Hepatic stellate cells (HSCs) are the primary fibrogenic cells in the liver, and their activation plays a crucial role in the development and progression of hepatic fibrosis. Here, we report that retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a key modulator of HSC activation and liver fibrosis. RXRα exerts its effects by modulating calcium/calmodulin-dependent protein kinase kinase β (CaMKKβ)-mediated activation of AMP-activated protein kinase-alpha (AMPKα). In addition, we demonstrate that K-80003, which binds RXRα by a unique mechanism, effectively suppresses HSC activation, proliferation, and migration, thereby inhibiting liver fibrosis in the CCl₄ and amylin liver NASH (AMLN) diet animal models. The effect is mediated by AMPKα activation, promoting mitophagy in HSCs. Mechanistically, K-80003 activates AMPKα by inducing RXRα to form condensates with CaMKKβ and AMPKα via a two-phase process. The formation of RXRα condensates is driven by its N-terminal intrinsic disorder region and requires phosphorylation by CaMKKβ. Our results reveal a crucial role of RXRα in liver fibrosis regulation through modulating mitochondrial activities in HSCs. Furthermore, they suggest that K-80003 and related RXRα modulators hold promise as therapeutic agents for fibrosis-related diseases.

Osteoporosis is a prevalent skeletal condition characterized by reduced bone mass and strength, leading to increased fragility. Buqi-Tongluo (BQTL) decoction, a traditional Chinese medicine (TCM) prescription, has yet to be fully evaluated for its potential in treating bone diseases such as osteoporosis. To investigate the mechanism by which BQTL decoction inhibits osteoclast differentiation in vitro and validate these findings through in vivo experiments. We employed MTS assays to assess the potential proliferative or toxic effects of BQTL on bone marrow macrophages (BMMs) at various concentrations. TRAcP experiments were conducted to examine BQTL's impact on osteoclast differentiation. RT-PCR and Western blot analyses were utilized to evaluate the relative expression levels of osteoclast-specific genes and proteins under BQTL stimulation. Finally, in vivo experiments were performed using an osteoporosis model to further validate the in vitro findings. This study revealed that BQTL suppressed receptor activator of NF-κB ligand (RANKL)-induced osteoclastogenesis and osteoclast resorption activity in vitro in a dose-dependent manner without observable cytotoxicity. The inhibitory effects of BQTL on osteoclast formation and function were attributed to the downregulation of NFATc1 and c-fos activity, primarily through attenuation of the MAPK, NF-κB, and Calcineurin signaling pathways. BQTL's inhibitory capacity was further examined in vivo using an ovariectomized (OVX) rat model, demonstrating a strong protective effect against bone loss. BQTL may serve as an effective therapeutic TCM for the treatment of postmenopausal osteoporosis and the alleviation of bone loss induced by estrogen deficiency and related conditions.
Animals ; NFATC Transcription Factors/genetics* ; Drugs, Chinese Herbal/pharmacology* ; Ovariectomy ; Osteoclasts/metabolism* ; Female ; Osteogenesis/drug effects* ; Rats, Sprague-Dawley ; Rats ; NF-kappa B/genetics* ; Osteoporosis/genetics* ; Signal Transduction/drug effects* ; Bone Resorption/genetics* ; Cell Differentiation/drug effects* ; Humans ; RANK Ligand/metabolism* ; Mitogen-Activated Protein Kinases/genetics* ; Transcription Factors

Objective: To explore the potential category patterns of risk prevention and control behaviors of HIV infection among young students who have sex with men (MSM) and their impact on HIV infection and late detection, aiming to optimize intervention strategies. Methods: From September 2017 to December 2024, a total of 1 637 MSM young students in Tianjin were recruited through both online and offline channels. Latent class analysis was applied to classify 11 HIV risk prevention and control behaviors [condom use during the most recent anal sex in the past 6 months, consistent condom use, use of water based lubricants, abstinence from recreational drugs, regular on site professional testing, fixed sexual partners, partner testing, awareness of partner s HIV testing results, testing before sexual activity, nucleic acid testing, and use of pre exposure prophylaxis (PrEP) or post exposure prophylaxis (PEP)]. Multivariate Logistic regression analyzed associations between demographic characteristics/intervention services factors and latent classes. Differences in HIV infection and late detection across behavior patterns were compared. Results: HIV risk prevention and control behaviors among MSM students were classified into three latent classes:condom dependent group (38.42%), low prevention group (27.73%), and comprehensive prevention group (33.85%). Students who received condom promotion/testing services were more likely to belong to the comprehensive prevention group ( OR =5.58), while those who received peer education were less likely to the comprehensive prevention group ( OR =0.43) (both P <0.01). Among the MSM student population, the HIV infection rate was 4.83%, with 2.26% of cases detected late. The HIV infection rate (1.45%) and late detection proportion (0.82%) in the comprehensive prevention group were lower than those in the low prevention group (7.89% and 3.83%, respectively) ( χ 2=16.20, 7.31, both P <0.01). Conclusions HIV risk prevention and control behaviors among MSM young students exhibit significant heterogeneity. Comprehensive prevention strategies can effectively reduce HIV infection and late detection risks. It is necessary to optimize peer education content and improve the accessibility of diversified prevention measures such as PrEP/PEP to enhance HIV prevention and control.

