BACKGROUND: Chronic kidney disease (CKD) is associated with common pathophysiological processes, such as inflammation and fibrosis, in both the heart and the kidney. However, the underlying molecular mechanisms that drive these processes are not yet fully understood. Therefore, this study focused on the molecular mechanism of heart and kidney injury in CKD. METHODS: We generated an microRNA (miR)-26a knockout (KO) mouse model to investigate the role of miR-26a in angiotensin (Ang)-II-induced cardiac and renal injury. We performed Ang-II modeling in wild type (WT) mice and miR-26a KO mice, with six mice in each group. In addition, Ang-II-treated AC16 cells and HK2 cells were used as in vitro models of cardiac and renal injury in the context of CKD. Histological staining, immunohistochemistry, quantitative real-time polymerase chain reaction (PCR), and Western blotting were applied to study the regulation of miR-26a on Ang-II-induced cardiac and renal injury. Immunofluorescence reporter assays were used to detect downstream genes of miR-26a, and immunoprecipitation was employed to identify the interacting protein of LIM and senescent cell antigen-like domain 1 (LIMS1). We also used an adeno-associated virus (AAV) to supplement LIMS1 and explored the specific regulatory mechanism of miR-26a on Ang-II-induced cardiac and renal injury. Dunnett's multiple comparison and t -test were used to analyze the data. RESULTS: Compared with the control mice, miR-26a expression was significantly downregulated in both the kidney and the heart after Ang-II infusion. Our study identified LIMS1 as a novel target gene of miR-26a in both heart and kidney tissues. Downregulation of miR-26a activated the LIMS1/integrin-linked kinase (ILK) signaling pathway in the heart and kidney, which represents a common molecular mechanism underlying inflammation and fibrosis in heart and kidney tissues during CKD. Furthermore, knockout of miR-26a worsened inflammation and fibrosis in the heart and kidney by inhibiting the LIMS1/ILK signaling pathway; on the contrary, supplementation with exogenous miR-26a reversed all these changes. CONCLUSIONS Our findings suggest that miR-26a could be a promising therapeutic target for the treatment of cardiorenal injury in CKD. This is attributed to its ability to regulate the LIMS1/ILK signaling pathway, which represents a common molecular mechanism in both heart and kidney tissues.
Animals ; MicroRNAs/metabolism* ; Angiotensin II/toxicity* ; Mice ; Renal Insufficiency, Chronic/chemically induced* ; Mice, Knockout ; Disease Models, Animal ; Male ; Signal Transduction/genetics* ; LIM Domain Proteins/genetics* ; Mice, Inbred C57BL ; Cell Line ; Humans

Protein tyrosine phosphatase nonreceptor type 2 (PTPN2) is a promising target for sensitizing solid tumors to immune checkpoint blockades. However, the highly polar active sites of PTPN2 hinder drug discovery efforts. Leveraging small interfering RNA (siRNA) technology, we developed a novel glutathione-responsive nano-platform HPssPT (HA/PEIss@siPtpn2) to silence PTPN2 and enhance immunotherapy efficacy in hepatocellular carcinoma (HCC). HPssPT showed potent transfection and favorable safety profiles. PTPN2 deficiency induced by HPssPT amplified the interferon γ signaling in HCC cells by increasing the phosphorylation of Janus-activated kinase 1 and signal transducer and activator of transcription 1, resulting in enhanced antigen presentation and T cell activation. The nano-platform was also able to promote the M1-like polarization of macrophages in vitro. The unique tropism of HPssPT towards tumor-associated macrophages, facilitated by hyaluronic acid coating and CD44 receptor targeting, allowed for simultaneous reprogramming of both tumor cells and tumor-associated macrophages, thereby synergistically reshaping tumor microenvironment to an immunostimulatory state. In HCC, colorectal cancer, and melanoma animal models, HPssPT monotherapy provoked robust antitumor immunity, thereby sensitizing tumors to PD-1 blockade, which provided new inspiration for siRNA-based drug discovery and tumor immunotherapy.

