Intestinal flora imbalance is closely related to the pathogenesis of rheumatoid arthritis (RA). The existing studies have explored the monomer components such as tripterygium glycosides, total glycosides of Chaenomeles speciosa, and triterpenoid saponins of Clematis, Chinese materia medica such as Tripterygium wilfordii, Caulis Sinomenii, Radix Paeoniae Alba, Fructus Gardeniae, Fructus Chebulae, Radix Ginseng, Radix et Rhizoma Rhei, Rhizoma Atractylodis Macrocephalae, Pterostilbene, and Ginger, as well as the mechanisms of Danggui Sini Decoction, Danggui Niantong Decoction, Duhuo Jisheng Decoction, Yunpi Jiedu Tongluo Qushi Decoction, Qingre Huoxue Decoction, Compound Fengshining, Qingre Yangyin Chushi Decoction, Aconitum Decoction, Zhijing Powder, Jinwu Jiangu Capsule, and Fermented Chinese Medicine Qushi Chubi Decoction in intervening RA by regulating intestinal flora, suggesting that Chinese materia medica can restore intestinal homeostasis, reduce joint inflammation and play a role in the prevention and treatment of RA by regulating immune response, improving intestinal mucosal barrier and regulating intestinal metabolites.

Kv1.3,a voltage-gated potassium channel,is highly expressed in T lymphocytes,the nervous system,and vascular smooth muscle cells.It plays a critical role in membrane excitability and electrical signal transduction,serving as an important target for studying T-cell function and providing a promising direction for developing therapeutics against autoimmune and inflammatory diseases.Therefore,the de-velopment of specific inhibitors of Kv1.3 channel has emerged as a novel therapeutic strategy for these disorders.In this study,we isolated and purified a novel Kv1.3-inhibitory peptide toxin,LmKTx13,from the venom of the scorpion Lychas mucronatus using reversed-phase high-performance liquid chroma-tography(RP-HPLC).LmKTx13 consists of 38 amino acid residues,including six cysteines that form three disulfide bonds.Whole-cell patch-clamp recordings revealed that LmKTx13 potently inhibited Kv1.3 with an IC50 of 7.92±3.0 nmol/L.Selectivity analysis showed that 2 μmol/L LmKTx13 also in-hibited Kv1.2 and Kv1.7,but exhibited no significant effects on other potassium channel subtypes or voltage-gated sodium channels.Further investigation into the mechanism demonstrated that LmKTx13 acts as a pore-blocking inhibitor of Kv1.3.By analyzing the effects of LmKTx13 on Kv1.3 channel gating ki-netics and performing sequence alignment of the pore regions of Kv1.3 and Kv1.5,we constructed site-directed mutants and identified the pore region of Kv1.3 as the critical binding site for LmKTx13.Key residues involved in the interaction included T425,G427,and H451.In summary,we discovered a no-vel pore-blocking Kv1.3 inhibitor,LmKTx13,from L.mucronatus venom,which exhibits high affinity and selectivity for Kv1.3.These findings highlight its potential as a potential lead molecule for developing Kv1.3-targeted therapeutics.

