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

Cholangiocarcinoma (CCA) is a fatal malignancy with steadily increasing incidence and poor prognosis. Since most CCA cases are diagnosed at an advanced stage, systemic therapies, including chemotherapy, radiotherapy, targeted therapy, and immunotherapy, play a crucial role in the management of unresectable CCA. The recent advances in targeted therapies and immunotherapies brought more options in the clinical management of unresectable CCA. This review depicts the advances of targeted therapies and immunotherapies for unresectable CCA, summarizes crucial clinical trials, and describes the efficacy and safety of different drugs, which may help further develop precision and individualization in the clinical treatment of unresectable CCA.
Humans ; Cholangiocarcinoma/drug therapy* ; Immunotherapy/methods* ; Bile Duct Neoplasms/drug therapy* ; Molecular Targeted Therapy/methods*

In 2022， Hainan provincial government launched the project for the prevention and control of viral hepatitis with the goals of a hepatitis B screening rate of 90%， a diagnostic rate of 90%， and a treatment rate of 80% among people aged 18 years and above by the year 2025， and the main intervention measures include population-based prevention， case screening， antiviral therapy， and health management. As of December 31， 2024， a total of 6.875 million individuals in the general population had been screened for hepatitis B， with a screening rate of 95.6%. A total of 184 710 individuals with positive HBsAg were identified， among whom 156 772 were diagnosed through serological reexamination， resulting in a diagnostic rate of 84.9%. A total of 50 742 patients with chronic hepatitis B were identified， among whom 42 921 had hepatitis B-specific health records established for health management， with a file establishment rate of 84.6%. A total of 31 553 individuals received antiviral therapy， with a treatment rate of 62.2%. A total of 2.503 million individuals at a high risk of hepatitis C were screened， among whom 4 870 tested positive for HCV antibody and 3 858 underwent HCV RNA testing， resulting in a diagnostic rate of 79.2%， and 1 824 individuals with positive HCV RNA were identified， among whom 1 194 received antiviral therapy， with a treatment rate of 65.5%. In addition， 159 301 individuals with negative HBsAg and anti-HBs and an age of 20 — 40 years were inoculated with hepatitis B vaccine free of charge. Through the implementation of the project for the prevention and control of viral hepatitis， a large number of hepatitis patients have been identified， treated， and managed in the province within a short period of time， which significantly accelerates the efforts to eliminate the crisis of viral hepatitis.

OBJECTIVE: To assess the osteogenesis height in maxillary sinus segment one year after zygomatic implantation by imaging methods, and evaluate the influence of patient factors, maxillary sinus anatomical factors and surgical factors on postoperative osteogenesis height. METHODS: This study is a retrospective study, including patients who underwent zygomatic implantation and whose zygomatic implants passed through the maxillary sinus at the Department of Implantology, Peking University School and Hospital of Stomatology from July 2017 to January 2022. Preoperative and postoperative cone beam CT (CBCT)was taken to measure and calculate the average osteogenesis height (AOH) in maxillary sinus segment of the zygomatic implants, then the residual bone height, the width and morphology of the maxillary sinus floor in the buccal and palatal directions were measured. Besides, the integrity of Schneiderian membrane during implant surgery, and the general information of the patients and zygomatic implants were recorded. By comparing anatomical situations and surgical characteristics, the differences of AOH under different conditions were analyzed. Then AOH was divided into two groups (obvious osteogenesis group and non-obvious osteogenesis group) using the median as the threshold, and the influencing factors of osteogenesis were evaluated using mixed effect generalized linear model univariable and multivariable analysis. RESULTS: A total of 47 zygomatic implants were implanted in 24 patients. During the average follow-up period of 12.1 months, there was no implant failure, and the implant survival rate was 100%. Postoperative CBCT showed that 43 zygomatic implants had osteogenic images in the maxillary sinus segment, most of which originated from the floor of the maxillary sinus, and the median AOH was 3.1 mm [interquartile range (IQR): 4.0 mm]. In terms of maxillary sinus width, there were 31 cases (66.0%) of wide type and 16 cases (34.0%) of narrow type. In the aspect of buccal and palatal morphology, 17 cases were taper (36.2%), 20 cases were round (42.6%), and 10 cases were flat (21.3%). The median of residual bone height was 2.8 mm (IQR: 2.2 mm) before operation. Univa-riate analysis of mixed effect generalized linear model showed that postoperative obvious osteogenic rate was related to the residual bone height (OR=2.09, P=0.006). Multivariate analysis showed that the resi-dual bone height (OR=2.55, P=0.022) and the shape of a taper maxillary sinus (OR=11.44, P=0.040) had a significant impact on the postoperative obvious osteogenic rate. CONCLUSION The maxillary sinus floor showed osteogenic images 1 year after the zygomatic implantation surgery. Larger residual bone height and the shape of a taper maxillary sinus may be favorable factors for osteogenesis.
Humans ; Maxillary Sinus/surgery* ; Cone-Beam Computed Tomography ; Retrospective Studies ; Zygoma/diagnostic imaging* ; Male ; Female ; Osteogenesis/physiology* ; Middle Aged ; Adult ; Dental Implants ; Aged ; Dental Implantation, Endosseous/methods*

