Purpose To explore the characteristics of gray matter(GM)volume changes in migraine patients using 7T MRI and voxel-based morphometry(VBM).Materials and Methods This prospective study enrolled 30 migraine patients and 41 age-and gender-matched healthy controls from Beijing Tiantan Hospital,Capital Medical University between November 2023 and November 2024.All participants underwent 7T MRI with 3D T1-weighted magnetization-prepared two rapid gradient-echo(MP2RAGE)sequences for structural brain imaging.VBM analysis was performed to quantify GM,white matter,cerebrospinal fluid and total brain volumes,followed by calculations of their relative percentages.The difference in GM volume between the two groups was compared to identify brain regions with characteristic GM volume changes in migraine patients.And the correlation between these characteristic GM volume alterations and clinical scales was analyzed.Results Migraine patients exhibited significantly lower total GM volume compared to healthy controls(t=2.096,P=0.040),while no group differences were observed in white matter or cerebrospinal fluid volumes(t=0.980,0.151;P=0.330,0.880).VBM analysis revealed reduced GM volume in the left orbitofrontal cortex(t=4.301,P=0.022),left hippocampus(t=5.226,P=0.006)and left parahippocampal gyrus(t=3.960,P=0.040)in the migraine group.Negative correlations were identified between:left orbitofrontal cortex GM volume and headache duration(r=-0.506,P=0.008),left hippocampal GM volume and patient health questionnaire-9 scores(r=-0.620,P=0.003),and left parahippocampal GM volume and visual analogue scale scores(r=-0.449,P=0.019).Conclusion VBM analysis based on 7T MP2RAGE data demonstrates characteristic GM volume reductions in the left orbitofrontal cortex,left hippocampus and left parahippocampal gyrus in migraine patients,with these structural alterations significantly correlate with depressive symptoms and headache burden.The observed microstructural abnormalities may reflect underlying pathophysiological mechanisms related to pain processing,emotional regulation and long-term disease burden in migraine.

Objective This study aimed to construct a risk scoring model based on DNA methylation featuresof ferroptosis-related gene,and systematically evaluate its predictive value for the prognosis and immunotherapy response of patients with colon canc-er.Methods Transcriptomic,DNA methylation,and clinical data of colon cancer patients were obtained from the Cancer Genome At-las(TCGA)and Gene Expression Omnibus(GEO)databases.Ferroptosis-related genes were identified from the FerrDb database.Fer-roptosis scores(FS)for each patient were calculated using the single-sample gene set enrichment analysis(ssGSEA)method,and con-struct a risk scoring model by combining differential methylation CpG sites with Cox regression analysis.The prognostic performance of the model was evaluated using receiver operating characteristic(ROC)curves,a nomogram,and decision curve analysis.The multiple algorithms were used to analyze the relationship between colon cancer models and immune cell infiltration,immunotherapy response,and chemotherapy sensitivity.Results A total of 49 ferroptosis-related genes significantly associated with overall survival(OS)were identified for calculating FS.The OS of colon cancer patients in the high-FS group was significantly shorter than that in the low-FS group(P=0.0075).The constructed DNA methylation risk score models included key CpG sites,and the ROC curves and multivariate Cox regression analysis at 1-,3-,and 5-years overall survival rate in the TCGA cohort and the GSE17536 validation cohort showed that the model was an independent prognostic factor for colon cancer patients.The low-risk group had higher immune scores and infil-tration levels of B cells and dendritic cells,while the high-risk group had a higher abundance of fibroblasts.Patients in the high-risk group showed upregulation of PD-L1 expression and higher immune phenotype scores.In addition,the model could also predict the sensitivity differences of commonly used chemotherapeutic drugs such as doxorubicin,gemcitabine,and paclitaxel.Conclusion The risk scoring model established using DNA methylation features of ferroptosis-related gene can be used to predict the prognosis of colon cancer patients and provide a new biomarker for achieving precision treatment.

