BACKGROUND:The Guilu Erxian Glue consists of Testudinis Plastrum,Cornu Cervi,Lycii Fructus,and Ginseng Radix.In earlier clinical observations,it is discovered that using Guilu Erxian Glue to treat patients with liver-kidney deficiency type knee osteoarthritis effectively alleviated knee pain,increased the range of motion,and improved walking ability.However,the exact mechanism by which oral administration of Guilu Erxian Glue can produce local therapeutic effects on the knee joint is still unclear.OBJECTIVE:To investigate the effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis and to evaluate its mechanism using 16S rDNA sequencing and machine learning analysis.METHODS:Totally 18 female SD rats were randomly divided into three groups:blank group,model group,and Guilu Erxian Glue group,with 6 rats in each group.A knee osteoarthritis model was prepared using the destabilization of the medial meniscus surgical method.After successful modeling,the Guilu Erxian Glue group was given a decoction of Guilu Erxian Glue by gavage,while the blank and model groups were given an equal amount of distilled water.After 28 days of continuous intervention,high performance liquid chromatography was used to detect the active ingredients of Guilu Erxian Glue.MRI imaging was used to observe the condition of rat knee articular cartilage.Fecal samples were collected;DNA was extracted using a kit,amplified and purified by PCR,and an Illumina sequencing library was constructed.The Illumina MiSeq platform was used for high-throughput sequencing to generate raw sequence data.After obtaining the raw data,QIIME2 software was used to process the data.Linear Discriminant Analysis Effect Size analysis and random forest algorithm were used to screen for differential species in microbial data.KEGG and MetaCyc functional pathway analyses were used to explore the association between key microbial communities and experimental groups.Linear discriminant analysis effect values and random forest algorithm were used to screen for differential species.Association networks were used to analyze the interactions between microbial communities,and machine learning methods were used to analyze the composition and changes of gut microbiota.RESULTS AND CONCLUSION:(1)LC-MS component identification was conducted on the traditional Chinese medicine formula of Guilu Erxian Glue,and a total of 7 effective ingredients were identified.(2)MRI imaging showed that synovitis scope of high-density shadows in rats of the Guilu Erxian Glue group was reduced,and the degeneration of medial femoral condyle cartilage was less than that in the model group.(3)16S rDNA sequencing showed that the model group rats exhibited significant microbial imbalance,with a significant decrease in the abundance of Firmicutes and Bacteroidetes at the phylum level,while the proportion of Proteobacteria increased significantly(P＜0.05).The gut microbiota structure of rats in the Guilu Erxian Glue group was significantly improved,and the proportion of Firmicutes and Bacteroidetes increased,restoring a more diverse microbiota composition,approaching that of the blank group(P＜0.05).(4)KEGG and MetaCyc functional pathway analysis showed that the Guilu Erxian Glue group significantly activated multiple metabolic pathways,including amino acid metabolism,lipid metabolism,and biotin synthesis pathways(P＜0.05).(5)The results indicate that Guilu Erxian Glue contains seven active ingredients,and the changes in gut microbiota of knee osteoarthritis rats were analyzed using 16S rDNA sequencing.Guilu Erxian Glue can significantly improve the imbalance of gut microbiota,restore the abundance of beneficial bacteria,and have a significant impact on the composition of gut microbiota,providing scientific basis for the efficacy and mechanism of Guilu Erxian Glue.