Objective To explore the predictive factors of recurrence of chronic suppurative otitis media(CSOM)after otoendoscopic surgery,and construct a risk quantified nomogram model.Methods The clinical data of 485 patients with CSOM who underwent otoendoscopic surgery in our hospital from February 2021 to February 2023 were retrospectively analyzed.The patients were divided into the recurrence group and the non-recurrence group according to the recurrence situation during the follow-up period.The clinical data of patients between the two groups were compared,and the predictive factors of postoperative recurrence were analyzed by Cox regression method.A risk quantified nomogram model was constructed based on these predictive factors.The predictive efficiency of the model was verified by receiver operating characteristic(ROC)curve,and the calibration degree of the model was verified by Hosmer-Lemeshow goodness of fit analysis,and the clinical net benefit of the model was evaluated by decision curve analysis(DCA)method.Results Follow-up ranged from 6 to 39 months,with a median of 21(11,32)months,the postoperative recurrence rate was 14.64%(71/485).Combined with recurrent upper respiratory tract infections(HR=3.019,95%CI:1.609 to 5.664),combined with chronic rhinosinusitis(HR=2.428,95%CI:1.529 to 3.856),combined with adenoid hypertrophy(HR=2.214,95%CI:1.381 to 3.551),middle ear risk index(MERI)score(HR=2.863,95%CI:1.445 to 5.675),the seven-item eustachian tube dysfunction questionnaire(ETDQ-7)score(HR=2.679,95%CI:1.505 to 4.765)and inadequate drainage of the surgical cavity(HR=2.373,95%CI:1.503 to 3.746)were the risk factors for postoperative recurrence(P<0.05).A risk quantified nomogram model of recurrence after otoendoscopic surgery in CSOM patients was constructed based on the predictive factors of Cox regression analysis,among them the risk value ranges of patients who combined with recurrent upper respiratory tract infections,combined with chronic rhinosinusitis,combined with adenoid hypertrophy,MERI score,ETDQ-7 score,and inadequate drainage of the surgical cavity were 0 to 65 points,0 to 56 points,0 to 52 points,0 to 76 points,0 to 64 points,and 0 to 76 points,respectively.The area under the curve of ROC,sensitivity and specificity of the model for predicting postoperative recurrence were 0.928(95%CI:0.875 to 0.948),85.92%and 88.89%,respectively.There was no significant difference between the predicted probability of postoperative recurrence and the actual probability(P>0.05).The threshold probability of postoperative recurrence predicted by the model in the range of 4%to 92%could obtain clinical net benefit.Conclusion The predictive factors of recurrence after otoendoscopic surgery in CSOM patients include combined with recurrent upper respiratory tract infections,combined with chronic rhinosinusitis,combined with adenoid hypertrophy,MERI score,ETDQ-7 score and inadequate drainage of the surgical cavity,the risk quantified nomogram model based on these factors is highly effective in predicting postoperative recurrence.

AIM To study the chemical constituents from dichloromethane fraction of Dalbergia odorifera T.Chen heartwood.METHODS Separation and purification were performed using silica gel,Sephadex LH-20,thin-layer chromatography,and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.RESULTS Twenty-four compounds were isolated and identified as 7,2′-dihydroxy-4′-methoxy-isoflavanol(1),vanillin(2),2,2′-oxybis-(1,4-di-tert-butylbenzene)(3),7-hydroxy-6-methoxyflavone(4),sativan(5),5-hydroxy-4′,7-dimethoxyisoflavone(6),2-hydroxy-4,4′-dimethoxychalcone(7),7,2′,3′,4′-tetramethoxydihydroisoflavone(8),2,4,2′-trihydroxy-4′-methoxybenzil(9),ethyl-3-hydroxy-3-phenyl-2-propenoate(10),6,7-dimethoxy-2,3-dihydr-ochromen-4-one(11),sophorophenolone(12),apocynin(13),ethyl-2,4-dihydroxybenzoate(14),ethylparaben(15),methyl-2,4-dihydroxybenzoate(16),5,7-dihydroxy-6-methoxyflavanone(17),7-hydroxyflavanone(18),mimosifoliol(19),7-hydroxy-4′-methoxyisoflavane(20),virolane(21),5-hydroxy-7-methoxychromone(22),3-hydroxyl-5-methoxy-stilbene(23),2′,4′-dihydroxydihydrochalcone(24).CONCLUSION Compound 8 is new natural product,2-6,15,17-18 are isolated from this plant for the first time,7,9-14,16,20-24 are first isolated from genus Dalbergia.