Objective To explore the mechanism of malt alcohol extract improving depression-like behavior induced by CUMS in rats by regulating gut microbiota.Methods The depression model of rats was established using an 8-weeks CUMS procedure,and the administration group was given low(59.6 mg·kg-1)and high(178.8 mg·kg-1)doses of malt alcohol extract,respectively.The depression-like behavior of rats was evaluated by classic behavioral test.The composition of intestinal microbiota of rats was analyzed by 16S rRNA sequencing.The morphological changes of colon were observed by hematoxylin and eosin(HE),the expression of ZO-1 and Occludin in colon was detected by immunofluorescence(IF),and the expression of IL-10,IL-1βand 5-HT were detected by ELISA.Results The low dose of malt alcohol extract attenuated the depressive behavior and restored the expression of 5-HT in the brain of CUMS rats.16S rRNA sequencing results showed that the diversity and relative abundance of gut microbiota changed after treatment with the low dose of malt alcohol extract.ELISA results showed that the low dose of malt alcohol extract significantly reversed the CUMS-induced reduction of IL-10 and elevation of IL-1 β.HE results showed that the low dose of malt alcohol extract significantly ameliorated CUMS-induced structural damage in colon.IF results showed increased protain expression of intestinal epithelial barrier tight junction proteins ZO-1 and Occludin by the low dose of malt alcohol extract.Conclusion The low dose of malt alcohol extract can ameliorate CUMS-induced depressive-like behavior in rats by modulating intestinal flora,restoring 5-HT expression in the brain,inhibiting inflammation,and repairing the intestinal barrier.

Objective To develop a predictive model for assessment of the risk of the patients on prolonged mechanical ventilation after coronary artery bypass grafting with extracorporeal circulation.Methods A convenience sampling method was employed to select 2 334 patients who received the coronary artery bypass grafting(CABG)with extracorporeal circulation in our hospital from January 2021 to December 2023 as the study subjects.Preoperative,intraoperative and postoperative data were collected through structured queries from the electronic medical record system of hospital.The study subjects were randomly divided into a training set(n=1 633)and a validation set(n=701)following a 3:1 ratio.A risk prediction model was established using Logistic regression based on the training set data.Model fit was assessed using Hosmer-Lemeshow test,and predictive performance of the model was evaluated with the area under curve(AUC)of the receiver operating characteristic(ROC)curve.Results A total of 2,334 patients were included,of whom 215(9.2%)experienced the prolonged mechanical ventilation(>24 hours).The model developed from the training set identified seven factors that contributed to a prolonged mechanical ventilation:age(OR=1.03),body mass index(BMI,OR=1.14),time of extracorporeal circulation(OR=1.01),intraoperative blood transfusion(OR=4.15),postoperative serum total bilirubin(OR=1.08),postoperative serum albumin(OR=0.92)and postoperative re-sternotomy(OR=5.49).The AUC of the model for prediction of prolonged mechanical ventilation after CABG with extracorporeal circulation was 0.761,with a 95%CI of 0.716-0.806,a maximum Youden index of 0.105,a sensitivity of 77.94%,and a specificity of 64.38%.Validation using the validation set data yielded an AUC of 0.733,with a 95%CI of 0.662-0.804,a sensitivity of 75.32%,a specificity of 57.97%,and a predictive accuracy of 73.61%.Conclusion The risk prediction model developed in this study for prolonged mechanical ventilation after a CABG with extracorporeal circulation demonstrates a good predictive performance.It provides a reference for the nurses to identify the patient in high-risk of prolonged mechanical ventilation after a CABG with extracorporeal circulation and to implement preventive nursing measures.

