Benign prostatic hyperplasia(BPH)is one of the major chronic complications of type 2 diabetes mellitus(T2DM),and sex steroid hormones are common risk factors for the occurrence of T2DM and BPH.The profiles of sex steroid hormones are simultaneously quantified by LC-MS/MS in the clinical serum of patients,including simple BPH patients,newly diagnosed T2DM patients,T2DM complicated with BPH patients and matched healthy individuals.The G protein-coupled estrogen receptor(GPER)inhibitor G15,GPER knockdown lentivirus,the YAP1 inhibitor verteporfin,YAP1 knockdown/overexpression lentivirus,targeted metabolomics analysis,and Co-IP assays are used to investigate the molecular mechanisms of the disrupted sex steroid hormones homeostasis in the pathological process of T2DM complicated with BPH.The homeostasis of sex steroid hormone is disrupted in the serum of patients,accompanying with the proliferated prostatic epithelial cells(PECs).The sex steroid hormone metabolic profiles of T2DM patients complicated with BPH have the greatest degrees of separation from those of healthy individuals.Elevated 17β-estradiol(E2)is the key contributor to the disrupted sex steroid hormone homeostasis,and is significantly positively related to the clinical characteristics of T2DM patients complicated with BPH.Activating GPER by E2 via Hippo-YAP1 signaling exacerbates high glucose(HG)-induced PECs prolifer-ation through the formation of the YAP1-TEAD4 heterodimer.Knockdown or inhibition of GPER-mediated Hippo-YAP1 signaling suppresses PECs proliferation in HG and E2 co-treated BPH-1 cells.The anti-proliferative effects of verteporfin,an inhibitor of YAP1,are blocked by YAP1 overexpression in HG and E2 co-treated BPH-1 cells.Inactivating E2/GPER/Hippo/YAP1 signaling may be effective at delaying the progression of T2DM complicated with BPH by inhibiting PECs proliferation.

Schistosomiasis was once hyper-endemic in Yunnan Province. Following concerted efforts for over 70 years, remarkable achievements have been made for schistosomiasis control in the province. In 2004, the Mid- and Long-term Plan for Schistosomiasis Prevention and Control in Yunnan Province was initiated in Yunnan Province, and the target for transmission control of schistosomiasis was achieved in the province in 2009. Following the subsequent implementation of the Outline for Key Projects in Integrated Schistosomiasis Control Program (2009—2015) and the 13th Five - year Plan for Schistosomiasis Control in Yunnan Province, no acute schistosomiasis had been identified in Yunnan Province for successive 12 years, and no local Schistosoma japonicum infections had been detected in humans, animals or Oncomelania hupensis snails for successive 6 years in the province by the end of 2020. The transmission of schistosomiasis was interrupted in Yunnan Province in 2020. This review summarizes the history of schistosomiasis, changes in schistosomiasis prevalence and progress of schistosomiasis control in Yunnan Province, and proposes the future priorities for schistosomiasis control in the province.