Objective To study the regulatory effect of Qufeng Xiaodian Formula on serum differential metabolites of allergic purpura,and provide scientific basis for the diagnosis and treatment of allergic purpura in traditional Chinese medicine.Methods Sixty rats were randomly divided into a blank control group(referred to as the blank group),a model group,a compound glycyrrhizin group,a low-dose Qu Feng Xiao Dian Fang group,a medium dose Qu Feng Xiao Dian Fang group,and a high-dose Qu Feng Xiao Dian Fang group according to a random number table method,with 10 rats in each group.The model group was constructed by combining dried ginger,pepper,and long pepper with ovalbumin to create an allergic purpura rat model.After successful modeling,each treatment group was intervened with corresponding drugs for 4 weeks.After 4 weeks,serum was collected and non targeted metabolomics screening of serum differential metabolites was performed using ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometer(UPLC-QTOF/MS).Subsequently,data extraction and multivariate statistical analysis will be conducted to identify potential metabolic pathways.Results Compared with the control group,there were 91 possible differential metabolites in the serum of the model group rats,corresponding to 20 metabolic pathways;Compared with the model group,there were a total of 43 possible differential metabolites in the serum of rats in the wind dispelling and disease eliminating group,corresponding to 15 metabolic pathways.Among them,there are a total of 12 metabolic pathways.Inflammatory metabolites such as arachidonic acid and ceramide can damage vascular endothelium.Ten biomarkers,including arachidonic acid and ceramide,were significantly abnormal in the serum of the model group rats compared to the normal group.The Qufeng Xiaodian formula can significantly reverse these metabolites and significantly enrich them in arachidonic acid metabolism and sphingolipid metabolism pathways.Conclusion Qufeng Xiaodian Formula has a certain regulatory effect on metabolites such as arachidonic acid and ceramide that affect vascular endothelial injury.

Objective:To investigate the effects of curcumin,berberine,and puerarin combination therapy on lipid levels in hyperlipidemic mice.Methods:A total of 40 male C57BL/6J mice were randomly divided into eight groups:normal control group(A),high-fat control group(B),curcumin group(C),berberine group(D),puerarin group(E),low-dose combination group of curcumin,berberine,and puerarin(F),high-dose combination group of curcumin,berberine,and puerarin(G),and positive control group(H),with 5 mice in each group.The normal control group was fed a standard diet,while the other groups were given a high-fat diet.After establishing the hyperlipidemic model,the mice were administered with physiological saline,curcumin(200 mg/kg),berberine(200 mg/kg),puerarin(300 mg/kg),low-dose combination of curcumin(50 mg/kg),berberine(50 mg/kg),and puerarin(100 mg/kg),high-dose combination of curcumin(200 mg/kg),berberine(200 mg/kg),and puerarin(300 mg/kg),or simvastatin(6 mg/kg)via gavage for three weeks.After treatment,serum was collected from the mice for biochemical analysis of lipid levels and liver function.Liver tissues were subjected to HE staining,Western blot analysis and real-time quantitative PCR.Results:Curcumin,berberine,and puerarin,whether administered individually or in combination,can reduce the body weight of hyperlipidemic mice(P＜0.01).Treatment with curcumin,berberine,and puerarin individually significantly reduced lipid levels in hyperlipidemic mice(P＜0.05)and alleviated liver damage caused by hyperlipidemia(P＜0.05).Furthermore,the high-dose combination of curcumin,berberine,and puerarin exhibited a more pronounced effect on improving lipid levels(P＜0.01)and provided greater protective effects on the liver compared to the positive control group(P＜0.05).Additionally,curcumin,berberine,and puerarin administered individually can each promote the expression of the LDLR gene in high-fat diet mice(increased by 90％,85％,and 98％,respectively)and reduce the expression of the ACC gene(decreased by 42％,45％,and 43％,respectively).The combination of all three compounds enhances the expression of the LDLR gene in high-fat diet mice(increased by 90％with low-dose combination and 169％with high-dose combination)and reduces the expression of the ACC gene(decreased by 38％with low-dose combination and 42％with high-dose combination).Conclusion:The combination of curcumin,berberine,and puerarin significantly improves lipid levels in hyperlipidemic mice and mitigates liver damage associated with hyperlipidemia.

