Regulatory effect and mechanism of macrophage polarization in liver fibrosis / 临床肝胆病杂志

Liver fibrosis is the healing reaction of chronic liver injury caused by various factors such as viral infection， alcohol， and chemical substances and is a key link in the progression of chronic liver diseases to liver cirrhosis and liver cancer. Liver macrophages are considered important mediators of liver injury and repair， and the polarization trend of macrophages has a bidirectional regulatory effect on liver fibrosis. This article reviews the role of different phenotypes of liver macrophages in the development and progression of liver fibrosis， in order to provide new ideas for the prevention and treatment of fibrosis.

The Catalytic Mechanism and Activity Modulation of Manganese Superoxide Dismutase / 生物化学与生物物理进展

Manganese superoxide dismutase catalyzes the dismutation of two molecules of superoxide radicals to one molecule of oxygen and one molecule of hydrogen peroxide. The oxidation of superoxide anion to oxygen by Mn3+SOD proceeds at a rate close to diffusion. The reduction of superoxide anion to hydrogen peroxide by Mn2+SOD can be progressed parallelly in either a fast or a slow cycle pathway. In the slow cycle pathway, Mn2+SOD forms a product inhibitory complex with superoxide anion, which is protonated and then slowly releases hydrogen peroxide out. In the fast cycle pathway, superoxide anion is directly converted into product hydrogen peroxide by Mn2+SOD, which facilitates the revival and turnover of the enzyme. We proposed for the first time that temperature is a key factor that regulates MnSOD into the slow- or fast-cycle catalytic pathway. Normally, the Mn2+ rest in the pent-coordinated state with four amino acid residues (His26, His74, His163 and Asp159) and one water (WAT1) in the active center of MnSOD. The sixth coordinate position on Mn (orange arrow) is open for water (WAT2, green) or O2• to coordinate. With the cold contraction in the active site as temperature decreases, WAT2 is closer to Mn, which may spatially interfere with the entrance of O2• into the inner sphere, and avoid O2•/Mn2+ coordination to reduce product inhibition. Low temperature compels the reaction into the faster outer sphere pathway, resulting in a higher gating ratio for the fast-cycle pathway. As the temperature increases in the physiological temperature range, the slow cycle becomes the mainstream of the whole catalytic reaction, so the increasing temperature in the physiological range inhibits the activity of the enzyme. The biphasic enzymatic kinetic properties of manganese superoxide dismutase can be rationalized by a temperature-dependent coordination model of the conserved active center of the enzyme. When the temperature decreases, a water molecule (or OH-) is close to or even coordinates Mn, which can interfere with the formation of product inhibition. So, the enzymatic reaction occurs mainly in the fast cycle pathway at a lower temperature. Finally, we describe the several chemical modifications of the enzyme, indicating that manganese superoxide dismutase can be rapidly regulated in many patterns (allosteric regulation and chemical modification). These regulatory modulations can rapidly and directly change the activation of the enzyme, and then regulate the balance and fluxes of superoxide anion and hydrogen peroxide in cells. We try to provide a new theory to reveal the physiological role of manganese superoxide dismutase and reactive oxygen species.

Mechanism of action of traditional Chinese medicine in treatment of nonalcoholic fatty liver disease based on intestinal microecology / 临床肝胆病杂志

Nonalcoholic fatty liver disease （NAFLD） is a multisystem disease associated with obesity， insulin resistance， and dyslipidemia and has a complex pathogenesis. Studies have shown that gut microbiota dysbiosis is closely associated with the onset of NAFLD， and traditional Chinese medicine treatment can improve the laboratory markers and clinical symptoms of NAFLD patients by regulating intestinal microbiota and its metabolites. This article elaborates on the association between NAFLD and gut microbiota， the involvement of gut microbiota dysbiosis in the pathogenesis of NAFLD， and the possible mechanism of traditional Chinese medicine treatment in improving NAFLD from the perspective of gut microbiota， in order to provide new ideas for the treatment of NAFLD.

