ObjectiveTo investigate the mechanism by which Gegen Qinliantang（GQT） improves skeletal muscle insulin resistance. MethodsThe db/m mice were used as the normal group， while db/db mice were assigned to a model group， low-dose （3.12 g·kg^-1）， medium-dose （6.24 g·kg^-1）， and high-dose （12.48 g·kg^-1） GQT groups， and a Western medicine group （semaglutide， 0.045 mg·kg^-1），n=6 in each group. All groups received corresponding interventions. Intraperitoneal glucose tolerance test （IPGTT）， intraperitoneal insulin tolerance test （IPITT）， and hematoxylin-eosin （HE） staining were used to evaluate insulin resistance and therapeutic efficacy. Serum lipid levels were measured using an automatic biochemical analyzer， and apoptosis in skeletal muscle was assessed via TUNEL assay. Transcriptome sequencing combined with gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses was performed to identify differentially expressed genes （DEGs）. Real-time quantitative polymerase chain reaction （Real-time PCR） was used to validate gene expression. Molecular docking was applied to evaluate the binding patterns between active components of GQT and key regulatory genes to elucidate pharmacological mechanisms. ResultsCompared with the model group， the medium-dose and high-dose GQT groups showed significantly reduced fasting blood glucose （FBG） levels （P<0.01）. Triglycerides （TG）， total cholesterol （TC）， and low-density lipoprotein cholesterol （LDL-C） were markedly decreased （P<0.01）， while high-density lipoprotein cholesterol （HDL-C） was significantly increased （P<0.01）. IPGTT， IPITT， and HE staining demonstrated that GQT enhanced insulin sensitivity and restored skeletal muscle morphology. GQT also alleviated apoptosis in skeletal muscle tissue. Transcriptome analysis revealed that GQT primarily affected biological processes such as oxidative phosphorylation， metabolic pathways， cellular processes， and protein binding. Real-time PCR results showed that CBR2， CDK6， F830016B08Rik， IL-1β， Rab27b， and COLEC12 were key regulatory genes. Molecular docking demonstrated that CBR2， IL-1β， Rab27b， and COLEC12 formed stable binding with the main active components of GQT. The therapeutic effects of high- and medium-dose GQT were comparable to those of the semaglutide group. ConclusionGQT improves skeletal muscle insulin resistance， potentially by regulating apoptosis as part of its underlying biological mechanism.

ObjectiveTo observe the clinical efficacy and safety of Yuyin Lidan granules （YYLD） in preventing the recurrence of common bile duct stones （CBDS） in patients with liver and gallbladder dampness-heat syndrome following endoscopic retrograde cholangiopancreatography （ERCP）. MethodsThis randomized， parallel， controlled trial enrolled postoperative CBDS-ERCP patients who met the inclusion and exclusion criteria. Sixty-four patients were randomly assigned to an observation group or a control group， with 32 cases in each. Both groups received conventional Western medical treatment after ERCP， while the observation group additionally received YYLD for 8 weeks. The follow-up period lasted for 1 year. The efficacy indicators included bile bilirubin levels， traditional Chinese medicine （TCM） syndrome scores， clinical efficacy rate， pancreatitis and inflammation markers， postoperative liver function， and CBDS recurrence rate at 1-year follow-up， which were used to jointly evaluate the clinical efficacy and safety of both groups. ResultsA total of 56 patients completed the study and were included in the final analysis， i.e.， 29 in the observation group and 27 in the control group. Baseline characteristics were comparable between the two groups. Compared with pre-treatment and with the control group after treatment， the bile bilirubin level in the observation group significantly decreased （P<0.05）. After treatment， the clinical cure and marked improvement rates were higher in the observation group than in the control group， showing a statistically significant difference in overall clinical efficacy （P<0.05）. Compared with pre-treatment， the primary and secondary symptoms in the observation group， as well as the primary symptom and the secondary symptom of nausea and vomiting in the control group （weeks 4 and 8）， were significantly reduced （P<0.05）. Compared with the control group after treatment， the observation group showed significant reductions in the primary symptom of loose stools/constipation （day 5 and week 4） and in three secondary symptoms， i.e.， bitter taste and sticky dry mouth， abdominal distension and poor appetite （throughout the treatment period）， and general heaviness and fatigue （day 5 and week 4）， with statistical differences （P<0.05）. Compared with pre-treatment， both groups showed decreased lipase and urinary amylase levels （P<0.05）. However， no significant between-group differences were observed in pancreatitis or inflammation-related indices after treatment. Compared with pre-treatment， all liver function indicators in the observation group and alanine aminotransferase （ ALT ）， γ-glutamyl transferase （ γ-GT ）， alkaline phosphatase （ALP）， and conjugated bilirubin in the control group significantly decreased at weeks 4 and 8 （P<0.05）. Compared with the control group after treatment， only serum total bilirubin and unconjugated bilirubin were significantly reduced in the observation group during the treatment period （P<0.05）. ConclusionYYLD combined with conventional Western medical treatment can effectively regulate bilirubin metabolism （in bile and serum）， improve TCM clinical symptoms， and prevent CBDS recurrence after ERCP in patients with liver and gallbladder dampness-heat syndrome. This regimen is safe and effective and is worthy of further clinical research and promotion.

