Aim To investigate the effect of total gly-cosides of peony on Th17/Treg balance in autoimmune thyroiditis(AIT)by regulating miR-155 expression.Methods Sixty female SD rats were randomly divided into a blank control group,a model group,high-dose,medium,and low-dose groups of total glycosides of peony,and a Western medicine control group(seleni-um yeast group).After eight weeks of modeling,the pathological changes in thyroid tissue were observed by HE staining,the expression of miR-155 in the thyroid of rats was detected by RT-PCR,the targeting effect of miR-155 on SOCS1 was verified by dual luciferase method,and the levels of TGAb,TPOAb,IL-10,and IL-17 in peripheral serum were detected by ELISA,the expression of thyroid SOCS1 was detected by WB,and the proportion of Th17 and Treg in CD4+cells of the spleen was detected by flow cytometry.Results Com-pared with the blank group,the expression of miR-155 in the thyroid gland of the model group rats significant-ly increased,and the serum levels of TGAb,TPOAb,and IL-17 significantly increased,with an increase in the proportion of Th17;the IL-10 level significantly decreased,the proportion of Treg decreased,and the expression of SOCS1 protein decreased,with statistical significance(P＜0.01);compared with the model group,the high,medium,and low dose groups of total glycosides of peony and selenium yeast groups showed a decrease in miR-155 expression,a decrease in TGAb,TPOAb,IL-17 levels,a decrease in Th17 pro-portion,an increase in IL-10 level,an increase in Treg proportion,and an increase in SOCS1 expression,all with statistical significance(P＜0.01).Moreover,the improvement in the medium dose group of total glyco-sides of peony was more significant.Conclusion To-tal glycosides of peony downregulate miR-155 expres-sion,regulate Th17/Treg balance,alleviate inflamma-tory response,and exert immune regulatory effects.

Objective To investigate the correlation between peripheral blood CD14+CD16+monocytes and IgG N-glycosyl levels and disease activity in patients with systemic lupus erythematosus(SLE).Methods A total of 109 SLE patients admitted to Xingtai Cental Hospital from August 2021 to November 2024 were retrospectively selected as the study objects.According to SLE disease activity index(SLE-DAI),the patients were divided into active group(n=52)and stable group(n=57).In addition,56 patients who underwent physical examination during the same period were selected as the control group.Clinical data of patients were collected,CD14+CD16+mononuclear cells were detected by flow cytometry(FCM),and IgG N-glycosyl levels were detected by hydrophilic interaction chromatography-mass spectrometry.Logistic regression analysis was performed to analyze the influencing factors of SLE-DAI,and multicollinearity test[variance inflation factor(VIF)]was performed for independent variables.The prediction model of disease activity was constructed.The effectiveness of the predictive model was evaluated by describing the recviver operator characteristic(ROC)curve and calculating the area under the curve(AUC)value.Hosmer-Lemeshow goodness-of-fit test predicted the calibration degree of the model.Results The levels of WBC,Hb,PLT,ALB,complement C3 and complement C4 in control group were higher than those in SLE group(t=8.917～22.171),and the levels of CRP were lower than those in SLE group(t=-17.359),with differences were statistical significance(all P<0.05).The CRP level and the proportion of CD14+CD16+mononuclear cells in the active group were higher than those in the stable group,and the differences were statistically significant(t=5.449,11.112,all P<0.05).The IgG glycosylation characteristics of galactosylation,sialylation and N-acetylglucosamine modification were lower than those in the stable group,and the differences were statistical significance(Z=-2.432～-0.158,all P<0.05).Spearman correlation analysis showed that the proportion of CD14+CD16+monocytes was significantly negatively correlated with IgG galactosylation,sialylation level and bisection N-acetylglucosamine modification(r=-0.656,-0.531,-0.608,all P<0.01).CD14+CD16+monocyte ratio was positively correlated with SLE-DIA(r=0.581,all P<0.01).IgG galactosylation,sialylation levels and bisection N-acetylglucosamine modification were negatively correlated with SLE-DIA(r=-0.645,-0.609,-0.503,all P<0.01).Logistic regression analysis showed that CRP>8.21mg/L,CD14+CD16+≥16.17%,sialylation<22.05%and isotropic N-acetylglucosamine modification<16.53%were independent risk factors for disease activity in SLE patients(Wald χ2=4.471～12.811,all P<0.05).The VIF values of the above independent variables were all less than 10.By establishing the Logistic regression prediction model and drawing the ROC curve,the AUC value for diagnosing SLE disease activity was 0.821(95%CI:0.733～0.905),the sensitivity,specificity and the Yodon index were 85.37%,75.67%,0.677,respectively.and the P values of Hosmer-Lemeshow goodness-of-fit test models were 0.568,respectively.Conclusion The proportion of CD14+CD16+monocytes in peripheral blood of SLE patients increase significantly,and the level of IgG glycosylation characteristics decrease,both of which are correlated with SLE-DIA.The predictive model constructed based on the two had a good ability to distinguish SLE-DIA from inactive state,with high sensitivity and moderate specificity conducive to early clinical recognition,and the model fitting effect is good.SLE-DIA can be evaluated more accurately.