BACKGROUND:The Guilu Erxian Glue consists of Testudinis Plastrum,Cornu Cervi,Lycii Fructus,and Ginseng Radix.In earlier clinical observations,it is discovered that using Guilu Erxian Glue to treat patients with liver-kidney deficiency type knee osteoarthritis effectively alleviated knee pain,increased the range of motion,and improved walking ability.However,the exact mechanism by which oral administration of Guilu Erxian Glue can produce local therapeutic effects on the knee joint is still unclear.OBJECTIVE:To investigate the effects of Guilu Erxian Glue on gut microbiota in rats with knee osteoarthritis and to evaluate its mechanism using 16S rDNA sequencing and machine learning analysis.METHODS:Totally 18 female SD rats were randomly divided into three groups:blank group,model group,and Guilu Erxian Glue group,with 6 rats in each group.A knee osteoarthritis model was prepared using the destabilization of the medial meniscus surgical method.After successful modeling,the Guilu Erxian Glue group was given a decoction of Guilu Erxian Glue by gavage,while the blank and model groups were given an equal amount of distilled water.After 28 days of continuous intervention,high performance liquid chromatography was used to detect the active ingredients of Guilu Erxian Glue.MRI imaging was used to observe the condition of rat knee articular cartilage.Fecal samples were collected;DNA was extracted using a kit,amplified and purified by PCR,and an Illumina sequencing library was constructed.The Illumina MiSeq platform was used for high-throughput sequencing to generate raw sequence data.After obtaining the raw data,QIIME2 software was used to process the data.Linear Discriminant Analysis Effect Size analysis and random forest algorithm were used to screen for differential species in microbial data.KEGG and MetaCyc functional pathway analyses were used to explore the association between key microbial communities and experimental groups.Linear discriminant analysis effect values and random forest algorithm were used to screen for differential species.Association networks were used to analyze the interactions between microbial communities,and machine learning methods were used to analyze the composition and changes of gut microbiota.RESULTS AND CONCLUSION:(1)LC-MS component identification was conducted on the traditional Chinese medicine formula of Guilu Erxian Glue,and a total of 7 effective ingredients were identified.(2)MRI imaging showed that synovitis scope of high-density shadows in rats of the Guilu Erxian Glue group was reduced,and the degeneration of medial femoral condyle cartilage was less than that in the model group.(3)16S rDNA sequencing showed that the model group rats exhibited significant microbial imbalance,with a significant decrease in the abundance of Firmicutes and Bacteroidetes at the phylum level,while the proportion of Proteobacteria increased significantly(P＜0.05).The gut microbiota structure of rats in the Guilu Erxian Glue group was significantly improved,and the proportion of Firmicutes and Bacteroidetes increased,restoring a more diverse microbiota composition,approaching that of the blank group(P＜0.05).(4)KEGG and MetaCyc functional pathway analysis showed that the Guilu Erxian Glue group significantly activated multiple metabolic pathways,including amino acid metabolism,lipid metabolism,and biotin synthesis pathways(P＜0.05).(5)The results indicate that Guilu Erxian Glue contains seven active ingredients,and the changes in gut microbiota of knee osteoarthritis rats were analyzed using 16S rDNA sequencing.Guilu Erxian Glue can significantly improve the imbalance of gut microbiota,restore the abundance of beneficial bacteria,and have a significant impact on the composition of gut microbiota,providing scientific basis for the efficacy and mechanism of Guilu Erxian Glue.

BACKGROUND: Metabolic-associated fatty liver disease (MAFLD) is the predominant form of chronic liver disease worldwide. This study was designed to investigate the proportion and characteristics of MAFLD within the general Chinese population and to identify the contributory risk factors for liver fibrosis among MAFLD individuals. METHODS: The participants were recruited from a cohort undergoing routine health evaluations at the Third Hospital of Hebei Medical University between May 2019 and March 2023. The diagnosis of MAFLD was based on the established clinical practice guidelines. The fibrosis-4 index score (FIB-4) was employed to evaluate hepatic fibrosis, with a FIB-4 score of ≥1.3 indicating significant fibrosis. Binary logistic regression analyses were used to determine risk factors associated with significant hepatic fibrosis in MAFLD. RESULTS: A total of 22,970 participants who underwent comprehensive medical examinations were included in the analysis. The overall proportion of MAFLD was 28.77% (6608/22,970), with 16.87% (1115/6608) of these patients showing significant fibrosis as assessed using FIB-4. Independent risk factors for significant liver fibrosis in MAFLD patients were male (odds ratio [OR] = 0.676, 95% confidence interval [CI]: 0.558-0.821), hepatitis B surface antigen (HBsAg) positivity (OR = 2.611, 95% CI: 1.557-4.379), body mass index ≥23.00 kg/m 2 (OR = 0.632, 95% CI: 0.470-0.851), blood pressure ≥130/85 mmHg (OR = 1.885, 95% CI: 1.564-2.272), and plasma glucose ≥5.6 mmol/L (OR = 1.815, 95% CI: 1.507-2.186) (all P <0.001). CONCLUSIONS The proportion of MAFLD in an urban Chinese population is 28.77%. About 16.87% of MAFLD patients presented with significant liver fibrosis. Independent risk factors for significant liver fibrosis in MAFLD patients should be noticed.
