ObjectiveTo investigate the differences in clinical features and outcomes between patients with hepatic Wilson's disease （WD） presenting with the syndrome of combined phlegm and stasis and the syndrome of dampness-heat internal accumulation. MethodsA retrospective cohort study was conducted by consecutively recruiting patients with hepatic WD from the Encephalopathy Center of the First Affiliated Hospital of Anhui University of Chinese Medicine between January 2022 and August 2025. According to traditional Chinese medicine （TCM） syndrome differentiation， the patients were assigned into a combined phlegm and stasis group and a dampness-heat internal accumulation group. All the patients received standard treatment. Baseline data， laboratory indicators， complications， Model for End-Stage Liver Disease （MELD） score， Child-Turcotte-Pugh （CTP） score， and Chronic Liver Failure-Sequential Organ Failure Assessment （CLIF-SOFA） score were recorded. The clinical features and outcomes of the two groups of patients were compared by t-test， U-test and multivariate logistic regression. ResultsA total of 141 patients with hepatic WD were included. The combined phlegm and stasis group comprised 68 patients with an average age of （28.22±10.47） years， including 43 males and 25 females. The dampness-heat internal accumulation group comprised 73 patients with an average age of （30.22±8.79） years， including 44 males and 29 females. Univariate analysis showed no statistically significant differences in age or gender between the two groups. The combined phlegm and stasis group had lower platelet （PLT）， alanine aminotransferase （ALT）， aspartate aminotransferase （AST）， creatine （CRE）， total cholesterol （TC）， and triglycerides （TG） levels （P<0.05 or P<0.01） and higher total bilirubin （TBIL） and prothrombin time （PT） （P<0.05） than the dampness-heat internal accumulation group. There were no statistically significant differences in the incidence of hepatic encephalopathy， infection， spontaneous bacterial peritonitis， ascites， or gastrointestinal bleeding between the two groups. The incidence of splenomegaly and the MELD score were higher in the combined phlegm and stasis group （P<0.05）. The CTP and CLIF-SOFA scores were also higher in the combined phlegm and stasis group， while these differences were not statistically significant. Eleven patients in the combined phlegm and stasis group and 9 patients in the dampness-heat internal accumulation group developed liver failure. Multivariate logistic regression analysis showed that PT （OR=1.794， 95%CI 1.249-2.576）， TBIL （OR=1.111， 95%CI 1.026-1.203）， ALT （OR=1.053， 95%CI 1.004-1.105）， and TCM syndrome （OR=5.420， 95%CI 1.384-21.227） were independent risk factors for the development of liver failure in hepatic WD. ConclusionCompared with the hepatic WD patients with the syndrome of dampness-heat internal accumulation， those with the syndrome of combined phlegm and stasis exhibit severe liver function impairment and disease conditions. Furthermore， TCM syndrome serves as an independent predictive factor for the occurrence of liver failure in patients with hepatic WD.