Objective:To investigate the value of biparametric-MRI (bpMRI) based peritumoral radiomics for preoperative prediction of extraprostatic extension (EPE) in prostate cancer (PCa).Methods:In this cross-sectional study, consecutive bpMRI of patients undergoing prostatectomy for PCa were retrospectively collected from the First Medical Center (center 1) and the Third Medical Center (center 2) of Chinese PLA General Hospital. A total of 274 patients were finally enrolled. Patients at center 1 from January 2020 to December 2022 were randomly divided into a training set (149 cases) and an internal validation set (63 cases) by stratified random sampling. Patients at center 2 from January 2023 to March 2024 were assigned to the external test set (62 cases). Patients were categorized into EPE-positive group and EPE-negative group according to pathological assessment postoperatively. In the training set, there were 49 cases in EPE-positive group and 100 cases in EPE-negative group. In the internal validation set, there were 26 cases in EPE-positive group and 37 cases in EPE-negative group. In the external test set, there were 22 cases in EPE-positive group and 40 cases in EPE-negative group. Axial T 2WI and apparent diffusion coefficient (ADC) images were manually annotated to obtain index lesion regions of interest (ROIs), with the peritumoral ROIs subsequently delineated by semi-automatic segmentation technique. Radiomics features were extracted from intra-tumoral, peri-tumoral, and intra-tumoral plus peri-tumoral ROIs. The training set data was employed to select and optimize features to build the radiomics models. The logistic regression analysis was used to develop radiomics, clinical, and integrated models. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC) in the external test set, and compared by the DeLong test. The sensitivity and specificity were compared by the exact McNemar test. Results:In the external test set, the peri-tumoral radiomics model based on bpMRI showed the highest performance in evaluating EPE, with an AUC of 0.739 (95% CI 0.611-0.842), which was identified as the optimal radiomics model. EPE grade ( OR=6.151, 95% CI 3.371-11.226, P<0.001) was incorporated into the clinical model, with an AUC of 0.780 (95% CI 0.657-0.875) in the external test set. The integrated model had an AUC of 0.817 (95% CI 0.698-0.904) in the external test set. There was no statistically significant difference in comparisons of AUCs among the three models (all P>0.05). The sensitivity of the integrated model (68.2%) showed no significant difference from those of the clinical model and the optimal radiomics model (77.3% and 86.4%, respectively; P=0.500 and P=0.289). However, the specificity of the integrated model (85.0%) was significantly higher than those of the clinical model (67.5%, P=0.016) and the optimal radiomics model (50.0%, P<0.001). Conclusion:A bpMRI-based peritumoral radiomics integrating clinical model demonstrates high performance for preoperative prediction of EPE in PCa.