Objective To investigate the efficacy of voriconazole in the treatment of pulmonary tuberculosis complicated with chronic pulmonary aspergillosis(CPA)based on CYP2C19 gene polymorphism detection and examine the factors affecting the efficacy for improving targeted therapy in clinical practice.Methods A total of 207 patients with pulmonary tuberculosis complicated with CPA treated in the Third People's Hospital of Kunming from December 2018 to November 2022 were randomly assigned to an observation group(105 cases)or a control group(102 cases).The patients in the control group received standard voriconazole treatment,while the patients in the observation group had their voriconazole regimen tailored based on CYP2C19 genotyping results.Plasma drug concentration levels,efficacy,and safety were compared between the two groups and in terms of CYP2C19 genotypes.Logistic regression analysis was used to identify the factors affecting treatment efficacy.Results The observation group showed significantly higher plasma voriconazole concentrations and overall antifungal efficacy compared to the control group(P＜0.05).In the observation group,CYP2C19 genotyping identified 37 extensive metabolizers(EM),47 intermediate metabolizers(IM),and 21 poor metabolizers(PM).Plasma concentration of voriconazole did not show significant difference between EM and IM(P＞0.05),but both PM and IM were associated with significantly lower plasma concentration of voriconazole than PM(P＜0.05).The clinical efficacy rate was 100％for PM,91.5％for IM,and 83.8％for EM(P＜0.05).The incidence of adverse events did not show significant difference among the three genotypes(P＞0.05).Logistic regression analysis revealed that lung cavitation,hypoalbuminemia,and agranulosis were significantly correlated with therapeutic efficacy(P＜0.05).Conclusions CYP2C19 gene polymorphism detection is valuable in clinical practice.It can inform anti-aspergillus therapy with voriconazole to effectively improve symptoms and clinical efficacy in patients with pulmonary tuberculosis complicated with CPA.Meanwhile,clinicians should be aware of the factors such as hypoproteinemia,agranulocytosis,and lung cavitation that may affect the efficacy of voriconazole.

Objective To compare the anti fungal efficacy and safety of amphotericin B cholesteryl sulfate complex(amphotericin B colloidal dispersion,ABCD)and amphotericin B for injection(amphotericin B deoxycholate,AmB-D)in the treatment of AIDS complicated with talaromycosis(TSM).Methods A total of 80 patients who were diagnosed with AIDS and complicated with TSM from December 2021 to January 2024 in Department of Infection,Kunming Third People's Hospital were included in the study.The patients were randomized to receive ABCD(n=40)via intravenous infusion or AmB-D(control,n=40)via Ⅳ infusion protected from light.The overall treatment efficacy rate,CD4+T lymphocyte count,routine blood tests,liver and kidney function tests,K+concentration,and the incidence of adverse drug reactions(ADR)during study were compared between the two treatment groups.Results The overall efficacy rate was 87.5％(35/40)in ABCD group and 80.0％(32/40)in the control(AmB-D)group(P＞0.05).WBC,hemoglobin,and platelet count were significantly higher after treatment compared with pretreatment levels(P＜0.05)in both groups.The CD4+T lymphocyte count was higher after treatment compared with pretreatment levels in both groups.And the CD4+T lymphocyte count in ABCD group was significantly higher than that in the control group(P＜0.05).The levels of total bilirubin,aspartate aminotransferase,alanine aminotransferase,blood urea nitrogen,and serum creatinine increased after treatment in both groups.Blood urea nitrogen and serum creatinine increased significantly in control group compared with ABCD group(P＜0.05).After treatment,serum K+concentration decreased significantly in control group compared with the pretreatment level and compared with ABCD group(P＜0.05).The incidence of adverse events in ABCD group was significantly lower than that in the control group.The time to renal injury was delayed significantly(P＜0.05).Conclusions In the treatment of AIDS complicated with TSM,the efficacy of ABCD was comparable to AmB-D.The incidence of hepatic impairment did not show significant difference between ABCD and AmB-D.However,ABCD is associated with less renal impairment,lower incidence of adverse events,and better safety,which is valuable for clinical use.

