Obesity represents a critical global health challenge characterized by a complex pathogenesis involving dysregulated adipogenesis and lipid metabolism. In recent years, long non-coding RNAs (lncRNAs) have been established as crucial regulators in the initiation and progression of obesity. These RNA molecules, typically exceeding 200 nucleotides in length, have emerged as key modulators of various biological processes through multiple molecular mechanisms. This review innovatively defines lncRNAs as “molecular switches” in energy metabolism—they regulate adipogenesis and lipid metabolism through key signaling pathways, and exert bidirectional control over obesity via ceRNA mechanisms or recruitment of chromatin-modifying complexes in tissues such as adipose and liver. Additionally, circulating lncRNAs, owing to their tissue specificity and stability, hold promise as non-invasive liquid biopsy biomarkers for obesity and related metabolic disorders. Furthermore, we systematically summarize lncRNA-based intervention strategies, including targeting pathogenic lncRNAs using antisense oligonucleotides (ASOs) or CRISPR/Cas gene editing systems, utilizing viral vectors (such as adeno-associated virus, AAV) to deliver or mimic beneficial lncRNAs in target tissues, and employing exercise as a non-pharmacological intervention that ameliorates obesity and its related complications at multiple levels, offering novel insights for personalized therapeutic approaches. We also critically assess the current challenges in clinical translation, particularly addressing issues related to delivery efficiency, target specificity, and long-term safety concerns. Future research should focus on the following directions: integrating multi-omics with functional screening to elucidate the regulatory networks of lncRNAs in obesity and its complications; leveraging artificial intelligence to construct predictive models of lncRNA-target gene interactions; developing efficient and safein vivo delivery systems, and optimizing drug design to enhance specificity and safety; establishing highly sensitive detection methods and stable circulating lncRNA biomarkers to enable precise patient stratification and real-time monitoring of therapeutic responses; investigating the synergistic effects of lncRNAs with existing treatments (e.g., GLP-1 receptor agonists, lifestyle interventions) to develop combination therapies and establish a multidimensional, personalized precision medicine framework for obesity. This review aims to provide novel perspectives for understanding the molecular mechanisms underlying obesity and to establish a solid theoretical foundation for developing lncRNA-targeted precision medicine strategies against obesity and its associated metabolic complications.

Obesity represents a critical global health challenge characterized by a complex pathogenesis involving dysregulated adipogenesis and lipid metabolism. In recent years, long non-coding RNAs (lncRNAs) have been established as crucial regulators in the initiation and progression of obesity. These RNA molecules, typically exceeding 200 nucleotides in length, have emerged as key modulators of various biological processes through multiple molecular mechanisms. This review innovatively defines lncRNAs as “molecular switches” in energy metabolism—they regulate adipogenesis and lipid metabolism through key signaling pathways, and exert bidirectional control over obesity via ceRNA mechanisms or recruitment of chromatin-modifying complexes in tissues such as adipose and liver. Additionally, circulating lncRNAs, owing to their tissue specificity and stability, hold promise as non-invasive liquid biopsy biomarkers for obesity and related metabolic disorders. Furthermore, we systematically summarize lncRNA-based intervention strategies, including targeting pathogenic lncRNAs using antisense oligonucleotides (ASOs) or CRISPR/Cas gene editing systems, utilizing viral vectors (such as adeno-associated virus, AAV) to deliver or mimic beneficial lncRNAs in target tissues, and employing exercise as a non-pharmacological intervention that ameliorates obesity and its related complications at multiple levels, offering novel insights for personalized therapeutic approaches. We also critically assess the current challenges in clinical translation, particularly addressing issues related to delivery efficiency, target specificity, and long-term safety concerns. Future research should focus on the following directions: integrating multi-omics with functional screening to elucidate the regulatory networks of lncRNAs in obesity and its complications; leveraging artificial intelligence to construct predictive models of lncRNA-target gene interactions; developing efficient and safein vivo delivery systems, and optimizing drug design to enhance specificity and safety; establishing highly sensitive detection methods and stable circulating lncRNA biomarkers to enable precise patient stratification and real-time monitoring of therapeutic responses; investigating the synergistic effects of lncRNAs with existing treatments (e.g., GLP-1 receptor agonists, lifestyle interventions) to develop combination therapies and establish a multidimensional, personalized precision medicine framework for obesity. This review aims to provide novel perspectives for understanding the molecular mechanisms underlying obesity and to establish a solid theoretical foundation for developing lncRNA-targeted precision medicine strategies against obesity and its associated metabolic complications.