OBJECTIVE: To explore the genetic etiology of 46 Chinese pedigrees affected with Hereditary multiple exostoses (HME) and provide genetic counseling and reproductive intervention. METHODS: Whole-exome sequencing and Sanger sequencing were carried out on 87 patients from the 46 pedigrees to analyze the variants of EXT1 and EXT2 genes. Pathogenicity of the variants was assessed based on the guidelines from the American College of Medical Genetics and Genomics and Association for Molecular Pathology (ACMG/AMP). Prenatal diagnosis and preimplantation genetic testing (PGT) were provided for couples with identified pathogenic mutations. This study was approved by the Medical Ethics Committee of the hospital (Ethics No.: LL-SC-SG-2014-010). RESULTS: In total 17 and 22 pathogenic variants were respectively identified in the EXT1 and EXT2 genes, among which 5 EXT1 and 12 EXT2 variants were unreported previously. Three patients with no family history were found to harbor de novo variants of the EXT1 gene. Twenty nine couples had opted for PGT or underwent prenatal diagnosis following natural conception, and 17 healthy babies were born. CONCLUSION This study has clarified the genetic etiology of 45 HME pedigrees and identified 17 novel variants, which has enriched the mutational spectrum of the EXT1 and EXT2 genes. Reproductive intervention through PGT and prenatal diagnosis have prevented the recurrence of HME in these families.
Humans ; Female ; Male ; Pedigree ; Exostoses, Multiple Hereditary/diagnosis* ; N-Acetylglucosaminyltransferases/genetics* ; Adult ; Exostosin 1 ; Asian People/genetics* ; Genetic Testing ; Exostosin 2 ; Mutation ; China ; Prenatal Diagnosis ; Pregnancy ; Genetic Counseling ; Preimplantation Diagnosis ; Exome Sequencing ; East Asian People

ObjectiveTo assess the predictive value of the bladder deformation index (BDI) in determining upper urinary tract (UUT) damage among patients with neurogenic bladder (NB). MethodsClinical data of 132 NB patients admitted to Beijing Bo'ai Hospital from January, 2015 to December, 2018 were retrospectively analyzed. Patients were divided into UUT damage group and normal UUT group according to the presence or absence of hydronephrosis. The demographics, biochemical parameters and video-urodynamics (VUDS) findings were collected, and BDI was calculated. Receiver operating characteristic (ROC) curves were utilized to evaluate the predictive capability. ResultsThere were 54 patients in UUT damage group and 33 in normal UUT group. The course of disease, creatinine level and BDI were siginificantly different between two groups (P < 0.05), while the area under the curve were 0.686, 0.836 and 0.928, respectively. ConclusionCourse of disease, creatinine level and BDI are associated with UUT damage in NB patients, and BDI demonstrates the highest sensitivity and specificity, which may play a role in diagnosis of UUT damage.

