This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

The efficacy mechanism of the alcoholic extract of Gnaphalium affine was investigated by observing its influence on oxidative stress and intestinal flora in rats modeled for chronic obstructive pulmonary disease(COPD). UPLC-MS was used to evaluate the quality of the alcoholic extract of G. affine, and 72 rats were randomly divided into six groups, with COPD models established in five groups by cigarette smoke combined with airway drip lipopolysaccharide, and the rats were given the positive drug of Danlong Oral Solution, as well as low-, medium-, and high-doses alcoholic extract of G. affine, respectively. After two weeks of continuous gastric gavage, the body weights and general morphology observations were performed; HE staining and Masson staining were used to verify the effects of the alcoholic extract of G. affine on alveolar inflammation and collagen deposition area in COPD rats; the oxidative stress indexes CAT and GSH in serum and SOD and MDA in lung tissue of the rats were measured, and the mRNA expression of HO-1, Nrf2, and NQO1 were determined by qRT-PCR. The protein expressions of HO-1, Nrf2, and NQO1 were determined by the Western blot method, and the mechanism by which the alcoholic extract of G. affine affected oxidative stress in COPD rats was explored. Finally, the influence of G. affine on the changes in intestinal flora caused by COPD was studied by 16S rRNA sequencing. The results showed that a total of 121 chemical components were identified by UPLC-MS, including 70 positive and 51 negative ion modes. In animal experiments, it was found that the alcoholic extracts of G. affine were able to reduce the percentage of collagen deposition, affect the oxidative stress indexes such as CAT, GSH, SOD, MDA, as well as the mRNA and protein expression of Nrf2, HO-1, and NQO1. The 16S rRNA sequencing results showed an increase in the level of Lactobacillales and a decrease in the level of Desulfovibrio and Desulfovibrionales, suggesting that the alcoholic extracts of G. affine could reverse the changes in intestinal flora caused by COPD. In conclusion, the alcoholic extracts of G. affine may exert anti-COPD effects by affecting the oxidative stress pathway and modulating the changes in intestinal flora.
Animals ; Oxidative Stress/drug effects* ; Pulmonary Disease, Chronic Obstructive/genetics* ; Rats ; Male ; Gastrointestinal Microbiome/drug effects* ; Rats, Sprague-Dawley ; Drugs, Chinese Herbal/administration & dosage* ; NF-E2-Related Factor 2/metabolism* ; Humans ; Lung/metabolism*

OBJECTIVE: To evaluate the dynamic changes of glucocorticoid (GC) dose and the feasibility of GC discontinuation in rheumatoid arthritis (RA) patients under the background of Chinese medicine (CM). METHODS: This multicenter retrospective cohort study included 1,196 RA patients enrolled in the China Rheumatoid Arthritis Registry of Patients with Chinese Medicine (CERTAIN) from September 1, 2019 to December 4, 2023, who initiated GC therapy. Participants were divided into the Western medicine (WM) and integrative medicine (IM, combination of CM and WM) groups based on medication regimen. Follow-up was performed at least every 3 months to assess dynamic changes in GC dose. Changes in GC dose were analyzed by generalized estimator equation, the probability of GC discontinuation was assessed using Kaplan-Meier curve, and predictors of GC discontinuation were analyzed by Cox regression. Patients with <12 months of follow-up were excluded for the sensitivity analysis. RESULTS: Among 1,196 patients (85.4% female; median age 56.4 years), 880 (73.6%) received IM. Over a median 12-month follow-up, 34.3% (410 cases) discontinued GC, with significantly higher rates in the IM group (40.8% vs. 16.1% in WM; P<0.05). GC dose declined progressively, with IM patients demonstrating faster reductions (median 3.75 mg vs. 5.00 mg in WM at 12 months; P<0.05). Multivariate Cox analysis identified age <60 years [P<0.001, hazard ratios (HR)=2.142, 95% confidence interval (CI): 1.523-3.012], IM therapy (P=0.001, HR=2.175, 95% CI: 1.369-3.456), baseline GC dose ⩽7.5 mg (P=0.003, HR=1.637, 95% CI: 1.177-2.275), and absence of non-steroidal anti-inflammatory drugs use (P=0.001, HR=2.546, 95% CI: 1.432-4.527) as significant predictors of GC discontinuation. Sensitivity analysis (545 cases) confirmed these findings. CONCLUSIONS RA patients receiving CM face difficulties in following guideline-recommended GC discontinuation protocols. IM can promote GC discontinuation and is a promising strategy to reduce GC dependency in RA management. (Trial registration: ClinicalTrials.gov, No. NCT05219214).
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Arthritis, Rheumatoid/drug therapy* ; Glucocorticoids/therapeutic use* ; Medicine, Chinese Traditional ; Retrospective Studies