Cardiac fibrosis is characterized by an elevated amount of extracellular matrix (ECM) within the heart. However, the persistence of cardiac fibrosis ultimately diminishes contractility and precipitates cardiac dysfunction. Circular RNAs (circRNAs) are emerging as important regulators of cardiac fibrosis. Here, we elucidate the functional role of a specific circular RNA CELF1 in cardiac fibrosis and delineate a novel feedback loop mechanism. Functionally, circ-CELF1 was involved in enhancing fibrosis-related markers' expression and promoting the proliferation of cardiac fibroblasts (CFs), thereby exacerbating cardiac fibrosis. Mechanistically, circ-CELF1 reduced the ubiquitination-degradation rate of BRPF3, leading to an elevation of BRPF3 protein levels. Additionally, BRPF3 acted as a modular scaffold for the recruitment of histone acetyltransferase KAT7 to facilitate the induction of H3K14 acetylation within the promoters of the Celf1 gene. Thus, the transcription of Celf1 was dramatically activated, thereby inhibiting the subsequent response of their downstream target gene Smad7 expression to promote cardiac fibrosis. Moreover, Celf1 further promoted Celf1 pre-mRNA transcription and back-splicing, thereby establishing a feedback loop for circ-CELF1 production. Consequently, a novel feedback loop involving CELF1/circ-CELF1/BRPF3/KAT7 was established, suggesting that circ-CELF1 may serve as a potential novel therapeutic target for cardiac fibrosis.

Isolated male epispadias typically presents with preputial defects and dorsal urethral dehiscence. A less common subtype, known as concealed epispadias, is distinguished by an intact prepuce. Despite its clinical relevance, there is limited literature on this variant. In this study, we retrospectively analyzed the clinical data of 86 pediatric patients with isolated male epispadias treated in Beijing Children's Hospital (Beijing, China) from May 2004 to July 2023, including 19 cases of concealed epispadias and 67 of nonconcealed epispadias. We compared clinical characteristics, preoperative diagnostics, surgical techniques, postoperative outcomes, and sexual function during follow-up between the concealed and nonconcealed groups. No significant differences were observed between the two groups regarding surgical methods, postoperative complications, or rates of urinary incontinence. However, notable distinctions were found in the age at initial diagnosis, timing of surgery, frequency of incontinence, location of the urethral meatus, and postoperative urinary incontinence scores (all P < 0.05). Given the absence of penopubic epispadias in concealed cases, we categorized glans and penile epispadias within nonconcealed epispadias as distal epispadias ( n = 40) and subsequently compared them with concealed epispadias cases. The postoperative urinary incontinence scores did not differ significantly between the concealed and distal epispadias groups. These findings suggest that concealed epispadias represents a relatively milder form of the condition, characterized by the absence of penopubic involvement, lower rates of urinary incontinence, and favorable surgical outcomes. However, the intact prepuce in concealed cases underscores the need for careful identification and early diagnosis.
Humans ; Male ; Retrospective Studies ; Epispadias/classification* ; China ; Tertiary Care Centers ; Child, Preschool ; Child ; Postoperative Complications/epidemiology* ; Urinary Incontinence/epidemiology* ; Urethra/surgery* ; Infant ; Penis/surgery* ; Adolescent ; Urologic Surgical Procedures, Male/methods* ; East Asian People