OBJECTIVES: To analyze the clinical characteristics of diffuse panbronchiolitis (DPB) in children and to enhance the clinical diagnosis and treatment of this disease. METHODS: A retrospective analysis was conducted on the clinical data of 6 children diagnosed with DPB who were hospitalized at The First Affiliated Hospital of Guangzhou Medical University from January 2011 to December 2019. RESULTS: Among the 6 patients, there were 2 males and 4 females; the age at diagnosis ranged from 7 to 12 years. All patients presented with cough, sputum production, and exertional dyspnea, and all had a history of sinusitis. Two cases showed positive serum cold agglutinin tests, and 5 cases exhibited pathological changes consistent with chronic bronchiolitis. High-resolution chest CT in all patients revealed centrilobular nodules diffusely distributed throughout both lungs with a tree-in-bud appearance. Five patients received low-dose azithromycin maintenance therapy, but 3 showed inadequate treatment response. After empirical anti-tuberculosis treatment, non-tuberculous Mycobacteria were found in the bronchoalveolar lavage fluid. Follow-up over 2 years showed 1 case cured, 3 cases significantly improved, and 2 cases partially improved. CONCLUSIONS The clinical presentation of DPB is non-specific and can easily lead to misdiagnosis. In cases where DPB is clinically diagnosed but does not show improvement with low-dose azithromycin treatment, special infections should be considered.
Humans ; Male ; Female ; Bronchiolitis/drug therapy* ; Retrospective Studies ; Child ; Haemophilus Infections/diagnosis*

OBJECTIVES: To evaluate the effectiveness of single-balloon and double-balloon enteroscopy in diagnosing pediatric small bowel diseases and assess the diagnostic efficacy of computed tomography enterography (CTE) for small bowel diseases using enteroscopy as the reference standard. METHODS: Clinical data from 576 children who underwent enteroscopy at Hunan Children's Hospital between January 2017 and December 2023 were retrospectively collected. The children were categorized based on enteroscopy type into the single-balloon enteroscopy (SBE) group (n=457) and double-balloon enteroscopy (DBE) group (n=119), and the clinical data were compared between the two groups. The sensitivity and specificity of CTE for diagnosing small bowel diseases were evaluated using enteroscopy results as the standard. RESULTS: Among the 576 children, small bowel lesions were detected by enteroscopy in 274 children (47.6%).There was no significant difference in lesion detection rates or complication rates between the SBE and DBE groups (P>0.05), but the DBE group had deeper insertion, longer procedure time, and higher complete small bowel examination rate (P<0.05). The complication rate during enteroscopy was 4.3% (25/576), with 18 cases (3.1%) of mild complications and 7 cases (1.2%) of severe complications, which improved with symptomatic treatment, surgical, or endoscopic intervention. Among the 412 children who underwent CTE, the sensitivity and specificity for diagnosing small bowel diseases were 44.4% and 71.3%, respectively. CONCLUSIONS SBE and DBE have similar diagnostic efficacy for pediatric small bowel diseases, but DBE is preferred for suspected deep small bowel lesions and comprehensive small bowel examination. Enteroscopy in children demonstrates relatively good overall safety. CTE demonstrates relatively low sensitivity but comparatively high specificity for diagnosing small bowel diseases.
Retrospective Studies ; Treatment Outcome ; Double-Balloon Enteroscopy/statistics & numerical data* ; Single-Balloon Enteroscopy/statistics & numerical data* ; Humans ; Male ; Female ; Child ; Operative Time ; Tomography, X-Ray Computed/statistics & numerical data* ; Sensitivity and Specificity ; Intestine, Small/surgery* ; Intestinal Diseases/surgery*