Objective:To investigate the correlation of SERPINC1 and SERPINE1 gene polymorphisms with venous thromboembolism (VTE) in patients with malignant tumors.Methods:A retrospective case-control study was conducted. A total of 227 patients with malignant tumors in the Cancer Hospital Affiliated to Xinjiang Medical University from November 2023 to February 2024 were selected, of which 47 cases developed VTE (VTE group) and 180 cases did not develop VTE (non-VTE group). The patients' venous blood was collected, and D-dimer level was analyzed by using fully automatic coagulation analyzer; fluorescence staining was performed by using digoxin staining solution, and SERPINC1 rs2227589 locus and SERPINE1 rs1799762 locus were used as candidate genes, and fluorescence sequencing was performed by using multichannel fluorescence quantitative analyzer, and the frequencies of C, T, 4G and 5G genes were calculated.Results:There were no statistically significant differences in the age, gender, smoking, alcohol consumption, anticoagulant use, diabetes mellitus, hypertension, coronary artery disease, surgical treatment, intravenous cannulae, radiotherapy, chemotherapy, and targeted therapy between the 2 groups (all P > 0.05). The level of D-dimer in the VTE group was higher than that in the non-VTE group [(8.7±6.9) kg/m 2vs. (2.8±1.0) kg/m 2], and the difference was statistically significant ( t = 5.15, P < 0.001). The differences in C and T genotypes and gene frequencies at the SERPINC1 rs2227589 locus between the VTE group and the non-VTE group were not statistically significant (all P > 0.05). The differences in 4G and 5G genotypes and gene frequencies at the SERPINE1 rs1799762 locus between the VTE group and the non-VTE group were statistically significant (all P < 0.05), and 4G allele frequency in the VTE group was higher than that in the non-VTE group (52.13% vs. 39.72%), and the difference was statistically significant ( χ2 = 4.70, P = 0.030). Conclusions:The elevated expression of 4G allele at the SERPINE1 rs1799762 locus in patients with malignant tumors is associated with development of VTE.