Objective To predict the potential geographic distribution of Oncomelania hupensis in Yunnan Province using random forest (RF) and maximum entropy (MaxEnt) models, so as to provide insights into O. hupensis surveillance and control in Yunnan Province. Methods The O. hupensis snail survey data in Yunnan Province from 2015 to 2016 were collected and converted into O. hupensis snail distribution site data. Data of 22 environmental variables in Yunnan Province were collected, including twelve climate variables (annual potential evapotranspiration, annual mean ground surface temperature, annual precipitation, annual mean air pressure, annual mean relative humidity, annual sunshine duration, annual mean air temperature, annual mean wind speed, ≥ 0 ℃ annual accumulated temperature, ≥ 10 ℃ annual accumulated temperature, aridity and index of moisture), eight geographical variables (normalized difference vegetation index, landform type, land use type, altitude, soil type, soil textureclay content, soil texture-sand content and soil texture-silt content) and two population and economic variables (gross domestic product and population). Variables were screened with Pearson correlation test and variance inflation factor (VIF) test. The RF and MaxEnt models and the ensemble model were created using the biomod2 package of the software R 4.2.1, and the potential distribution of O. hupensis snails after 2016 was predicted in Yunnan Province. The predictive effects of models were evaluated through cross-validation and independent tests, and the area under the receiver operating characteristic curve (AUC), true skill statistics (TSS) and Kappa statistics were used for model evaluation. In addition, the importance of environmental variables was analyzed, the contribution of environmental variables output by the models with AUC values of > 0.950 and TSS values of > 0.850 were selected for normalization processing, and the importance percentage of environmental variables was obtained to analyze the importance of environmental variables. Results Data of 148 O. hupensis snail distribution sites and 15 environmental variables were included in training sets of RF and MaxEnt models, and both RF and MaxEnt models had high predictive performance, with both mean AUC values of > 0.900 and all mean TSS values and Kappa values of > 0.800, and significant differences in the AUC (t = 19.862, P < 0.05), TSS (t = 10.140, P < 0.05) and Kappa values (t = 10.237, P < 0.05) between two models. The AUC, TSS and Kappa values of the ensemble model were 0.996, 0.954 and 0.920, respectively. Independent data verification showed that the AUC, TSS and Kappa values of the RF model and the ensemble model were all 1, which still showed high performance in unknown data modeling, and the MaxEnt model showed poor performance, with TSS and Kappa values of 0 for 24%(24/100) of the modeling results. The modeling results of 79 RF models, 38 MaxEnt models and their ensemble models with AUC values of > 0.950 and TSS values of > 0.850 were included in the evaluation of importance of environmental variables. The importance of annual sunshine duration (SSD) was 32.989%, 37.847% and 46.315% in the RF model, the MaxEnt model and their ensemble model, while the importance of annual mean relative humidity (RHU) was 30.947%, 15.921% and 28.121%, respectively. Important environment variables were concentrated in modeling results of the RF model, dispersed in modeling results of the MaxEnt model, and most concentrated in modeling results of the ensemble model. The potential distribution of O. hupensis snails after 2016 was predicted to be relatively concentrated in Yunnan Province by the RF model and relatively large by the MaxEnt model, and the distribution of O. hupensis snails predicted by the ensemble model was mostly the joint distribution of O. hupensis snails predicted by RF and MaxEnt models. Conclusions Both RF and MaxEnt models are effective to predict the potential distribution of O. hupensis snails in Yunnan Province, which facilitates targeted O. hupensis snail control.

To explore the effectiveness of "near peer learning" (NPL) in the electromyography(EMG)teaching module for neurology residents.

OBJECTIVE To establish the fingerprint of Sophora flavescens， and to screen differential components and determine their contents.　METHODS HPLC fingerprints of 12 batches of S. flavescens were established by using Similarity Evaluation System of Chromatographic Fingerprints of TCM （2012 edition）； common peaks were identified and their similarities were evaluated. Chemical pattern recognition analysis [cluster analysis （CA），principal component analysis （PCA） and orthogonal partial least squares-discriminant analysis（OPLS-DA）] were performed with SIMCA 14.1 and SPSS 23.0 software， and differential components which influenced the quality of S. flavescens were screen with variable importance in the projection（VIP）＞1 as standard. Meanwhile， the contents of 4 kinds of differential components were determined by the same HPLC method.　RESULTS There were 17 common peaks in the fingerprints of 12 batches of S. flavescens，and their similarities were all higher than 0.96. A total of 6 common peaks were identified， i.e. oxymatrine （peak 1）， oxysophocarpine （peak 2）， matrine （peak 10）， trifolirhizin （peak 14）， kurarinone （peak 16） and norkurarinone （peak 17）. Results of CA， PCA and OPLS-DA showed that 12 batches of S. flavescens were divided into 3 categories according to producing area， i.e. S1-S7 （Shangzhou District of Shaanxi Province） were grouped into one category， S8-S10 （Yichuan County of Henan Province） into one category and S11-S12 （Chifeng City of Inner Mongolia） into one category. VIPs of matrine， norkurarinone， kurarinone and oxysophocarpine and the chemical components represented by peak 11 and 9 were all greater than 1. The contents of matrine， norkurarinone， kurarinone and oxysophocarpine in 12 batches of S. flavescens were 2.65-4.93， 1.54-3.44， 9.63-12.94 and 5.08-6.10 mg/g， respectively. CONCLUSIONS HPLC fingerprint of S. flavescens is established successfully in the study， and can be used to screen 6 differential components by combining with chemical pattern recognition analysis， which can provide reference for quality control of S. flavescens.