Characteristics of anterior segment structure in first-degree relatives of patients with primary angle-closure glaucoma / 国际眼科杂志(Guoji Yanke Zazhi)

AIM: To investigate the characteristics of anterior segment structure in first-degree relatives of patients with primary angle-closure glaucoma(PACG).METHODS: A total of 48 first-degree relatives of PACG patients aged 40-60 who were treated in the Affiliated Eye Hospital of Nanchang University from September 2020 to October 2022 were selected as the observation group. Additionally, 40 cases(40 eyes)of healthy individuals without glaucoma and family history of glaucoma at the same age group were collected as the control group. They were divided into younger group(40-49 years old)and elder group(50-60 years old). All subjects were examined with ultrasound biomicroscopy(UBM)and were measured using camera measure software. The parameters mainly included anterior chamber depth(ACD), anterior chamber area(ACA), anterior chamber width(ACW), anterior segment depth(ASD), angle open distance(AOD500), trabecular iris angle(TIA), trabecular iris area(TISA500), lens vault(LV), iris curve(IC), iris thickness(IT500), scleral ciliary process angle(SCPA), and iris ciliary process distance(ICPD).RESULTS: ACD, ACA, AOD500, TISA500 and TIA in the observation group were lower than those of the control group, and LV and IC were higher than those of the control group(all P<0.05). ACD, ACA, AOD500, TISA500, and TIA of the elder group were lower than those in the age-matched control group, while LV and IC were larger than those of the age-matched control group(all P<0.05). ACD, AOD500, TISA500, and TIA of the younger observation group were smaller than those of the age-matched control group, but LV and IC were significantly larger than those of the age-matched control group(all P<0.05). ACD, ACA, AOD500, TISA500 and TIA of the elder observation group were significantly lower than those of the younger observation group, and LV and IC were significantly larger than those of the younger observation group(all P<0.05). There was a difference in the distribution of ACD between the observation group and the control group(P<0.05), and the proportion of moderate to severe shallow anterior chambers was 10 times that of the control group. Correlation analysis showed that TISA500 was positively correlated with ACD and ACA, and negatively correlated with LV and IC, and TISA500 was mainly influenced by LV. IC had a positive correlation with LV and a negative correlation with ACD and ACA.CONCLUSION: First-degree relatives of PACG with normal axial length have a high risk of angle closure. The anterior segment structures of first-degree relatives of PACG are more crowded than normal individuals, and the lens forward shift may be the initial influencing factor for narrow angle.

Research progress of long-term efficacy after implantation of implantable collamer lens V4c / 国际眼科杂志(Guoji Yanke Zazhi)

With the rapid development of science and technology and the wide application of electronic products, the number of patients with high myopia is gradually increasing. Meanwhile, owing to the continuous optimization of surgical skils and the continuous advancement in materials of posterior chamber intraocular lens and manufacturing processes, implantable collamer lens(ICL)V4c implantation has gradually become one of the main surgeries for the treatment of high myopia. In the rapid era of social information, people pay more attention to the long-term efficacy after ICL V4c implantation, they not only want clear vision, but also the pursuit of visual comfort and durability. Therefore, this paper will specifically discuss the research progress of the post-implantation efficacy of ICL V4c with at least 2 a of follow-up observation within 3 a, aiming to review the latest research progress on the long-term efficacy of ICL V4c implantation from the three dimensions of visual quality, safety, efficacy and stability and possible surgical complications after ICL V4c implantation.

Effects of Jiawei Jingqin Decoction （加味荆芩汤） on Inflammatory and Immune Responses in Rosacea Model Mice / 中医杂志

