Objective:To investigate the mechanism of the synergistic anti-leukemia effect of the combination of Bcl-2 inhibitor venetoclax(VEN)and histone deacetylase(HDAC)inhibitor chidamide(CDM)in T-cell acute lymphoblastic leukemia(T-ALL).Methods:The effect of VEN combined with CDM on the proliferation of T-ALL CEM and MOLT-4 cell lines was detected by CCK-8 assay.And the effects on the cell cycle and apoptosis were detected by flow cytometry.Cell cycle protein and apoptosis-related protein expression were detected by Western blot.The key pathways of VEN combined with CDM in T-ALL were screened through network pharmacology analysis,and verifying them in T-ALL cell lines,T-ALL patient cells and public databases.Results:VEN combined with CDM displayed a synergistic effect on cell proliferation of CEM and MOLT-4 cells.In cell cycle experiment,VEN combined with CDM induced G0/G1 phase arrest in CEM and MOLT-4 cells.Western blot experiment showed that VEN combined with CDM could significantly downregulate the expression of cyclin E2 and CDK2 and upregulate the expression of p21Waf1/Cip1.In the apoptosis experiment,VEN combined with CDM could significantly induce the apoptosis of CEM and MOLT-4 cells.Western blot experiment demonstrated that VEN combined with CDM promoted endogenous apoptosis by downregulating Mcl-1 and upregulating Bax and cleaved caspase-3 protein levels.Network pharmacology analysis identified 10 hub genes.KEGG enrichment analysis revealed the cell cycle,PI3K-AKT signaling pathway,and its downstream FoxO signaling pathway were significantly enriched.GO enrichment analysis revealed the G1/S transition of mitotic cell cycle,cyclin-dependent protein kinase holoenzyme complex,and kinase activity were significantly enriched.Western blot experiment showed that VEN combined with CDM could significantly downregulate the protein level of PI3K,AKT,and p-AKT,and upregulate FoxO1 in CEM and MOLT-4 cells.In T-ALL patients,FoxO1 showed significantly lower expression compared to the normal donors,and the same result was verified in the GSE13159 and GSE26713 datasets.Conclusion:The combination of VEN and CDM exerts synergistic anti-leukemia effects by inhibiting cellular proliferation,inducing G0/G1,phase arrest and promoting apoptosis through PI3K/AKT/FoxO1 axis in T-ALL.

AIM To study the chemical constituents from the roots of Siraitia grosvenorii(Swingle)C.Jeffrey and their α-glucosidase inhibitory activities.METHODS The 95％ethanol extract was isolated and purified by silica gel,MCI,ODS and HSCCC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The α-glucosidase inhibitory activities were evaluated by PNPG method,after which molecular docking was performed.RESULTS Twenty-one compounds were isolated and identified as vanillin(1),siraitic acid B(2),cucurbitacin B(3),salicylic acid(4),ferulic acid(5),p-hydroxybenzaldehyde(6),(+)-lariciresinol(7),(+)-isolariciresinol(8),liballinol(9),3-(hydroxyacetyl)indole(10),2E-4-hydroxy-nonenoic acid(11),vomifolilol(12),vanillic acid(13),indole-3-carboxylic acid(14),ω-hydroxypropioguaiacone(15),p-hydroxybenzoic acid(16),p-coumaric acid(17),dehydrodipinocarpine(18),secoisolariciresinol(19),sesquimarocanol A(20),threo-guaiacylglycerol-β-O-4-lariciresinol ether(21).IC50 values of compounds 4,10,18 and 21 were(0.42±0.060)-(0.89±0.037)mg/mL.CONCLUSION Compounds 4,10-12,15,16,18,and 21 are isolated from the roots of this plant for the first time.Compounds 4,10,18,21 have α-glucosidase inhibitory activities,and 18 has the strongest activity.

Ferroptosis is a cell death pattern associated with the regulation of the Nrf2/GPX4 signaling pathway.Activating the Nrf2/GPX4 signaling pathway can regulate the expression of genes and proteins related to oxidative stress,alleviate stress damage,and inhibit cell ferroptosis.At present,research on the intervention of traditional Chinese medicine in ferroptosis has made certain progress.Through literature research,it can be found that some traditional Chinese medicine active monomers can activate the Nrf2/GPX4 signaling pathway to inhibit ferrop-tosis,play a protective role in tissues and organs,and have ther-apeutic potential in various diseases.Some traditional Chinese medicine active monomers exhibit characteristics of multi organ protective effects and bidirectional regulation.This article discus-ses the relevant research on the inhibition of ferroptosis by acti-vating the Nrf2/GPX4 signaling pathway with traditional Chinese medicine active monomers,and proposes suggestions to provide reference and ideas for further basic and applied research.