Objective To summarize and explore the current state,hotspots,and trends in the field of surgical treatment for intracerebral hemorrhage(ICH)over the past decade through a bibliometric and visualization analysis of relevant literature.Methods Relevant Chinese and English literature on the surgical treatment of ICH,published from January 1,2014 to April 1,2024,was retrieved and screened from CNKI and Web of Science databases.Visualization analysis was conducted using CiteSpace,VOSviewer,and other software to analyze the number of published papers,authors,countries,institutions,etc.Social network analysis diagrams of authors,keyword clustering network analysis diagrams,keyword burst strength,and keyword timeline maps were also utilized.Results(1)A total of 3 456 relevant papers were included,with 2 173 in Chinese and 1 283 in English.From 2014 to 2021,the annual number of Chinese publications on ICH surgery was higher than that of English publications,but the number of Chinese publications began to decline from 2016.The number of English publications showed an overall increasing trend.(2)A total of 6 367 authors were identified from the English literature,with notable collaboration networks led by researchers such as Mocco J,Hanley DF,Ziai WC,You C,and Tang ZP.The Chinese literature included 6 522authors,with prominent collaboration networks led by Wang LK,Cai Q,Ku HB,Zhang S,and Zhu SQ.(3)Analysis of the countries involved in the English literature showed that 31 countries participated in research on ICH surgery,with China leading in the number of publications(505),followed by the United States(330)and Germany(106).The top three countries in centrality were the United States(0.32),China(0.16),and Canada(0.11).The top three institutions in English literature publications were Johns Hopkins University(51 papers),Ohio State University(39 papers),and Harvard University(38 papers).In China,Sichuan University(32 papers),Huazhong University of Science and Technology(30 papers),and Capital Medical University(27 papers)had multiple English publications;Wuhan University People's Hospital(15 papers),Affiliated Hospital of Guizhou Medical University(13 papers),and Affiliated Hospital of Yan'an University(13 papers)had multiple Chinese publications.There was close collaboration among research institutions in the English literature,whereas Chinese researchers often established research teams within their medical units with relatively less collaboration between teams.(4)Research on ICH surgery primarily focused on surgical methods,complications,and comprehensive perioperative treatment.Research hotspots included hypertensive ICH,minimally invasive surgical techniques,and perioperative management and treatment."neuroendoscopy"was the most recent emergent keyword in Chinese literature with high centrality and the strongest burst strength,while"randomized trial"had the highest burst strength in English literature.Research trends included the integration of artificial intelligence with minimally invasive techniques to optimize ICH surgery management and treatment strategies,analysis of risk factors,and evaluation of imaging value.Conclusions Over the past decade,the overall publication volume on the surgical treatment of ICH has been in a stable development phase,with research directions covering surgical techniques,diagnosis and treatment,evaluation,and management.Core research teams led by key authors were the main contributors to the publications.Future research hotspots and trends in ICH surgery may include the optimization of surgical techniques,complication management,large-scale multicenter clinical trials and integration of artificial intelligence with minimally invasive techniques.

Objective: To evaluate the effectiveness of health belief model-based health education intervention in improving blood pressure control of patients with hypertension in community settings. Methods: From September 2016 to September 2017, 400 newly diagnosed patients with hypertension were recruited from 6 community healthcare centers with comparable population size and health services in the Shunyi District of Beijing. All community healthcare centers were randomly assigned to the intervention group (206 patients) and the control group (194 patients). Patients in the intervention group received 3 lectures (20-30 min for each) of health belief model-based health education. Patients in the control group received usual care. The basic characteristics, health beliefs, and health literacy were collected, and blood pressure was measured before and after the intervention, respectively. The difference-in-difference model was used to analyze the change of blood pressure and the influencing factors between two groups before and after the intervention. Results: A total of 134 patients in the intervention group and 129 patients in the control group completed the study. After adjusting for the age, gender, family income, medical insurance, chronic diseases and family history, the score of perceived barriers was increased by 1.65 (P=0.016), and perceived seriousness was decreased by 0.73 (P=0.018). The systolic blood pressure of patients was decreased by 7.37 mmHg (1 mmHg=0.133 kPa, P=0.001) and diastolic blood pressure was decreased by 4.07 mmHg (P=0.014), respectively. The β (95%CI) values were -7.37 (-11.88,-2.86) and -4.07 (-7.30, -0.84). The perceived susceptibility and self-efficacy had a significant influence on the blood pressure of patients (P<0.05). Conclusion Health belief model-based health education intervention could significantly improve the blood pressure control of patients with hypertension in the community settings.

BACKGROUND:Human embryonic stem cels exhibit self-renewal and multi-differentiation potential, and can differentiate into endothelial cels under certaininduction conditions.
OBJECTIVE:To explore induced conditions of the human embryonic stem cels differentiating into endothelial cels and to investigate the effect of vascular endothelial growth factors on theendothelial differentiation of human embryonic stem cels.
METHODS:After resuscitation,passage40 human embryonic stem cel lines H9 weresubjected to suspension culture to prepare embryos, and after 5-day culture,these cels werecultured in attachment medium to differentiate into embryoid bodies,folowed by induction with50 μg/L vascular endothelial growth factors. Passage 2 and 15 embryonic stem cels after induced differentiation weretaken for Dil-Ac-LDL uptake test and immunohistochemical staining, respectively.
RESULTS AND CONCLUSION:After 1-day culture, cord-like or polygonal monolayer cels around embryoid bodies showed bud-like andradialgrowth witharelative rapid speed merging into surrounding colonies; at 2-3 days, the number of suspension cels increased further, but the smal-round cels in the center began to die; at 5 days, embryoid bodies started to passage, and aggregated cels exhibited typical paving stone-like appearance. Moreover, some human embryonic cels after induced differentiation could actively takeupfluorescent labeled LDL,andred fluorescent particlesappeared.Additionaly, passage 15 embryonic stem cels after induced differentiation could express CD31 and FLK-1.These findings suggest that human embryonic stem cels induced by vascular endothelial growth factors can differentiate into endothelial cels.

