(YAP1)by down-regulating Ajuba level and decreasing extracellular matrix(ECM)deposition.This study aimed to inves-tigate the influence of these factors on modifying the degree of renal fibrosis in rats with diabetic nephropathy.METH-ODS:Eighteen Sprague-Dawley(SD)rats were randomly divided into three groups:the normal control(NC)group,the diabetes mellitus(DM)group,and the DM group treated with BMP7 overexpressing adeno-associated virus(DM+rAAV-BMP7).Each group consisted of six rats.Diabetic kidney disease(DKD)was established in the DM and DM+rAAV-BMP7 groups by injecting 55 mg/kg streptozotocin(STZ)via the tail vein.NRK-52E cells were divided into three groups:the normal glucose(NG)group,the high glucose(HG)group,and the high glucose group treated with recombinant hu-man BMP7(HG+rhBMP7)group.Pathological changes in renal tissues were observed using hematoxylin and eosin(HE)and Sirius red staining.Immunohistochemical staining was performed to examine the expression sites of Ajuba and YAP1 in the renal cortex.Western blot analysis was conducted to determine the expression levels of BMP7,Ajuba,YAP1,colla-gen type Ⅲ(Col-Ⅲ),and fibronectin(FN)in the rat renal cortex and NRK-52E cells.RT-qPCR was used to measure the mRNA levels of Ajuba and YAP1 in the rat renal cortex.RESULTS:Biochemical indices revealed significantly ele-vated levels of blood glucose,serum creatinine,triglycerides,total cholesterol,and 24-hour urinary protein in the DM group compared to the NC group(P<0.05).In the DM+rAAV-BMP7 group,the levels of serum creatinine,24-hour uri-nary protein,triglycerides,and total cholesterol were lower than those in the DM group(P<0.05).Pathological staining demonstrated that the renal interstitium of the DM group exhibited inflammatory cell infiltration,fibrous tissue,collagen fi-ber deposition,disordered renal tubule arrangement,atrophy,and vacuolar degeneration,which were ameliorated in the DM+rAAV-BMP7 group.Immunohistochemistry revealed that Ajuba and YAP1 were mainly expressed in the cytoplasm and nucleus,with high expression in the cytoplasm of the DM group,which was significantly decreased in the DM+rAAV-BMP7 group.Western blot results indicated that the protein levels of FN,Col-Ⅲ,Ajuba,and YAP1 were up-regulated in the DM and the HG groups(P<0.05),but significantly down-regulated in the DM+rAAV-BMP7 group(P<0.05).RT-qP-CR results demonstrated that the mRNA levels of Ajuba and YAP1 were higher in the DM group and significantly lower in the DM+rAAV-BMP7 group(P<0.05).CONCLUSION:The overexpression of BMP7 can ameliorate renal fibrosis in rats with DKD.This effect is likely mediated by the down-regulation of Ajuba,reduction of YAP1 expression,and subse-quent inhibition of ECM deposition.

Objective:To investigate the predictive value of early thyroid function changes on the efficacy of patients with Graves′ disease (GD) after 131I therapy. Methods:Data of patients with GD (59 males, 214 females; age (37.4±11.4) years) who underwent single therapy of 131I in Tianjin Medical University General Hospital from November 2017 to January 2019 were retrospectively analyzed. Symptoms, signs and laboratory tests (serum free triiodothyronine (FT 3) and serum free thyroxine (FT 4)) of patients were observed to assess the efficacy of 131I treatment. Efficacy was divided into complete remission (CR), partial remission (PR), non-remission (NR) or relapse. The changes of thyroid function (ΔFT 3=FT 3 before treatment-FT 3 after treatment)/FT 3 before treatment×100%; ΔFT 4=FT 4 before treatment-FT 4 after treatment)/FT 4 before treatment×100%) 1 month after 131I therapy in each efficacy group and differences among them were compared by using independent-sample t test, χ2 test, one-way analysis of variance and the least significant difference t test. ROC curves were drawn to analyze the predictive values of early thyroid function changes on the efficacy of 131I treatment for GD. Logistic regression analyses were performed to identify the influencing factors for the efficacy of 131I therapy. Results:CR rate and total effective rate of 273 GD patients after single therapy of 131I were 67.03%(183/273) and 92.67%(253/273), respectively. After 1 month, CR rate of euthyroidism group ( n=95) was significantly higher than that of hyperthyroidism group ( n=178; 81.05%(77/95) vs 59.55%(106/178); χ2=4.60, P=0.032). ΔFT 3 and ΔFT 4 at the first month were statistically significant and decreased sequentially in the CR group ( n=183), PR group ( n=70), NR or relapse groups ( n=20; F values: 15.40, 12.54, both P<0.001). ROC curve analysis showed that patients with ΔFT 3≥73.64% and (or) ΔFT 4≥59.03% had a higher probability of achieving CR, with sensitivities of 84.3% and 86.7%, and specificities of 62.6% and 62.6%, respectively. Logistic regression analysis showed that 24 h radioactive iodine uptake (odds ratio ( OR)=1.095, 95% CI: 1.031-1.139), dose of 131I given per gram of thyroid tissue ( OR=1.562, 95% CI: 1.321-1.694), ΔFT 3 ( OR=1.354, 95% CI: 1.295-1.482), ΔFT 4 ( OR=1.498, 95% CI: 1.384-1.608) were factors affecting the outcome of patients with GD treated with 131I treatment (all P<0.05). Conclusion:Effects of 131I treatment can be predicted based on the change of the thyroid function at the first month after 131I treatment in patients with GD.

