Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

This study investigated the regulatory potential of salidroside (SAL), a primary active compound in Rhodiola rosea L., on osteoclast differentiation by modulating the hypoxia-inducible factor 1-alpha (HIF-1a) pathway in osteoblasts. Luciferase reporter assay and chromatin immunoprecipitation (ChIP) assay were employed to validate whether the receptor activator of nuclear factor-?B ligand (RANKL) is the downstream target gene of HIF-1a in osteoblasts. The study also utilized lipopolysaccharide (LPS)-induced mouse osteolysis to examine the impact of SAL on osteolysis in vivo. Furthermore, conditioned medium (CM) from SAL-pretreated osteoblasts was used to investigate the paracrine effects on osteoclastogenesis through the HIF-1a pathway. Hypoxic condition-induced overexpression of HIF-1a upregulated RANKL levels by binding to the RANKL promoter and enhancing transcription in osteoblastic cells. In vivo, SAL significantly alleviated bone tissue hypoxia and decreased the expression of HIF-1a by downregulating the expression of RANKL, vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), and angiopoietin-like 4 (ANGPTL4). In the paracrine experiment, conditioned media from SAL-pretreated osteoblasts inhibited differentiation through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. RANKL emerges as the downstream target gene regulated by HIF-1a in osteoblasts. SAL significantly alleviates bone tissue hypoxia and bone loss in LPS-induced osteolysis through the HIF-1a/RANKL, VEGF, IL-6, and ANGPTL4 pathways. SAL inhibits osteoclast differentiation by regulating osteoblast paracrine secretion.
Animals ; Osteoblasts/cytology* ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics* ; Glucosides/administration & dosage* ; Cell Differentiation/drug effects* ; Phenols/administration & dosage* ; Mice ; Osteoclasts/metabolism* ; RANK Ligand/genetics* ; Rhodiola/chemistry* ; Osteogenesis/drug effects* ; Signal Transduction/drug effects* ; Interleukin-6/genetics* ; Male ; RAW 264.7 Cells ; Osteolysis/genetics* ; Humans ; Mice, Inbred C57BL

OBJECTIVE: To investigate the relationship between physical activity and genetic risk and their combined effects on the risk of developing chronic obstructive pulmonary disease. METHODS: This prospective cohort study included 318,085 biobank participants from the UK. Physical activity was assessed using the short form of the International Physical Activity Questionnaire. The participants were stratified into low-, intermediate-, and high-genetic-risk groups based on their polygenic risk scores. Multivariate Cox regression models and multiplicative interaction analyses were used. RESULTS: During a median follow-up period of 13 years, 9,209 participants were diagnosed with chronic obstructive pulmonary disease. For low genetic risk, compared to low physical activity, the hazard ratios ( HRs) for moderate and high physical activity were 0.853 (95% confidence interval [ CI]: 0.748-0.972) and 0.831 (95% CI: 0.727-0.950), respectively. For intermediate genetic risk, the HRs were 0.829 (95% CI: 0.758-0.905) and 0.835 (95% CI: 0.764-0.914), respectively. For participants with high genetic risk, the HRs were 0.809 (95% CI: 0.746-0.877) and 0.818 (95% CI: 0.754-0.888), respectively. A significant interaction was observed between genetic risk and physical activity. CONCLUSION Moderate or high levels of physical activity were associated with a lower risk of developing chronic obstructive pulmonary disease across all genetic risk groups, highlighting the need to tailor activity interventions for genetically susceptible individuals.
Humans ; Pulmonary Disease, Chronic Obstructive/epidemiology* ; Exercise ; Male ; Female ; Middle Aged ; Prospective Studies ; Aged ; Genetic Predisposition to Disease ; Risk Factors ; United Kingdom/epidemiology* ; Incidence ; Adult