Objective To investigate risk factors for residual lesions after initial transurethral resection of bladder tumors(TURBT)and risk factors for tumor recurrence after second TURBT in patients with non-muscle-invasive bladder cancer(NMIBC)in order to provide reference for clinical management.Methods A case-control study design was adopted to include 120 NMIBC patients who underwent initial TURBT and then second surgery within 2～8 weeks in our department from January 2017 to January 2025.Based on the presence of residual lesions after the initial TURBT or not,the patients were divided into a residual lesion group(n=34)and a non-residual lesion group(n=86).Chi-square test and multivariate logistic regression analysis were performed to identify potential risk factors for residual lesions following the initial TURBT.Univariate and multivariate Cox regression models were used to analyze potential risk factors for tumor recurrence after the second TURBT.Results The residual lesion rate after initial TURBT was 28.33％.Chi-square test analysis revealed that tumor stage T1(Chi-square=5.756,P=0.016)and broad tumor base(Chi-square=4.331,P=0.037)were factors influencing residual lesions after initial TURBT.Multivariate logistic regression analysis identified tumor stage T1(OR=3.047,95％CI:1.128～8.226,P=0.028)as an independent risk factor for residual lesions after initial TURBT.The tumor recurrence rate after second TURBT was 17.5％.Multivariate Cox regression analysis identified tumor stage T1(OR=4.258,95％CI:1.248～14.532,P=0.021),intravesical chemotherapy instillation after second TURBT(OR=3.539,95％CI:1.284～9.752,P=0.015),history of urinary system tumors(OR=3.002,95％CI:1.145～7.873,P=0.025)and high platelet-to-lymphocyte(PLR)ratio(OR=2.798,95％CI:1.115～7.023,P=0.028)as independent risk factors for tumor recurrence after second TURBT.Conclusion Tumor stage T1 and broad tumor base are risk factors for residual lesions after initial TURBT,while tumor stage T1,intravesical chemotherapy instillation after second TURBT,history of urinary system tumors and high PLR ratio are risk factors for tumor recurrence after second TURBT.Comprehensive analysis on above 4 indicators can effectively assess the risk of tumor recurrence in NMIBC patients following second TURBT,and timely early medical intervention is beneficial for improving patient outcomes.

Objective:To analyze the clinical characteristics, RAN-binding protein 2 ( RANBP2) gene variations, and prognosis in Chinese acute necrotizing encephalopathy (ANE) patients. Methods:A retrospective analysis of ANE cases registered in the Peking Union Medical College Hospital Encephalitis Registry System from 2022 to 2024, involving patients from Peking Union Medical College Hospital and other hospitals, was conducted. A descriptive study was performed on the clinical characteristics, treatments and prognosis, cerebrospinal fluid examination results, and imaging findings of these patients based on adjusted ANE diagnostic criteria. Whole-exome sequencing technology was used to detect gene mutations in these patients.Results:A total of 18 ANE cases were included, ranged in age from 2 to 72 [20(5, 43)] years. The male-to-female ratio was 4∶5. All patients were found with precipitating infections including COVID-19, influenza A virus and Mycoplasma pneumoniae infections. All patients presented with fever, with varying degrees of consciousness disturbance observed in 16 cases, and seizures in 10 cases. All patients underwent lumbar puncture, with normal or mildly elevated white cell counts [3(2, 13)×10 6/L] and mildly to moderately elevated protein levels [1.90(0.92, 4.65) g/L]. A total of 6 patients were found with extremely elevated interleukin-6 level [950(164, 2 000) pg/ml] in cerebrospinal fluid. Bilateral symmetric thalamic lesions were typical imaging features of ANE, while involvement of other areas such as cortical and subcortical white matter, brainstem, and cerebellum was also observed. A total of 14 patients performed genetic tests while 4 patients were identified with RANBP2 gene mutations (c.1754C>T in 3 cases, c.1966A>G in 1 case). All patients received immunotherapy, and 7 patients died at discharge while other patients presented with neurological sequelae of varying degrees. Conclusions:ANE is a rare and severe parainfectious encephalopathy that can occur in both children and adults. Clinically, it is characterized by rapidly progressing encephalopathy following systematic infection, with bilateral symmetric thalamic lesions. The detection of RANBP2 gene mutations could help make the diagnosis.

