ObjectiveTo explore the improving effect of Huangqi Chifengtang（HCT） on atherosclerosis（AS）， and elucidate its mechanism in relation to adenosine monophosphate-activated protein kinase（AMPK）/peroxisome proliferator-activated receptor α（PPARα） signaling pathway and nucleotide-binding oligomerization domain（NOD）-like receptor thermal protein domain associated protein 3（NLRP3） inflammasome. MethodsEight C57BL/6J mice were set as the normal group， and 32 ApoE^-/- mice were randomly divided into the model group， the positive drug group（atorvastatin， 5 mg·kg^-1·d^-1）， HCT low- and high-dose groups（1.95， 3.90 g·kg^-1·d^-1）. ApoE^-/- mice were fed with high-fat and high-cholesterol feed to establish an AS mouse model. After modeling， they were orally administered corresponding dose of drugs for 28 days， while the normal and model groups received an equal volume of physiological saline via oral gavage. Hematoxylin-eosin（HE） staining was used to observe the pathological status of the aorta and liver in mice， Biochemical testing and enzyme-linked immunosorbent assay（ELISA） were used to detect the levels of total cholesterol（TC）， triglycerides（TG）， low-density lipoprotein cholesterol（LDL-C）， alanine aminotransferase（ALT）， aspartate aminotransferase（AST）， C-reactive protein（CRP）， interleukin（IL）-1β， IL-18 in the serum， as well as superoxide dismutase（SOD）， malondialdehyde（MDA）， and reduced glutathione（GSH） in the liver. Real-time fluorescence quantitative polymerase chain reaction（Real-time PCR） was used to measure the mRNA expression levels of NLRP3， apoptosis-associated speck-like protein（ASC）， cysteinyl aspartate specific proteinase-1（Caspase-1）， Toll-like receptor 4（TLR4） in the aorta， and fatty acid synthase（FAS）， stearoyl-CoA desaturase 1（SCD1）， PPARα， and carnitine palmitoyltransferase 1A（CPT1A） in the liver. Immunohistochemistry was used to determine the protein expressions of NLRP3， Caspase-1， and ASC in the aorta， and Western blot was used to measure the protein expressions of AMPK， p-AMPK， sterol regulatory element binding protein-1c（SREBP-1c）， CPT1A， and FAS in the liver. ResultsCompared with the normal group， the model group showed a significant increase in lipid plaque deposition in the aorta and lipid accumulation in the liver， the levels of TC， TG， LDL-C， AST， ALT， IL-1β， IL-18 and CRP in the serum were significantly increased（P<0.01）， and the mRNA and protein expressions of aortic TLR4， NLRP3， Caspase-1 and ASC were significantly upregulated（P<0.01）. The levels of SOD and GSH in the liver were significantly reduced， while the level of MDA was significantly increased（P<0.01）. The mRNA expressions of FAS and SCD1 in the liver were significantly downregulated， while the mRNA expressions of PPARα and CPT1A were significantly upregulated. The protein expressions of p-AMPK/AMPK and CPT1A in the liver were significantly reduced， while the expressions of SREBP-1c and FAS proteins were significantly increased（P<0.01）. Compared with the model group， the low- and high-dose HCT groups showed significant improvements in aortic plaques and hepatic lipid deposition. The levels of TC， LDL-C， AST， IL-1β and IL-18 in the serum of the low-dose HCT group， as well as TC， TG， LDL-C， AST， ALT， IL-1β， IL-18 and CRP in the serum of the high-dose HCT group， were significantly reduced（P<0.01）. The mRNA expressions of TLR4， NLRP3 and Caspase-1 in the aorta of the low-dose HCT group， as well as TLR4， NLRP3， Caspase-1 and ASC in the aorta of the high-dose HCT group， were significantly downregulated（P<0.01）. The protein expressions of Caspase-1 and ASC in the aorta of the low-dose HCT group， as well as NLRP3， Caspase-1 and ASC in the high-dose HCT group， were significantly downregulated（P<0.01）. The levels of SOD and GSH in the liver of the low- and high-dose HCT groups were significantly increased， while the level of MDA in the high-dose HCT group was significantly decreased（P<0.05， P<0.01）. In the HCT-treated group， the mRNA expressions of FAS and SCD1 in the liver were significantly upregulated， while the mRNA expressions of PPARα and CPT1A were significantly downregulated， the protein expressions of p-AMPK/AMPK and CPT1A in the liver were significantly increased， while the protein expressions of SREBP-1c and FAS were significantly decreased（P<0.05， P<0.01）. ConclusionHCT can improve lipid metabolism by activating the AMPK/PPARα pathway and inhibit NLRP3 inflammasome-mediated inflammatory responses， thereby reducing hepatic lipid deposition and AS plaque formation.