BACKGROUND:Inflammation and apoptosis play key roles in the pathological process of cervical spondylotic myelopathy.Previous studies have shown that Pueraria lobata decoction has favorable therapeutic effects on cervical spondylotic myelopathy.OBJECTIVE:To investigate the effects and mechanism of Pueraria lobata decoction in neuroinflammatory response and apoptosis in rats with cervical spondylotic myelopathy.METHODS:Sixty Sprague-Dawley rats were randomly divided into six groups:a normal group,a sham-operated group,a model group,and three groups that received low,medium,and high doses of Pueraria lobata decoction.An animal model of cervical spondylotic myelopathy was constructed through compression of the spinal cord with water-absorbing and expanding material.Gastric administration of Pueraria lobata decoction(4.86,9.72,and 19.44 g/kg)was given in the three Pueraria lobata decoction groups 2 weeks after surgery,and the resting groups were given saline by gavage,once daily for 4 weeks.Motor function evaluation(Basso-Beattie-Bresnahan score)was performed in rats on days 1,7,14,21 and 28 after drug administration.At 4 weeks after drug administration,hematoxylin-eosin staining was used to observe the pathomorphologic changes in spinal cord tissue;immunofluorescence double staining was used for the detection of microglial cell polarization in spinal cord tissue;quantitative fluorescence PCR was used to detect the changes in the expression of interleukin-6 and interleukin-1β mRNA;western blot assay was used to detect the protein expression of p-NF-κB p65,NF-κB p65,NLRP3,ASC,Cleaved Caspase-1,Bax,Bcl-2,Cleaved Caspase-3,NOX4,p-Drp1,Drp1,and Mfn2 in spinal cord tissues;TUNEL assay was used to detect apoptosis in spinal cord tissues;and DHE staining was used to detect reactive oxygen species levels in rat spinal cord tissues.RESULTS AND CONCLUSION:(1)Compared with the normal and sham-operated groups,reduced Basso-Beattie-Bresnahan scores were observed in the model group(P<0.05),spinal cord neurons were crumpled and malformed with vacuolike changes.The Basso-Beattie-Bresnahan scores in the low-,medium-and high-dose Pueraria lobata decoction groups were significantly higher than those in the model group(P<0.05),and spinal cord neuronal damage reduced significantly.(2)Compared with the normal and sham-operated groups,there were elevated levels of Iba-1 and inducible nitric oxide synthase proteins and increased interleukin-6 and interluekin-1β mRNA expression in the spinal cord tissue of rats in the model group(P<0.05).The expression levels of Iba-1,inducible nitric oxide synthase,p-NF-κB,NLRP3,ASC and cleaved caspase-1 proteins as well as interleukin-6 and interleukin-1β mRNAs in the spinal cord tissues of rats in the low-,medium-and high-dose Pueraria lobata decoction groups were reduced compared with those in the model group(P<0.05).(3)Compared with the normal and sham-operated groups,the rate of TUNEL-positive cells and the levels of Bax and cleaved caspase-3 proteins were increased in the spinal cord tissues of rats in the model group(P<0.05),while the expression of Bcl-2 protein was reduced(P<0.05).Compared with the model group,the above indexes were significantly improved in the low-,medium-and high-dose Pueraria lobata decoction groups.(4)Compared with the normal and sham-operated groups,the model group exhibited increased levels of reactive oxygen species,along with elevated expression of NOX4 and p-Drp1 proteins(P<0.05)and reduced expression of Mfn2 protein(P<0.05)in the rat spinal crod tissue.Compared with the model group,the low-,medium-,and high-dose Pueraria lobata decoction groups exhibited reduced levels of reactive oxygen species,as well as decreased expression of NOX4 and p-Drp1 proteins(P<0.05)and increased expression of Mfn2 protein(P<0.05)in the rat spinal cord tissue.To conclude,Pueraria lobata decoction inhibits neuroinflammatory responses and neuronal apoptosis in the rat model of cervical spondylotic myelopathy,and the mechanism of action may be related to the regulation of the NOX4/reactive oxygen species/DRP1 signaling pathway.