Cemental tear is a rare and indetectable condition unless obvious clinical signs present with the involvement of surrounding periodontal and periapical tissues. Due to its clinical manifestations similar to common dental issues, such as vertical root fracture, primary endodontic diseases, and periodontal diseases, as well as the low awareness of cemental tear for clinicians, misdiagnosis often occurs. The critical principle for cemental tear treatment is to remove torn fragments, and overlooking fragments leads to futile therapy, which could deteriorate the conditions of the affected teeth. Therefore, accurate diagnosis and subsequent appropriate interventions are vital for managing cemental tear. Novel diagnostic tools, including cone-beam computed tomography (CBCT), microscopes, and enamel matrix derivatives, have improved early detection and management, enhancing tooth retention. The implementation of standardized diagnostic criteria and treatment protocols, combined with improved clinical awareness among dental professionals, serves to mitigate risks of diagnostic errors and suboptimal therapeutic interventions. This expert consensus reviewed the epidemiology, pathogenesis, potential predisposing factors, clinical manifestations, diagnosis, differential diagnosis, treatment, and prognosis of cemental tear, aiming to provide a clinical guideline and facilitate clinicians to have a better understanding of cemental tear.
Humans ; Dental Cementum/injuries* ; Consensus ; Diagnosis, Differential ; Cone-Beam Computed Tomography ; Tooth Fractures/therapy*

OBJECTIVE: The results of limited studies on the relationship between environmental pollution and dementia have been contradictory. We analyzed the combined effects of PM _2.5 and smoking on the prevalence of dementia and cognitive impairment in an elderly community-dwelling Chinese population. METHODS: We assessed 24,117 individuals along with the annual average PM _2.5 concentrations from 2012 to 2016. Dementia was confirmed in the baseline survey at a qualified clinical facility, and newly suspected dementia was assessed in 2017, after excluding cases of suspected dementia in 2015. National census data were used to weight the sample data to reflect the entire population in China, with multiple logistic regression performed to analyze the combined effects of PM _2.5 and smoking frequency on dementia and cognitive impairment. RESULTS: Individuals exposed to the highest PM _2.5 concentration and smoked daily were at higher risk of dementia than those in the lowest PM _2.5 concentration group ( OR, 1.603; 95% CI [1.626-1.635], P < 0.0001) and in the nonsmoking group ( OR, 1.248; 95% CI [1.244-1.252]; P < 0.0001). Moderate PM _2.5 exposure and occasional smoking together increased the short-term risk of cognitive impairment. High-level PM _2.5 exposure and smoking were associated with an increased risk of dementia, so more efforts are needed to reduce this risk through environmental protection and antismoking campaigns. CONCLUSION High-level PM _2.5 exposure and smoking were associated with an increased risk of dementia. Lowering the ambient PM _2.5, and smoking cessation are recommended to promote health.
Humans ; Dementia/etiology* ; Male ; Aged ; Female ; Cognitive Dysfunction/etiology* ; China/epidemiology* ; Particulate Matter/analysis* ; Smoking/epidemiology* ; Air Pollutants/analysis* ; Aged, 80 and over ; Environmental Exposure/adverse effects* ; Prevalence ; Middle Aged

