Objective To examine the role and mechanism of clopidogrel in the development of salt-sensitive hypertension.Methods 8-week-old Dahl salt-sensitive(Dahl SS)rats and control salt-resistant(SS13BN)rats were divided randomly into six groups and fed for 8 weeks with normal salt(0.4％NaCl,NS),high salt(8％NaCl,HS),or high salt combined with clopidogrel gavage(8％NaCl+10 mg/(kg·d))clopidogrel,HS+CLO).Arterial systolic blood pressure was measured continuously over 8 weeks by the tail-cuff method,and systolic blood pressure was measured by carotid cannulation after 8 weeks(56 days).Renal histopathology was observed by hematoxylin and eosin staining,and renal inflammatory cell infiltration was detected by immunohistochemistry.Peripheral blood platelet activation and platelet-leukocyte aggregation were analyzed by flow cytometry,and the renal inflammation-related proteins tumor necrosis factor-α,interleukin(IL)-1β,IL-6,and key proteins in the p38MAPK/nuclear factor(NF)-κB signaling pathway were detected by Western blot.Results Compared with the NS group,Dahl SS HS rats had significantly increased blood pressure(P＜0.05),aggravated renal tissue damage,increased inflammatory cell infiltration,increased expression of inflammatory cytokines(P＜0.05),elevated peripheral blood platelet activation(P＜0.05)and platelet-leukocyte aggregation(P＜0.05),and increased expression of p38MAPK/NF-κB signaling pathway proteins(P＜0.05).Clopidogrel effectively alleviated these phenotypes induced by high salt in Dahl SS rats.Conclusions Clopidogrel alleviated high-salt-induced salt-sensitive hypertension and decreased renal inflammatory responses and dysfunction in Dahl SS rats by inhibiting platelet activation and the p38MAPK/NF-κB signaling pathway.

Objective:To understand the difficulties in the development of community-based integrated general and specialized medical care in Shanghai, and to provide a scientific basis for further proposing strategies to promote the development of integrated general and specialized medical care.Methods:A mixed-methods study was used in this study. In the first stage, a quantitative method was used. From August to December 2023, 30 community health centers (CHCs) were randomly selected from 239 CHCs in the city that provided integrated general specialist care. In each of these CHCs, a questionnaire was administered to a manager and a general practitioner involved in integrated care for specific diseases. The content of the questionnaire included general demographic information and questions related to the integration of general and specialized care, covering six aspects: community-specific disease diagnosis and treatment, examination items, drug configuration, patient sources, support from specialists, and referrals. In the second stage, a qualitative method was used. From January to February 2024, face-to-face semi-structured interviews were conducted with the managers and general practitioners of the CHCs who had completed the questionnaire survey in the previous stage, to further understand the reasons for the difficulties in integrating general and specialist care.Results:(1) Quantitative research: a total of 30 community health center managers and 30 general practitioners participated in the questionnaire survey. The survey found that the top four difficulties were: lack of technology for diagnosis and treatment of special diseases (49, 81.7%), shortage of clinical medical technical examination (36, 60.0%), and insufficient drug configuration (33, 55.0%) and few patients with special diseases in the community (33, 55.0%). (2) Qualitative research: 12 community health center managers and 10 general practitioners participated in the interviews. The interviews explained the difficulties identified in the research from different angles, such as "lack of support from higher-level medical institutions, lack of ancillary examinations and drugs, and a single form of cooperation between and lower-level medical institutions". At the same time, the interviewees mentioned the difficulty of "insufficient staff involved in community-based integrated care", which complemented the research.Conclusions:There are difficulties in many aspects of community-based comprehensive and specialized treatment, such as collaboration between hospitals and community health institutions, specialist and general practitioner resources, patient sources, specialized treatment-related examination items and drugs, which need to be solved in a variety of ways to further promote the development of community-based integration of general practice and specialty care.

Objective:To understand the difficulties in the development of community-based integrated general and specialized medical care in Shanghai, and to provide a scientific basis for further proposing strategies to promote the development of integrated general and specialized medical care.Methods:A mixed-methods study was used in this study. In the first stage, a quantitative method was used. From August to December 2023, 30 community health centers (CHCs) were randomly selected from 239 CHCs in the city that provided integrated general specialist care. In each of these CHCs, a questionnaire was administered to a manager and a general practitioner involved in integrated care for specific diseases. The content of the questionnaire included general demographic information and questions related to the integration of general and specialized care, covering six aspects: community-specific disease diagnosis and treatment, examination items, drug configuration, patient sources, support from specialists, and referrals. In the second stage, a qualitative method was used. From January to February 2024, face-to-face semi-structured interviews were conducted with the managers and general practitioners of the CHCs who had completed the questionnaire survey in the previous stage, to further understand the reasons for the difficulties in integrating general and specialist care.Results:(1) Quantitative research: a total of 30 community health center managers and 30 general practitioners participated in the questionnaire survey. The survey found that the top four difficulties were: lack of technology for diagnosis and treatment of special diseases (49, 81.7%), shortage of clinical medical technical examination (36, 60.0%), and insufficient drug configuration (33, 55.0%) and few patients with special diseases in the community (33, 55.0%). (2) Qualitative research: 12 community health center managers and 10 general practitioners participated in the interviews. The interviews explained the difficulties identified in the research from different angles, such as "lack of support from higher-level medical institutions, lack of ancillary examinations and drugs, and a single form of cooperation between and lower-level medical institutions". At the same time, the interviewees mentioned the difficulty of "insufficient staff involved in community-based integrated care", which complemented the research.Conclusions:There are difficulties in many aspects of community-based comprehensive and specialized treatment, such as collaboration between hospitals and community health institutions, specialist and general practitioner resources, patient sources, specialized treatment-related examination items and drugs, which need to be solved in a variety of ways to further promote the development of community-based integration of general practice and specialty care.