ObjectiveThis study aims to investigate the molecular mechanism by which Guizhi Fulingwan （GFW） inhibits ferroptosis in endometriosis （EMT） through the regulation of the hypoxia inducible factor-1α/heme oxygenase 1 （HIF-1α/HO-1） signaling pathway. MethodsMachine learning was employed to identify ferroptosis-related biomarkers associated with EMT. Network pharmacology was utilized to identify the active components of GFW and its potential therapeutic targets against EMT， including core targets. Functional enrichment analysis was conducted to explore the biological processes， molecular functions， cellular components， and signaling pathways associated with the potential targets. An EMT rat model was established via autologous transplantation. Thirty female Sprague-Dawley （SD） rats were randomly divided into five groups： sham-operated， model， positive control （dienogest at 0.2 mg·kg^-1）， low-dose GFW （2.5 g·kg^-1）， and high-dose GFW （5 g·kg^-1）. After modeling， the rats received their respective treatment by oral gavage for 28 consecutive days， while the sham and model groups received equal volumes of distilled water. Serum and ectopic endometrial tissues were collected. Hematoxylin and eosin （HE） staining was employed to evaluate morphological alterations in ectopic lesions. Quantitative real-time polymerase chain reaction （Real-time PCR） and Western blot were conducted to assess mRNA and protein expression of HIF-1α， HO-1， glutathione peroxidase 4 （GPX4）， spermidine/spermine N1-acetyltransferase （SAT1）， and prostaglandin-endoperoxide synthase 2 （PTGS2）. Tissue levels of malondialdehyde （MDA）， glutathione （GSH）， and ferrous iron （Fe²⁺） were quantified using commercial assay kits. Serum levels of interleukin-6 （IL-6） and transforming growth factor-β₁ （TGF-β₁） were measured via enzyme-linked immunosorbent assay （ELISA）. ResultsFive ferroptosis-related biomarkers in EMT were identified： ALOX12， CHAC1， SAT1， AST1， and HO-1. Network pharmacology analysis revealed 42 active components of GFW and 192 potential therapeutic target genes related to EMT treatment， with FOS， JUN， HO-1 identified as core targets. Functional enrichment analysis indicated that the potential targets were primarily involved in oxidative stress response and reactive oxygen species metabolism and were enriched in the HIF-1 signaling pathway. Compared to the sham-operated group， the model group exhibited significant increases in both mRNA and protein expression of HIF-1α， HO-1， and PTGS2， as well as elevated tissue levels of Fe²⁺ and MDA. Conversely， GSH levels and the expression of GPX4 and SAT1 were markedly reduced， and serum levels of IL-6 and TGF-β₁ levels were significantly higher （P<0.01）. Compared with the model group， all GFW-treated groups showed significant downregulation of HIF-1α and HO-1， reduced Fe²⁺ levels， and downregulated expression of MDA， PTGS2， IL-6， and TGF-β₁. Meanwhile， GSH， GPX4， and SAT1 expression levels were significantly increased （P<0.05， P<0.01）， effectively ameliorating iron overload and oxidative stress， thereby demonstrating therapeutic efficacy in EMT， with the high-dose GFW demonstrating the most pronounced therapeutic effects. ConclusionGFW exerts therapeutic effects on endometriosis by regulating the HIF-1α/HO-1 signaling pathway to rectify iron metabolism disorders and attenuate free iron-induced oxidative damage. It upregulates the antioxidative defense system to inhibit lipid peroxidation cascades and modulates inflammatory cytokine networks. These effects collectively disrupt the pathological interaction between ferroptosis and chronic inflammation， providing a novel theoretical foundation for the clinical application of GFW in EMT treatment.

BACKGROUND: Spicy food consumption has been reported to be inversely associated with mortality from multiple diseases. However, the effect of spicy food intake on the incidence of vascular diseases in the Chinese population remains unclear. This study was conducted to explore this association. METHODS: This study was performed using the large-scale China Kadoorie Biobank (CKB) prospective cohort of 486,335 participants. The primary outcomes were vascular disease, ischemic heart disease (IHD), major coronary events (MCEs), cerebrovascular disease, stroke, and non-stroke cerebrovascular disease. A Cox proportional hazards regression model was used to assess the association between spicy food consumption and incident vascular diseases. Subgroup analysis was also performed to evaluate the heterogeneity of the association between spicy food consumption and the risk of vascular disease stratified by several basic characteristics. In addition, the joint effects of spicy food consumption and the healthy lifestyle score on the risk of vascular disease were also evaluated, and sensitivity analyses were performed to assess the reliability of the association results. RESULTS: During a median follow-up time of 12.1 years, a total of 136,125 patients with vascular disease, 46,689 patients with IHD, 10,097 patients with MCEs, 80,114 patients with cerebrovascular disease, 56,726 patients with stroke, and 40,098 patients with non-stroke cerebrovascular disease were identified. Participants who consumed spicy food 1-2 days/week (hazard ratio [HR] = 0.95, 95% confidence interval [95% CI] = [0.93, 0.97], P <0.001), 3-5 days/week (HR = 0.96, 95% CI = [0.94, 0.99], P = 0.003), and 6-7 days/week (HR = 0.97, 95% CI = [0.95, 0.99], P = 0.002) had a significantly lower risk of vascular disease than those who consumed spicy food less than once a week ( Ptrend <0.001), especially in those who were younger and living in rural areas. Notably, the disease-based subgroup analysis indicated that the inverse associations remained in IHD ( Ptrend = 0.011) and MCEs ( Ptrend = 0.002) risk. Intriguingly, there was an interaction effect between spicy food consumption and the healthy lifestyle score on the risk of IHD ( Pinteraction = 0.037). CONCLUSIONS Our findings support an inverse association between spicy food consumption and vascular disease in the Chinese population, which may provide additional dietary guidance for the prevention of vascular diseases.