Aim To investigate the protective effects and potential mechanisms of Radix Angelica sinensis and Radix Hedysari ultrafiltrate(RAS-RH)on X-ray-induced cellular damage in Raw264.7 macrophages.Methods An integrated approach combining network pharmacology,molecular docking,and bioinformatics a-nalysis was employed to predict therapeutic targets and signaling pathways of RAS-RH in coronary heart dis-ease(CHD).Subsequent in vitro validation was per-formed using an X-ray(6 Gy)-induced macrophage in-jury model with four experimental groups:control,radi-ation-only model,and three RAS-RH-treated groups at varying concentrations.Cell viability was assessed by CCK-8 assay,apoptosis by flow cytometry with Annexin V-FITC/PI staining,mitochondrial membrane potential by JC-1 fluorescence,and inflammatory cytokine levels(IL-1 β,IL-6,IL-18,TNF-α)by ELISA.Molecular mechanisms were investigated through Western blot and qRT-PCR analyses of TLR4/NLRP3/Caspase-1 sig-naling pathway components and Bcl-2 family proteins.Results Network pharmacology revealed RAS-RH's multi-target action on apoptosis and inflammation-relat-ed pathways,particularly NF-κB and Bcl-2 signaling.Molecular docking identified strong binding affinities between RAS-RH components and TLR4/NLRP3 pro-teins.In vitro studies demonstrated that RAS-RH treat-ment significantly improved cell viability(P＜0.01),reduced apoptosis(P＜0.01),restored mitochondrial membrane potential(P＜0.05),and attenuated radia-tion-induced ultrastructural damage including mem-brane disruption and cytoplasmic vacuolization.ELISA showed marked suppression of pro-inflammatory cyto-kines(P＜0.01).Transmission electron microscopy(TEM)analysis revealed that RSA-RH ameliorated pyroptosis-associated ultrastructural alterations,inclu-ding plasma membrane disruption and cytoplasmic vac-uolization.Protein and gene expression analyses con-firmed downregulation of TLR4/NLRP3/Caspase-1 pathway and modulation of Bcl-2/Bax ratio.Conclu-sion RAS-RH exerts radioprotective effects through dual regulation of pyroptosis and apoptosis pathways,suggesting its potential as an adjuvant therapy for radia-tion-induced cardiovascular complications in CHD pa-tients.

Objective:To describe the prevalence of non-alcoholic fatty liver disease (NAFLD) in people living with HIV in Taizhou, Zhejiang Province, and identify the factors associated with NAFLD in this population.Methods:A cross-sectional survey was conducted from 2021 to 2023. Based on the routine follow-up management of people living with HIV, liver ultrasound examination, physical examination and laboratory test were conducted to collect the information about the diagnosis of NAFLD and biochemical indicators in this population. Logistic regression model was used to identify the factors associated with the prevalence of NAFLD.Results:In the 2 550 study participants, the prevalence of NAFLD was 21.5% (548/2 550), abnormal liver function was found in 23.7% (604/2 550) of the study participants, and liver fibrosis was found in 45.2% (1 152/2 550) of the study participants. Multivariable logistic regression analyses showed that being women (a OR=0.55, 95% CI: 0.42-0.73), being overweight or obese (a OR=3.22, 95% CI: 2.59-4.01), having diabetes (a OR=3.37, 95% CI: 2.15-5.29), having dyslipidemia (a OR=2.96, 95% CI: 2.25-3.89), CD4 + T lymphocyte (CD4) counts <200 cells/μl (a OR=0.61, 95% CI: 0.42-0.88), and receiving Efavirenz (EFV) + Lamivudine (3TC) + Zidovudine (AZT) for antiretroviral therapy (ART)(a OR=1.52, 95% CI: 1.17-1.98) were associated with NAFLD. NAFLD was positively associated with abnormal liver function (a OR=2.01, 95% CI: 1.60-2.52) and inversely associated with liver fibrosis (a OR=0.76, 95% CI: 0.59-0.98). The 45-59 age group (a OR=7.05, 95% CI: 5.65-8.80), CD4 counts <200 cells/μl (a OR=1.45, 95% CI: 1.06-1.97) and receiving Nevirapine (NVP)+3TC+AZT of ART (a OR=1.87,95% CI: 1.44-2.43) were the main factors associated with liver fibrosis. Conclusions:The prevalence of NAFLD in people living with HIV Taizhou was more than 20.0%, with a significant proportion of them having abnormal liver function and liver fibrosis. Being overweight or obese, suffering from diabetes, having dyslipidemia, low CD4 counts, and receiving specific ART were associated with NAFLD. NAFLD, CD4 counts and specific ART were the main factors associated with abnormal liver function and liver fibrosis.