In view of the characteristics of H5N6 subtype avian influenza virus(AIV)that it has both high pathogenicity and the risk of cross-species transmission,posing a serious threat to the poultry farming industry and public health security,in order to effectively prevent and control the spread of H5N6 avian influenza,a rapid,sensitive and specific detection technolo-gy was established in this study.The specific monoclonal antibodies against the neuraminidase N6 protein of avian influenza A virus subtype H5N6 were obtained through hybridoma and monoclonal antibody technology.These antibodies were coupled and labeled with carboxyl-functionalized fluorescent quantum dots,along with previously prepared specific antibodies against the hemagglutinin H5 protein.A rapid fluorescence immunochromatographic detection method for the H5N6 subtype of avian influ-enza virus was established according to the principle of double-antibody sandwich immunochromatography.This method a-chieved a detection sensitivity of 1 ng/mL for recombinant hemagglutinin H5 subtype protein and 0.1 ng/mL for recombinant neuraminidase N6 subtype protein.Moreover,the method exhibited no cross-reactivity with other influenza subtypes or patho-gens,such as Newcastle disease(ND),infectious bronchitis(IB),and infectious laryngotracheitis(ILT),thus demonstrating good specificity.The method effectively identified the highly pathogenic avian influenza virus H5 subtype and directly distin-guished the H5N6 subtype with good accuracy.The fluorescent quantum dot immunochromatographic typing detection method established herein met the sensitivity,specificity,and accuracy requirements for H5N6 subtype detection,and can be further used for rapid detection of the H5 and H5N6 subtypes of avian influenza virus.

Stroke is one of the main diseases that threaten human health,including ischemic stroke and hemorrhagic stroke,with the former being the main cause.The important pathogenesis of ischemic stroke includes neuroinflammation,oxidative stress,and excitatory toxic damage,and neuroinflammation plays an impor-tant role in the pathogenesis and rehabilitation process of ische-mic stroke.Microglia are inherent immune cells in the central nervous system,which monitor the site of injury and respond to the immune response as soon as a stroke occurs.The activated microglia are mainly polarized into pro-inflammatory M1 type and anti-inflammatory M2 type.The latter improves neurological dys-function by inhibiting neuroinflammation,promoting neuronal re-generation and myelin repair,and maintaining the integrity of the blood-brain barrier.It suggests that it may be a potential target for treating ischemic stroke by combating acute phase injury and promoting chronic phase rehabilitation.Precise regulation of M1/M2 activation has important therapeutic value in cerebral protection in ischemic stroke.This article focuses on the role of M2 microglia in ischemic stroke and the mechanism of various drugs or acupuncture and moxibustion therapy regulating the transformation of microglia into M2 type,in order to provide theo-retical basis for clinical treatment of stroke and new drug devel-opment.