Objective:To investigate the effect of Toll‐like receptor 3(TLR3) gene deficiency on the degree of liver fibrosis in mouse model of carbon tetrachloride(CCl4 )‐induced liver fibrosis .Methods :A total of 20 wild‐type male mice and 20 male mice with TLR3 gene deficiency (TLR3‐/‐) were divided into wild‐type control group and wild‐type model group ,TLR3‐/‐ control group and TLR3‐/‐ model group ,respectively ,with 10 mice in each group .The control group was injected with corn‐oil by intraperitoneal injection while the model group was injected with CCl4 by intraperitoneal injection .After 8 weeks ,blood sample wascollectedandserumlevelofalanineaminotransferase(ALT),aspartatetransaminase(AST),totalbilirubin(TBIL),and albumin(Alb) was analyzed by automatic biochemical analyzer .And the degree of collagen deposition in liver tissue was evaluated by Masson trichrome staining .And the activation of hepatic stellate cells was detected by immunohistochemistry staining of α‐smooth muscle actin(α‐SMA).And hydroxyproline content of liver tissue was detected with detection kit . Furthermore ,real‐time fluorescence polymerase chain reaction was used to detect the expression of liver fibrotic marker type I collagen ,and inflammatory cytokines including tumor necrosis factor‐alpha (TNF‐α) , interleukin‐6 (IL‐6 ) and monocyte chemotactic protein‐1(MCP‐1) ,as well as pro‐fibrotic molecule including transforming growth factor‐beta (TGF‐β) ,tissue inhibitor of metalloproteinase 1(TIMP1) and platelet‐derived growth factor receptor(PDGFR) .Results:TLR3 gene deficiency had no effect on CCl4‐induced change regarding serum level of ALT ,AST ,TBIL ,ALB .TLR3 gene deficiency aggregated the CCl4‐induced collagen deposition and hepatic stellate cell activation in liver tissue .And it promoted the CCl4‐induced elevation of hydroxyproline content and expression increase of fibrotic marker type I collagen .Furthermore ,the expression increase of inflammatory cytokines including TNF‐α,IL‐6 and MCP‐1 ,as well as that of pro‐fibrotic molecule including TGF‐β,TIMP1 and PDGFR ,was promoted .Conclusions :TLR3 gene deficiency could promote liver collagen deposition and hepatic stellate cell activation in mouse model of CCl4‐induced liver fibrosis ,and it could promote inflammatory cytokine release and pro‐fibrotic molecule up‐regulation .All above suggest that TLR3 is a protective gene during liver fibrosis pathological process .

Objective To investigate the expression of matrixmetalloprotein -9(MMP-9)and E-cad-herin in triple negative breast cancer ( TNBC) and its relationship with the clinicopathologic features of TNBC .To analyze the function of MMP -9 and E-cadherin in TNBC .Methods Immunohistochemical method was used to detect the expression of MMP -9 and E-cadherin in 127 cases of TNBC.Results The MMP-9 positive rate was 53.54%and E-cadherin positive grade was 32.28%in TNBC.Expression of MMP-9 was correlated with tumor size(P=0.007),histological grade(P=0.006),TNM stage(P=0.003),lymph node metastasis(P=0.000)and lymph duct invasive(P=0.000).Expression of E-cadherin was correlated with lymph node metasta-sis(P=0.016)and lymph duct invasive(P=0.015).However,they were not correlated with other factors .Con-clusion The expression of MMP -9 and E -cadherin was correlated with invasion and metastasis in TNBC , which could be an important research topic in the future studies .

Purpose To explore the clinical characteristics of small intestinal tumors and its diagnosis. MethodsRetrospective analysis of cases. ResultsLdomyoma was most common among the benign small intestinal tumors(12/17),adenocarcinomawas most common among the malignant small intestinal tumors(45/ 76). The feature of the small intestinal tumors could be hemorrhage, abdominal pain, abdominal mass, fever and jaundice. Upper gastrointestinal tract barium oontrast study was performed in 28 cases,and the results of 21 cases were positive. Mesenteric arteriography was performed in 9 cases. It was confirmed by surgery that the results matched with the lesions. ConclusionsMesenteric arteriography is of great value in diagnosis of the small intestinal tumors endoscope retrograde cholangiopancreatography(ERCP), CT are also helpful.