Gorham-Stout disease(GSD) is a rare osteolytic disorder characterized by spontaneous and progressive osteolysis, along with abnormal angiogenesis and lymphangiogenesis, with no new bone formation. We present a case of a 15-year-old female admitted due to " recurrent right leg pain for 5 years, 11 months after undergoing right femoral fracture surgery". Through comprehensive integration of the patient's clinical phenotype, laboratory tests, imaging findings, pathological examinations, and molecular biological test results, GSD was considered highly likely. A multidisciplinary treatment approach was conducted, including a combination of zoledronic acid and sirolimus to inhibit osteolysis, along with rehabilitation training and orthopedic intervention, providing a personalized and comprehensive treatment strategy.

ObjectiveTo explore the mechanism of Yishen Qubi Tongluo Formula （益肾祛痹通络方， YQTF） in the treatment of rheumatoid arthritis（RA）. MethodsNetwork pharmacology was employed to retrieve and screen the active components and potential targets of YQTF as well as RA-related targets using databases including TCMSP， BATMAN， ETCM and GEO. The intersection of targets related to active components and RA-related targets was identified， and a protein-protein interaction （PPI） network was constructed. Gene Ontology （GO） functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis were performed， and a drug-active component-common target network of YQTF in the treatment of RA was established. The core components of YQTF were molecularly docked with key targets. Human rheumatoid arthritis synovial fibroblast cell line MH7A was divided into blank group， model group， methotrexate group and YQTF group. The blank group was cultured with 10% fetal bovine serum， while the other three groups were stimulated with 10 μg/L of recombinant human tumor necrosis factor-α （TNF-α） for 24 h to establish the RA cell model. On this basis， the methotrexate group was treated with methotrexate suspension at a concentration of 20 μmol/L， and the YQTF group was treated with 10% YQTF-medicated serum. After 48 h of intervention， the levels of TNF-α and interleukin-17A（IL-17A）contents in cell supernatants were detected by enzyme-linked immunosorbent assay （ELISA）， and mRNA expressions of phosphatidylinositol 3-kinase（PI3K）， protein kinase B（AKT） and mammalian target of rapamycin（mTOR） were detected by real-time quantitative polymerase chain reaction （RT-qPCR）. ResultsNetwork pharmacological analysis identified 209 active components and 583 potential target genes of YQTF， as well as 818 RA-related targets. A total of 29 common targets were obtained from the intersection of drug-related targets and RA-related targets. Quercetin，β-sitosterol， kaempferol， stigmasterol and luteolin were the core active components of YQTF for the treatment of RA， while matrix metalloproteinase-9 （MMP9）， prostaglandin-endoperoxide synthase 2 （PTGS2）， Toll-like receptor 4 （TLR4）， tumor protein p53 （TP53） and transcription factor AP-1 subunit JUN were the key targets. The GO and KEGG pathway enrichment analysis showed that the involved biological processes and pathways were mainly associated with antioxidant responses， PI3K-AKT signaling pathway and Toll-like receptor （TLR） signaling pathway. Molecular docking results showed that MMP9 and PTGS2 exhibited high binding affinities with quercetin， β-sitosterol， kaempferol， stigmasterol and luteolin； TLR4 exhibited high binding activities with β-sitosterol， stigmasterol and luteolin； and TP53 showed high binding affinity with luteolin. The results of cell experiments showed that compared with the control group， the contents of TNF-α and IL-17A as well as the mRNA expressions of AKT and mTOR in the model group significantly increased （P＜0.05 or P＜0.01）. Compared with the model group， all the above indicators significantly decreased in the YQTF group， while the contents of TNF-α and the mRNA expression of AKT significantly decreased in the methotrexate group （P＜0.05 or P＜0.01）. ConclusionThe mechanism of YQTF in the treatment of RA may be associated with reducing inflammatory cytokine secretion and inhibiting the activation of the PI3K-AKT-mTOR signaling pathway.