Humans ; Male ; Female ; Prospective Studies ; Middle Aged ; Aged ; Vascular Diseases/etiology* ; Risk Factors ; China/epidemiology* ; Adult ; Proportional Hazards Models ; Cerebrovascular Disorders/epidemiology* ; East Asian People

The prevalence of Class III malocclusion varies among different countries and regions. The populations from Southeast Asian countries (Chinese and Malaysian) showed the highest prevalence rate of 15.8%, which can seriously affect oral function, facial appearance, and mental health. As anterior crossbite tends to worsen with growth, early orthodontic treatment can harness growth potential to normalize maxillofacial development or reduce skeletal malformation severity, thereby reducing the difficulty and shortening the treatment cycle of later-stage treatment. This is beneficial for the physical and mental growth of children. Therefore, early orthodontic treatment for Class III malocclusion is particularly important. Determining the optimal timing for early orthodontic treatment requires a comprehensive assessment of clinical manifestations, dental age, and skeletal age, and can lead to better results with less effort. Currently, standardized treatment guidelines for early orthodontic treatment of Class III malocclusion are lacking. This review provides a comprehensive summary of the etiology, clinical manifestations, classification, and early orthodontic techniques for Class III malocclusion, along with systematic discussions on selecting early treatment plans. The purpose of this expert consensus is to standardize clinical practices and improve the treatment outcomes of Class III malocclusion through early orthodontic treatment.
Humans ; Malocclusion, Angle Class III/classification* ; Orthodontics, Corrective/methods* ; Consensus ; Child

This study aimed to comprehensively examine the association of gallstones, cholecystectomy, and cancer risk. Multivariable logistic regressions were performed to estimate the observational associations of gallstones and cholecystectomy with cancer risk, using data from a nationwide cohort involving 239 799 participants. General and gender-specific two-sample Mendelian randomization (MR) analysis was further conducted to assess the causalities of the observed associations. Observationally, a history of gallstones without cholecystectomy was associated with a high risk of stomach cancer (adjusted odds ratio (aOR)=2.54, 95% confidence interval (CI) 1.50-4.28), liver and bile duct cancer (aOR=2.46, 95% CI 1.17-5.16), kidney cancer (aOR=2.04, 95% CI 1.05-3.94), and bladder cancer (aOR=2.23, 95% CI 1.01-5.13) in the general population, as well as cervical cancer (aOR=1.69, 95% CI 1.12-2.56) in women. Moreover, cholecystectomy was associated with high odds of stomach cancer (aOR=2.41, 95% CI 1.29-4.49), colorectal cancer (aOR=1.83, 95% CI 1.18-2.85), and cancer of liver and bile duct (aOR=2.58, 95% CI 1.11-6.02). MR analysis only supported the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer. This study added evidence to the causal effect of gallstones on stomach, liver and bile duct, kidney, and bladder cancer, highlighting the importance of cancer screening in individuals with gallstones.