Metabolic-associated fatty liver disease (MAFLD) and osteoporosis (OP) are two very common metabolic diseases. A growing body of experimental evidence supports a pathophysiological link between MAFLD and OP. MAFLD is often associated with the development of OP. Rutaecarpine (RUT) is one of the main active components of Chinese medicine Euodiae Fructus. Our previous studies have demonstrated that RUT has lipid-lowering, anti-inflammatory and anti-atherosclerotic effects, and can improve the OP of rats. However, whether RUT can improve both fatty liver and OP symptoms of MAFLD mice at the same time remains to be investigated. In this study, we used C57BL/6 mice fed a high-fat diet (HFD) for 4 months to construct a MAFLD model, and gave the mice a low dose (5 mg·kg^-1) and a high dose (15 mg·kg^-1) of RUT by gavage for 4 weeks. The effects of RUT on liver steatosis and bone metabolism were then evaluated at the end of the experiment [this experiment was approved by the Experimental Animal Ethics Committee of Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences (approval number: IMB-20190124D₃03)]. The results showed that RUT treatment significantly reduced hepatic steatosis and lipid accumulation, and significantly reduced bone loss and promoted bone formation. In summary, this study shows that RUT has an effect of improving fatty liver and OP in MAFLD mice.

Objective To evaluate the performance of the artificial intelligence (AI)-enabled snail identification system for recognition of Oncomelania hupensis robertsoni and Tricula in schistosomiasis-endemic areas of Yunnan Province. Methods Fifty O. hupensis robertsoni and 50 Tricula samples were collected from Yongbei Township, Yongsheng County, Lijiang City, a schistosomiasis-endemic area in Yunnan Province in May 2024. A total of 100 snail sample images were captured with smartphones, including front-view images of 25 O. hupensis robertsoni and 25 Tricula samples (upward shell opening) and back-view images of 25 O. hupensis robertsoni and 25 Tricula samples (downward shell opening). Snail samples were identified as O. hupensis robertsoni or Tricula by schistosomiasis control experts with a deputy senior professional title and above according to image quality and morphological characteristics. A standard dataset for snail image classification was created, and served as a gold standard for recognition of snail samples. A total of 100 snail sample images were recognized with the AI-enabled intelligent snail identification system based on a WeChat mini program in smartphones. Schistosomiasis control professionals were randomly sampled from stations of schistosomisis prevention and control and centers for disease control and prevention in 18 schistosomiasis-endemic counties (districts, cities) of Yunnan Province, for artificial identification of 100 snail sample images. All professionals are assigned to two groups according the median years of snail survey experiences, and the effect of years of snail survey experiences on O. hupensis robertsoni sample image recognition was evaluated. A receiver operating characteristic (ROC) curve was plotted, and the sensitivity, specificity, accuracy, Youden’s index and the area under the curve (AUC) of the AI-enabled intelligent snail identification system and artificial identification were calculated for recognition of snail sample images. The snail sample image recognition results of AI-enabled intelligent snail identification system and artificial identification were compared with the gold standard, and the internal consistency of artificial identification results was evaluated with the Cronbach’s coefficient alpha. Results A total of 54 schistosomiasis control professionals were sampled for artificial identification of snail sample image recognition, with a response rate of 100% (54/54), and the accuracy, sensitivity, specificity, Youden’s index, and AUC of artificial identification were 90%, 86%, 94%, 0.80 and 0.90 for recognition of snail sample images, respectively. The overall Cronbach’s coefficient alpha of artificial identification was 0.768 for recognition of snail sample images, and the Cronbach’s coefficient alpha was 0.916 for recognition of O. hupensis robertsoni snail sample images and 0.925 for recognition of Tricula snail sample images. The overall accuracy of artificial identification was 90% for recognition of snail sample images, and there was no significant difference in the accuracy of artificial identification for recognition of O. hupensis robertsoni (86%) and Tricula snail sample images (94%) (χ² = 1.778, P > 0.05). There was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (88%) and downward shell openings (92%) (χ² = 0.444, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less (75%) and more than 6 years (90%) (χ² = 7.792, P < 0.05). The accuracy, sensitivity, specificity and AUC of the AI-enabled intelligent snail identification system were 88%, 100%, 76% and 0.88 for recognition of O. hupensis robertsoni snail sample images, and there was no significant difference in the accuracy of recognition of O. hupensis robertsoni snail sample images between the AI-enabled intelligent snail identification system and artificial identification (χ² = 0.204, P > 0.05). In addition, there was no significant difference in the accuracy of artificial identification for recognition of snail sample images with upward (90%) and downward shell openings (86%) (χ² = 0.379, P > 0.05), and there was a significant difference in the accuracy of artificial identification for recognition of snail sample images between schistosomiasis control professionals with snail survey experiences of 6 years and less and more than 6 years (χ² = 5.604, P_adjusted < 0.025). Conclusions The accuracy of recognition of snail sample images is comparable between the AI-enabled intelligent snail identification system and artificial identification by schistosomiasis control professionals, and the AI-enabled intelligent snail identification system is feasible for recognition of O. hupensis robertsoni and Tricula in Yunnan Province.