ObjectiveThis paper aims to conduct the feature analysis and correlation analysis on the ocular collateral features and differential metabolites in patients with chronic hepatitis B （CHB） complicated by glucose metabolism disorder （GMD），particularly those with the damp-heat syndrome type，by integrating shadowless scleral imaging and metabolomics technologies. MethodsA total of 313 patients were recruited from the Hepatology and Endocrinology Outpatient Departments of Public Health Clinical Center of Chengdu according to the inclusion/exclusion criteria，and they were divided into a CHB group and a CHB complicated by GMD groups （damp-heat syndrome group and non-damp-heat syndrome group）. All patients underwent high-definition ocular image acquisition and feature extraction using an intelligent analysis system for shadowless scleral imaging to analyze the differences in the counting of morphological feature scores of ocular collaterals among groups. By using a digital sampling method，24 patients from each group were randomly selected，along with 20 healthy volunteers，for untargeted metabolomic analysis of peripheral serum. Differential metabolites were identified，statistically analyzed，and subjected to potential biomarker analysis and pathway enrichment. Spearman method was performed to conduct the correlation analysis on the differential ocular collateral features and differential metabolites，followed by correlation network construction. ResultsCompared with those in the CHB group，patients with CHB complicated by GMD showed significant changes in ocular collateral feature scores such as "hillock"，"blood vessels"，and "pale dusky coloration" （P<0.05）. In comparison with those in the healthy group，metabolites including N-acetylglucosamine，acetylhomoserine，and myo-inositol （AUC>0.7） were identified as potential biomarkers for the disease. Compared with those in the CHB complicated by GMD group with non-damp-heat syndrome，patients with damp-heat syndrome exhibited significant changes in feature scores of "plaques"，"yellow coloration"，"spleen"，and "gallbladder" （P<0.05）. In comparison with those in the healthy group，metabolites such as O²′-4a-cyclic tetrahydrobiopterin，theobromine，xanthurenic acid，and L-glutamic acid 5-phosphate （AUC>0.7） were identified as potential biomarkers for the damp-heat syndrome type. The Spearman correlation analysis reveals weak to moderate linear correlations between the differential scleral collateral features and metabolites. By constructing a "disease-syndrome" network of ocular diagnosis and metabolites，"xanthurenic acid-gallbladder" and "theobromine-plaque/yellow coloration" were identified as specific molecular-phenotypic correlated biomarker clusters for CHB complicated by GMD with dampness-heat syndrome. ConclusionPatients with CHB complicated by GMD demonstrate differential ocular diagnostic features and serum metabolites corresponding to disease states and dampness-heat syndrome. These objective biomarkers can guide both clinical syndrome differentiation and medication. The macro-micro integration based on ocular feature clusters and potential metabolic biomarkers offers an innovative approach to a combined traditional Chinese and Western medicine diagnosis and treatment model for this disease.