Objective This study aimed to construct a risk scoring model based on DNA methylation featuresof ferroptosis-related gene,and systematically evaluate its predictive value for the prognosis and immunotherapy response of patients with colon canc-er.Methods Transcriptomic,DNA methylation,and clinical data of colon cancer patients were obtained from the Cancer Genome At-las(TCGA)and Gene Expression Omnibus(GEO)databases.Ferroptosis-related genes were identified from the FerrDb database.Fer-roptosis scores(FS)for each patient were calculated using the single-sample gene set enrichment analysis(ssGSEA)method,and con-struct a risk scoring model by combining differential methylation CpG sites with Cox regression analysis.The prognostic performance of the model was evaluated using receiver operating characteristic(ROC)curves,a nomogram,and decision curve analysis.The multiple algorithms were used to analyze the relationship between colon cancer models and immune cell infiltration,immunotherapy response,and chemotherapy sensitivity.Results A total of 49 ferroptosis-related genes significantly associated with overall survival(OS)were identified for calculating FS.The OS of colon cancer patients in the high-FS group was significantly shorter than that in the low-FS group(P=0.0075).The constructed DNA methylation risk score models included key CpG sites,and the ROC curves and multivariate Cox regression analysis at 1-,3-,and 5-years overall survival rate in the TCGA cohort and the GSE17536 validation cohort showed that the model was an independent prognostic factor for colon cancer patients.The low-risk group had higher immune scores and infil-tration levels of B cells and dendritic cells,while the high-risk group had a higher abundance of fibroblasts.Patients in the high-risk group showed upregulation of PD-L1 expression and higher immune phenotype scores.In addition,the model could also predict the sensitivity differences of commonly used chemotherapeutic drugs such as doxorubicin,gemcitabine,and paclitaxel.Conclusion The risk scoring model established using DNA methylation features of ferroptosis-related gene can be used to predict the prognosis of colon cancer patients and provide a new biomarker for achieving precision treatment.

Objective To compare the anti fungal efficacy and safety of amphotericin B cholesteryl sulfate complex(amphotericin B colloidal dispersion,ABCD)and amphotericin B for injection(amphotericin B deoxycholate,AmB-D)in the treatment of AIDS complicated with talaromycosis(TSM).Methods A total of 80 patients who were diagnosed with AIDS and complicated with TSM from December 2021 to January 2024 in Department of Infection,Kunming Third People's Hospital were included in the study.The patients were randomized to receive ABCD(n=40)via intravenous infusion or AmB-D(control,n=40)via Ⅳ infusion protected from light.The overall treatment efficacy rate,CD4+T lymphocyte count,routine blood tests,liver and kidney function tests,K+concentration,and the incidence of adverse drug reactions(ADR)during study were compared between the two treatment groups.Results The overall efficacy rate was 87.5％(35/40)in ABCD group and 80.0％(32/40)in the control(AmB-D)group(P＞0.05).WBC,hemoglobin,and platelet count were significantly higher after treatment compared with pretreatment levels(P＜0.05)in both groups.The CD4+T lymphocyte count was higher after treatment compared with pretreatment levels in both groups.And the CD4+T lymphocyte count in ABCD group was significantly higher than that in the control group(P＜0.05).The levels of total bilirubin,aspartate aminotransferase,alanine aminotransferase,blood urea nitrogen,and serum creatinine increased after treatment in both groups.Blood urea nitrogen and serum creatinine increased significantly in control group compared with ABCD group(P＜0.05).After treatment,serum K+concentration decreased significantly in control group compared with the pretreatment level and compared with ABCD group(P＜0.05).The incidence of adverse events in ABCD group was significantly lower than that in the control group.The time to renal injury was delayed significantly(P＜0.05).Conclusions In the treatment of AIDS complicated with TSM,the efficacy of ABCD was comparable to AmB-D.The incidence of hepatic impairment did not show significant difference between ABCD and AmB-D.However,ABCD is associated with less renal impairment,lower incidence of adverse events,and better safety,which is valuable for clinical use.