ObjectiveTo investigate the potential mechanisms of Jiawei Jingqin Decoction （加味荆芩汤） in the treatment of rosacea. MethodsFifty 8-week-old female BALB/c mice were randomly divided into normal control group， model group， and Jiawei Jingqin Decoction low， medium， and high-dose groups， with 10 mice in each group. Except for the normal control group， mice in the other groups were injected with 40μl of antimicrobial peptide LL-37 at a concentration of 320 μmol/L on the back， repeated once every 12 hours for a total of 4 injections， to induce the rosacea mouse model. The mice in the normal control group were injected with 40 μl of PBS solution at the same time. After successful modeling， the mice in the Jiawei Jingqin Decoction low， medium， and high-dose groups were orally administered Jiawei Jingqin Decoction at doses of 4.35， 8.71， and 17.42 g/（kg·d） respectively， while the mice in the normal control group and the model group were orally administered 20 ml/（kg·d） of normal saline. All groups were treated once daily for 5 days. The changes in skin lesions were observed， and the erythema area was measured and scored. Skin tissue at the injection site was collected for histopathological examination using HE staining， and the number of mast cells was detected using toluidine blue staining. The levels of interleukin-6 （IL-6）， interleukin-1β （IL-1β）， and tumor necrosis factor-alpha （TNF-α） in the skin lesion tissues were measured using the ELISA method. The mRNA expression levels of key factors in the innate immune response pathway of rosacea disease mechanism， including Toll-like receptor 2 （TLR2）， downstream molecules serine protease kallikrein 5 （KLK5） and matrix metalloproteinase 9 （MMP-9）， as well as related inflammatory factors （IL-1β， IL-6， TNF-α）， and adaptive immune CD4+ T cell-related factors interferon-gamma （INF-γ） mRNA were detected using RT-qPCR. Immunohistochemical staining was performed to detect the protein expression of KLK5， MMP-9， and the number of CD4+ T-positive cells. Western blot analysis was used to determine the protein expression levels of CD4+ T cell-related factors including IFN-γ， CC chemokine receptor 5 （CCR5）， signal transducer and activator of transcription 1 （STAT1）， signal transducer and activator of transcription 3 （STAT3）. ResultsThe skin at the injection site on the back of mice in the normal control group appeared normal without any skin lesions or erythema， and histopathological examination showed no infiltration of inflammatory cells. The model group had significantly higher erythema scores and larger erythema areas compared to the normal control group （P＜0.05）， and histopathological examination revealed a significant infiltration of inflammatory cells， with some signs of deep connective tissue damage. Compared to the model group， the Jiawei Jingqin Decoction medium and high-dose groups showed a significant decrease in erythema scores and erythema areas （P＜0.05）， as well as a reduction in inflammatory exudates and inflammatory cell infiltration. However， the Jiawei Jingqin Decoction low-dose group did not show significant difference （P＞0.05）， but there was a slight reduction in inflammatory cell infiltration compared to the model group. When compared to the normal control group， the rosacea skin tissues of the model group showed an increase in the number of mast cells， levels of IL-1β， IL-6， TNF-α， mRNA expression of IL-1β， IL-6， TNF-α， TLR2， INF-γ， KLK5， MMP-9， protein expression of KLK5， MMP-9， and the number of CD4+ T-positive cells （P＜0.05）. Compared to the model group， the Jiawei Jingqin Decoction medium and high-dose groups showed a decrease in the number of mast cells， levels of IL-1β， mRNA expression of IL-1β， TNF-α， and the number of CD4+ T-positive cells. The Jiawei Jingqin Decoction high-dose group showed a decrease in IL-6， TNF-α levels， mRNA expression of IL-6， TLR2， INF-γ， MMP-9， protein expression of MMP-9， KLK5， and the number of CD4+ T-positive cells， as well as a decrease in IFN-γ and STAT1 protein expression （P＜0.05） compared to the Model group. ConclusionJiawei Jingqin Decoction has significant improvement effect on the skin symptoms of roseacne in a mouse model. Its mechanism might be related to regulating skin immune inflammatory reactions， thereby reducing the release of pathogenic factors and inflammatory factors.

Two-sample bidirectional Mendelian randomization for analyzing the causal effect between gastroesophageal reflux disease and migraine headaches / 西安交通大学学报(医学版)

【Objective】 To explore the causal association between the onset of gastroesophageal reflux disease (GERD) and migraine and to provide genetic evidence, a two-sample bidirectional Mendelian randomization (MR) method was used in this study. 【Methods】 Single nucleotide polymorphism (SNP) information for both samples was obtained from publicly available genome-wide association study (GWAS) databases, in which the appropriate SNPs were selected as instrumental variables, and then bidirectional MR analysis used five MR analysis methods including inverse variance weighting (IVW), MR-Egger regression, weighted median, weighted mode and simple mode methods, followed by sensitivity analysis. 【Results】 IVW showed positive results of forward MR analysis with GERD as exposure [OR=1.398 7, 95%CI (1.181 7-1.655 6), P=9.59×10-5] , while no positive significance of reverse MR analysis results with migraine as exposure (P>0.05). The same results were obtained in methods other than MR-Egger method. Meanwhile, none of the instrumental variables were found to be horizontally polytomous (P=0.92, P=0.64), and the results were robust after the leave-one-out method to exclude single SNPs. 【Conclusion】 There may be a unidirectional causal association between GERD and migraine, and GERD is a risk factor for migraine development.

