Ursodeoxycholic acid(UDCA)is a naturally occurring,low-toxicity,and hydrophilic bile acid(BA)in the human body that is converted by intestinal flora using primary BA.Solute carrier family 7 member 11(SLC7A11)functions to uptake extracellular cystine in exchange for glutamate,and is highly expressed in a variety of human cancers.Retroperitoneal liposarcoma(RLPS)refers to liposarcoma originating from the retroperitoneal area.Lipidomics analysis revealed that UDCA was one of the most significantly down-regulated metabolites in sera of RIPS patients compared with healthy subjects.The augmentation of UDCA concentration(≥25 μg/mL)demonstrated a suppressive effect on the proliferation of liposarcoma cells.[15N2]-cystine and[13Cs]-glutamine isotope tracing revealed that UDCA impairs cystine uptake and glutathione(GSH)synthesis.Mechanistically,UDCA binds to the cystine transporter SLC7A11 to inhibit cystine uptake and impair GSH de novo synthesis,leading to reactive oxygen species(ROS)accumulation and mitochondrial oxidative damage.Furthermore,UDCA can promote the anti-cancer effects of ferroptosis inducers(Erastin,RSL3),the murine double minute 2(MDM2)inhibitors(Nutlin 3a,RG7112),cyclin dependent kinase 4(CDK4)inhibitor(Abemaciclib),and glutaminase inhibitor(CB839).Together,UDCA functions as a cystine exchange factor that binds to SLC7A11 for antitumor activity,and SLC7A11 is not only a new transporter for BA but also a clinically applicable target for UDCA.More importantly,in combination with other antitumor chemotherapy or physiotherapy treatments,UDCA may provide effective and promising treatment strategies for RLPS or other types of tumors in a ROS-dependent manner.

AIM To study the chemical constituents from the branches and leaves of Michelia yunnanensis Franch.ex Finet & Gagnep.and their anti-inflammatory activities.METHODS The methanol extract was isolated and purified by silica gel,MCI,Sephadex LH-20 and semi-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.Their anti-inflammatory activities were evaluated by RAW264.7 model.RESULTS Twenty compounds were isolated and identified as dihydrodehydrodiconifenyl alcohol(1),8-hydroxypinoresinol(2),lariciresinol(3),isolariciresinol(4),(7S,8R)-4-hydroxy-3,3',5'-trimethoxy-8',9'-dinor-8,4'-oxyneoligna-7,9-diol-7'-aldehyde(5),thero-2,3-bis-(4-hydroxy-3-methoxypheyl)-3-methoxy-propanol(6),evofolin B(7),(E)-p-coumaryl alcohol γ-O-methyl ether(8),ω-hydroxypropioguaiacone(9),sinapaldehyde(10),isoscopoletin(11),6-hydroxy-5,7-dimethoxycoumarin(12),2α,3α-dihydroxy-2-methylbutyrolactone(13),6-hydroxy-3(1-hydroxy-1-methylethyl)-6-methyl-2-cyclohexen-1-one(14),benzofuran-2-carboxaldehyde(15),3,4-dihydroxy-5-methoxybenzaldehyde(16),3,5-dimethoxy-4-hydroxybenzaldehyde(17),3,4-dihydroxybenzaldehyde(18),3,4-dihydroxybenzoic methyl ester(19),vanillic acid(20).The inhibition rate of compound 1 on NO was 45.39％±0.32％.CONCLUSION Compounds 1-16,18-20 are first isolated from this plant.Compound 1 has anti-inflammatory activity.