Objective To investigate the expression of prolyl 4-hydroxylase β-polypeptide(P4HB)in glioblastoma multiforme(GBM)and its impact on clinical prognosis,as well as on the proliferation and migration of U87 cells.Methods(1)According to the Cancer Genome Atlas(TCGA)database,GTEx database and GEPIA2 database,the difference expression of P4HB in GBM and normal brain tissues were analyzed by R software.(2)A total of 52 patients with GBM who underwent surgical treatment from February 2017 to December 2019 were collected from Department of Neurosurgery,the Second People's Hospital of Guiyang.The normal brain tissues of 10 patients were selected as controls.Immunohistochemical method was used to detect the expression level of P4HB in tumor tissues and normal tissues.The Kaplan-Meier method with the log-rank test was employed for survival analysis.Receiver operating characteristic(ROC)curve was used to analyze the predictive valuable of P4HB expression in survival rate of GBM.Univariate and multivariate Cox regression analysis were used to identify the expression of P4HB and related clinicopathological factors affecting the survival and prognosis of the patients.(3)Human GBM U87 cells were randomly assigned into three groups:control group,NC-siRNA group and P4HB-siRNA group.P4HB expression was interfered with by the transfection of siRNA in P4HB-siRNA group.Real-time quantitative polymerase chain reaction(qRT-PCR)was used to detect the content of P4HB mRNA in U87 cells.Cell counting kit-8(CCK-8)and immunofluorescence assay were used to analyze the effects of P4HB on the proliferation of U87 cells.Scratch test was used to analyze the effects of P4HB on cell migration.Results The expression of P4HB was significantly upregulated in GBM tissues compared with normal brain tissues(P<0.05).The γδ T cells(r=-0.227)and follicular helper T cells(r=-0.226)were negatively correlated with the expression of P4HB,while natural killer cell(r=0.417),macrophages(r=0.374),neutrophils(r=0.344),and immature dendritic cells(r=0.263)were positively correlated with the expression of P4HB.Kaplan-Meier survival analysis showed that the progression-free survival and disease-specific survival of GBM patients with high P4HB expression were significantly lower than those with low expression(P<0.05).ROC curve showed that the area under the curve(AUC)of P4HB in predicting overall survival rate of GBM patients was 0.982,and 1-year,3-year,and 5-year survival was 0.655,0.724,0.861,respectively.The immunohistochemistry results suggested that P4HB protein was significantly highly expressed in GBM tumors.Survival analysis indicated that high expression of P4HB was associated with bad prognosis in GBM patients(P<0.05).Multivariate Cox regression analysis indicated that high expression of P4HB and TERT promoter mutations were the independent prognostic risk factors for GBM(P<0.05).Compared with control group and NC-siRNA group,the expression levels of P4HB were decreased significantly after transfected with siRNA in U87 cells of P4HB-siRNA group(P<0.01),and the proliferation ability and the wound healing rate were decreased significantly in P4HB-siRNA group(P<0.001).Conclusions P4HB is significantly highly expressed in GBM,which indicates that the prognosis of patients is poor.Knockout of P4HB could inhibit cellular proliferation and migration of GBM U87 cells.P4HB may be used as the relevant predictive marker and potential therapeutic target in GBM.

Objective:To investigate the expression of KCTD8 gene in breast ductal carcinoma and its correlation with clinical factors and prognosis.Methods:Immunohistochemistry technology(IHC)were employed to detect protein expression levels of KCTD8 in 27 pairs of breast ductal carci-noma and its paired adjacent tissues.Analyzing the correlation between changes in KCTD8 expres-sion of protein and clinical factors using statistical techniques.RNA expression and methylation data of breast cancer(including intraductal cancer)were analysed from TCGA database.Result:The pro-tein expression of KCTD8 gene in 27 pairs of breast ductal carcinoma tissues showed a decreasing trend compared to adjacent tissues(P＜0.05),and the decreased expression level of protein was cor-related with the tumor size of patients(P＜0.05).The analysis results of the TCGA database indicate that the expression and hypemethylation of KCTD 8 gene in breast cancer(including intraductal can-cer)tissues affected the prognosis of patients.Conclusion:The reduced protein expression level of KCTD8 gene in breast ductal carcinoma may be involved in the development and affect the prog-nosis of patients.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.