Exploration and Practice of Basic Medical Laboratory Safety Management / 中山大学学报(医学科学版)

Scientific research laboratory is the base of scientific research and talent training in the university. During the construction and development of “world-class universities and first-class disciplines”， laboratory safety management has been facing urgent challenges. Based on the laboratory management methods of Zhongshan School of Medicine of Sun Yat-sen University， we analyzed the classification and characteristics of discipline laboratories， laboratory safety access training and assessment， and summarized the actual situation and construction of safety management system for basic medical laboratories. This paper expounded on laboratory management， such as management system construction， safety management， safety inspection and supervision， safety awareness of all staff and system execution， so as to provide a feasible and creative scientific guidance and basis for university laboratory biosafety management， and establish a healthy and safe experimental environment to ensure the safety of laboratory work.

TSHR Variant Screening and Phenotype Analysis in 367 Chinese Patients With Congenital Hypothyroidism

Background@#Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. @*Methods@#In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. @*Results@#Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. @*Conclusions@#We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Clinical and Structural Characteristics of NEU1 Variants Causing Sialidosis Type 1

Objective@#Sialidosis type 2 has variants that are both catalytically inactive (severe), while sialidosis type 1 has at least one catalytically active (mild) variant. This study aimed to discuss the structural changes associated with these variants in a newly reported family carrying N-acetyl-α-neuraminidase-1 (NEU1) variants and explore the clinical characteristics of different combinations of variants in sialidosis type 1. @*Methods@#First, whole-exome sequencing and detailed clinical examinations were performed on the family. Second, structural analyses, including assessments of energy, flexibility and polar contacts, were conducted for several NEU1 variants, and a sialidase activity assay was performed. Third, previous NEU1 variants were systematically reviewed, and the clinical characteristics of patients in the severe-mild and mild-mild groups with sialidosis type 1 were analyzed. @*Results@#We report a novel family with sialidosis type 1 and the compound heterozygous variants S182G and V143E. The newly identified V143E variant was predicted to be a mild variant through structural analysis and was confirmed by a sialidase activity assay. Cherry-red spots were more prevalent in the severe-mild group, and ataxia was more common in the mild-mild group. Impaired cognition was found only in the severe-mild group. Moreover, patients with cherry-red spots and abnormal electroencephalographies and visual evoked potentials had a relatively early age of onset, whereas patients with myoclonus had a late onset. @*Conclusion@#Changes in flexibility and local polar contacts may be indicators of NEU1 pathogenicity. Sialidosis type 1 can be divided into two subgroups according to the variant combinations, and patients with these two subtypes have different clinical characteristics.

Spatial transcriptomics reveals that metabolic characteristics define the tumor immunosuppression microenvironment via iCAF transformation in oral squamous cell carcinoma / 国际口腔科学杂志·英文版

Tumor progression is closely related to tumor tissue metabolism and reshaping of the microenvironment. Oral squamous cell carcinoma (OSCC), a representative hypoxic tumor, has a heterogeneous internal metabolic environment. To clarify the relationship between different metabolic regions and the tumor immune microenvironment (TME) in OSCC, Single cell (SC) and spatial transcriptomics (ST) sequencing of OSCC tissues were performed. The proportion of TME in the ST data was obtained through SPOTlight deconvolution using SC and GSE103322 data. The metabolic activity of each spot was calculated using scMetabolism, and k-means clustering was used to classify all spots into hyper-, normal-, or hypometabolic regions. CD4T cell infiltration and TGF-β expression is higher in the hypermetabolic regions than in the others. Through CellPhoneDB and NicheNet cell-cell communication analysis, it was found that in the hypermetabolic region, fibroblasts can utilize the lactate produced by glycolysis of epithelial cells to transform into inflammatory cancer-associated fibroblasts (iCAFs), and the increased expression of HIF1A in iCAFs promotes the transcriptional expression of CXCL12. The secretion of CXCL12 recruits regulatory T cells (Tregs), leading to Treg infiltration and increased TGF-β secretion in the microenvironment and promotes the formation of a tumor immunosuppressive microenvironment. This study delineates the coordinate work axis of epithelial cells-iCAFs-Tregs in OSCC using SC, ST and TCGA bulk data, and highlights potential targets for therapy.