Humans ; Male ; Female ; Liver Cirrhosis/pathology* ; Middle Aged ; Risk Factors ; Adult ; Fatty Liver/pathology* ; Aged ; China/epidemiology* ; Logistic Models ; Urban Population ; East Asian People

Basket trial, as an innovative clinical trial design concept, marks the transformation of medical research from the traditional large-scale and single-disease treatment to the precise and individualized treatment. By gradually incorporating the Bayesian method during development, the trial design becomes more scientific and reasonable and increases its efficiency. The fundamental principle of the Bayesian method is the utilization of prior knowledge in conjunction with new observational data to dynamically update the posterior probability. This flexibility enhances the basket trial's capacity to effectively adapt to variations during the research process. Consequently, it enables researchers to dynamically adjust research strategies based on accumulated data and improve the predictive accuracy regarding treatment responses. In addition, the design concept of the basket trial aligns with the traditional Chinese medicine(TCM) principle of "homotherapy for heteropathy". The principle of "homotherapy for heteropathy" emphasizes that under certain conditions, different diseases may have the same treatment. Similarly, basket trials allow using a uniform trial design across multiple diseases, offering enhanced operational and significant practical value in the realm of TCM, particularly within the context of syndrome-based disease research. By introducing basket trials, the design of TCM clinical studies will be more scientific and yield higher-quality evidence. This study systematically categorized various Bayesian methods and models utilized in basket trials, evaluated their strengths and weaknesses, and identified their appropriate application contexts, so as to offer a practical guide for designing basket trials in the realm of TCM.
Bayes Theorem ; Humans ; Medicine, Chinese Traditional/methods* ; Research Design ; Clinical Trials as Topic/methods* ; Drugs, Chinese Herbal/therapeutic use*

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 evaluate the efficacy and safety of enteric-coated metformin hydrochloride capsules(Junlida?)in patients with T2DM and poor glycemic control under lifestyle interventions.Methods In this study,419 patients with T2DM were recruited from 15 research centers from July 2020 to March 2022,and randomly divided into observation(Obs)group(n=209)and control group(Con,n=210)using a multicenter,randomized,double-blind,non-inferiority trial design.Patients in the Obs group were treated with enteric-coated Metformin hydrochloride capsules(Junlida?),and patients in the Con group were treated with Metformin hydrochloride tablets(Glucophage?).The optimal effective dose of 2 g/d was achieved within 4 weeks,and the reasonable dose was maintained until the end of treatment.The treatment period was 24 weeks.HbA1c and its compliance rate,FPG,and body weight were compared between the two groups in full analysis set(FAS)and protocol set(PPS).Safety and adverse events(AE)were evaluated in safety set(SS).Results A total of 414 participants were randomized(207 cases in Obs group and 207 cases in Con group).414 cases in FAS population(207 cases in Obs group and 207 cases in Con group),and 328 cases in PPS population(164 cases in Obs group and 164 cases in Con group),and 414 cases in SS population(207 cases in Obs group and 207 cases in Con group).After treatment,HbA1c,FPG and body weight were lower in both groups(P<0.05)in FAS and PPS.HbA1c compliance rate was not significantly different between the two groups in FAS and PPS(P>0.05).The results of non-inferiority test showed that the lower limit was>-0.4%in both FAS(-0.154,95%CI-0.384～0.069)and PPS(-0.139,95%CI-0.390～0.112),and the Obs group reached non-inferiority end point.The achievement rate,compliance rate,safety index and incidence of AE were not significantly different between the two groups(P>0.05).Conclusions Junlida? demonstrated non-inferiority to Glucophage? in glycemic control and can be safely and effectively used in patients with diabetes.