This review has introduced the Coronary Artery Tree description and Lesion EvaluaTion(CatLet or Hexu)angiographic scoring system,which,based solely on coronary angiography results,has characterized 6 types of right coronary artery,3 types of left descending artery,and 3 types of diagonal size,together resulting in 54 types of coronary circulation pattern.This novel angiographic scoring system can be utilized to account for coronary anatomy in its diversity,severity and complexity of diseased coronary arteries,and their subtended myocardial territories in jeopardy.The CatLet angiographic scoring system is unique in that the importance of a coronary artery is weighted according to its subtended myocardial segments,by which the variability of coronary artery has been accounted for and measured.Researchers at home and abroad have increasingly paid attention to its clinical utilities,which warrant further validation in the context of large sample size,prospective,and randomized controlled trials.The CatLet angiographic scoring system is accessible at www.catletscore.com.

Objective:To investigate the clinical efficacy of moxibustion(Mox)combined with low-dose tadalafil(TAD)in the treatment of diabetes mellitus-induced erectile dysfunction(DMED)with the syndrome of Qi deficiency and blood stasis.Meth-ods:According to the inclusion and exclusion criteria,we selected 90 patients with DMED for this trial and equally randomized them into a Mox,a TAD,and a Mox combined with TAD(Mox+TAD)group to be treated by mild Mox applied to the acupoints Zusanli,Sanyinjiao and Yinlingquan qd alt,oral medication with low-dose TAD at 5 mg per dose qd,and combination of the above two thera-pies,respectively,all for 4 weeks.We obtained from the patients their IIEF-5 scores,traditional Chinese medicine(TCM)symptoms scores,Erectile Hardness Scale(EHS)scores,corpus cavernosal hemodynamic indexes,and the peak systolic velocity(PSV),end diastolic velocity(EDV)and resistance index(RI)of the corpus cavernosal arteries before and after treatment,and compared them among the three groups.Results:The total effectiveness rate was significantly higher in the Mox+TAD(90.0％)than in the Mox(46.7％)and TAD groups(60.0％)(P＜0.05).Compared with the baseline,the IIEF-5 and EHS scores were increased,while the TCM symptoms scores decreased in all the three groups after treatment,more significantly in the Mox+TAD group than in the other two(P＜0.05).And the PSV and RI were remarkably increased,while the EDV decreased(P＜0.05)in all the three groups(P＜0.05)after treatment,with PSV even higher in the Mox+TAD than in the Mox and TAD groups(P＜0.05).Conclusion:Moxi-bustion combined with tadalafil has a definite efficacy and safety for the treatment of DMED,which can effectively improve the erectile function of the patients by increasing penile blood supply,benefiting qi and activating blood circulation.

This study was aimed at investigating the effects of demethylase fat mass and obesity-associated protein(FTO)and methyltransferase methyltransferase like protein 3(METTL3),key molecules in N6-methyladenosine(m6A)modification,on the replication and proliferation of Japanese encephalitis virus(JEV).Recombinant lentiviruses were generated by packaging the FTO and green fluorescent protein into lentiviral vectors.Neuro2a cells,a mouse neuroblastoma cell line,were infected with the lentivirus,and stable FTO-expressing cell lines were obtained through puromycin selection.Successful overexpression of FTO was confirmed through fluorescence microscopy,real-time quantitative PCR,and western blot analysis.When Neuro2a cells overexpressing FTO were infected with JEV,the overexpression of FTO decreased JEV replication in the cells,and increased the expression of interferon(IFN)and related molecules.Additionally,treatment of JEV-infected Neuro2a cells with the METTL3-specific inhibitor STM2457 resulted in a dose-dependent decrease in JEV replication and viral protein expression.These findings suggested that lowering m6A methylation levels inhibits JEV replication,thus shedding light on the regulatory role of methylation modification in JEV replication.