Objective To analyze the pollution characteristics of 12 kinds of metals and metalloid elements in PM_2.5 in Xi'an city, and to assess the health risks. Methods In 2018, PM2.5 samples were collected regularly every month at two monitoring points in Lianhu District and Yanta District of Xi'an City. The content of twelve metal and metalloid elements (Sb, Al, As, Be, Cd, Cr, Hg, Pb, Mn, Ni, Se, and Ti) in the samples were determined. The test results were statistically analyzed and evaluated according to different regions and seasons. The health risk assessment model recommended by the US Environmental Protection Agency (EPA) was used to assess the health risks of the metal and metalloid elements. Results A total of 165 PM_2.5 samples were collected and analyzed. The qualified rates of As and Cd were 51.52% and 83.03%, respectively, and there was no significant difference between regions (P＞0.05). The qualified rate of As in each season from high to low was summer> autumn> winter> spring. The average concentration of As was 8.21 ng/m³, being 1.37 times higher than the standard. The average concentration of As in each season exceeded the standard, and the order from high to low was winter> spring> autumn> summer. The average concentrations of other elements did not exceed the standard. HQ value and HI value of As, Cd, Cr, Pb, Mn, Ni, Hg, Ti and Se were all less than 1. The ILCR value of carcinogenic elements As, Cd, Cr and Ni was between 3.63×10^-07 ~2.58×10^-05. The ILCR value was highest for As, followed by Cr. The ILCR value was highest in winter, followed by spring and autumn, and lowest in summer. The order of ILCR value was adult males> adult females> children and adolescents. Conclusion The pollution of metal and metalloid elements in the atmospheric PM_2.5 in Xi'an in the winter is most serious. Arsenic and chromium in PM_2.5 pose a higher potential health risk to the population through the respiratory route.

Objective:To investigate the role of mitofusion 2 (Mfn2) in high glucose (HG)-induced endoplasmic reticulum stress (ERS) and apoptosis of podocytes.Methods:(1) Streptozocin was used to induce a diabetes mellitus (DM) rat model. Renal histopathological changes in rats were observed by HE staining. Expression of Mfn2 and CCAAT/enhancer-binding protein homologous protein (CHOP) in glomeruli was observed by immunohistochemistry. Protein levels of Mfn2, protein kinase RNA-like ER kinase (PERK), phospho(p)-PERK, and CHOP in glomeruli were analyzed by Western blotting. (2) Conditionally immortalized human podocytes (HPC) cultured in vitro were divided into control, mannitol (MA) and HG groups. Expression of Mfn2 was observed by immunofluorescence. Protein levels of Mfn2, p-PERK, PERK and CHOP in HPC were analyzed by Western blotting. Podocyte apoptosis in each group was evaluated by flow cytometry with AnnexinⅤ-PE/7AAD double staining method. (3) HPC were divided into control, HG, HG+Mfn2-Myc plasmid-transfected and HG+control plasmid-transfected groups. Protein levels of Mfn2, p-PERK, PERK and CHOP in HPC were analyzed by Western blotting. Expression of CHOP was observed by immunofluorescence. Mitochondrial membrane potential in each group was observed by mitochondrial membrane potential assay kit with JC-1. Podocyte apoptosis in each group was evaluated by flow cytometry with AnnexinⅤ-PE/7AAD double staining method. Results:(1) Compared with the control group, the glomerular mesangial matrix of the DM group rats was significantly proliferated, and the expression of Mfn2 was down-regulated with the expression of ERS-related proteins p-PERK/PERK and CHOP up-regulated (all P<0.05). (2) Compared with the control group, Mfn2 was down-regulated and p-PERK/PERK and CHOP were up-regulated in HPC of HG group (all P<0.05). Apoptosis of HPC was also increased in HG group. There was no significant difference in the above indicators between the control group and the mannitol group (all P>0.05). (3) Compared with the HG group, mitochondrial membrane potential of HPC was alleviated and apoptosis of HPC was decreased in HG+Mfn2-Myc plasmid-transfected group ( P<0.05). P-PERK/PERK and CHOP were down-regulated in HG+Mfn2-Myc plasmid-transfected group (both P<0.05). There was no significant difference in the above indicators between the HG group and the HG+control plasmid-transfected group (all P>0.05). Conclusions:Mfn2 down-regulation in HG-stimulated podocytes may induce ERS to increase apoptosis of podocytes. Up-regulation of Mfn2 can alleviate the HG-induced ERS and apoptosis in podocytes.