Background: s/Aims: Non-invasive models stratifying clinically significant portal hypertension (CSPH) are limited. Herein, we developed a new non-invasive model for predicting CSPH in patients with compensated cirrhosis and investigated whether carvedilol can prevent hepatic decompensation in patients with high-risk CSPH stratified using the new model. Methods: Non-invasive risk factors of CSPH were identified via systematic review and meta-analysis of studies involving patients with hepatic venous pressure gradient (HVPG). A new non-invasive model was validated for various performance aspects in three cohorts, i.e., a multicenter HVPG cohort, a follow-up cohort, and a carvediloltreating cohort. Results: In the meta-analysis with six studies (n=819), liver stiffness measurement and platelet count were identified as independent risk factors for CSPH and were used to develop the new “CSPH risk” model. In the HVPG cohort (n=151), the new model accurately predicted CSPH with cutoff values of 0 and –0.68 for ruling in and out CSPH, respectively. In the follow-up cohort (n=1,102), the cumulative incidences of decompensation events significantly differed using the cutoff values of <–0.68 (low-risk), –0.68 to 0 (medium-risk), and >0 (high-risk). In the carvediloltreated cohort, patients with high-risk CSPH treated with carvedilol (n=81) had lower rates of decompensation events than non-selective beta-blockers untreated patients with high-risk CSPH (n=613 before propensity score matching [PSM], n=162 after PSM). Conclusions Treatment with carvedilol significantly reduces the risk of hepatic decompensation in patients with high-risk CSPH stratified by the new model.

Objective:To investigate the effect of different programmed death receptor 1 (PD-1)/programmed death receptor ligand 1 (PD-L1) inhibitors combined with chemotherapy in the first-line treatment of extensive-stage small cell lung cancer (ES-SCLC).Methods:All randomized controlled trials (RCT) of PD-1/PD-L1 inhibitors for the first-line treatment of ES-SCLC from the establishment of the database to March 2025 were searched in CNKI database, Wanfang database, VIP Chinese Science and Technology Journal database, China Biomedical Literature Service System, PubMed database, Cochrane Library database and Embase database. Literatures were screened according to inclusion and exclusion criteria, and data were extracted. A network meta-analysis was performed using R 4.3.1 software to analyze the survival and safety of patients with ES-SCLC treated with PD-1/PD-L1 inhibitors combined with chemotherapy and chemotherapy±placebo first-line treatment.Results:A total of 8 RCT involving 3 832 patients with ES-SCLC were included in this analysis. PD-1/PD-L1 inhibitors included pembrolizumab, serplulimab, toripalimab, tislelizumab, adebrelimab, durvalumab, atezolizumab and benmelstobart, and benmelstobart combined with anti-vascular targeted drug anlotinib; the chemotherapy regimen was etoposide combined with platinum-based drugs. Except for durvalumab combined with chemotherapy compared with chemotherapy alone, the control group of the rest was chemotherapy combined with placebo. The included study data were complete and the risk of bias was small, and there was no closed loop in the outcome measures, so the consistency model was uniformly used for analysis. The results of network meta-analysis showed that compared with the control group, PD-1/PD-L1 inhibitors combined with chemotherapy benefited the progression-free survival (PFS) of patients (all P < 0.05), among which benmelstobart and anlotinib combined with chemotherapy had the best improvement in PFS ( HR = 0.32, 95% CI: 0.25-0.40, P < 0.05), and this regimen could benefit the PFS of patients more than other PD-1/PD-L1 inhibitors combined with chemotherapy and serplulimab combined with chemotherapy could benefit the PFS of patients more than pembrolizumab, toripalimab, adebrelimab, durvalumab, and atezolizumab combined with chemotherapy (all P < 0.05). The results of network meta-analysis showed that compared with the control group, all PD-1/PD-L1 inhibitors combined with chemotherapy benefited the overall survival (OS) of patients (all P < 0.05), among which benmelstobart and anlotinib combined with chemotherapy had the best improvement in OS ( HR = 0.61, 95% CI: 0.47-0.79, P < 0.05), but there was no statistically significant difference in OS benefit between each PD-1/PD-L1 inhibitor combined with chemotherapy (all P > 0.05). Ranking of the efficacy of all interventions, the P-scores for PFS and OS were the highest for benmelstobart and anlotinib combined with chemotherapy, which were 0.99 and 0.89, respectively. The results of the network meta-analysis showed that, except for the higher risk of ≥ grade 3 adverse reactions in benmelstobart and anlotinib combined with chemotherapy group compared to the control group ( OR = 2.01, 95% CI: 1.09-3.73, P < 0.05), there was no statistically significant difference in the risk of ≥ grade 3 adverse reactions between the other PD-1/PD-L1 inhibitors combined with chemotherapy group and the control group, or between all PD-1/PD-L1 inhibitors combined with chemotherapy groups (all P > 0.05). Among all PD-1/PD-L1 inhibitors combined with chemotherapy regimens, the tislelizumab combined with chemotherapy regimen had the lowest incidence of ≥grade 3 adverse reactions, with a P-score of 0.70. Conclusions:For the first-line treatment of ES-SCLC patients, the combination of PD-1/PD-L1 inhibitors and chemotherapy regimen has better survival benefits than chemotherapy regimen. Among them, compared with other PD-1/PD-L1 inhibitors, benmelstobart and anlotinib may benefit patients' survival more, but its related adverse reactions should be noted.