Objective To design a Five-Elements Music Software based on Traditional Chinese Medicine's(TCM)theory of five elements music therapy and music emotion classification.The software is intended to provide appropriate music selections tailored to the negative emotional states of cancer patients and evaluate its effectiveness in psychological rehabilitation.Methods ①Music screening and classification:Qualitative analysis was used by six experts in TCM,psychology,nursing,and musicology to screen five elements music and classify corresponding emotional categories.②Software design and development:Based on screening and classification of music materials,design and develop a"Five Elements Music Software Based on Emotion Classification".③Software application evaluation:Recruit 50 cancer patients from the"Beijing Anti Cancer Paradise"as participants to have a trial listening experience with music software,and fill out a satisfaction questionnaire to evaluate its application effect.Results This study established a music database containing 150 pieces of five-elements musical tunes and completed the classification of emotional categories.Among the included subjects,80%of the recruited objects were satisfied with the experience of the five elements music software,of which the application experience of female patients was significantly better than that of male patients,and breast cancer patients were better than other cancer patients,with a statistically significant difference(P<0.05).The five elements music Software in clinic showed comparing with other two groups after four weeks,there was a significant difference for HAMD when comparing five elements music software group and the other two groups(P<0.05).Conclusion The five-element music software designed based on emotion classification effectively meets the psychological rehabilitation needs of cancer patients.It provides appropriate music selections and convenient listening method to regulate cancer-related negative emotions,extending psychological rehabilitation from the hospital to the home.

Objective:To explore the genotype and the clinical phenotype of SCN2A-related developmental delay in children. Methods:A case series study was adopted. Collect clinical data from 10 cases of children with SCN2A gene variants diagnosed with global developmental delay/intellectual disability who were admitted to the Children′s Hospital between July 2019 and March 2023. Summarize the clinical phenotype and genotype based on clinical data such as general information, clinical manifestations, imaging examinations, laboratory tests, genetic testing results, and comprehensive pediatric neuropsychological development assessment. Results:A total of 10 patients were recruited, including 7 males and 3 females, with an age range of 27 days to 5 years and 9 months. 9 patients underwent children′s neuropsychological and behavioral assessments, and the results were consistent with global developmental delay, including 2 mild cases, 4 moderate cases, and 3 severe cases. 3 cases had autism spectrum disorder, and 2 cases had epilepsy. 6 patients underwent complete head MRI examination, and 4 of them showed abnormalities, including delayed myelination, widening of the local extra brain space in the frontal lobe, and abnormal frontal lobe morphology. All 10 cases had point variants. Among them, 9 cases are de novo and 1 case is maternal inheritance. Out of 10 cases, there were 5 cases with copy number variations, but all of them were of unknown significance. Among the 10 variants, 8 have been reported and 2 have not been reported, namely c.4145A>T(p.N1382I) and c.4937T>A(p.I1646N). In this study, 4 out of 10 patients with SCN2A variants had variation sites located in the S4 segment of domain which constitute Nav1.2, the sodium ion channel encoded by SCN2A. The developmental quotient level was lower when the variation sites were located in the S4 segment of domain, and the difference was statistically significant ( t=-3.101, P=0.017), indicating that the severity of developmental delay may be related to the localization of amino acids corresponding to variant sites within the protein domain. Conclusion:SCN2A mutations are strongly associated with diverse neurodevelopmental disorders. In this study, the phenotypic spectrum of SCN2A variants encompassed epilepsy, global developmental delay, and autism spectrum disorder. Affected individuals exhibited early-onset developmental delays, predominantly moderate to severe in severity. Voltage-sensing domain dysfunction in sodium channels may constitute a critical pathomechanism underlying neurodevelopmental impairments. Further electrophysiological characterization and molecular mechanistic studies are warranted todelineate the genotype-phenotype correlations between specific variant loci and clinical severity.