Coronavirus disease 2019(COVID-19),which is caused by SARS-CoV-2,varies with regard to symptoms and mortality rates among populations.Humoral immunity plays critical roles in SARS-CoV-2 infection and recovery from COVID-19.However,differences in immune responses and clinical features among COVID-19 patients remain largely unknown.Here,we report a database for COVID-19-specific IgG/IgM immune responses and clinical parameters(named COVID-ONE-hi).COVID-ONE-hi is based on the data that contain the IgG/IgM responses to 24 full-length/truncated proteins corresponding to 20 of 28 known SARS-CoV-2 proteins and 199 spike protein peptides against 2360 serum samples collected from 783 COVID-19 patients.In addition,96 clinical parameters for the 2360 serum samples and basic information for the 783 patients are integrated into the database.Furthermore,COVID-ONE-hi provides a dashboard for defining samples and a one-click analysis pipeline for a single group or paired groups.A set of samples of interest is easily defined by adjusting the scale bars of a variety of parameters.After the"START"button is clicked,one can readily obtain a comprehensive analysis report for further interpretation.COVID-ONE-hi is freely available at www.COVID-ONE.cn.

Objective: To investigate and analyze the drinking water quality among rural primary and secondary schools in Guanzhong area in 2018, and to provide a basis for the targeted improvement of water supply facilities. Methods: Develop a questionnaire on the basic situation of centralized water supply in rural schools, according to the Standard Test Method for Drinking Water (GB/T 5750—2006) and the Sanitary Standard for Drinking Water (GB 5749—2006) for the rural school network in Guanzhong area. The peripheral water collection and testing carried out single factor and multifactor statistical analysis on the relationship between water quality influencing factors and water quality pass rate. Results: The total qualified rate of drinking water quality in rural schools in Guanzhong area was 59.1%. Univariate analysis showed that water quality rate was affected by four factors including water source type, engineering type, sanitation permit and disinfection equipment use, and the difference was statistically significant(P<0.05). Unconditional two-class logistic regression analysis showed that disinfection (OR=3.14), engineering type (OR=2.05), and sanitation permit (OR=1.99)(P<0.05) affected the water quality pass rate. Conclusion It is recommended to further strengthen the investment in the renovation of water supply for rural schools in Guanzhong area, and specifically strengthen water supply treatment and standard disinfection.

Objective To construct a model of Graves'disease ( GD ) with ( or ) Graves'ophthalmopathy ( GO) in BALB/c mice by immunization with pcDNA3. 1/TSHR289. Methods pcDNA3. 1/TSHR289 was injected into the bilateral gastrocnemius muscle of 35 model mice and electroporation was immediately performed. 10 control mice were injected with sterile saline and electroporated, while 5 blank mice were injected with sterile saline only. Each group of mice was immunized at 1, 4, 7, and 10 weeks, respectively. Serum total T4 , TSH, TSAb, and TSBAb were measured before immunization, 2 weeks after each immunization, as well as 5 and 8 weeks after the last immunization. CT scan was used to evaluate the morphological changes of the eyes of the mice.99m TcO4- imaging was used to measure the thyroid uptake function, and the pathological changes of the thyroid and orbital tissues were evaluated by HE staining. Results After the 2nd time immunization, the serum concentrations of TT4 , TSAb and TSBAb in GD mice were significantly higher than those of control and blank groups( F=13.781, 31.435, 36.112, P<0.01, respectively).The TSH continued to be significantly lower than that of control and blank groups(F=13.966, P<0.01) . After the 4th time immunizations, the ability of uptaking99m TcO4- in GD mice thyroid was significantly enhanced compared with the control group. The thyroid goiter with a large amount of lymphocyte infiltration, and the thyroid follicle was thin. CT scan of GO mice showed thickening and swelling of the extraocular muscles, and no abnormalities in tendon and muscle attachment points. HE staining showed thickening of extraocular muscle fibers, lymphocyte infiltration of extraocular muscles and orbital tissue, increased hyaluronic acid, and infiltration of fat cells. Conclusion GD or GO model can be successfully induced by multiple intramuscular injection of pcDNA3.1/TSHR289 in BALB/c mice.