Patients with chronic kidney disease (CKD) are at increased risk of fractures, and accurate assessment of this risk remains a major clinical challenge. Traditional tools such as bone mineral density and fracture risk assessment tool show limited predictive performance in CKD population. In recent years, novel approaches including trabecular bone score, vertebral fracture assessment, hip structural analysis, quantitative computed tomography, high-resolution peripheral quantitative computed tomography, artificial intelligence, and bone turnover markers have been introduced for fracture risk assessment. These emerging techniques provide more comprehensive evaluation strategies, yet their clinical utility remains to be fully validated. This review summarizes current research progress on fracture risk assessment methods in CKD patients and highlights potential directions for improving risk prediction in CKD population.

Objective To construct a nursing registry platform for percutaneous coronary intervention(PCI)to provide data support for subsequent real-world research on PCI nursing.Methods From April to December 2023,we established a variable list and data dictionary based on literature review and expert discussion,and constructed a web-based PCI nursing registry platform based on registry-related standards.Results A total of 191 variables were screened in this study,and a corresponding data dictionary was developed for each variable according to the variable name,variable code,variable definition,variable type,variable value range,data source and data collection node.Three levels of account privileges has been set up in the platform,which can realize different data management privileges,and the data can be saved only after filling in and reviewing at each level.The platform is also equipped with automatic data checking function,which reduces data filling errors and improves data quality.Conclusion The constructed PCI nursing registration platform has strong scientific and professional characteristics,and can provide data support for subsequent research,and the content and functions of the platform can be further optimized in the future.

Ischemic stroke is a sudden neurological disorder caused by local cerebral ischemia and persistent cerebral infarc-tion due to impaired blood supply of the brain.IS,with a high disability and mortality rate,is a high incidence disease in Chi-na.Mitochondria play a central role in the pathological and physiological processes of IS.Mitochondrial quality control(MQC)is the cornerstone of maintaining mitochondrial function and the integrity of mitochondrial network,playing an indispen-sable role in promoting neuronal survival and restoring neural vascular unit homeostasis after IS.IS belongs to stroke in tradi-tional Chinese medicine,and is the first of the four major diffi-cult diseases of"stroke,phthisis,swell,and dysphagia".The syndrome of IS belongs to the deficiency in origin and excess in superficies.Traditional Chinese medicine has thousands of years of experience in treating ischemic stroke.Numerous pharmaco-logical studies have found that the therapeutic effect of traditional Chinese medicine on ischemic stroke is closely related to the mechanism of mitochondrial quality control.Therefore,this arti-cle provides a review of the mechanism of MQC in IS and tradi-tional Chinese medicine targeted intervention for MQC,in order to provide reference and inspiration for new treatment for IS.