Objective To evaluate the effects of transcatheter aortic valve replacement(TAVR)on left ventricular reverse remodeling(LVRR)and outcomes in patients with mixed aortic valve disease(MAVD)and predominant aortic stenosis(AS).Methods Patients undergoing TAVR at our center between January 2020 and December 2022 were enrolled consecutively.Propensity score matching(PSM)(1∶1 ratio)was used to reduce selection bias.Transthoracic echocardiography(TTE)was used to monitor left ventricular ejection fraction(LVEF)and other structural parameters over time.The study outcome was a composite of cardiovascular death and rehospitalization due to cardiovascular causes.Linear mixed-effects models and logistic regression were utilized for comparing echocardiographic changes across groups and identifying independent risk factors for no-LVRR,respectively.Results After PSM,126 patients were included.MAVD group exhibited larger structural parameters(left ventricular end-systolic/end-diastolic diameter and volume,left ventricular mass index)and a lower left ventricular ejection fraction(LVEF)(all P＜0.05).However,more pronounced improvements in left ventricular structure and hemodynamics were observed during follow-up.Multivariate logistic regression analysis indicated that the left ventricular mass index(LVMI)was an independent predictor of left ventricular reverse remodeling(LVRR)after TAVR,whereas persistent moderate or greater mitral regurgitation(MR)and paravalvular leak(PVL)significantly reduced the incidence of LVRR.During a median follow-up period of 23 months,a total of 31 endpoint events occurred,and there was no statistically significant difference in long-term prognosis between the two groups(Log-rank P=0.330).Conclusions Compared to patients in the AS group,those in the MAVD group exhibited more severe left ventricular remodeling before TAVR.However,more significant LVRR was observed during postoperative follow-up.Additionally,the long-term prognosis was comparable between the two groups.

Head and neck squamous cell carcinoma(HNSCC)is a highly prevalent malignancy with poor prognosis.Treatment strategies to date have achieved limited success in significantly improving overall survival rates.γδ T cells,a unique subset of immune cells in the tumor microenvironment,can link adaptive and innate immune functions.While γδ T cells can effectively recognize and eliminate HNSCC tumor cells,certain subsets of these cells can secrete interleukin-17,contributing to tumor progression.Nevertheless,due to their remarkable cyto-toxic activity,γδ T cells have been identified as promising candidates for antitumor immunotherapy.This article reviews the biological back-ground of γδ T cells,their role in tumor immunity in HNSCC,and recent advances in γδ T cell immunotherapy,aiming to provide new in-sights into HNSCC diagnosis and treatment.

Aim To explore the mechanism of baicalin combined with heat stimulation in treating acute lym-phoblastic leukemia(ALL)based on network pharma-cology and in vitro experiments.Methods The CCK-8 assay was used to screen the suitable conditions for heat stimulation to interfere ALL cell lines Jurkat,CCRF-CEM,Hut-78 and a normal lymphocyte HMy2.CIR,and the effects of baicalin combined with heat stimulation on the proliferation of three ALL cell lines and a normal lymphocyte were tested.The key targets of baicalin combined with fever stimulation for the treatment of ALL were obtained based on network phar-macological analysis,and the potential mechanisms were predicted by gene ontology(GO)annotation and kyoto encyclopedia of genes and genomes(KEGG)en-richment.The expression levels of TNF-α,AKT1,TYMS and CASP3 mRNA in ALL cell lines Jurkat and CCRF-CEM were examined by RT-qPCR with baicalin alone and baicalin combined with heat stimulation.Results The optimal conditions for heat stimulation to intervene ALL cells were 41 ℃ for 24 h,and heat stimulation combined with baicalin synergistically inhibited the growth of ALL cell lines and effectively reduced the cy-totoxicity of baicalin.Based on the network pharmaco-logical analysis,55 intersecting targets of baicalin with ALL diseases and 77 intersecting targets of baicalin with fever were obtained.The results of GO annotation and KEGG enrichment suggested that baicalin com-bined with fever stimulation to intervene ALL might be associated with influencing intracellular reactive oxygen species metabolism,DNA transcription and apoptotic processes involved in cysteine enzymes.Apoptosis,TNF and IL-17 signaling pathways were the key pathways for baicalin combined with heat stimulation in treating ALL.Under heat stimulation at 41 ℃ using SDHA gene as housekeeping gene,in vitro experiments showed that baicalin significantly up-regulated the expression of TNF-α and CASP3,and down-regulated the expression of TYMS in ALL cells.Conclusions Based on net-work pharmacologic analyses and in vitro experiments,baicalin combined with heat stimulation can regulate TNF-α and CASP3 gene levels in ALL cells and de-stroy cellular structure to promote cell apoptosis,thus synergistically treating ALL.