Humans ; Mendelian Randomization Analysis ; Gallstones/complications* ; Female ; Male ; Cholecystectomy/statistics & numerical data* ; Middle Aged ; Risk Factors ; Aged ; Adult ; Neoplasms/etiology* ; Stomach Neoplasms/epidemiology*

Objective:To explore the efficacy and safety of negative-pressure wound therapy (NPWT) in treating infected wounds in orthopedic trauma patients.Methods:China National Knowledge Infrastructure, China Biomedical Literature Database, Wanfang Data Knowledge Service Platform, PubMed, Web of Science, Cochrane Library, and CINAHL were searched for randomized controlled trials (RCT) and cohort studies examining the impact of NPWT on wound healing in orthopedic trauma infections. The retrieval time was from the establishment of the databases to October 2024. RevMan 5.4 software was used for Meta-analysis. The patients were divided into two groups according to different treatment methods: the intervention group, treated with NPWT, and the control group, treated with conventional treatment. The observed indicators included clinical efficacy, wound healing quality, length of hospital stay, wound healing time, incidence of complications, secondary surgery rate, and duration of antibiotic use. Publication bias analysis was performed on the observed indicators through Begg and Egger tests.Results:A total of 13 studies were included, comprising 11 RCT and 2 cohort studies, involving a total of 3 538 patients, with 1 762 in the intervention group and 1 776 in the control group. The meta-analysis results indicated that the intervention group had better clinical efficacy ( OR=7.08, 95% CI 5.31, 9.45, P<0.01), higher wound healing quality ( MD=4.15, 95% CI 3.99, 4.32, P<0.01), shorter length of hospital stay ( MD=-13.38, 95% CI -14.39, -12.38, P<0.01), shorter wound healing time ( MD=-8.11, 95% CI -10.22, -6.00, P<0.01), lower incidence of complications, lower secondary surgery rate ( OR=0.22, 95% CI 0.09, 0.57, P<0.01), and shorter duration of antibiotic use ( MD=-7.61, 95% CI -8.06, -7.16, P<0.01) when compared with the control group. No significant publication bias was observed in the aforementioned indicators ( P>0.05). Conclusion:Compared with the conventional treatment, NPWT can enhance the clinical efficacy and wound healing quality of infected wounds in orthopedic trauma patients, shorten length of hospital stay and wound healing time, reduce the incidence of complications and secondary surgery rates, and shorten the duration of antibiotic use.

Objective:To compare the efficacy of Union Plate combined with robotic placement of infra-acetabular and posterior column screws and common reconstruction plate combined with freehand placement of infra-acetabular and posterior column screws in the treatment of complex acetabular fractures.Methods:The data of 42 patients with complex acetabular fractures treated in Union Hospital, Tongji Medical College, Huazhong University of Science and Technology from June 2020 to June 2023 were retrospectively analyzed. Among them, 22 patients were treated with Union Plate combined with robotic placement of posterior column screws and infra-acetabular screws (Union Plate robot group). 20 cases were treated with common reconstruction plate combined with posterior column screw and infra-acetabular screw fixation by hand (reconstruction plate freehand group). The Union Plate robot group included 16 males and 6 females, aged 43.7±11.6 years (range, 24-67 years). Letournel-Judet classification: 14 cases of double-column fractures, 5 cases of anterior column with posterior semi-transverse fractures, 3 cases of "T" -shaped fractures. There were 15 males and 5 females in the reconstruction plate freehand group, aged 42.9±12.0 years (range, 22-66 years). Letournel-Judet classification: 15 cases of double-column fractures, 3 cases of anterior column with posterior semi-transverse fractures, 2 cases of "T" -shaped fractures. The operative time, intraoperative blood loss, intraoperative fluoroscopy times, frame screw placement time, fracture healing time, perfect frame screw placement rate (grade 0 rate) assessed according to the Lonstein criteria, reduction quality assessed according to the Matta criteria, the modified Merle d'Aubign-Postel score and postoperative complications were compared between the two groups.Results:All 42 patients were followed up for 10 to 30 months, with an average of 13 months. The fracture healing time was 3.4±0.4 months in the Union Plate robot group and 3.6±0.4 months in the reconstruction plate freehand group, with no statistical