AIM To investigate the mechanism of Jiedu Yizhi Formula on cognitive function and neuroinflammation in a mouse model of Alzheimer's disease(AD).METHODS 50 APP/PS1 double transgenic mice were randomly divided into the model group,the donepezil group,and the low-dose,moderate-dose,and high-dose Jiedu Yizhi Formula group(1.78,3.56 and 7.12 g/kg),with 10 mice in each group,in contrast to the 10 WT mice of the blank group.Following anesthesia administration and 8-week oral gavage regimen with respective drugs,all mice underwent final tissue sample collection.The mice had their learning and memory ability assessed by Morris water maze and nesting behavior scores;their pathology of brain tissue and Aβ expression observed using HE,Nissl and IHC staining;their polarization of microglia and the expression of inflammatory factors in hippocampal tissue detected by IF and ELISA;their hippocampal expression of PI3K/Akt/mTOR signaling pathway detected by RT-qPCR and Western blot.RESULTS Compared with the blank group,the model group had lower scores in total swimming distance,frequency in crossing the platform,residence time in the target quadrant,and nesting behavior scores(P＜0.05,P＜0.01);prolonged evasion latency(P＜0.01);more disorganized arrangement of pyramidal cells,solidification and deep staining,unclear demarcation,irregular cell shapes,reduction of Nyctinidia,and increased Aβ deposition in the brain tissue(P＜0.01);elevated expression of hippocampal microglia M1-type markers CD16/32 and lba-1(P＜0.01);decreased levels of M2-type marker CD206(P＜0.05);elevated levels of TNF-α and IL-1β(P＜0.01);decreased expressions of IL-13 and IL-4(P＜0.01);and decreased levels of PI3K,Akt and mTOR mRNA,and reduced p-PI3K,p-Akt and p-mTOR protein expressions(P＜0.01).Compared to the model group,the donepezil group and the Jiedu Yizhi Formula groups showed statistically significant improvements in the aforementioned indexes(P＜0.05,P＜0.01),with the magnitude of improvement being higher in the high-dose Jiedu Yizhi Formula group.CONCLUSION Jiedu Yizhi Formula suppresses microglia Ml-type polarization while enhancing M2-type polarization via activation the PI3K/Akt/mTOR signaling pathway,which subsequently reduces inflammatory cytokine secretion.This mechanism attenuates Aβ deposition in brain tissues and ameliorates cognitive dysfunction in AD mouse models.

Aim To study the effect of p-benzoyl sali-droside(pOBz)on angiogenesis after ischemic stroke and to explore the underlying mechanism.Methods The MCAO model was prepared by suture method.Rats were divided into four groups:sham,MCAO,pOBz administration,and edaravone positive control,treated for seven days.The mNSS was used to assess the neurological impairment.Western blotting was em-ployed to detect CD31,NICD,and Hes-1 protein ex-pression,while immunofluorescence staining was ap-plies to quantify CD31-positive cells in ischemic brain tissue.In vitro an OGD/R model was established in HUVECs.Following treatment with varying pOBz con-centrations(0.01,0.1,1 μmol·L-1),the CCK-8 as-say was uses to measure cell viability,and in vitro tube formation assay was utilized to evaluate angiogenesis.Western blotting was employed again to assess CD31,NICD and Hes-1 protein levels.To further elucidate the mechanism,HUVEC were treated with the Notch inhibitor DAPT prior to grouping and pOBz administra-tion,and the same parameters were evaluated.Results pOBz significantly reduced the mNSS score of MCAO rats,increased CD31-positive cell counts,and upregu-lated CD31,NICD,and Hes-1 protein expression(P＜0.01).In vitro results further showed that pOBz could dose-dependently increase the survival rate and angio-genesis ability of HUVEC induced by OGD/R,and promote CD31,NICD and Hes-1 proteins(P＜0.01),and Notch inhibitor DAPT could reverse the above effects of pOBz.Conclusion pOBz promotes angio-genesis in HUVEC,and its mechanism involves activa-tion of the Notch signaling pathway.

Objective To elucidate the impact of chronic kidney disease(CKD)on the clinical outcomes of patients with left main coronary artery disease(LMCAD)undergoing intravascular ultrasound(IVUS)-guided percutaneous coronary intervention(PCI).Methods This retrospective study enrolled consecutive patients with LMCAD who underwent IVUS-guided PCI at Wuhan Asia Heart Hospital between January 2017 and December 2020.Patients were stratified into CKD and non-CKD groups according to the presence of CKD.Clinical data were systematically retrieved from the electronic health record system.Demographic,clinical,and angiographic characteristics were compared between groups.The primary endpoint was major adverse cardiovascular events(MACE),defined as a composite of all-cause mortality,myocardial infarction,and ischemic stroke.Results A total of 325 LMCAD patients[mean age(62.56±9.86)years;73.54％male]were included,with 31 patients(9.54％)in the CKD group.During a median follow-up of 5 years,CKD patients exhibited significantly older age[(70.13±9.77)years vs.(61.77±9.54)years,P＜0.001],higher prevalence of three-vessel disease(64.52％vs.38.10％;P=0.040)and left main bifurcation lesion(45.16％vs.37.76％,P=0.011),greater IVUS-detected calcification burden(P=0.029),and higher median SYNTAXⅡ scores[(34.10(30.30,39.25)vs.26.75(22.42,31.58),P＜0.001)].The cumulative incidence of MACE was significantly higher in the CKD group compared to the non-CKD group(32.26％vs.9.18％,P＜0.001).Univariate Cox regression analysis and Kaplan-Meier survival curves confirmed a 5.877-fold increased risk of MACE in CKD patients(95％CI 2.765-12.494).After adjusting for age and cardiac function,CKD remained an independent predictor of MACE(HR 3.611,95％CI 1.634-7.978).Conclusions LMCAD patients with concomitant CKD present with advanced age,impaired cardiac function,more extensive coronary disease,and severe calcification.The presence of CKD is associated with a significantly worse long-term prognosis.