[Abstract] [Objective] To investigate the therapeutic effect of platelet-rich plasma (PRP) subcutaneous injection combined with gypenosides (GPs) oral administration on BALB/c mouse psoriatic inflammation and explore its mechanism of action. [Methods] The 6-8 week-old female SPF BALB/c mice were randomly divided into five groups: control, model, PRP, GPs and PRP+GPs group, with 5 mice in each group. Imiquimod (IMQ) was used to induce psoriasis-like skin inflammation on the back of mice except the control group. The onset and severity of psoriasis-like inflammation in different treatment groups were evaluated by observing skin lesions, skin thickness and measuring PASI score. HE staining and Ki67 staining were used to evaluate the pathological changes and proliferation of keratinocytes in psoriasis-like skin lesions. Blood cell count, enzyme-linked immunosorbent assay and Western blot were used to explore the changes in circulating white blood cell count, cytokines IL-17A and TNF-α, and related signaling pathway proteins p-STAT3 and p-P38. [Results] At the end of the experiment (on day 6), scale scores of model, PRP, GPs and PRP+GPs group were 3.6±0.49, 1.8±0.75, 1.8±0.75, 1.2±0.40, respectively; the ratios of skin thickness (μm) were 0.86±0.18, 0.59±0.10, 0.56±0.07 and 0.42±0.09; PASI scores were 10.6±1.02, 4.0±0.63, 4.0±1.10 and 3.2±0.75. Compared with the model group, the number of scales (P<0.01), patch thickness (P<0.01) and PASI score decreased (P<0.0001) showed a certain therapeutic effect, and PRP+GPs group had the best effect. Pathological examination showed that both the epidermal layer thickness (P<0.01) and epidermal cell proliferation (P<0.05) decreased in all treatment groups; IL-17A expression levels were 9.02±2.54, 16.56±3.49, 10.01±1.83, 11.12±2.48 and 10.50±2.16, and TNF-α expression levels were 223.36±70.34, 377.36±58.47, 265.42±45.14, 262.94±33.29 and 268.94±26.80 respectively. The expression of skin tissue IL-17A (P<0.05) and TNF-α (P<0.05) decreased, along with the decreased expression of related signaling pathway proteins p-STAT3 and p-P38. [Conclusion] PRP combined with GPs can reduce the expression of IL-17A and TNF-α through the STAT3 and P38 signaling pathways, thereby alleviating inflammation and inhibiting the overproliferation of keratinocytes, thus improving psoriasis-like skin inflammation in BALB/c mice.

Objective:To explore the effect of dietary modification-assisted multimodal therapy in the prevention and treatment of chronic prostatitis.Methods:A total of 132 cases of chronic prostatitis treated in the Outpatient Department of our hospital were randomly divided into an observation group(n=68)and a control group(n=64),the former following the Mediterranean dietary pattern,the latter adhering to their own dietary habits,and meanwhile both receiving lifestyle guidance,psychological counseling,symptomatic medication and physiotherapy according to their specific symptoms.The patients were followed up for 4 weeks,therapeutic effects were observed and comparisons were made between the two groups in the NIH-CPSI scores before and after treatment.Re-sults:Compared with the baseline,the quality of life(QOL)scores,pain and urination discomfort scores and total NIH-CPSI scores were significantly decreased in both the observation and the control groups after treatment(P<0.05),even more decreased in the former than in the latter,but with no statistically significant difference between the two(P>0.05).The rate of therapeutic effective-ness was higher in the observation group than in the control(87.1%vs 79.7%,but showed no statistically significant difference be-tween the two groups(P>0.05).Conclusion:Multimodal therapy is suitable for the management of different clinical manifesta-tions of individual patients,while dietary habits vary from person to person as well as from region to region.Therefore,scientific dietary modification for the prevention and treatment of CP/CPPS needs further exploration.