Objective:To analyze the distribution characteristics of plasma renin concentration (PRC) in patients with aldosterone-producing adenoma (APA) and its impact on diagnosis.Methods:In this retrospective case series, clinical data from 200 patients with APA (80 men and 120 women; mean age 45.6 years) in the First Affiliated Hospital of Chongqing Medical University from November 2013 to January 2022 were evaluated. PRC was determined by automated chemiluminescence immunoassay. The distribution characteristics of PRC were analyzed, and 8.2 mU/L was used as the low renin cutoff to evaluate whether renin was suppressed.Results:The median PRC was 1.6 mU/L (range, 0.4-41.5 mU/L). There were 116 patients with APA with PRC of ≤2 mU/L, 41 patients with 28.2 mU/L) in 8.0% (16/200) of the patients with APA. And PRC was not suppressed in 2.5% (5/200) of the patients with APA, resulting in a primary aldosteronism negative screening outcome.Conclusions:Although most patients with APA have low PRC, there are a small number (8%) of patients whose PRC has not been fully suppressed, which can lead to missed diagnoses during primary aldosteronism screening. While primary aldosteronism is highly suspected, further investigations are required to determine the diagnosis, even if PRC is not fully suppressed at screening.

Objective:To identify the influencing factors for community elderly health services provided by general practitioners (GPs) using the social ecological theory, for reference in improving their participation and satisfaction.Methods:According to the social ecological theory, an ecological model for GPs to carry out community elderly health services was constructed from four levels: public policy ecology, community health service ecology, interpersonal relationship ecology, and individual characteristics ecology of general practitioners. A survey questionnaire was designed with six latent variables: public health policy support, public health service and basic medical service supply, doctor-patient relationship, individual participation and individual satisfaction. The questionnaire was distributed to 220 GPs from 11 primary healthcare institutions in Jiangsu province, China, who were randomly selected between October and November 2021. Exploratory and confirmatory analyses of the model were conducted using AMOS 25.0.Results:A total of 207 valid questionnaires were collected, and all the KMO values of the six latent variables were greater than 0.7, while the composite reliability values and average variance extracted values greater than 0.7 and 0.5, respectively. Both the reliability and validity of the data met the analysis requirements. Exploratory analysis revealed that public health policy support had a direct positive effect on both public health service and basic medical service supply (both effect sizes being 0.37). Public health service had a direct positive effect on doctor-patient relationship, individual participation and individual satisfaction (effect sizes being 0.52, 0.22, and 0.31, respectively). The direct effect of basic medical service supply on doctor-patient relationship was not significant (effect size being 0.03), but it had a direct positive effect on public health service (effect size being 0.46). Doctor-patient relationship had a direct positive effect on individual participation (effect size being 0.51), but its direct effect on individual satisfaction was not significant (effect size being 0.06). Individual participation had a direct positive effect on individual satisfaction (effect size being 0.52). Conclusions:By optimizing the public policy ecosystem, community health service ecosystem, and interpersonal relationship ecosystem, the participation and satisfaction of general practitioners can be systematically improved.

BACKGROUND: Cancer stem-like cells (CSCs) are a small subset of cells in tumors that exhibit self-renewal and differentiation properties. CSCs play a vital role in tumor formation, progression, relapse, and therapeutic resistance. B7-H3, an immunoregulatory protein, has many protumor functions. However, little is known about the mechanism underlying the role of B7-H3 in regulating gastric cancer (GC) stemness. Our study aimed to explore the impacts of B7-H3 on GC stemness and its underlying mechanism. METHODS: GC stemness influenced by B7-H3 was detected both in vitro and in vivo . The expression of stemness-related markers was examined by reverse transcription quantitative polymerase chain reaction, Western blotting, and flow cytometry. Sphere formation assay was used to detect the sphere-forming ability. The underlying regulatory mechanism of B7-H3 on the stemness of GC was investigated by mass spectrometry and subsequent validation experiments. The signaling pathway (Protein kinase B [Akt]/Nuclear factor erythroid 2-related factor 2 [Nrf2] pathway) of B7-H3 on the regulation of glutathione (GSH) metabolism was examined by Western blotting assay. Multi-color immunohistochemistry (mIHC) was used to detect the expression of B7-H3, cluster of differentiation 44 (CD44), and Nrf2 on human GC tissues. Student's t -test was used to compare the difference between two groups. Pearson correlation analysis was used to analyze the relationship between two molecules. The Kaplan-Meier method was used for survival analysis. RESULTS: B7-H3 knockdown suppressed the stemness of GC cells both in vitro and in vivo . Mass spectrometric analysis showed the downregulation of GSH metabolism in short hairpin B7-H3 GC cells, which was further confirmed by the experimental results. Meanwhile, stemness characteristics in B7-H3 overexpressing cells were suppressed after the inhibition of GSH metabolism. Furthermore, Western blotting suggested that B7-H3-induced activation of GSH metabolism occurred through the AKT/Nrf2 pathway, and inhibition of AKT signaling pathway could suppress not only GSH metabolism but also GC stemness. mIHC showed that B7-H3 was highly expressed in GC tissues and was positively correlated with the expression of CD44 and Nrf2. Importantly, GC patients with high expression of B7-H3, CD44, and Nrf2 had worse prognosis ( P = 0.02). CONCLUSIONS B7-H3 has a regulatory effect on GC stemness and the regulatory effect is achieved through the AKT/Nrf2/GSH pathway. Inhibiting B7-H3 expression may be a new therapeutic strategy against GC.
Humans ; Cell Line, Tumor ; Neoplasm Recurrence, Local ; NF-E2-Related Factor 2/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Signal Transduction ; Stomach Neoplasms