significance ( t=2.179, P=0.035). The operative time and intraoperative blood loss of the Union Plate robot group were 138.3±30.7 min and 735.7±159.8 ml, respectively, which were lower than 163.9±48.7 min and 843.5±181.1 ml in the reconstruction plate freehand group. The differences were statistically significant ( P<0.05). The time and intraoperative fluoroscopy times of the Union Plate robot group were 19.9±3.2 min and 17.1±4.9 times, respectively, which were less than 42.5±6.7 min and 45.4±4.9 times of the reconstruction plate freehand group, and the differences were statistically significant ( P<0.05). According to the Lonstein evaluation, there were 42 cases of class 0 and 2 cases of class I in the Union Plate robot group, and the perfect frame screw placement rate was 96%(42/44). There were 30 cases of grade 0, 8 cases of grade I and 2 cases of grade II in the reconstruction plate freehand group, and the perfect frame screw placement rate was 75%(30/40). There was significant difference between the two groups (χ 2=7.426, P=0.024). According to the Matta criteria, 15 cases of Union Plate robot group were excellent, 4 cases were good, and 3 cases were poor, with an excellent and good rate of 86%(19/22). In the reconstruction plate free hand group, 13 cases were excellent, 4 cases were good, and 3 cases were poor, with an excellent and good rate of 85%(17/20). There was no significant difference between the two groups (χ 2=0.048, P=0.976). At the last follow-up visit, the modified Merle d'Aubign-Postel score of the Union Plate robot group was 16.9±1.7 points and that of the reconstruction plate freehand group was 16.5±2.2 points, with no statistical significance ( t=0.593, P=0.557). In the Union Plate robot group, wound fat liquefaction and lateral femoral cutaneous nerve injury occurred in 1 case, the complication rate was 9%(2/22). There were 4 cases of fat liquefaction, 1 case of lateral femoral cutaneous nerve injury, and 1 case of traumatic hip arthritis in the reconstruction plate freehand group. The complication rate was 30%(6/20), and the difference in complication rate was not statistically significant (χ 2=1.769, P=0.183). Conclusions:The clinical efficacy of Union Plate combined with robotic placement of posterior column screws and infra-acetabular screws in the treatment of complex acetabular fractures is comparable to that of reconstruction plate combined with freehand placement of posterior column screws and infra-acetabular screws. However, the use of Union Plate combined with robotic placement of frame screws can shorten the operative time and the time of frame screw placement. The amount of intraoperative blood loss and intraoperative fluoroscopy times were reduced, and the accuracy of frame screw placement was higher.

Objective To investigate the mechanism of Wenjing Decoction in treating endometriosis(EMT)using bioinformatics methods and in vitro experiments.Methods The active components and corresponding targets of Wenjing Decoction were obtained from the TCMSP database,while EMT-related targets were identified using the GEO database.Functional enrichment analysis was conducted on the targets to predict core targets for treating EMT with Wenjing Decoction.Molecular docking was performed on core targets-drug ligands,and in vitro experiments validated the findings.Results Through screening the TCMSP database,117 active components of Wenjing Decoction were identified,corresponding to 248 targets;5 312 EMT-related differential genes were gathered from GEO database,identifying 97 potential targets of Wenjing Decoction for treating EMT,with core targets being IL6,TNF and EGFR.Functional enrichment analysis of EMT differential genes showed enrichment in pathways such as neuroactive ligand-receptor interaction,MAPK signaling pathway,endocytosis,calcium signaling pathway,autophagy and PI3K-Akt signaling pathway.Molecular docking showed that IL6,TNF,EGFR bind stably to their corresponding drug ligands.In vitro experiments indicated that Wenjing Decoction could inhibit the PI3K/Akt/mTOR pathway,promote LC3 Ⅰ to LC3 Ⅱ conversion,enhance the expression of Beclin-1,and reduce P62 expression.Moreover,Wenjing Decoction could hinder the expression of the endometriosis-specific biomarker CA125,decrease EGFR,IL-6 and TNF-α expressions in ectopic endothelial cells,inhibiting proliferation.Conclusion Wenjing Decoction can treat EMT through multiple pathways and targets,with the key mechanism being the reversal of autophagy inhibition via down-regulating of the PI3K/Akt/mTOR pathway.