Aim To study the mechanism of salidro-side combined with rosavin in rats with ischemic stroke.Methods The MCAO rats was established by using thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside com-bined with rosavin group,and positive control group;the drug was given continuously for seven days.Western blot was used to detect apoptosis indicators.Proteomics was used to analyse differential proteins(DEPs).STEP receptor inhibitor was injected into the lateral ventricles,the rats were administered for seven days,then the apoptosis indicators were detected.Re-sults Salidroside combined with rosavin could reduce neurological function scores in MCAO rats and inhibit cell apoptosis.Quantitative proteomics identified 496 DEPs in brain tissue and discovered core proteins STEP,p38,and CRTC1.Salidroside combined with rosavin could promote the STEP and CRTC1 while in-hibiting p38 protein.After treatment with STEP inhibi-tor,those effects were reversed.Conclusion Salidro-side combined with rosavin can inhibit cell apoptosis in MCAO rats,which is closely related to the regulation of the STEP/p38/CRTC1 signaling pathway.

Aim To study the mechanism of salidro-side combined with rosavin in rats with ischemic stroke.Methods The MCAO rats was established by using thread-embolic method.The rats were divided into the sham group,MCAO group,salidroside com-bined with rosavin group,and positive control group;the drug was given continuously for seven days.Western blot was used to detect apoptosis indicators.Proteomics was used to analyse differential proteins(DEPs).STEP receptor inhibitor was injected into the lateral ventricles,the rats were administered for seven days,then the apoptosis indicators were detected.Re-sults Salidroside combined with rosavin could reduce neurological function scores in MCAO rats and inhibit cell apoptosis.Quantitative proteomics identified 496 DEPs in brain tissue and discovered core proteins STEP,p38,and CRTC1.Salidroside combined with rosavin could promote the STEP and CRTC1 while in-hibiting p38 protein.After treatment with STEP inhibi-tor,those effects were reversed.Conclusion Salidro-side combined with rosavin can inhibit cell apoptosis in MCAO rats,which is closely related to the regulation of the STEP/p38/CRTC1 signaling pathway.

Objective To elucidate the impact of chronic kidney disease(CKD)on the clinical outcomes of patients with left main coronary artery disease(LMCAD)undergoing intravascular ultrasound(IVUS)-guided percutaneous coronary intervention(PCI).Methods This retrospective study enrolled consecutive patients with LMCAD who underwent IVUS-guided PCI at Wuhan Asia Heart Hospital between January 2017 and December 2020.Patients were stratified into CKD and non-CKD groups according to the presence of CKD.Clinical data were systematically retrieved from the electronic health record system.Demographic,clinical,and angiographic characteristics were compared between groups.The primary endpoint was major adverse cardiovascular events(MACE),defined as a composite of all-cause mortality,myocardial infarction,and ischemic stroke.Results A total of 325 LMCAD patients[mean age(62.56±9.86)years;73.54％male]were included,with 31 patients(9.54％)in the CKD group.During a median follow-up of 5 years,CKD patients exhibited significantly older age[(70.13±9.77)years vs.(61.77±9.54)years,P＜0.001],higher prevalence of three-vessel disease(64.52％vs.38.10％;P=0.040)and left main bifurcation lesion(45.16％vs.37.76％,P=0.011),greater IVUS-detected calcification burden(P=0.029),and higher median SYNTAXⅡ scores[(34.10(30.30,39.25)vs.26.75(22.42,31.58),P＜0.001)].The cumulative incidence of MACE was significantly higher in the CKD group compared to the non-CKD group(32.26％vs.9.18％,P＜0.001).Univariate Cox regression analysis and Kaplan-Meier survival curves confirmed a 5.877-fold increased risk of MACE in CKD patients(95％CI 2.765-12.494).After adjusting for age and cardiac function,CKD remained an independent predictor of MACE(HR 3.611,95％CI 1.634-7.978).Conclusions LMCAD patients with concomitant CKD present with advanced age,impaired cardiac function,more extensive coronary disease,and severe calcification.The presence of CKD is associated with a significantly worse long-term prognosis.