Objective To investigate the characteristics of Chinese medicine syndromes and the possible metabolic substance basis of spontaneously hypertensive rat(SHR).Methods 10-week-old SPF SHR and WKY of the same strain were divided into SHR group and WKY group with 8 rats in each group.The general state,temperament,peripheral vascular filling,tongue characteristics,diet,water intake,urine and feces volume and characteristics,blood pressure,heart rate,respiratory rate,pain threshold,and open field behavior of SHR rats were observed and tested comprehensively to identify the possible syndrome types of Chinese medicine.At the same time,liquid chromatography tandem mass spectrometry was used to analyze non-targeted serum metabolites to preliminarily reveal the material basis of blood pressure elevation and Chinese medicine syndrome manifestations.Results Compared with WKY group,the scores of dark yellow hair color,irritable degree and peripheral capillary filling were higher in SHR group(P＜0.0001).Red tongue color,dry tongue,little body fluid;24 h diet and water intake,urine volume and fecal volume were less(P＜0.05),fecal water content was lower(P＜0.001);systolic blood pressure(SBP),diastolic blood pressure(DBP),mean arterial pressure(MAP),heart rate(HR)and respiratory rate(RR)were significantly higher(P＜0.05);Lower pain threshold(P＜0.0001);The open field experiment shows that the moving distance and residence time of the edge are longer(P＜0.001).Serum non-targeted metabolomics result showed that,compared with WKY group,the SHR group had 114 metabolites with significant differences(P＜0.05).These differential metabolites were mainly lipids and lipid-like molecules(40.35％),organic acids and derivatives(22.8％),and organoheterocyclic compounds(15.79％).A total of 25 metabolic pathways were identified by KEGG enrichment analysis.Further differential abundance analysis showed that 16 pathways were activated,only 4 pathways were inhibited,and 5 pathways were not significantly changed.The glutamatergic synapse and GABAergic synapse were activated,while the serotonergic synapse was inhibited.Conclusions The symptoms of SHR include impatience and irritability,peripheral vascular dilation and collateral circulation formation,bulbar conjunctival congestive swelling,red tongue coloration,a dry tongue,constipation,red-yellow urine of low volume,and a rapid heart rate and high respiratory rate.All these suggest that SHR is a syndrome of hypertension with hyperactivity of liver-yang.The material basis of SHR is not only related to lipid,amino acid,and carbohydrate metabolism disorders,but also may be related to metabolic disorders of glutaminergic,GABAergic,and serotonergic neural pathways.

Objective:To observe the effect of Ba Duan Jin combined with Du Mai fumigation on improving sleep quality and negative emotions in perimenopausal insomnia patients.Methods:This study was a single-center prospective randomized controlled trial,80 perimenopausal insomnia patients who were admitted to Zhuzhou Maternal and Child Health Hospital from December 2023 to August 2024 were selected.Patients were randomly divided into control group(treated with Du Mai fumigation)and study group(treated with Ba Duan Jin combined with Du Mai fumigation)used random number table method,with 40 cases in each group.The clinical efficacy,sleep quality[Pittsburgh Sleep Quality Index(PSQI)],negative emotions[Self Rating Anxiety Scale(SAS),Self Rating Depression Scale(SDS)],clinical symptoms(Kupperman score),improvement in quality of life[the short form-36 health survey(SF-36)Score],and incidence of adverse reactions between two groups were compared before and after treatment.Results:The clinical total efficiency rate in the study group was higher than that in the control group(P＜0.05).2 weeks and 4 weeks after treatment,PSQI,SAS,SDS and Kupperman scores in the study group were lower than those in the control group,and SF-36 score was higher than that in the control group(P＜0.05).Neither group showed significant adverse reactions.Conclusion:Ba Duan Jin combined with Du Mai fumigation on improving sleep quality and negative emotions in perimenopausal insomnia patients,can effectively improve sleep quality,alleviate negative emotions,and enhance quality of life,without any significant adverse reactions.

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.

Objective:To observe the effect of Ba Duan Jin combined with Du Mai fumigation on improving sleep quality and negative emotions in perimenopausal insomnia patients.Methods:This study was a single-center prospective randomized controlled trial,80 perimenopausal insomnia patients who were admitted to Zhuzhou Maternal and Child Health Hospital from December 2023 to August 2024 were selected.Patients were randomly divided into control group(treated with Du Mai fumigation)and study group(treated with Ba Duan Jin combined with Du Mai fumigation)used random number table method,with 40 cases in each group.The clinical efficacy,sleep quality[Pittsburgh Sleep Quality Index(PSQI)],negative emotions[Self Rating Anxiety Scale(SAS),Self Rating Depression Scale(SDS)],clinical symptoms(Kupperman score),improvement in quality of life[the short form-36 health survey(SF-36)Score],and incidence of adverse reactions between two groups were compared before and after treatment.Results:The clinical total efficiency rate in the study group was higher than that in the control group(P＜0.05).2 weeks and 4 weeks after treatment,PSQI,SAS,SDS and Kupperman scores in the study group were lower than those in the control group,and SF-36 score was higher than that in the control group(P＜0.05).Neither group showed significant adverse reactions.Conclusion:Ba Duan Jin combined with Du Mai fumigation on improving sleep quality and negative emotions in perimenopausal insomnia patients,can effectively improve sleep quality,alleviate negative emotions,and enhance quality of life,without any significant adverse reactions.

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.