Objectives: . Idiopathic sudden sensorineural hearing loss (ISSNHL) is a significant cause of hearing loss. Intratympanic steroid injection (ITSI) is commonly used as an initial or salvage treatment; however, the lack of a standardized treatment protocol has resulted in variability in clinical practice. In addition, no efficient prediction model currently exists to support personalized management. Therefore, this study aimed to develop tailored management strategies for ISSNHL using a machine-learning model. Methods: . This retrospective multicenter cohort study was conducted between January 2015 and December 2020, with data analysis performed between January 2021 and March 2024. Patients were selected based on the International Classification of Diseases, 10th Revision criteria for ISSNHL, along with relevant medication and procedure codes. Patients with pure-tone audiogram results not meeting ISSNHL criteria, better initial hearing in the affected ear, an identifiable etiology, no post-treatment audiogram, or delayed treatment (>6 weeks) were excluded. We included 770 patients diagnosed with ISSNHL who received ITSI. The primary outcome was the area under the receiver operating characteristic curve for prediction performance. Recovery status was determined using the last pure-tone audiogram. Modeling was conducted on the Quanta for Medical Care AI platform using five machine-learning algorithms and a nested cross-validation framework, in which feature selection and hyperparameter tuning were performed in the inner folds and model performance was evaluated in the outer folds. Results: . A random forest classifier outperformed the other models in predicting hearing outcomes, achieving an area under the receiver operating characteristic curve of 0.788. Time to ITSI was the most influential treatment-related factor, with ITSI administered within 10 days of hearing loss being associated with better outcomes. This model can be used to provide personalized prognostic estimates under different treatment protocols. Conclusion . The machine-learning-based prediction model facilitates personalized treatment strategies and timely treatment adjustments for ISSNHL, thereby optimizing the likelihood of complete recovery.

Objective To evaluate the dissolution effects of pediatric ammonium urate stones in solutions with different pH values, so as to provide reference for the clinical treatment of this type of stones. Methods Eight pure ammonium urate stones(ammonium urate content ≥90%)of similar size and mass(median mass 4.6 g)were obtained from 8 children(＜14 years)undergoing percutaneous nephrolithotomy at the People's Hospital of Xinjiang Uygur Autonomous Region. The stones were placed in sodium chloride solutions with pH values of 5.0, 6.0, 7.0, and 8.5 and artificial urine with pH values of 4. 6, 5.0, 7.0, and 8.5 at a constant temperature of 37 ℃. The mass of the stones was recorded before placement and at 24, 48, and 72 h after placement. The dissolution rates of the stones were calculated. Results The pediatric ammonium urate stones could be dissolved in sodium chloride solution, and the total dissolution rate was the highest(94.6%)after 72 hours when the pH value was 6.0. The total dissolution rate of ammonium urate stones in artificial urine after 72 hours were all over 50%, and the total dissolution rate was the highest(79.7%)when the pH value was 4.6. Conclusion Pediatric ammonium urate stones are soluble in sodium chloride solution and artificial urine, and the total dissolution rate is higher in acidic environment.

ObjectiveTo investigate the intervention effect of Tengli Kangliu prescription （TKP） on the carcinogenesis of colorectal adenoma （CRA） induced by azoxymethane （AOM）/dextran sulphate sodium salt （DSS） in C57BL/6 mice and decipher the potential mechanism through regulating the signal transducer and activator of transcription 3 （STAT3） pathway to target M2-type macrophages. MethodsA total of 55 male C57BL/6 mice were randomized into a blank group （n=10）， a model group （n=15）， a celecoxib （0.02 g·kg^-1·d^-1） group （n=15）， a TKP （42.43 g·kg^-1·d^-1） group （n=15）. The mice in the model， TKP， and celecoxib groups were modeled for CRA lesions through the AOM/DSS three-cycle protocol. The intervention in each group began one week after free access to DSS and lasted for 12 weeks， and the blank group received 20 mL·kg^-1·d^-1 normal saline through gavage. Throughout the study period， changes in body mass and survival rate were recorded， alongside measurements of colorectal length and spleen mass. Histological changes of the colonic tissue were observed by HE staining. Immunohistochemical （IHC） staining was performed to detect the positive expression of CD68 and CD11c in the colorectal tissue. Western blot was employed to assess the protein levels of STAT3， phosphorylated （p）-STAT3， B-cell lymphoma 2 （Bcl-2）， and Bcl-2-associated X protein （Bax） in the intestinal tissue. Real-time quantitative PCR was employed to analyze the mRNA levels of arginase 1 （Arg1）， CD206， and vascular endothelial growth factor （VEGF）. Enzyme-linked Immunosorbent assay（ELISA） was employed to measure the serum concentrations of Th2-type cytokines interleukin （IL）-4， IL-6， and IL-13 in mice. ResultsCompared with the blank group， the model group exhibited symptoms including diarrhea， hematochezia， and body mass loss， accompanied by shortened colon length， mucosal damage， and multiple tumors. In addition， the model group showcased up-regulated protein levels of STAT3， p-STAT3， and Bcl-2， down-regulated protein level of Bax， increased positive expression of CD68 and CD11c， and up-regulated mRNA levels of Arg1， CD206， and VEGF in the colon tissue， together with elevated serum levels of IL-4， IL-13， and IL-6 （P<0.05）. Compared with the model group， the above-mentioned indicators were partially reversed in both TKP group and celecoxib group， with superior effects observed in the TKP group （P<0.05）. ConclusionTKP significantly improves the survival quality of the mouse model of AOM/DSS-induced CRA by reducing intestinal inflammation and decreasing colorectal tumor number and size. It may delay the progression of AOM/DSS-induced colorectal tumor-like lesions by inhibiting activation of the STAT3/p-STAT3 signaling pathway in the intestinal tissue， targeting regulation of M2-type macrophages， and improving the tumor microenvironment， thereby suppressing CRA carcinogenesis.

