Osteoporosis(OP) is a senile bone disease characterized by an imbalance between bone remodeling and bone formation. Targeting pathogenesis of kidney deficiency, spleen deficiency, and blood stasis, Bushen Jianpi Huoxue Decoction has a significant effect on the treatment of OP by tonifying kidney, invigorating spleen, and activating blood circulation. MicroRNA(miRNA) and the anti-apoptotic protein B-cell lymphoma-2-like protein 1(BCL2L1) are closely related to bone cell metabolism. Therefore, in this study, the binding of miR-140-5p to BCL2L1 was detected by dual luciferase assay and polymerase chain reaction(PCR). After silencing or overexpressing miR-140-5p, the apoptosis, autophagy, and osteogenic function of human fetal osteoblast cell line 1.19(HFOB1.19) were observed by flow cytometry and Western blot. Bushen Jianpi Huoxue Decoction-containing serum was prepared by intragastric administration of Bushen Jianpi Huoxue Decoction in rats. Different concentrations of Bushen Jianpi Huoxue Decoction-containing serum were used to treat HFOB1.19 with or without miR-140-5p mimic. The expression of osteogenic proteins in each group was observed, and the role of miR-140-5p/BCL2L1 in apoptosis and autophagy of HFOB1.19 was studied, along with the effect of Bushen Jianpi Huoxue Decoction on these processes. As indicated by the dual luciferase assay, miR-140-5p bound to BCL2L1. Flow cytometry and Western blot showed that miR-140-5p promoted apoptosis and inhibited autophagy in HFOB1.19. After intervention with high, medium, and low doses of Bushen Jianpi Huoxue Decoction-medicated serum, compared with the miR-140-5p NC group, the expression of osteocalcin(OCN), osteopontin(OPN), Runt-related transcription factor 2(RUNX2), and transforming growth factor beta 1(TGF-β1) decreased in the miR-140-5p mimic group, while the expression of bone morphogenetic protein 2(BMP2) showed no significant difference under high-dose intervention. Therefore, miR-140-5p/BCL2L1 can promote apoptosis and inhibit autophagy in HFOB1.19. Bushen Jianpi Huoxue Decoction can affect the osteogenic effect of miR-140-5p through BMP2.
MicroRNAs/metabolism* ; Autophagy/drug effects* ; Apoptosis/drug effects* ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Animals ; Cell Line ; bcl-X Protein/metabolism* ; Osteoblasts/metabolism* ; Rats ; Osteoporosis/physiopathology* ; Male ; Rats, Sprague-Dawley ; Osteogenesis/drug effects*

Pyroptosis is an identified programmed cell death that has been highly linked to endoplasmic reticulum (ER) dynamics. However, the crucial proteins for modulating dynamic ER membrane curvature change that trigger pyroptosis are currently not well understood. In this study, a biotin-labeled chemical probe of potent pyroptosis inducer α-mangostin (α-MG) was synthesized. Through protein microarray analysis, reticulon-4 (RTN4/Nogo), a crucial regulator of ER membrane curvature, was identified as a target of α-MG. We observed that chemically induced proteasome degradation of RTN4 by α-MG through recruiting E3 ligase UBR5 significantly enhances the pyroptosis phenotype in cancer cells. Interestingly, the downregulation of RTN4 expression significantly facilitated a dynamic remodeling of ER membrane curvature through a transition from tubules to sheets, consequently leading to rapid fusion of the ER with the cell plasma membrane. In particular, the ER-to-plasma membrane fusion process is supported by the observed translocation of several crucial ER markers to the "bubble" structures of pyroptotic cells. Furthermore, α-MG-induced RTN4 knockdown leads to pyruvate kinase M2 (PKM2)-dependent conventional caspase-3/gasdermin E (GSDME) cleavages for pyroptosis progression. In vivo, we observed that chemical or genetic RTN4 knockdown significantly inhibited cancer cells growth, which further exhibited an antitumor immune response with anti-programmed death-1 (anti-PD-1). In translational research, RTN4 high expression was closely correlated with the tumor metastasis and death of patients. Taken together, RTN4 plays a fundamental role in inducing pyroptosis through the modulation of ER membrane curvature remodeling, thus representing a prospective druggable target for anticancer immunotherapy.
Pyroptosis/immunology* ; Humans ; Endoplasmic Reticulum/immunology* ; Animals ; Nogo Proteins/antagonists & inhibitors* ; Mice ; Cell Line, Tumor ; Xanthones/pharmacology* ; Neoplasms/pathology* ; Mice, Nude