Objective:To automatically synthesize Al 18F-1, 4, 7-triazacyclononane-1, 4, 7-triacetic acid (NOTA)-fibroblast activation protein inhibitor (FAPI)-04, perform PET/CT imaging in vivo, and evaluate its diagnostic efficacy on tumors. Methods:Al 18F-NOTA-FAPI-04 was produced in All-in-one automatic synthesis module and its quality control was conducted by high performance liquid chromatography (HPLC) equipped with a radioactive detector. Al 18F-NOTA-FAPI-04 PET/CT imaging was performed in normal BALB/c mice ( n=3) and 4T1 breast cancer models ( n=3) to determine its biodistribution. Then Al 18F-NOTA-FAPI-04 and 18F-FDG PET/CT imaging were performed in a hepatocellular carcinoma patient (male, 51 years old). Results:The synthesis time of Al 18F-NOTA-FAPI-04 was about 35 min, and the radiochemical yield was (25.2±1.9)% (attenuation correction, n=3). The product was colorless transparent solution with pH value of 7.0-7.5, and the specific activity was (46.11±3.07) GBq/μmol (attenuation correction, n=3). The radiochemical purity was above 99.0% and was still above 98.0% at room temperature after 6 h. PET/CT imaging in mice showed that physiological uptake of Al 18F-NOTA-FAPI-04 was mainly in biliary system and bladder, and Al 18F-NOTA-FAPI-04 highly concentrated in tumor xenografts. PET/CT imaging in the patient showed that Al 18F-NOTA-FAPI-04 obtained high tumor background ratio (TBR) values of 4.1, 8.9, 5.4, 4.8, 2.2 in parasternal lymph nodes, anterior diaphragmatic lymph nodes, hilar lymph nodes, pancreaticoduodenal ligament lymph nodes, abdominal aortic lymph nodes, respectively, while TBR values were 1.0, 2.8, 5.0, 2.1, 1.1 by 18F-FDG. Conclusions:Al 18F-NOTA-FAPI-04 can be synthesized with short time, high radiochemical yield and good stability using All-in-one module. Al 18F-NOTA-FAPI-04 PET/CT imaging has high contrast and excellent diagnostic efficacy on tumors.

TCP (teosinte branched1/cincinnata/proliferating cell factor) is a group of plant-specific transcription factors that play important roles in plant growth and development. To date, there are no report about TCP transcription factors in eggplant (Solanum melongena L). In this study, twenty-nine eggplant TCP (SmTCP) family genes distributed on 11 chromosomes were identified from the genome database of eggplant using bioinformatics methods. The results showed that all members of the family contained sequences encoding TCP conserved domains with length of amino acids ranging from 201 to 538 and exon numbers of 1 or 2. Subcellular localization revealed that three SmTCP proteins (SmTCP02/03/21) were located in the cytoplasm and the other SmTCP proteins were located in the nucleus. The 29 TCP transcription factors were divided into ClassⅠ (PCF) and ClassⅡ (CIN and CYC/TB1) by phylogenetic tree and sequence analysis. Collinearity analysis showed that 17 pairs (21) of SmTCP genes had collinearity, and these collinearity genes belonged to segmental duplication. Analysis of gene expression patterns showed that all 29 members of SmTCP gene family were expressed in 15 tissues or organs, but the expression patterns were different. Among them, four gene (SmTCP18/19/20/25) of CIN subfamily were highly expressed in leaves at different growth stages. Analysis of cis-acting elements in the promoter region of SmTCP showed that there were four types of cis-acting elements, which were light response related cis-acting elements, growth and development related cis-acting elements, hormone response related cis-acting elements and stress related cis-acting elements. In summary, the molecular basis of SmTCP genes in eggplant and the influence of TCP gene on the growth and development of eggplant provided a theoretical basis for molecular breeding of eggplant.
Gene Expression Regulation, Plant ; Phylogeny ; Plant Proteins/metabolism* ; Solanum melongena/metabolism* ; Transcription Factors/metabolism*