Objective To examine the role and mechanism of clopidogrel in the development of salt-sensitive hypertension.Methods 8-week-old Dahl salt-sensitive(Dahl SS)rats and control salt-resistant(SS13BN)rats were divided randomly into six groups and fed for 8 weeks with normal salt(0.4％NaCl,NS),high salt(8％NaCl,HS),or high salt combined with clopidogrel gavage(8％NaCl+10 mg/(kg·d))clopidogrel,HS+CLO).Arterial systolic blood pressure was measured continuously over 8 weeks by the tail-cuff method,and systolic blood pressure was measured by carotid cannulation after 8 weeks(56 days).Renal histopathology was observed by hematoxylin and eosin staining,and renal inflammatory cell infiltration was detected by immunohistochemistry.Peripheral blood platelet activation and platelet-leukocyte aggregation were analyzed by flow cytometry,and the renal inflammation-related proteins tumor necrosis factor-α,interleukin(IL)-1β,IL-6,and key proteins in the p38MAPK/nuclear factor(NF)-κB signaling pathway were detected by Western blot.Results Compared with the NS group,Dahl SS HS rats had significantly increased blood pressure(P＜0.05),aggravated renal tissue damage,increased inflammatory cell infiltration,increased expression of inflammatory cytokines(P＜0.05),elevated peripheral blood platelet activation(P＜0.05)and platelet-leukocyte aggregation(P＜0.05),and increased expression of p38MAPK/NF-κB signaling pathway proteins(P＜0.05).Clopidogrel effectively alleviated these phenotypes induced by high salt in Dahl SS rats.Conclusions Clopidogrel alleviated high-salt-induced salt-sensitive hypertension and decreased renal inflammatory responses and dysfunction in Dahl SS rats by inhibiting platelet activation and the p38MAPK/NF-κB signaling pathway.

Objective To investigate the efficacy of high-resolution computed tomography (HRCT)imaging radiomics for the classification and diagnosis of rheumatoid arthritis associated interstitial lung disease(RA-ILD).Methods A total of 261 patients diagnosed with RA-ILD admitted in our hospital from January 2019 to July 2023 were recruited in this study.There were 143 cases of usual interstitial pneumonia (UIP )and 118 cases of nonspecific interstitial pneumonia (NSIP).All the patients underwent HRCT.A U-net deep learning lung segmentation model was applied to obtain HRCT images for automatic lung segmentation,and 1688 imaging histologic features were extracted from each lung segmentation. Variance thresholding,univariate feature selection,and least absolute shrinkage and selection operator (LASSO ) were used for feature dimensionality reduction step by step,and various machine learning algorithms were conducted to construct the RA-ILD diagnostic histology model.The diagnostic value of each model was compared using receiver operating characteristic (ROC)curve and area under curve (AUC),and the accuracy,sensitivity and specificity of the models were evaluated.Results Feature screening finally identified 18 best features from the HRCT images of RA-ILD patients.Statistical difference was found in the distribution of Radiomics score (Radscore)between the UIP and NSIP patients in both the training and test sets (P<0.01 ).Among the 5 imaging histology models,the support vector machine (SVM)algorithm had an AUC value of 0.943 (95％CI:0.916～0.966),a sensitivity of 0.787 and a specificity of 0.912,respectively for the training set,and an AUC value of 0.909 (95％CI:0.849～0.969),a sensitivity of 0.625 and a specificity of 0.897,respectively for the testing set.Conclusion Our constructed RA-ILD classification and diagnosis model performs well,and the model based on SVM algorithm shows the best potential in classifying and diagnosing RA-ILD.