Functional dyspepsia (FD), characterized by persistent or recurrent dyspeptic symptoms without identifiable organic, systemic or metabolic causes, is an increasingly recognized global health issue. The objective of this guideline is to equip clinicians and nursing professionals with evidence-based strategies for the management and treatment of adult patients with FD using traditional Chinese medicine (TCM). The Guideline Development Group consulted existing TCM consensus documents on FD and convened a panel of 35 clinicians to generate initial clinical queries. To address these queries, a systematic literature search was conducted across PubMed, EMBASE, the Cochrane Library, China National Knowledge Infrastructure (CNKI), VIP Database, China Biology Medicine (SinoMed) Database, Wanfang Database, Traditional Medicine Research Data Expanded (TMRDE), and the Traditional Chinese Medical Literature Analysis and Retrieval System (TCMLARS). The evidence from the literature was critically appraised using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. The strength of the recommendations was ascertained through a consensus-building process involving TCM and allopathic medicine experts, methodologists, pharmacologists, nursing specialists, and health economists, leveraging their collective expertise and empirical knowledge. The guideline comprises a total of 43 evidence-informed recommendations that span a range of clinical aspects, including the pathogenesis according to TCM, diagnostic approaches, therapeutic interventions, efficacy assessments, and prognostic considerations. Please cite this article as: Zhang SS, Zhao LQ, Hou XH, Bian ZX, Zheng JH, Tian HH, Yang GH, Hong WS, He YY, Liu L, Shen H, Li YP, Xie S, Shu J, Zeng BF, Li JX, Liu Z, Xiao ZH, Xiao JD, Zheng PY, Huang SG, Chen SL, Fei GJ. International clinical practice guideline on the use of traditional Chinese medicine for functional dyspepsia (2025). J Integr Med. 2025; 23(5):502-518.
Dyspepsia/drug therapy* ; Humans ; Medicine, Chinese Traditional/methods* ; Practice Guidelines as Topic ; Drugs, Chinese Herbal/therapeutic use*

Objective:To evaluate the long-term effectiveness of lingual mucosal graft ureteroplasty (LMGU) for managing long-segment (≥5 cm) ureteral strictures in a multi-institutional cohort of patients.Methods:A multi-center retrospective case series study was conducted on clinical data from 42 patients undergoing LMGU for long-segment ureteral strictures (≥5 cm) across five institutions between February 2017 and June 2024. The cohort comprised 31 males and 11 females, with an age of (43.4±12.0) years (range: 15 to 64 years) and a body mass index of (24.6±2.6) kg/m2 (range: 16.0 to 30.0 kg/m2). Strictures involved the left ureter in 24 cases and right ureter in 18 cases, demonstrating a stricture length of (6.4±1.5) cm (range: 5.0 to 11.5 cm). Surgical interventions included either onlay ureteroplasty or augmented anastomotic ureteroplasty, selected according to intraoperative findings. Intraoperative parameters, postoperative complications, and follow-up outcomes were analyzed.Results:Laparoscopic surgery was performed in 22 cases and robot-assisted surgery in 20 cases. Among the 42 patients, 22 underwent onlay ureteroplasty while 20 received augmented anastomotic ureteroplasty. The graft length was (5.9±1.8) cm (range: 3.0 to 12.0 cm), operative time (191.5±55.6) minutes (range: 105.0 to 350.0 minutes), and intraoperative estimated blood loss (86.7±73.6) ml (range: 10.0 to 400.0 ml). All procedures were successfully completed without conversion to open surgery. The postoperative hospital stay was (7.6±2.0) days (range: 4.0 to 15.0 days), with double-J stent removal at 6 to 8 weeks postoperatively. During a follow-up of (49.1±25.0) months (range: 12.0 to 99.0 months), no stricture recurrence was observed in any patient.Conclusion:LMGU is a safe, feasible, and effective long-term technique for managing long-segment (≥5 cm) ureteral strictures.