The Expert Consensus on the Deployment of DeepSeek in Medical Institutions serves as a detailed guideline for the deployment of DeepSeek in medical institutions. It was developed by experts in the fields of healthcare， hospital management， medical information， health policy， law， and medical ethics from nearly 30 leading domestic medical and academic research institutions， based on relevant domestic and international laws and regulations as well as the practices of medical institutions. It aims to provide medical institutions with a scientific， standardized， and secure deployment guideline to ensure that the application of artificial intelligence （AI） technologies in healthcare， including but not limited to DeepSeek， conforms to the unique characteristics of the healthcare industry and effectively promotes the improvement of medical service levels. From the three aspects of pre-deployment evaluation， deployment implementation， and post-deployment management and monitoring， the key factors that medical institutions should consider when introducing DeepSeek were elaborated in detail， including medical demand compatibility， technical capabilities and infrastructure， legal and ethical risks， data preparation and management， model selection and optimization， system integration and training， performance monitoring and continuous optimization， risk management and emergency response， as well as compliance review and evaluation. This provides a comprehensive deployment framework for medical institutions to ensure the safety and effectiveness of technology applications.

Background/Aims: Metabolic dysfunction-associated steatohepatitis (MASH) is a significant risk factor for gallstone formation, but mechanisms underlying MASH-related gallstone formation remain unclear. Golgi membrane protein 1 (GOLM1) participates in hepatic cholesterol metabolism and is upregulated in MASH. Here, we aimed to explore the role of GOLM1 in MASH-related gallstone formation. Methods: The UK Biobank cohort was used for etiological analysis. GOLM1 knockout (GOLM1-/-) and wild-type (WT) mice were fed with a high-fat diet (HFD). Livers were excised for histology and immunohistochemistry analysis. Gallbladders were collected to calculate incidence of cholesterol gallstones (CGSs). Biles were collected for biliary lipid analysis. HepG2 cells were used to explore underlying mechanisms. Human liver samples were used for clinical validation. Results: MASH patients had a greater risk of cholelithiasis. All HFD-fed mice developed MASH, and the incidence of gallstones was 16.7% and 75.0% in GOLM1-/- and WT mice, respectively. GOLM1-/- decreased biliary cholesterol concentration and output. In vivo and in vitro assays confirmed that GOLM1 facilitated cholesterol efflux through upregulating ATP binding cassette transporter subfamily G member 5 (ABCG5). Mechanistically, GOLM1 translocated into nucleus to promote osteopontin (OPN) transcription, thus stimulating ABCG5-mediated cholesterol efflux. Moreover, GOLM1 was upregulated by interleukin-1β (IL-1β) in a dose-dependent manner. Finally, we confirmed that IL-1β, GOLM1, OPN, and ABCG5 were enhanced in livers of MASH patients with CGSs. Conclusions In MASH livers, upregulation of GOLM1 by IL-1β increases ABCG5-mediated cholesterol efflux in an OPN-dependent manner, promoting CGS formation. GOLM1 has the potential to be a molecular hub interconnecting MASH and CGSs.