Survey on the recognition of the post competency index system among Chinese rural general practice assistant physicians and analysis of influencing foctors / 中华全科医师杂志

Objective:To investigate the recognition of the post competency index system among rural general practice assistant physicians and its influencing factors.Methods:This study was a cross-sectional survey. A questionnaire survey on the recognition of post competency index system was conducted from October 2020 to September 2021 among rural general practice assistant physicians from 10 provinces/municipalities selected by stratified cluster sampling method. The recognition of rural general practice assistant physicians at all levels of indexs and the factors influencing recognition were analyzed.Results:A total of 1 123 questionnaires were distributed and 1 024 valid ones were collected with a recovery rate of 91.18%. Of the 1 024 respondents, 529 were male(51.7%) and 435 were aged 40-49 years(42.5%), which was the highest proportion by age group. The average overall recognition score of the index system was 4.41, and the scores of the primary indexes were 4.32-4.45. Three primary indexes had the highest recognition scores: professional competence, basic health care services, and interpersonal communication and teamwork. The recognition scores on the second level index were 4.18-4.61, and the proportion of recognition scores greater than 4 was over 80%. There were significant differences in the recognition scores of the index system among assistant physicians with different working years, educational background, professional title and work unit ( F/H=6.41, 14.83, 12.45, 7.53, P<0.01). Educational background(associate degree: B=0.091, P=0.015; bachelor degree and above: B=0.196, P<0.001) and professional title(intermediate professional title and above: B=-0.234, P<0.001) were the independent factors influencing the recognition degree of the index system for rural general practice assistant physicians. Conclusions:The post competency index system is generally recognized by rural general practice assistant physician, and academic qualifications and professional title status may influence its recognition.

Application feasibility of the post competency index system of rural general practice assistant physicians / 中华全科医师杂志

Objective:To evaluate the application feasibility of the post competency index system of rural general practice assistant physicians, and to analyze and compare the post competency of rural general practice assistant physicians with different characteristics through a survey among rural general practice assistant physicians in China.Methods:This study was a cross-sectional study. A questionnaire survey was conducted among rural general practice assistant physicians in 10 provinces/municipalities selected by stratified cluster sampling method from October 2020 to September 2021. The post competency scores were self-evaluated based on the post competency index system of rural general practice assistant physicians. The results of the survey were analyzed and the application feasibility of the index system was evaluated.Results:A total of 1 123 questionnaires were distributed and 1 024 valid questionnaires were returned with a recovery rate of 91.2%. Of the 1 024 respondents, 529 were males (51.7%), 435 were aged 40-49 years (42.5%), 434 had a secondary school education or less (42.4%), and 531 were junior practitioners (51.9%). The Cronbach′s α coefficient of the overall questionnaire was 0.987, and the Cronbach′s α coefficient of the first level index ranged from 0.897 to 0.974. The cumulative variance contribution rate of exploratory factor analysis was 72.012%. The confirmatory factor analysis showed χ2/ df=3.926, RMSEA=0.076, CFI=0.858, IFI=0.859, indicating that the model fit was basically good. The average self-evaluation scores of the first level index ranged from 3.95 to 4.25, and the average self-evaluation scores of the second level index ranged from 3.74 to 4.36. There were significant differences in self-evaluation scores of post competency among rural general practice assistant physicians with different working years, professional titles, working units and economic regions( F=4.67, 10.54, 22.16 and 20.90,all P<0.05). People with low self-evaluation scores of post competency had the following characteristics: working 10-19 years, intermediate or above titles, working in community health service centers, located in the eastern region.People with high self-evaluation scores of post competency had the following characteristics: primary professional title, working in the village clinic. Conclusion:The competency index system of rural general practice assistant physicians has good application feasibility,and it can be used to evaluate post competency for the education and training of rural general practice assistant physicians.

Exploration of surgical treatment indications for invasive pulmonary aspergillosis and mucormycosis in children / 中华胸心血管外科杂志

Objective:To review and analyze clinical data of patients with invasive pulmonary aspergillosis and mucormycosis, and to explore the surgical indication.Methods:Clinical data of 10 patients with invasive pulmonary aspergillosis and mucormycosis were analyzed retrospectively from March 2018 to November 2022 in our hospital, Department of Thoracic Surgery.Results:The age of children varied from 2.58 years old to 16.00 years old and 6 children were males while 4 females. Five patients suffer from invasive pulmonary aspergillosis. Five patients suffer from invasive pulmonary mucormycosis. The operative indication of 7 patients was the risk of massive bleeding in the airway. The surgical indication for two patients is to control infection and continue treating malignant tumors. One patient chose surgical treatment because the infection could not be cured after long-term antifungal treatment but the focus was limited. Two patients died of sudden acute hemoptysis before operation, the prognosis of 8 patients undergoing surgical treatment was good.Conclusion:The lethal rate of invasive pulmonary aspergillosis and mucormycosis is very high. Antifungal drug treatment combined with timely surgical treatment can save patients lives.