Paraplegia caused by spinal cord injury is a serious neurological complication, for which surgery is currently the main treatment method. Due to different surgical approaches, patients are usually expected to maintain a passive prone position for a long time or switch between the supine and prone positions. Affected by multiple factors such as neurogenic sensory disorders, pathological changes in muscle tone and operative duration, the risk of intraoperative acquired pressure injury (IAPI) is significantly increased. Current clinical prevention strategies for IAPI in these patients predominantly focus on localized pressure relief during positioning, lacking systematic, standardized comprehensive prevention protocols or evidence-based guidelines. To address it, Department of Nursing, Orthopedics Branch, China International Exchange and Promotive Association for Medical and Health Care, Spinal Trauma Professional Committee, Orthopedics Branch, Chinese Medical Doctor Association, Nursing Group of Spine and Spinal Cord Professional Committee of Chinese Association of Rehabilitation Medicine organized experts in relevant fields to formulate Guideline for the prevention of intraoperative acquired pressure injury in paraplegic patients with spinal cord injury ( version 2025), based on evidence-based medical evidence and latest research results and clinical practice at home and abroad. Eleven recommendations were put forward from the aspects of preoperative risk assessment, intraoperative prevention strategies, postoperative handover and monitoring, and supportive mechanisms for IAPI prevention, aiming to standardize the prevention measures and management strategies of IAPI in paraplegic patients with spinal cord injury and accelerate the recovery of patients and improve the therapeutic effect.

Objective To develop a deep learning model based on fundus retinal images to improve the detection rate of mild cognitive impairment(MCI)in patients with coronary heart disease,achieve early intervention and improve prognosis.Methods The study was a single-center cross-sectional study that retrospectively included patients diagnosed with coronary heart disease(CHD)by coronary angiography(≥50％ stenosis of at least one coronary vessel)from Beijing Anzhen Hospital between November 2021 and December 2022.The whole data set was randomly divided into the training set and the testing set according to the ratio of 8∶2 for model development.After that,the patient data of the same center from January 2023 to April 2023 were included in the time verification method to verify the model.The diagnostic criteria for MCI were MMSE＜27 or MoCA＜26.Four kinds of convolutional neural network(CNN)architectures were used to train fundus images,and a comprehensive vision model of MCI detection was established through model integration.The area under the curve(AUC),sensitivity and specificity of the receiver operating curve(ROC)were used to evaluate the performance of the AI model.Results We collected 5 880 eligible fundus images from 3 368 CHD patients.Based on the results of the MMSE scale,the algorithm was labeled,including 2 898 males and 527 MCI patients.The AUC of the deep learning model in the test group is 0.733(95％CI 0.688-0.778),and the sensitivity of the algorithm in the test group is 0.577(95％CI 0.528-0.625)by using the operating point with the maximum sum of sensitivity and specificity.With a specificity of 0.758(95％CI 0.714-0.802),corresponding to a validated AUC of 0.710(95％CI 0.601-0.818).Based on the results of the MoCA scale,the algorithm labels 2 437 males and 1 626 MCI patients.The AUC of the deep learning model in the test group was 0.702(95％CI 0.671-0.733).The operating point with the maximum sum of sensitivity and specificity was selected,and the sensitivity of the algorithm was 0.749(95％CI 0.719-0.778)and the specificity was 0.561(95％CI 0.527-0.595),corresponding to the AUC value of the verification group was 0.674(95％CI 0.622-0.726).Conclusions The deep learning algorithm model based on fundus images has good diagnostic performance,and may be used as a new non-invasive,convenient and rapid screening method for MCI in CHD population.

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.

BACKGROUND:Unlike non-inflammatory cell apoptosis,pyroptosis is a form of inflammatory cell death,characterized by membrane integrity disruption and release of pro-inflammatory intracellular substances.Thus,it is associated with various diseases.The sirtuin family is a group of histone deacetylases dependent on nicotinamide adenine dinucleotide.In addition to deacetylation,it also possesses other enzymatic activities such as desuccinylation,demalonylation,adenosine diphosphate-ribosylation and playing crucial roles in the regulation of pyroptosis.OBJECTIVE:To review the role of the sirtuins in pyroptosis.METHODS:The first author conducted a search on PubMed,Web of Science,CNKI,and WanFang Data from inception to March 2024,using the Chinese and English search terms"Sirtuins,Sirtuin1,Sirtuin2,Sirtuin3,Sirtuin4,Sirtuin5,Sirtuin6,Sirtuin7,pyroptosis",resulting in the inclusion of 71 articles.RESULTS AND CONCLUSION:(1)The sirtuin family all participates in the regulation of pyroptosis.(2)Overexpression of sirtuin1 and sirtuin4 can inhibit pyroptosis through various pathways,thus alleviating the damage caused by pyroptosis to the organism.(3)In addition to affecting the classical pathway of pyroptosis,sirtuin3 can also inhibit pyroptosis by enhancing mitochondrial reactive oxygen species scavenging capacity and mitosis.(4)Sirtuin5 is involved in the regulation of intracellular metabolism and energy balance,including energy intake,storage,and consumption.(5)Sirtuin6 can influence pyroptosis through various pathways and also affect macrophage M1 polarization,generation of reactive oxygen species,and cleavage of pyroptosis-related factor sclerotin D to inhibit pyroptosis.(6)Overexpression of sirtuin7 can suppress pyroptosis.(7)Sirtuin2,unlike other family members,can restrain pyroptosis only after knockdown,but there are fewer reports,requiring more in-depth and comprehensive research.