This study aims to determine the nephrotoxic effects of 3-monochloropropanel-1,2-diol(3-MCPD)on female and male SD rats.A nephrotoxicity model was established by gavage of dif-ferent doses of 3-MCPD,and 80 SD rats were randomly divided into four groups:the control group(0 mg/kg 3-MCPD),low-dose group(15 mg/kg 3-MCPD),medium-dose group(30 mg/kg 3-MCPD),high-dose group(60 mg/kg 3-MCPD),with half female and half male.The body mass and food intake of the rats were recorded weekly,and the urine and blood and kidney tissues were col-lected after 28 consecutive days of gavage,and the blood erythrocyte count(WBC),white blood cell count(RBC),hemoglobin(HGB),erythrocyte-compaction-transfer-value(HCT),creatinine(CREA),serum urea nitrogen(BUN),and the indexes of blood phosphorus(P)and calcium(Ca)were detected;the level of kidney injury molecule(KIM-1)was measured by ELISA kit;the renal pathological changes was observed by histopathology method;and transcriptome sequencing was used to analyze differential genes in female and male rats.The results showed that 3-MCPD did not significantly affect the growth of male rats,but high doses significantly reduced the weight and food intake of female rats.The high-dose group of 3-MCPD caused a significant decrease in RBC,HGB,and HCT levels in both male and female rats,resulting in a significant increase in KIM-1 and P,and a significant decrease in Ca,but only a significant increase in CREA and BUN in female rats.Histopathology showed that in the high-dose group of male rats,only mild renal tubular dilation,epithelial cell edema,and clear tubular type were observed in the kidneys,while in female rats,a large number of renal sacs,clear tubular type,and interstitial inflammatory cells with fibrosis were observed in the kidneys.Transcriptome sequencing showed 1 712 differentially expressed genes in the high-dose group of female rats and 1 153 differentially expressed genes in the high-dose group of male rats.KEGG enrichment analysis showed that both male and female rats in the high-dose group experienced oxidative stress and cell apoptosis,but 3-MCPD may also participate in the process of kidney damage in females by inhibiting autophagy and inducing iron death pathways.The above results indicate that high-dose 3-MCPD has a more significant nephrotoxic effect on fe-male rats.

To understand the epidemiological and clinical features of patients with non-tuberculous mycobacteria(NTM)lung disease in a hospital for infectious diseases in Xinjiang,and to provide basis for prevention and control of NTM in Xinjiang.The strain distribution,epidemiological features and clinical features of 78 patients with NTM lung disease in the Sixth People′s Hospital of Xinji-ang Uygur Autonomous Region were analysed from June 2021 to June 2024,and a comparative analysis of the clinical features of 156 patients with pulmonary tuberculosis in this hospital during the same period was performed.Among 78 patients with NTM lung disease,the bacteria identified by molecular biology accounted for the top three cases:24 cases of Mycobacterium avium intracellulare complex,16 cases of Mycobacterium Kansaii and 11 cases of Mycobacterium Gordonae.There was no statistically significant difference in gender(χ2=0.009),age(χ2=2.670),smoking history(χ2=0.064),and BMI(χ2=0.896)between the NTM lung disease group and the pulmonary tuberculosis group(P>0.05).However,there were statistically significant differences in the combined bronchiectasis(χ2=19.068),immune-related indicators CD4(Z=-3.498)and CD3(Z=-3.187),and chest CT cavities on imaging(χ2=9.308)be-tween the two groups(P<0.05).There was no statistically significant difference in clinical symptoms such as cough(χ2=0.188)and expectoration(χ2=0.044)between the two groups(P>0.05).The common underlying diseases of NTM lung disease were diabetes mellitus(23.08%),hypertension(21.79%),bronchiectasis(20.51%)and others.The common clinical symptoms of NTM lung disease include cough,sputum,fatigue,poor appetite and others.The common manifestations of chest CT in NTM lung disease were Patchy cord shadows(62.82%),nodule(51.28%),pleural thickening(46.15%),calcification(41.03%)and others.Multivariate Logistic regression analysis showed that bronchiectasis(OR=8.019)is risk factor for NTM lung disease.The dominant strains of NTM in this study were My-cobacterium avium intracellulare complex,Mycobacterium kansasii and Mycobacterium Gordonae.NTM lung disease and pulmonarytuber-culosis have similar clinical manifestations and are difficult to distinguish,especially for patients with bronchiectasis,it is necessary to actively investigate NTM lung disease,provide basis for early diagnosis and treatment of NTM lung disease,and gradually form a system-atic and standardized NTM lung disease diagnosis and treatment system according to local conditions.