OBJECTIVE: Glucocorticoid-induced osteoporosis (GIOP) is a common complication of prolonged glucocorticoid therapy. Chlorogenic acid (CGA), a polyphenol with antioxidant properties that is extracted from traditional Chinese medicines such as Eucommiae Cortex, has potential anti-osteoporotic activity. This study aimed to investigate the possible effects of CGA on GIOP in mice and murine long bone osteocyte Y4 (MLO-Y4) cells and explore the underlying molecular mechanisms. METHODS: The protective effects of CGA were initially evaluated in the GIOP mouse model induced by dexamethasone (Dex). The micro-computed tomography, hematoxylin-eosin staining, silver nitrate staining, and serum detection were used to assess the efficacy of CGA for improving bone formation in vivo. Then, network pharmacology analysis was used to predict the potential targets and molecular mechanisms underlying the therapeutic efficacy of CGA against GIOP. After that, 2',7'-dichlorofluorescein diacetate staining, flow cytometry, real-time quantitative reverse transcription polymerase chain reaction, and Western blotting were used to verify the mechanisms of CGA against GIOP in vitro. RESULTS: Animal experiments showed that CGA treatment effectively attenuated Dex-induced decreases in bone mass and strength and improved disrupted osteocyte morphology in mice. The protein-protein interaction analysis highlighted erb-b2 receptor tyrosine kinase (ERBB2), which is also known as human epidermal growth factor receptor 2 (HER2), caspase-3, kinase insert domain receptor, matrix metallopeptidase 9, matrix metallopeptidase 2, proto-oncogene tyrosine-protein kinase Src, and epidermal growth factor receptor as core targets. The Kyoto Encyclopedia of Genes and Genomes analysis revealed several significantly enriched pathways (P < 0.05), including the ERBB, phosphoinositide 3 kinase-AKT serine/threonine kinase 1 (AKT), and mechanistic target of rapamycin kinase (mTOR) pathways. Cellular experiments verified that CGA enhanced bone formation and promoted autophagy while inhibiting apoptosis in MLO-Y4 cells exposed to Dex, which was associated with the upregulated expression of HER2 and activation of the HER2/AKT/mTOR signaling pathway. CONCLUSION CGA exerted anti-osteoporotic effects against GIOP, partially through targeting osteocytes and modulating the HER2/AKT/mTOR signaling pathway. Please cite this article as: Xie AN, Zhang SZY, Zhang Y, Cao JL, Wang CL, Wang LB, Wu HJ, Zhang J, Dai WW. Chlorogenic acid mitigates glucocorticoid-induced osteoporosis via modulation of HER2/AKT/mTOR signaling pathway. J Integr Med. 2025; 23(6):670-682.
Animals ; Chlorogenic Acid/therapeutic use* ; Osteoporosis/metabolism* ; Signal Transduction/drug effects* ; Proto-Oncogene Proteins c-akt/metabolism* ; TOR Serine-Threonine Kinases/metabolism* ; Mice ; Glucocorticoids/adverse effects* ; Receptor, ErbB-2/metabolism* ; Proto-Oncogene Mas ; Dexamethasone/adverse effects* ; Osteocytes/drug effects* ; Osteogenesis/drug effects* ; Male ; Cell Line ; Mice, Inbred C57BL ; Humans

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To develop a diagnostic model combining the CT angiography(CCTA)-derived myocardial radiomics signatures with the CT-derived fractional flow reserve(CT-FFR)based on coronary CCTA and investigate the diagnostic accuracy of the hybrid model for hemodynamically significant coronary artery disease(CAD).Methods The patients presenting stable angina pectoris,diagnosed with CAD,and clinically referred for CCTA examination and invasive coronary angiography were prospectively recruited.Radiomics features of the left ventricular myocardium were extracted from the three main perfusion territories demarcated according to the coronary blood supply.The extracted features were first selected by the minimum redundancy maximum relevance feature ranking method.A least absolute shrinkage and selection operator Logistic regression algorithm with leave-one-out cross-validation was then employed to construct a radiomics model.The CT-FFR value was generated for each blood vessel.The area under the receiver operating characteristics curve(AUC_ROC),sensitivity,and specificity were adopted to evaluate the performance of each model against the reference standard invasive coronary angiography/FFR.Results A total of 70 patients[42 men and 28 women;(61±10) years old] were included in this study and complemented CCTA examination,with 175 vessels and the corresponding myocardial territories undergoing invasive coronary angiography/FFR.A total of 1 656 specific radiomics parameters were extracted,from which 14 features were selected to establish the radiomics model.The AUC_ROC,sensitivity,and specificity were 0.797(95%CI=0.732-0.861),77.1%,and 73.7%for the radiomics model,0.892(95%CI=0.841-0.943),81.4%,and 88.8%for the CT-FFR model,and 0.928(95%CI=0.890-0.965),83.3%,and 88.4%for the hybrid model,respectively.The hybrid model outperformed the radiomics model and CT-FFR alone(P=0.040).Conclusions The radiomics signatures of the vessel-related myocardium from CCTA could provide incremental value to the diagnostic performance of CT-FFR and improve vessel-specific ischemia detection.The hybrid model combining CT-FFR with radiomics signatures is potentially feasible for improving the diagnostic accuracy for hemodynamically significant CAD.
Coronary Angiography/methods* ; Tomography, X-Ray Computed ; Humans ; Hemodynamics ; Coronary Artery Disease/diagnostic imaging* ; Male ; Female ; Middle Aged ; Aged ; Radiomics ; Angina Pectoris/diagnostic imaging* ; China ; Image Processing, Computer-Assisted ; Coronary Vessels/diagnostic imaging*