Objective:To identify the risk factors for acute graft-versus-host disease (aGVHD) in patients with acute myeloid leukemia (AML) undergoing haploidentical hematopoietic stem cell transplantation (HID-HSCT) .Methods:A total of 141 AML patients who underwent HID-HSCT at the Institute of Hematology & Blood Diseases Hospital, Chinese Academy of Medical Sciences, from January 2020 to July 2021 were included. The cumulative incidence of aGVHD was analyzed using the Fine-Gray competing risk model, with relapse and death as competing events, to compare differences between groups. Potential risk factors were evaluated by univariable and multivariable Cox proportional hazards regression analyses to determine their independent effects on aGVHD.Results:Among the 141 patients, 86 (61.0%) were male and 55 (39.0%) were female, with a median age at transplantation of 34 years. Within 100 days post-transplant, 59 patients developed grade Ⅱ-Ⅳ aGVHD, whereas 86 patients experienced no or grade Ⅰ aGVHD (the grade 0-Ⅰ aGVHD group) . Survival analysis showed that the 3-year overall survival was 68.7% (95% CI: 57.7%-81.9%) in the grade Ⅱ-Ⅳ aGVHD group, compared with 78.8% (95% CI: 70.4%-88.3%) in the grade 0 - Ⅰ aGVHD group, with the difference not being statistically significant ( P=0.190) . Univariable analysis identified donor age ( P=0.020, HR=1.020, 95% CI: 1.000-1.040) and the female donor-male recipient sex combination ( P=0.033, HR=1.980, 95% CI: 1.160-3.380) as risk factors for grade Ⅱ-Ⅳ aGVHD. Multivariable analysis confirmed that donor age ( P=0.005, HR=1.026, 95% CI: 1.008-1.047) and the female donor-male recipient sex combination ( P=0.002, HR=2.339, 95% CI: 1.354-4.037) were independent risk factors for aGVHD. Patients receiving grafts from donors aged >45 years had a significantly higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD compared with those receiving grafts from donors ≤45 years [54.7% (95% CI: 42.3%-67.0%) vs 31.6% (95% CI: 21.0%-42.1%) , P=0.006]. Similarly, patients with the female donor-male recipient sex combination had a higher 100-day cumulative incidence of grade Ⅱ-Ⅳ aGVHD than those with other sex combinations [56.8% (95% CI: 40.4%-73.1%) vs 36.9% (95% CI: 27.5%-46.3%) , P=0.015]. Conclusion:Older donor age and the female donor-male recipient sex combination remain independent risk factors for aGVHD in patients with AML undergoing HID-HSCT.

Objective To investigate the organ protective role and the underlying mechanism of nafamostat mesylate(NM)in a renal ischemia-reperfusion injury(RIRI)model.Methods A total of 21 healthy male Sprague-Dawley(SD)rats were randomly assigned to 3 groups(n=7 in each group),including the sham operation group(Sham group),the RIRI group,and the NM intervention group(NM group).The RIRI and NM groups underwent ischemia-reperfusion injury(IRI)modeling.The NM group was given an intraperitoneal injection of NM at 0.75 mg/kg before modeling.Venous blood and renal tissue samples were then collected from the rats 24 hours after modeling.The levels of serum creatinine,cystatin C,and serum inflammatory factors were determined using the serum samples.Hematoxylin-eosin(HE)staining and TUNEL stainings were performed on the renal tissues to evaluate the damage of the renal tissues.The localization and expression of HMGB1 were analyzed by immunofluorescence and Western blotting,respectively.Single-cell RNA sequencing of the nuclei was performed to obtain the single-cell transcriptome of the kidneys from the rats in the RIRI and the NM groups and to acquire the RIRI cell profile.The cells were annotated according to the cell marker genes to explore the cell type composition in the disease model and the functional status of immune cells between the groups.Results 1)Compared with those of the Sham group,the levels of cystatin C,creatinine,and inflammatory factors in the RIRI and NM groups were significantly increased,and the expression levels in the NM group were lower than those in the RIRI group(P＜0.05).Compared with those of the RIRI group,the tubular injury score and apoptosis rate in the NM group were significantly decreased(P＜0.05),but those of both the NM and RIRI groups were higher than those of the sham group.Compared with that in the RIRI group,the expression of HMGB1 in the NM group was significantly decreased(P＜0.05),but the expression levels in both the RIRI and NM groups were higher than that in the sham group.Immunofluorescence showed that there was increased cytoplasmic expression of HMGB1 in both the NM and RIRI groups,with the increase being more prominent in the RIRI group.2)A total of 13 major cell populations were identified through the single-nucleus sequencing results.The proportion of tubular cells in the NM group was higher,with the HMGB1 gene being highly expressed in the damaged proximal convoluted tubular cells.The proportion of the polarized Macro3 cell subpopulation in the macrophages in the NM group was lower compared to that in the RIRI group.Conclusion NM may play a protective role in a rat model of RIRI,and its underlying mechanisms may be related to the regulation of the functional abnormalities of HMGB1-mediated macrophages.