Objective:To investigate the effect of circulating plasma cell(CPC)on the prognosis of multiple myeloma(MM),and to es-tablish and validate a modified CPC-RISS staging system based on CPC and RISS.Methods:A retrospective analysis was performed for the clinical data of 639 treatment-na?ve patients with MM who were treated in Department of Hematology,Xijing Hospital,from January 2006 to June 2023.Peripheral blood smear was used to calculate the percentage of CPC in patients,and the impact of CPC and other related factors on the prognosis of MM patients was analyzed.A CPC-RISS staging system was established based on RISS stage and the percentage of CPC,and the differences in survival and prognosis were analyzed between patients with different stages.Results:Compared with the patients without CPC,detectable CPC was significantly associated with various high-risk factors for MM,and the MM patients with CPC had a lower complete remission rate and shorter overall survival time and progression-free survival time.The modified CPC-RISS staging system was used to classify the patients with MM into four stages,and there were significant differences in median survival time and progression-free survival time between the patients with different stages of MM.Conclusion:The MM pa-tients with the presence of CPC exhibit more aggressive features,worse response to treatment,and a reduction in long-term survival rate.The modified CPC-RISS staging system can effectively predict the prognosis of treatment-na?ve MM patients.

Objective To investigate the multi-target mechanisms of quercetin in treating endometriosis(EMT)through integrative network pharmacology analysis.Methods Active targets of quercetin were collected from the TCMSP database,while EMT-related differentially expressed genes(DEGs)were identified through the Gene Expression Omnibus(GEO)dataset.A comparative analysis was conducted to pinpoint potential therapeutic targets of quercetin for EMT treatment.Functional enrichment analyses were employed to investigate the biological functions associated with these targets,and a protein-protein interaction(PPI)network was conducted to identify core targets.Molecular docking and dynamics simulations were performed to validate the binding characteristics between quercetin and the core targets.The top 2 target protein pairs,HSP90AB1 and AR,exhibiting the lowest binding energy,were selected for subsequent cellular experimental validation.Human EMT-immortalized ectopic endometrial epithelial cell line 12Z(n=6,independent replicates)was subjected,and CCK-8 assay was used to determine ehe effects of quercetin on cell viability and proliferation,and the half-maximal inhibitory concentration(IC50)was calculated at 48 h after treatment.Then the 12Z cells were treated with quercetin at a concentration gradient of 0,30,60 and 90 μmol/L,the migration and invasion abilities were assessed with cell scratch and cell invasion assays.Western blotting was conducted to detect the changes in the expression of HSP90AB1 and AR proteins after different doses of treatment.Results There were 49 potential EMT-related therapeutic targets and 10 core targets identified.Functional enrichment analyses revealed that these targets were significant enriched in inflammation-related signaling pathways,including AGE-RAGE,ErbB and TNF;immune-related pathways,such as Th17 cell differentiation,T/B cell receptor signaling;angiogenesis-related pathways like VEGF;and hormonal regulatory pathways involving estrogen and GnRH.Molecular docking demonstrated that quercetin exhibited favorable binding activity(binding energy<-5 kcal/mol)with all core target proteins,with particularly strong binding energies(<-7 kcal/mol)observed for AR,EGFR,FOS,ERBB2,and HSP90AB1.Molecular dynamics simulations revealed that quercetin forms sustained hydrogen bond interactions with AR and HSP90AB1,facilitating the formation of stable complexes.CCK-8 assay,cell scratch assay,and transwell invasion assay indicated that quercetin inhibited the proliferative activity,and migrative and invasive abilities of 12Z cells in a concentration-dependent manner,with more pronounced inhibitory effects observed at 60 and 90 μmol/L quercetin(P<0.001);Western blotting revealed that treatment of 12Z cells with varying quercetin concentrations for 48 h up-regulated the expression of HSP90AB1 and AR,with the most significant increase observed at 90 μmol/L quercetin(HSP90AB1,P<0.05;AR,P<0.001).The restored expression levels of HSP90AB1 and AR showed positive correlations with the proliferative activity,migrative and invasive abilities of ectopic endometrial cells.Conclusion Quercetin effectively addresses endometriosis through multiple molecular targets and signaling pathways,and stabilization of the HSP90AB1/AR complex and subsequent protein upregulation represents a key therapeutic mechanism.