OBJECTIVES: To develop and validate a preoperative clinical-radiomics model for predicting overall survival (OS) and disease-free survival (DFS) in patients with extrahepatic cholangiocarcinoma (eCCA) undergoing radical resection. METHODS: In this retrospective study, consecutive patients with pathologically-confirmed eCCA who underwent radical resection at our institution from 2015 to 2022 were included. The patients were divided into a training cohort and a validation cohort according to the chronological order of their CT examinations. Least absolute shrinkage and selection operator (LASSO)-Cox regression was employed to select predictive radiomic features and clinical variables. The selected features and variables were incorporated into a Cox regression model. Model performance for 1-year OS and DFS prediction was assessed using calibration curves, area under receiver operating characteristic curve (AUC), and concordance index (C-index). RESULTS: This study included 123 patients (mean age 64.0 ± 8.4 years, 85 males/38 females), with 86 in the training cohort and 37 in the validation cohort. The OS-predicting model included four clinical variables and four radiomic features. It achieved a training cohort AUC of 0.858 (C-index = 0.800) and a validation cohort AUC of 0.649 (C-index = 0.605). The DFS-predicting model included four clinical variables and four other radiomic features. It achieved a training cohort AUC of 0.830 (C-index = 0.760) and a validation cohort AUC of 0.717 (C-index = 0.616). CONCLUSIONS The preoperative clinical-radiomics models show promise as a tool for predicting 1-year OS and DFS in eCCA patients after radical surgery.
Humans ; Male ; Female ; Retrospective Studies ; Middle Aged ; Cholangiocarcinoma/mortality* ; Prognosis ; Bile Duct Neoplasms/mortality* ; Tomography, X-Ray Computed/methods* ; Aged ; Radiomics

Body weight abnormalities, including overweight, obesity, and underweight, have become a dual public health challenge in Chinese adults: overweight and obesity lead to a variety of chronic complications, while underweight increases the risks of malnutrition, sarcopenia, and organ dysfunction. To systematically address these issues, multidisciplinary experts in endocrinology, sports science, nutrition, and psychiatry from various regions have held multiple weight management seminars. Based on the latest epidemiological data and clinical evidence, they expanded the guideline to include assessment and intervention strategies for underweight, in addition to the core content of obesity management. This guideline outlines the etiological mechanisms, evaluation methods, and multidimensional management strategies for overweight and obesity, covering key areas such as diagnosis and assessment, medical nutrition therapy, exercise prescription, pharmacological intervention, and psychological support. It is intended to provide a scientific and standardized approach to weight management across the adult population, aiming to curb the rising prevalence of obesity, mitigate complications associated with abnormal body weight, and improve nutritional status and overall quality of life.

The aim of this updated guideline is to provide comprehensive recommendations for the management of gout in patients with common comorbidities, such as chronic kidney disease(CKD), cardiovascular disease(CVD), diabetes, osteoarthritis(OA), and gastrointestinal disorders. This guideline was developed by a multidisciplinary expert panel consisting of specialists in endocrinology, rheumatology, nephrology, cardiology, gastroenterology, and methodology. The development process adhered to standard methodologies, including PICO(population, intervention, comparator, and outcomes) question deconstruction, systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation(GRADE) for evidence and recommendation evaluation, Delphi voting, and expert consensus. The guideline presents 26 evidence-based recommendations addressing 7 clinical questions for patients with hyperuricemia and gout in the context of comorbidities. Key recommendations include the maintenance of strict serum urate targets, particularly for patients with CKD stage≥3, chronic gouty arthritis, and OA, in order to prevent disease progression. In patients with CVD or diabetes, intra-articular triamcinolone is preferred over systemic glucocorticoids. Prioritized anti-inflammatory treatments for patients with CKD, gastrointestinal diseases and OA are recommended. The guideline also introduces emerging therapies, such as interleukin-1 inhibitors and selective urate transport inhibitors, as potential treatment options for refractory cases. The update offers a comprehensive, patient-centered approach to managing gout, particularly in individuals with associated comorbidities. Multidisciplinary collaboration and emerging new treatments and evidence ensure the optimization of the recommendations.