BACKGROUND:Unlike non-inflammatory cell apoptosis,pyroptosis is a form of inflammatory cell death,characterized by membrane integrity disruption and release of pro-inflammatory intracellular substances.Thus,it is associated with various diseases.The sirtuin family is a group of histone deacetylases dependent on nicotinamide adenine dinucleotide.In addition to deacetylation,it also possesses other enzymatic activities such as desuccinylation,demalonylation,adenosine diphosphate-ribosylation and playing crucial roles in the regulation of pyroptosis.OBJECTIVE:To review the role of the sirtuins in pyroptosis.METHODS:The first author conducted a search on PubMed,Web of Science,CNKI,and WanFang Data from inception to March 2024,using the Chinese and English search terms"Sirtuins,Sirtuin1,Sirtuin2,Sirtuin3,Sirtuin4,Sirtuin5,Sirtuin6,Sirtuin7,pyroptosis",resulting in the inclusion of 71 articles.RESULTS AND CONCLUSION:(1)The sirtuin family all participates in the regulation of pyroptosis.(2)Overexpression of sirtuin1 and sirtuin4 can inhibit pyroptosis through various pathways,thus alleviating the damage caused by pyroptosis to the organism.(3)In addition to affecting the classical pathway of pyroptosis,sirtuin3 can also inhibit pyroptosis by enhancing mitochondrial reactive oxygen species scavenging capacity and mitosis.(4)Sirtuin5 is involved in the regulation of intracellular metabolism and energy balance,including energy intake,storage,and consumption.(5)Sirtuin6 can influence pyroptosis through various pathways and also affect macrophage M1 polarization,generation of reactive oxygen species,and cleavage of pyroptosis-related factor sclerotin D to inhibit pyroptosis.(6)Overexpression of sirtuin7 can suppress pyroptosis.(7)Sirtuin2,unlike other family members,can restrain pyroptosis only after knockdown,but there are fewer reports,requiring more in-depth and comprehensive research.

Objective To develop a deep learning model based on fundus retinal images to improve the detection rate of mild cognitive impairment(MCI)in patients with coronary heart disease,achieve early intervention and improve prognosis.Methods The study was a single-center cross-sectional study that retrospectively included patients diagnosed with coronary heart disease(CHD)by coronary angiography(≥50％ stenosis of at least one coronary vessel)from Beijing Anzhen Hospital between November 2021 and December 2022.The whole data set was randomly divided into the training set and the testing set according to the ratio of 8∶2 for model development.After that,the patient data of the same center from January 2023 to April 2023 were included in the time verification method to verify the model.The diagnostic criteria for MCI were MMSE＜27 or MoCA＜26.Four kinds of convolutional neural network(CNN)architectures were used to train fundus images,and a comprehensive vision model of MCI detection was established through model integration.The area under the curve(AUC),sensitivity and specificity of the receiver operating curve(ROC)were used to evaluate the performance of the AI model.Results We collected 5 880 eligible fundus images from 3 368 CHD patients.Based on the results of the MMSE scale,the algorithm was labeled,including 2 898 males and 527 MCI patients.The AUC of the deep learning model in the test group is 0.733(95％CI 0.688-0.778),and the sensitivity of the algorithm in the test group is 0.577(95％CI 0.528-0.625)by using the operating point with the maximum sum of sensitivity and specificity.With a specificity of 0.758(95％CI 0.714-0.802),corresponding to a validated AUC of 0.710(95％CI 0.601-0.818).Based on the results of the MoCA scale,the algorithm labels 2 437 males and 1 626 MCI patients.The AUC of the deep learning model in the test group was 0.702(95％CI 0.671-0.733).The operating point with the maximum sum of sensitivity and specificity was selected,and the sensitivity of the algorithm was 0.749(95％CI 0.719-0.778)and the specificity was 0.561(95％CI 0.527-0.595),corresponding to the AUC value of the verification group was 0.674(95％CI 0.622-0.726).Conclusions The deep learning algorithm model based on fundus images has good diagnostic performance,and may be used as a new non-invasive,convenient and rapid screening method for MCI in CHD population.