Nonunion of osteoporotic vertebral fractures (OVF), predominantly affecting the elderly, can lead to intractable pain, vertebral collapse, progressive kyphotic deformity, and neurological impairment, significantly compromising patients′ quality of life. There exists considerable debate on diagnosis and management of OVF, encompassing key issues such as clinical diagnosis and staging criteria for nonunion, surgical indications and procedure selection, and postoperative rehabilitation planning. Currently, there lacks standardized clinical guideline and expert consensus on the diagnosis and management of OVF nonunion in China. To address this gap, Minimally Invasive Surgery Group of Chinese Orthopedic Association, Osteoporosis Committee of Chinese Association of Orthopedic Surgeons, Prevention and Rehabilitation Committee for Osteoporosis of Chinese Association of Rehabilitation Medicine and Minimally Invasive Orthopedic Surgery Branch of China Association for Geriatric Care jointly organized domestic experts in spinal surgery, endocrinology, and rehabilitation to formulate the Clinical guideline for the diagnosis and treatment for nonunion of osteoporotic vertebral fractures ( version 2025), based on existing literature and clinical experience and adhering to principles of scientific rigor and practicality. The guideline provided 13 evidence-based recommendations encompassing diagnosis and treatment of OVF nonunion, aiming to standardize its clinical management.

Objective:To comprehensively evaluate the application of Common Data Model (CDM) of Observational Medical Outcomes Partnership (OMOP) in China, and provide reference for the implementation of data standardization and evidence sharing in China.Methods:PubMed, Embase, Web of Science, CNKI, VIP, WanFang and SinoMed databases were used for literature retrieval to collect the research papers of OMOP CDM application for data standardization in China until March 15, 2023. The information about institutions, types and numbers of patients were extracted.Results:A total of 14 research papers, including 9 in English and 5 in Chinese, were selected. The research papers published since 2018 were collected, which focused on patients with hypertension, diabetes, and depression. A total of 12 institutions or platforms transformed data into OMOP CDM. Jiangsu Provincial People's Hospital was the first one to apply the CDM and demonstrated its feasibility in China. Additionally, the regional information system in Yinzhou District of Ningbo, Zhejiang Province, standardized the multi-dimensional data of patients with diabetes and hypertension. Based on this platform, a series of prediction models for complications in patients with diabetes were constructed. Another major database in Beijing Anding Hospital applied OMOP CDM to analyze the characteristics of patients with late-life depression and dementia.Conclusions:This study analyzed the application of OMOP CDM in China. Through in-depth analysis of specific cases, the study provided guidance for the future cross-regional evidence sharing and collaboration.

Objective To explore the active monitoring strategies for hypoglycemia in hospitalized dia-betic patients,as well as their clinical symptom characteristics and influencing factors.Methods A retrospec-tive search was conducted on all inpatients in a tertiary hospital in 2023.The hospital's electronic medical re-cord system was manually retrieved through the inpatient numbers of the patients.Adult inpatients with dia-betes who experienced hypoglycemia were included as the research subjects,and the general conditions and possible hypoglycemia-related risk factors were collected.Embed the hypoglycemic electronic trigger program in China Hospital Pharmacovigilance System(CHPS),reviewed the original medical records of patients with positive trigger triggering,and calculated the positive predictive value(PPV).Searched for the number of hy-poglycemic adverse reaction cases voluntarily reported by this hospital during the same period from National Adverse Reaction Monitoring System and compared with the actual number of hypoglycemic cases discovered.Patients with suspected drug-induced hypoglycemia were divided into the symptomatic group and the asymp-tomatic group based on whether they presented hypoglycemia-related symptoms.Multivariate logistic regres-sion analysis was applied to analyze the influencing factors.Results A total of 1 001 adult hospitalized diabet-ic patients with hypoglycemia were included in the study.Among them,725 cases were suspected of drug-in-duced hypoglycemia,and 495 cases were suspected of hypoglycemia caused by drug interactions.After manual review,131 cases of drug-induced hypoglycemia patients had clinical symptoms,and hypoglycemic adverse re-action events should be reported,PPV of this trigger for symptomatic hypoglycemia was 18.1%(131/725).However,the number of hypoglycemic adverse reactions spontaneously reported through National Adverse Reaction Monitoring System by this hospital during the same period was 4 cases,and the reporting rate was only 3.1%(4/131).Multivariate logistic regression analysis showed that aging and grade 2 hypoglycemia were risk factors for the occurrence of related symptoms in patients with suspected drug-induced hypoglycemia(P<0.05),while surgery,type 2 glucosuria,unclassified diabetes,and the use of insulin secretagogues were protective factors(P<0.05).Conclusion Drug-induced hypoglycemia dominates among hospitalized diabetic patients,and age,hypoglycemia grade,inpatient department using insulin secretagogues,diabetes diagnosis and classification are closely related to the occurrence of clinical hypoglycemia-related symptoms.Active monito-ring through CHPS can effectively increase the detection rate and reporting rate of hypoglycemic adverse e-vents in hospitalized diabetic patients.