Objective To study the regulatory effect of Qufeng Xiaodian Formula on serum differential metabolites of allergic purpura,and provide scientific basis for the diagnosis and treatment of allergic purpura in traditional Chinese medicine.Methods Sixty rats were randomly divided into a blank control group(referred to as the blank group),a model group,a compound glycyrrhizin group,a low-dose Qu Feng Xiao Dian Fang group,a medium dose Qu Feng Xiao Dian Fang group,and a high-dose Qu Feng Xiao Dian Fang group according to a random number table method,with 10 rats in each group.The model group was constructed by combining dried ginger,pepper,and long pepper with ovalbumin to create an allergic purpura rat model.After successful modeling,each treatment group was intervened with corresponding drugs for 4 weeks.After 4 weeks,serum was collected and non targeted metabolomics screening of serum differential metabolites was performed using ultra-high performance liquid chromatography quadrupole time-of-flight tandem mass spectrometer(UPLC-QTOF/MS).Subsequently,data extraction and multivariate statistical analysis will be conducted to identify potential metabolic pathways.Results Compared with the control group,there were 91 possible differential metabolites in the serum of the model group rats,corresponding to 20 metabolic pathways;Compared with the model group,there were a total of 43 possible differential metabolites in the serum of rats in the wind dispelling and disease eliminating group,corresponding to 15 metabolic pathways.Among them,there are a total of 12 metabolic pathways.Inflammatory metabolites such as arachidonic acid and ceramide can damage vascular endothelium.Ten biomarkers,including arachidonic acid and ceramide,were significantly abnormal in the serum of the model group rats compared to the normal group.The Qufeng Xiaodian formula can significantly reverse these metabolites and significantly enrich them in arachidonic acid metabolism and sphingolipid metabolism pathways.Conclusion Qufeng Xiaodian Formula has a certain regulatory effect on metabolites such as arachidonic acid and ceramide that affect vascular endothelial injury.

Objective:To describe the prevalence of non-alcoholic fatty liver disease (NAFLD) in people living with HIV in Taizhou, Zhejiang Province, and identify the factors associated with NAFLD in this population.Methods:A cross-sectional survey was conducted from 2021 to 2023. Based on the routine follow-up management of people living with HIV, liver ultrasound examination, physical examination and laboratory test were conducted to collect the information about the diagnosis of NAFLD and biochemical indicators in this population. Logistic regression model was used to identify the factors associated with the prevalence of NAFLD.Results:In the 2 550 study participants, the prevalence of NAFLD was 21.5% (548/2 550), abnormal liver function was found in 23.7% (604/2 550) of the study participants, and liver fibrosis was found in 45.2% (1 152/2 550) of the study participants. Multivariable logistic regression analyses showed that being women (a OR=0.55, 95% CI: 0.42-0.73), being overweight or obese (a OR=3.22, 95% CI: 2.59-4.01), having diabetes (a OR=3.37, 95% CI: 2.15-5.29), having dyslipidemia (a OR=2.96, 95% CI: 2.25-3.89), CD4 + T lymphocyte (CD4) counts <200 cells/μl (a OR=0.61, 95% CI: 0.42-0.88), and receiving Efavirenz (EFV) + Lamivudine (3TC) + Zidovudine (AZT) for antiretroviral therapy (ART)(a OR=1.52, 95% CI: 1.17-1.98) were associated with NAFLD. NAFLD was positively associated with abnormal liver function (a OR=2.01, 95% CI: 1.60-2.52) and inversely associated with liver fibrosis (a OR=0.76, 95% CI: 0.59-0.98). The 45-59 age group (a OR=7.05, 95% CI: 5.65-8.80), CD4 counts <200 cells/μl (a OR=1.45, 95% CI: 1.06-1.97) and receiving Nevirapine (NVP)+3TC+AZT of ART (a OR=1.87,95% CI: 1.44-2.43) were the main factors associated with liver fibrosis. Conclusions:The prevalence of NAFLD in people living with HIV Taizhou was more than 20.0%, with a significant proportion of them having abnormal liver function and liver fibrosis. Being overweight or obese, suffering from diabetes, having dyslipidemia, low CD4 counts, and receiving specific ART were associated with NAFLD. NAFLD, CD4 counts and specific ART were the main factors associated with abnormal liver function and liver fibrosis.