Humans ; Heparin/therapeutic use* ; Extracorporeal Membrane Oxygenation ; Respiratory System ; Respiratory Insufficiency

Humans ; Cardiovascular Diseases/chemically induced* ; East Asian People ; Risk Factors ; Heart Disease Risk Factors ; Lipids ; Anticholesteremic Agents/adverse effects* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Treatment Outcome

BACKGROUND: At present, more and more studies predict invasive adenocarcinoma (IAC) through three-dimensional features of pulmonary nodules, but few studies have confirmed that three-dimensional features have more advantages in diagnosing IAC than traditional two-dimensional features of pulmonary nodules. This study analyzed the differences of chest computed tomography (CT) features between IAC and minimally invasive adenocarcinoma (MIA) from three-dimensional and two-dimensional levels, and compared the ability of diagnosing IAC. The non-invasive adenocarcinoma group includes precursor glandular lesions (PGL) and minimally invasive adenocarcinoma (MIA). METHODS: The clinical data of 1,045 patients with ground glass opacity (GGO) from January to December 2019 were collected. Then the correlation between preoperative CT image characteristics and pathological results were analyzed retrospectively. The independent influencing factors for the identification of IAC were screened out according to two-dimensional and three-dimensional classification by multivariate Logistic regression and the cut-off point for the identification of IAC was found out through the receiver operating characteristic (ROC) curve. At last, the ability of diagnosing IAC was evaluated by Yoden index. RESULTS: The diameter of nodule, the diameter of solid component, the diameter of mediastinal window nodule in two-dimensional factors, and the volume of nodule, the volume of solid part and the average CT value in three-dimensional factors were independent risk factors for the diagnosis of IAC. These factors were arranged by Yoden index: solid partial volume (0.601)>nodule volume (0.536)>solid component diameter (0.525)>nodule diameter (0.518)>mediastinal window nodule diameter (0.488)>proportion of solid component volume (0.471)>1-tumor disappearance ratio (TDR) (0.468)>consolidation tumor ratio (CTR) (0.394)>average CT value (0.380). CONCLUSIONS The CT features of three-dimensional are better than two-dimensional in the diagnosis of IAC, and the size of solid components is better than the overall size of nodules.
Humans ; Lung Neoplasms/pathology* ; Retrospective Studies ; Neoplasm Invasiveness ; Multiple Pulmonary Nodules/diagnostic imaging* ; Adenocarcinoma/pathology*

Background The pathogenesis of beryllium-induced pulmonary fibrosis is unknown and there is no specific treatment for the disease as yet. MicroRNA (miRNA) may play a role in the process of beryllium-induced pulmonary fibrosis. Objective To construct a microRNA-21 (miR-21) interfering cell line, and to investigate the effect of miR-21 on beryllium sulfate (BeSO₄)-induced fibrosis in human lung adenocarcinoma alveolar basal epithelial cells (A549 cells) and its potential mechanism. Methods The miR-21 target genes were predicted by the online database miRBase and verified by experiments using dual luciferase reporter gene. After transfecting A549 with miR-21interference lentivirus, puromycin was used to select a stable cell line. An in vitro model of pulmonary fibrosis was established using BeSO₄ infecting A549 cells with a concentration of 10 μmol·L⁻¹ and an exposure time of 48 h. Then the treated cells were divided into control group, model group, miR-21 interference group, and miR-21 interference control group. Real-time fluorescent quantitative PCR (RT-qPCR) was used to detect the relative expression level of miR-21 gene. Western blotting was used to detect the relative expression levels of TGF-β1/Smads pathway related proteins [Smad2, Smad3, p-Smad2, p-Smad3, Smad7, and transforming growth factor-β1 (TGF-β1)], myofibrosis cell marker α-smooth muscle actin (α-SMA), andextracellular matrix collagen-I (COL-I) and collagen-Ⅲ (COL-Ⅲ). Results The miRBase predicted that miR-21 had a binding site with Smad7, and the results of the dual luciferase reporter gene experiment showed that the target gene of miR-21 was Smad7. The construction of miR-21 interfered with A549 cell line was successful. Compared with the control group, the relative expression of miR-21 gene in the model group increased by 97.57%; the relative expression of Smad7 protein in the model group decreased by 15.48%; the relative protein expression of Smad2, Smad3, p-Smad2, p-Smad3, TGF-β1, α-SMA, COL-I, and COL-Ⅲ increased by 13.55%, 35.72%, 18.35%, 35.75%, 25.52%, 31.58%, 24.61%, and 11.66% respectively (P<0.05). Compared with the interference control group, the miR-21 gene expression level in the interference group decreased by 28.96%; the relative expression of Smad7 protein increased by 19.07%; the relative protein expression of Smad2, Smad3, p-Smad2, p-Smad3, TGF-β1, α-SMA, COL-I, and COL-Ⅲ decreased by 8.01%, 19.95%, 14.56%, 19.37%, 11.95%, 10.96%, 18.81%, and 31.36% repectively (P<0.05). There was no statistically significant difference in the gene abd protein expression levels of each gene between the model group and the interference control group (P>0.05). Conclusion In an in vitro model of pulmonary fibrosis induced by beryllium compounds, miR-21 may promote fibrosis by targeting Smad7 to regulate the TGF-β1/Smad signaling pathway.

Diabetes mellitus is a metabolic disease characterized by hyperglycemia. It is found that the incidence and mortality of abdominal aortic aneurysm (AAA) in diabetes mellitus patients are lower than that in non-diabetes mellitus patients. This review will present the protective role of diabetes mellitus and its treatment on the aortic disease process, aiming to provide more support for the clinical treatment of AAA.