Laparoscopic subtotal cholecystectomy (LSC) has been a safe and viable alternative to conversion to laparotomy in cases of severe cholecystitis. The objective of this study is to determine the utility of intraoperative choledochoscopy in LSC for the exploration of the gallbladder, cyst duct, and subsequent stone clearance of the cystic duct in cases of severe cholecystitis. A total of 72 patients diagnosed with severe cholecystitis received choledochoscopy-assisted laparoscopic subtotal cholecystectomy (CALSC). A choledochoscopy was performed to explore the gallbladder cavity and/or cystic duct, and to extract stones using a range of techniques. The clinical records, including the operative records and outcomes, were subjected to analysis. No LSC was converted to open surgery, and no bile duct or vascular injuries were sustained. All stones within the cystic duct were removed by a combination of techniques, including high-frequency needle knife electrotomy, basket, and electrohydraulic lithotripsy. A follow-up examination revealed the absence of residual bile duct stones, with the exception of one common bile duct stone, which was extracted via endoscopic retrograde cholangiopancreatography. In certain special cases, CALSC may prove to be an efficacious treatment for the management of severe cholecystitis. This technique allows for optimal comprehension of the situation within the gallbladder cavity and cystic duct, facilitating the removal of stones from the cystic duct and reducing the residue of the non-functional gallbladder remnant.

Lactylation (Kla), a protein post-translational modification characterized by the covalent conjugation of lactyl groups to lysine residues in proteins, is widely present in living organisms. Since its discovery in 2019, it has attracted much attention for its role in regulating major pathological processes such as tumorigenesis, neurodegenerative diseases, and cardiovascular diseases. By mediating core biological processes such as signal transduction, epigenetic regulation, and metabolic homeostasis, lactylation contributes to disease progression. However, the lactylation donor lactyl-CoA has a low intracellular concentration, and the specific enzyme catalyzing lactylation is not yet clear, which has become an urgent issue in lactate research. A groundbreaking study in 2024 found that alanyl-transfer t-RNA synthetase 1/2 (AARS1/2), members of the aminoacyl-tRNA synthetase (aaRS) family, can act as protein lysine lactate transferases, modifying histones and metabolic enzymes directly with lactate as a substrate, without relying on the classical substrate lactyl-CoA, promoting a new stage in lactate research. Although exercise significantly increases lactate levels in the body and can induce changes in lactylation in multiple tissues and cells, the regulation of lactylation by exercise is not entirely consistent with lactate levels. Research has found that high-intensity exercise can induce upregulation of lactate at 37 lysine sites in 25 proteins of adipose tissue, while leading to downregulation of lactate at 27 lysine sites in 22 proteins. The level of lactate is not the only factor regulating lactylation through exercise. We speculate that the lactate transferase AARS1/2 play an important role in the process of lactylation regulated by exercise, and AARS1/2 should also be regulated by exercise. This review introduces the molecular biology characteristics, subcellular localization, and multifaceted biological functions of AARS, including its canonical roles in alanylation and editing, as well as its newly identified lactate transferase activity. We detail the discovery of AARS1/2 as lactylation catalysts and the specific process of them as lactate transferases catalyzing protein lactylation. Furthermore, we discuss the pathophysiological significance of AARS in tumorigenesis, immune dysregulation, and neuropathy, with a focus on exploring the expression regulation and possible mechanisms of AARS through exercise. The expression of AARS in skeletal muscle regulated by exercise is related to exercise time and muscle fiber type; the skeletal muscle AARS2 upregulated by long-term and high-intensity exercise catalyzes the lactylation of key metabolic enzymes such as pyruvate dehydrogenase E1 alpha subunit (PDHA1) and carnitine palmitoyltransferase 2 (CPT2), reducing exercise capacity and providing exercise protection; physiological hypoxia caused by exercise significantly reduces the ubiquitination degradation of AARS2 by inhibiting its hydroxylation, thereby maintaining high levels of AARS2 protein and exerting lactate transferase function; exercise induced lactate production can promote the translocation of AARS1 cytoplasm to the nucleus, exert lactate transferase function upon nuclear entry, regulate histone lactylation, and participate in gene expression regulation; exercise induced lactate production promotes direct interactions between AARS and star molecules such as p53 and cGAS, and is widely involved in the occurrence and development of tumors and immune diseases. Elucidating the regulatory mechanism of exercise on AARS can provide new ideas for improving metabolic diseases and promote health through exercise.