Objective : To investigate the brain microvascular tissue block culture method for extracting primary rat brain microvascular endothelial cells and identify its effect. Methods : Brain tissue from 4-week-old Sprague Dawley rats was screened, pre-digested and solidified to obtain brain microvascular segments. These segments were subsequently placed in a CO2incubator for primary culture. The target cells were identified by cell morphology and immunocytochemical staining for factor Ⅷ-related antigen. Results : After a 48-hour culture periodin vitro, the short spindle cells crawled out from around the brain microvascular segments. After 72 hours, island-like cell culsters formed. After 96 hours the clusters fused and the cells formed a typical monolayer, cobble stone-like, and mosaic arrangement. Factor Ⅷ-related antigen immunocytochemical staining showed that the cytoplasm of the cells appeared brown-red, indicating positive expression; DAB stained the nucleus, showing blue-dark. Conclusion The brain microvascular tissue block culture method can isolate and culture primary rat brain microvascular endothelial cells.

ObjectiveTo investigate the value of different noninvasive diagnostic models in the diagnosis of esophageal and gastric varices since there is a high risk of esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and to provide a basis for the early diagnosis of esophageal and gastric varices. MethodsA total of 108 patients with significant portal hypertension due to compensated hepatitis B cirrhosis who attended Guangdong Provincial Hospital of Traditional Chinese Medicine from November 2017 to November 2023 were enrolled， and according to the presence or absence of esophageal and gastric varices under gastroscopy， they were divided into esophageal and gastric varices group （GOV group） and non-esophageal and gastric varices group （NGOV group）. Related data were collected， including age， sex， imaging findings， and laboratory markers. The chi-square test was used for comparison of categorical data between groups； the least significant difference t-test was used for comparison of normally distributed continuous data between groups， and the Mann-Whitney U test was used for comparison of non-normally distributed continuous data between groups. The receiver operating characteristic （ROC） curve was plotted to evaluate the diagnostic value of five scoring models， i.e.， fibrosis-4 （FIB-4）， LOK index， LPRI， aspartate aminotransferase-to-platelet ratio index （APRI）， and aspartate aminotransferase/alanine aminotransferase ratio （AAR）. The binary logistic regression method was used to establish a combined model， and the area under the ROC curve （AUC） was compared between the combined model and each scoring model used alone. The Delong test was used to compare the AUC value between any two noninvasive diagnostic models. ResultsThere were 55 patients in the GOV group and 53 patients in the NGOV group. Compared with the NGOV group， the GOV group had a significantly higher age （52.64±1.44 years vs 47.96±1.68 years， t=0.453， P<0.05） and significantly lower levels of alanine aminotransferase ［42.00 （24.00 — 17.00） U/L vs 82.00 （46.00 — 271.00） U/L， Z=-3.065， P<0.05］， aspartate aminotransferase ［44.00 （32.00 — 96.00） U/L vs 62.00 （42.50 — 154.50） U/L，Z=-2.351， P<0.05］， and platelet count ［100.00 （69.00 — 120.00）×10⁹/L vs 119.00 （108.50 — 140.50）×10⁹/L， Z=-3.667， P<0.05］. The ROC curve analysis showed that FIB-4， LOK index， LPRI， and AAR used alone had an accuracy of 0.667， 0.681， 0.730， and 0.639， respectively， in the diagnosis of esophageal and gastric varices （all P<0.05）， and the positive diagnostic rates of GOV were 69.97%， 65.28%， 67.33%， and 58.86%， respectively， with no significant differences in AUC values （all P>0.05）， while APRI used alone had no diagnostic value （P>0.05）. A