Research progress on the interaction between macro-phages and fibroblasts in ARDS pulmonary fibrosis / 实用医学杂志

Acute respimtory distress syndrome(ARDS)is an acute diffuse inflammatory lung injury caused by various internal and external lung injury factors.It has complex pathogenesis,rapid onset and high mortality,which seriously endangers human life and health.Pulmonary fibrosis is one of the important pathologic processes of ARDS occurrence and development,and it is also an important cause of death in ARDS patients.To a certain extent,the severity of pulmonary fibrosis in ARDS is determined by the dynamic balance of macrophage-fibroblast interactions.Therefore,this article aims to review the interaction mechanism of macrophage-fibroblasts in the pro-cess of ARDS pulmonary fibrosis,and provide new methods and ideas for the diagnosis and treatment of ARDS pul-monary fibrosis.

Safety risk assessment of in vitro heart in antitumor drug development / 中国组织工程研究

BACKGROUND:Tyrosine kinase inhibitors,as well as other types of small-molecule cancer drugs,can cause severe cardiotoxicity. OBJECTIVE:To perform a heart safety re-evaluation by observing the effects of antitumor drugs on isolated heart electrocardiograph,cardiac action potential and associated ion channels and cytotoxicity. METHODS:Extracorporeal cardiac perfusion was given to the isolated rabbit heart using Langendorff perfusion:Sunitinib(0.3,3,10 μmol/L),Crizotinib(0.3,1,3 μmol/L),and Doxorubicin(1,30 μmol/L)were perfused sequentially for 120 minutes to record electrocardiograph and left ventricular pressure.A blank control group was set for comparison.Manual patch clamp was used to record the effects of Crizotinib,Sunitinib,Doxorubicin on hERG,Cav1.2,Nav1.5 channel currents and action potential in human induced pluripotent stem cell derived cardiomyocytes.Adenosine triphosphate level in human induced pluripotent stem cell derived cardiomyocytes was detected by CellTiter-Glo luminescent cell viability assay. RESULTS AND CONCLUSION:Isolated rabbit heart using Langendorff perfusion:Compared with the blank ontrol group,Sunitinib and Crizotinib at≥3 μmol/L decreased heart rate(P<0.01)and prolonged QT/QTc interval(P<0.01),and reduced left ventricular pressure to different extents.Manual patch clamp recording:Compared with the blank control group,Sunitinib and Crizotinib at 3 μmol/L inhibited the activities of hERG,Nav1.5 and Cav1.2 channels and significantly prolonged the duration of action potential(P<0.01).According to the analysis of the test article,the difference between the labeled concentration and the measured concentration of the recovered solution was not significant.Cell viability assays:Compared with the blank control group,adenosine triphosphate content in human induced pluripotent stem cell derived cardiomyocytes significantly decreased after treatment with Sunitinib(IC50=4.64 μmol/L),Doxorubicin(IC50=4.21 μmol/L)and Crizotinib(IC50=2.87 μmol/L),indicating that cell viability significantly decreased(P<0.01).To conclude,this study successfully established an early cardiac safety evaluation method for antitumor drugs,which provides good support and help for the subsequent development of antitumor drugs.

High-quality development driven by the Party building"115 project" / 现代医院

The Party committee of Ordos Central Hospital has effectively utilized its leadershipby steering direction,over-seeing the broader context,making strategic decisions,fostering reform,and ensuring execution.In alignment with the hospital's specific context,the innovative"115 Project"for Party building has been implemented.This initiative reaffirms the comprehen-sive leadership of the Party,aiming to build a high-quality regional medical center.The execution of five major projects has been instrumental in driving the high-quality development of the hospital,guided by Party building.Focusing on the clinical demands of major diseases and aiming to substantially enhance the capacity for emergency and critical care management,the hospital Party committee have made concerted efforts to bolster the hospital's personnel,key disciplines,scientific research,medical quality and safety,and information systems.These efforts have culminated notable advancements in the hospital's developments.