Objective To explore the clinical characteristics of myelodysplastic syndrome(MDS)with U2 small nuclear RNA cofactor 1(U2AF1)mutation in different age groups,as well as the efficacy and prognosis of an arsenic-containing traditional Chinese medicine(TCM)compound prescription(Qinghuang Capsules combined with Bushen Yijing Formula).Methods A retrospective analysis was conducted on the clinical data of patients with MDS who were hospitalized in the Hematology Department Ward of Xiyuan Hospital,China Academy of Chinese Medical Sciences,and received arsenic-containing TCM compound treatment from November 30,2020,to September 30,2023.Stratified by age,the U2AF1 mutation and wild-type groups aged＜65 years and≥65 years were compared in terms of sex,TCM syndrome,World Health Organization classification,MDS Revised International Prognostic Score System(IPSS-R)score,blood routine indicators,serum lactate dehydrogenase content,nephroblastoma 1(WT1)expression level,bone marrow puncture and biopsy indicators,and chromosomal prognostic grades,et al.Furthermore,the efficacy of arsenic-containing TCM compound were compared in the U2AF1 mutation and wild-type groups among different age groups,as well as the influence of age on the survival prognosis of MDS patients with U2AF1 mutation.Results A total of 201 patients with MDS were included.104 patients were under 65 years old,among whom 20 had U2AF1 mutation,and 84 had wild-type.Ninety-seven patients were aged 65 years or older,among whom 19 patients had the U2AF1 mutation and 78 had the wild-type.Among patients aged＜65 years,the U2AF1 mutation group had a higher proportion of male patients and very low-risk/low-risk patients with an IPSS-R score≤3(P＜0.05),a lower mean corpuscular volume(MCV)(P＜0.05),and a relatively higher proportion of peripheral blood cell line 1 reduction than the wild-type group(P＜0.05).Among patients aged≥65 years,the MCV in the U2AF1 mutation group was lower(P＜0.05),and the expression level of the bone marrow WT1 gene and the proportion of patients with reticular fiber grade 4 were relatively higher than in the wild-type group(P＜0.05).The total effective rate of the arsenic-containing TCM compound for patients with U2AF1 mutation was 61.5％(24/39),and the total response rate was 30.8％(12/39).The total effective rate for the wild-type patients was 67.9％(110/162),and the total response rate was 29.6％(48/162).No significant difference was observed in the total effective and response rates.Kaplan-Meier survival analysis of 39 patients with U2AF1 mutation revealed that the median overall survival(mOS)of patients older than 65 years had not been reached.The 1-,2-,and 3-year survival rates were 93.8％,84.4％,and 84.4％,respectively.The mOS of the patients aged≥65 years was 35 months(95％confidence interval[CI]:7.559-62.441),and the 1-,2-,and 3-year survival rates were 66.2％,58.9％,and 29.4％,respectively.The mOS of patients in the aged≥65 years group was significantly lower than that in the aged＜65 years group(P＜0.05),and no significant difference was observed in median progression-free survival between the two groups.Conclusion The U2AF1 mutation is closely associated with the clinical characteristics of MDS.However,age and the presence of U2AF1 mutation have no significant effect on the total effective and response rates of arsenic-containing TCM compound.Age is a significant factor influencing the prognosis of patients with MDS with U2AF1 mutation.Patients aged 65 years or older have a shorter survival time than those younger than 65 years.

Objective To explore the mechanism of malt alcohol extract improving depression-like behavior induced by CUMS in rats by regulating gut microbiota.Methods The depression model of rats was established using an 8-weeks CUMS procedure,and the administration group was given low(59.6 mg·kg-1)and high(178.8 mg·kg-1)doses of malt alcohol extract,respectively.The depression-like behavior of rats was evaluated by classic behavioral test.The composition of intestinal microbiota of rats was analyzed by 16S rRNA sequencing.The morphological changes of colon were observed by hematoxylin and eosin(HE),the expression of ZO-1 and Occludin in colon was detected by immunofluorescence(IF),and the expression of IL-10,IL-1βand 5-HT were detected by ELISA.Results The low dose of malt alcohol extract attenuated the depressive behavior and restored the expression of 5-HT in the brain of CUMS rats.16S rRNA sequencing results showed that the diversity and relative abundance of gut microbiota changed after treatment with the low dose of malt alcohol extract.ELISA results showed that the low dose of malt alcohol extract significantly reversed the CUMS-induced reduction of IL-10 and elevation of IL-1 β.HE results showed that the low dose of malt alcohol extract significantly ameliorated CUMS-induced structural damage in colon.IF results showed increased protain expression of intestinal epithelial barrier tight junction proteins ZO-1 and Occludin by the low dose of malt alcohol extract.Conclusion The low dose of malt alcohol extract can ameliorate CUMS-induced depressive-like behavior in rats by modulating intestinal flora,restoring 5-HT expression in the brain,inhibiting inflammation,and repairing the intestinal barrier.