combined model （LAF） was established based on the binary logistic regression analysis and had an AUC of 0.805 and a positive diagnostic rate of GOV of 75.80%， with a significantly higher AUC than FIB-4， LOK index， LPRI， and AAR used alone （Z=-2.773，-2.479，-2.206， and-2.672， all P<0.05）. ConclusionFIB-4， LOK index， LPRI， and AAR have a similar diagnostic value for esophageal and gastric varices in patients with compensated hepatitis B cirrhosis and significant portal hypertension， and APRI alone has no diagnostic value. The combined model LAF had the best diagnostic efficacy， which provides a certain reference for clinical promotion and application.

BACKGROUND:The use of 3D-printed patient-specific instruments in opening wedge high tibial osteotomy has advantages such as shorter operative time,fewer fluoroscopic exposures,and higher correction accuracy.However,previous studies have reported issues such as significant damage to surrounding soft tissues and improper fixation of the plates. OBJECTIVE:To investigate the clinical efficacy of using 3D-printed patient-specific instruments combined with customized locking plate in opening wedge high tibial osteotomy for the treatment of knee osteoarthritis. METHODS:A total of 20 patients diagnosed with knee osteoarthritis were divided into the 3D group(n=10)and the conventional group(n=10)according to surgical methods.The 3D group underwent opening wedge high tibial osteotomy using 3D-printed patient-specific instruments combined with customized locking plate,while the conventional group underwent opening wedge high tibial osteotomy using conventional methods.The operative time,fluoroscopic exposures,incision length,pre-and postoperative hip-knee-ankle angle,medial proximal tibial angle,posterior tibial slope,the difference between the planned and actual correction angle,preoperative and 1,3,6 months postoperative knee range of motion and Lysholm score,and incidence of complications were analyzed and compared between the two groups. RESULTS AND CONCLUSION:(1)The operative time and fluoroscopic exposures were significantly shorter in the 3D group compared to the conventional group,with a statistically significant difference(P<0.001).(2)Both groups showed a significant improvement in postoperative hip-knee-ankle angle and medial proximal tibial angle compared to preoperative values,with a statistically significant difference(P<0.001),while there was no significant change in posterior tibial slope.In the 3D group,the postoperative hip-knee-ankle angle,medial proximal tibial angle,and posterior tibial slope differed from their respective preoperative planned values by(-0.22±0.72)°,(-0.20±0.73)°,and(0.23±0.37)°,but the differences were not statistically significant.The difference between the planned and actual correction angle of 3D group was significantly smaller than that of conventional group(P<0.05).(3)Both groups showed a gradual increase in knee range of motion and Lysholm scores after surgery(P<0.001).Compared to the conventional group,the 3D group had superior knee range of motion at 1 and 3 months postoperatively,as well as a higher Lysholm score at 1 month postoperatively,with statistically significant differences(P<0.05).There were no statistically significant differences in Lysholm score at 3 months and knee range of motion and Lysholm score at 6 months between the two groups(P>0.05).(4)Complications occurred in neither groups.(5)The above results indicate that both 3D-printed patient-specific instruments combined with customized locking plate and conventional methods have good clinical efficacy.However,the former has a shorter operative time,fewer fluoroscopic exposures,and faster postoperative recovery of knee joint function.Additionally,3D-printed patient-specific instruments can achieve preoperative planning accurately.