Construction and Application of Characteristic Intelligent Pharmacy Service Platform in Ethnic Areas / 医药导报

Objective To construct a characteristic intelligent pharmacy service platform in ethnic areas,to optimize pharmacist resources,and to improve the quality of pharmacy services.Methods Taking Liangshan Yi autonomous prefecture of Sichuan Province as an example,the pharmaceutical care software was improved and innovated by adding various forms of medication guidance in Yi language.Results The platform was initially operated and 150 Yi language medication guidance was established.The platform pushes 461 medication guidance content daily,including 276 Yi and Han medication guidance.Patients can receive them through WeChat's official account or short message service(SMS),and the medication guidance rate has been significantly improved.Conclusion The characteristic pharmaceutical service platform in the Yi region can substantially improve the quality of pharmaceutical service,meet the individual demands of Yi patients and provide new ideas and methods for pharmaceutical service in other ethnic areas.

Association of individual and area level socioeconomic status with depressive symptoms for older adults—evidence from China Health and Retirement Longitudinal Study / 中华健康管理学杂志

Objective:To analyze the impact of individual and regional level socioeconomic characteristics on the mental health of middle-aged and older adults based on data from the China Health and Retirement Longitudinal Study.Methods:This study was a cohort study. Using the data from the China Health and Retirement Longitudinal Study, subjects without depression were screened in the baseline survey, the depression status of the selected subjects was tracked and observed for seven years. Descriptive statistical analysis, multivariate logistic analysis, joint analysis were used to analyze the influence of factors such as gender, personal annual income, education level, urban and rural areas, and eastern, central, and western regions on the risk of depression among middle-aged and elderly people.Results:The 7-year follow-up results showed that the prevalence of depression symptoms in the study subjects was 42.24%; compared with men, women′s risk of developing depression symptoms was significantly increased ( OR=1.782); compared with junior college education and above, middle school (including technical secondary school), primary and lower education levels had a significantly increased risk of developing depression symptoms ( OR=1.476, 2.134); compared with annual income of more than 10 000 yuan, subjects with an annual income of 10 000 yuan or below had significantly increased risk of developing depression symptoms ( OR=1.251). At the same time, compared with the urban area, the risk of developing depression symptoms was significantly increased in the rural areas ( OR=1.389). Compared with the eastern area, the risk of developing depression symptoms was significantly higher in the central and western areas ( OR=1.342, 1.730). The joint analysis results showed that compared with high-income and high-education men, low-income low-education women, high-income low-education women, low-income middle-education women, and high-income middle-education women were at the top four odd ratios for developing depression symptoms ( OR=5.050, 3.662, 3.047, 2.641); compared with men in eastern cities, rural women in the west, rural women in the middle, women in the western cities, and rural women in the east ranked the first four odd ratios for developing depression symptoms ( OR=4.286, 3.216, 2.642, 2.158). Conclusion:Socioeconomic factors at the individual and regional levels have a significant impact on the risk of developing depressive symptoms in middle-aged and older adults, and mental health management of middle-aged and older adults with low socioeconomic status should be strengthened.

Effects of RNA demethylase FTO inhibitor on function ofglioblastoma stem cells / 中国药理学通报

Aim To investigate the effect of m6A demethylase FTO inhibitor(FB23-2)on human glioblastoma stem cell activity. Methods The effects of FB23-2 and Temozolomide on GSC were detected by CCK-8 assay and neurosphere formation assay. The effect of FB23-2 on self-renewal of GSC was detected by limited dilution assay in vitro. The effect of FB23-2 on the proliferation of GSC was detected by EdU method. The effect of FB23-2 on apoptosis of glioblastoma stem cells was detected by flow cytometry. Results CCK-8 assay showed that FB23-2 could effectively inhibit the cell viability of GSC with IC50 values of 7.11 μmol·L-1 and 4.63 μmol·L-1,respectively. The size and number of GSC neural sphere in FB23-2 treatment group were significantly reduced compared with control group. In vitro limited dilution experiment showed that FB23-2 effectively inhibited the self-renewal ability of GSC. EdU incorporation experiment showed that compared with the control group,the treatment group decreased to(70.59±13.74)% and(50.33±4.53)%,respectively. The apoptotic rates of the treated group were(12.16±1.90)% and(16.77±1.17)% by flow cytometry. Conclusions FTO inhibitor FB23-2 can effectively inhibit GSC growth,self-renewal and the formation of neural sphere. In addition,FB23-2 can inhibit the proliferation of GSC and induce its apoptosis.