OBJECTIVES: To investigate the effects of periodontitis induced by Prevotella nigrescens (Pn) combined with ligation on cognitive functions in mice. METHODS: Twenty-four C57BL/6J mice were randomly divided into control group, ligation group, and ligation + Pn treatment (P+Pn) group. Experimental periodontitis was induced by silk ligation of the first molars followed by topical application of Pn for 6 weeks. After modeling, alveolar bone resorption was assessed using micro-CT and histological analysis. Learning and memory abilities of the mice were evaluated using open field test (OFT), novel object recognition test (NORT), and Morris water maze test (MWM). Seven weeks after the start of modeling, the mice were sacrificed for examining histopathological changes in the hippocampus using HE and Nissl staining. RESULTS: After 6 weeks of molar ligation, micro-CT revealed horizontal alveolar bone resorption and furcation exposure in the mice, and histological analysis showed apical migration of the junctional epithelium, epithelial ridge hyperplasia, and lymphocyte infiltration, and these changes were obviously worsened in P+Pn group. Alveolar bone height decreased significantly in both ligation groups compared to the control group. Cognitive tests showed that the mice in both of the ligation groups traveled shorter distances in OFT, showed reduced novel object preference in NORT, and exhibited longer escape latencies in MWM, and the mice in P+Pn group had significantly poorer performances in the tests. Histologically, obvious neuronal cytoplasmic degeneration, necrosis, nuclear pyknosis, vacuolation, and reduced Nissl bodies and viable neurons were observed in the hippocampal regions of the mice in the two ligation groups. CONCLUSIONS Pn infection aggravates alveolar bone destruction, accelerates necrosis and causes morphological abnormalities of neuronal cells in the hippocampus to reduce cognitive functions of mice with periodontitis.
Animals ; Periodontitis/microbiology* ; Mice ; Mice, Inbred C57BL ; Cognition ; Alveolar Bone Loss ; Hippocampus/pathology* ; Male ; Inflammation ; Maze Learning

Objective:To compare and observe the visual acuity and ocular anatomical outcome of different subtypes in open-globe injury (OGI) Ⅲ.Methods:A retrospective study. A total of 187 eyes of 187 patients with OGI involving zone Ⅲ who were admitted to the Department of Ophthalmology of The First Affiliated Hospital of Army Medical University from January 2020 to December 2023 were included in the study. According to the 2022 International Globe and Adnexal Trauma Epidemiology Study groups consensus, zone Ⅲ was further divided into Ⅲa zone (5-8 mm posterior to the limbus) and Ⅲb zone (>8 mm posterior to the limbus), with 58 eyes (31%, 58/187) in group Ⅲa and 129 eyes (69%, 129/187) in group Ⅲb. Best corrected visual acuity (BCVA) was examined using the international standard decimal visual acuity chart, converted into the logarithm of the minimum angle of resolution (logMAR) visual acuity when recorded. The injured zone, initial visual acuity, final visual acuity, retinal detachment (RD), uveal prolapse, and proliferative vitreoretinopathy (PVR) were collected. The follow-up time after surgery ≥ 6 months. The final visual acuity and anatomical prognosis of the two groups were observed. Silicone oil dependence, phthisis, and enucleation were defined as poor anatomical outcomes. Multiple linear regression analysis was performed to analyze the impact of zone Ⅲb of OGI on the final visual acuity.Results:At the 6-month follow-up, the logMAR BCVA of group Ⅲa and group Ⅲb was 1.49±1.0 and 2.51±0.85; there was a statistically significant difference in the logMAR BCVA between the two groups ( t=-2.736, P<0.05). Compared with group Ⅲa, the proportion with light perception in group Ⅲb was higher, and the proportions with visual acuity of hand movement, counting fingers, and >0.01 were lower, and the differences were all statistically significant ( P<0.05). Compared with group Ⅲa, RD and PVR were more likely to occur in group Ⅲb, and the differences were all statistically significant ( χ2= 16.696, 8.697; P<0.05). Among the affected eyes in group Ⅲa and group Ⅲb, there were 14 eyes (24.1%, 14/58) and 95 eyes (73.6%, 95/129) with poor final anatomical outcomes respectively; the incidence of poor final anatomical outcomes in group Ⅲb was higher, and the difference was statistically significant ( χ2= 40.332, P<0.01). The results of multiple linear regression analysis showed that initial visual acuity, RD, and uveal prolapse were independent risk factors affecting the final visual acuity (odds ratio=2.407, 4.162, 3.413; P<0.05). Conclusions:Patients with OGI in zone Ⅲb have a worse visual prognosis and a higher incidence of poor anatomical outcomes. The subclassification of zone Ⅲ is helpful for better predicting the prognosis of OGI clinically.