Objective: To understand the environmental sanitation situation of rural schools in different geographical areas of Shaanxi, and to provide scientific basis for improving hygiene and sanitation in Chinese rural schools. Methods: Each year during 2016 to 2018, 150 townships in 30 counties of rural areas were randomly selected in various districts and cities throughout the province. In each township one junior high school and one elementary school were randomly selected, and the data was obtained through resource access, interviews, and on-site observations. The data was statistically analyzed and evaluated according to the northern, central and southern regions. Results: The differences of drinking ways among students in the schools were of statistical significance(χ2=25.89,P<0.01). The major drinking water method of students in the monitoring schools of the three regions all was providing boiled water, accounting for 56.16%, 65.88%, 50.39%, all of which have direct drinking unboiled water phenomenon; The water supply method of the self-provided centralized water supply school is mainly precipitation filtration in the central and southern regions, accounting for 38.46%, 53.21%, and untreated in the northern region(60.61%); The differences of the proportions of having sanitary toilets, detached toilets in schools, having toilets in teaching buildings, and having toilets in dormitory buildings in three regions were of statistical significance(χ2=32.04, 12.73, 20.78, 33.11, P<0.01) The proportion of schools with squat toilets in men’s toilets was greater than that of women’s(χ2=86.53, 44.77, 21.88, P<0.01). The differences of the proportion of schools with faucets available in toilets and within 5 meters around toilets, with sinks in or around the toilets, with sinks equipped with soap in or around the toilets were of statistical significance(χ2=90.02, 10.40, 41.96, P<0.01). Conclusion During 2016 to 2018, the environment sanitation of the three major rural primary and middle schools in Shaanxi Province needs to improve corresponding supporting facilities, and increase publicity to improve teachers and students’ awareness of health and safety.

Alzheimer’ s disease ( AD) is one of the most common dementia of neurodegenerative disorders, which results from the deposition of amyloid-beta ( Aβ) and there are no curative treatments for this disease at present.It had been proved that prion protein is the receptor for Aβand it plays a key role in the progress of AD with dual-side effects. Prion protein can not only transfer neurotoxicity to neurons but also protect them from neurotoxicity of Aβ.The polymor-phisms of prion protein encoding gene ( PRNP) affect the AD incubation period and clinical symptoms in humans and other animals.The discovery of PRNP mutational mouse fills the gaps of existing AD mouse models in this research area, which is potential for the studies of pathogenesis, new drugs design and testing aspects.The role and effects of prion protein in AD pathogenesis were summarized in this paper, furthermore, the discovery and utility of PRNP gene mutational mouse in research on AD and/or amyloid diseases were reviewed, and in order to provide some guidance for AD animal model study.

BACKGROUND:Some scholars have prepared zein/chitosan composite membrane based on blending methods, and preliminary evaluation ofitsphysical and chemical properties showsthat chitosan partly improvesthe mechanical properties and hydrophilic properties of zein. Therefore, zein/chitosan composite membrane presumably has good cytocompati bility, which is beneficial to osteogenic differentiation of bone marrow mesenchymal stem cels.
OBJECTIVE:To explore the effect of zein/chitosan composite membrane on the differentiation of bone marrow mesenchymal stem cels into osteoblasts and its feasibility asabone tissue-engineered material.
METHODS:With 60% acetic acid as solvent, zein/chitosan composite membrane was prepared by blending and casting method. The structure and physicochemical properties of the composite membrane were investigated by Fourier transform infrared spectroscopy, tensile testing, water absorption testing and scanning electron microscopy. And the cytocompatibility of the membrane was evaluated byin vitrocel cufture. Besides,bone marrow mesenchymal stem celsfrom Sprague-Dawley ratwere isolatedvia adherence screening method, andthe effects of thecompositemembrane on theosteogenic differentiation ofthese celswere observedby scanning electron microscopy, fluorescent labeling and alkaline phosphatase assay.
RESULTS AND CONCLUSION:The tensile strength, water absorption and hydrophilicity of the films were improved with the chitosan increased; chitosan could promote cel proliferation indicating the good cytocompatibility of the composite films. Moreover, osteogenic induction occurredin bone marrow mesenchymal stem cels cultured on the compositem embrane, and with an increase of chitosan, the induction was promoted. In conclusion, zein/chitosan composite membrane can be applied widely in the field of bone tissue engineering.