Objective To explore the association between gut microbiota and liver cirrhosis in East Asian populations by using Mendelian randomization(MR)methods.Methods Genome wide association study(GWAS)datasets on gut microbiota were obtained from National GeneBank Big Data Platform and GWAS datasets on liver cirrhosis were obtained from IEU Open GWAS database,by using gut microbiota as the exposure factor and liver cirrhosis as the outcome variable.Inverse variance weighted(IVW)method was adopted as the main analytical method,with the constrained maximum likelihood and model averaging(cML-MA)method as a secondary analysis method,to verify the causal relationship between gut microbiota and liver cirrhosis.The robustness of the results were further validated through sensitivity analysis and leave-one-out analysis.Results The primary IVW analysis preliminarily identified 16 gut microbiota species associated with liver cirrhosis.An increased abundance of Clostridium L2-50,Marvinbryantia,Sulfate-reducing bacteria,Treponema socranskii,Coprococcus,Ruminococcaceae,Sanguinibacter,Vibrio funis,Thermanaerovibrio,and Mitsuokella was found to elevate the risk of liver cirrhosis.Conversely,an increased abundance of Desulfovibrio,Clostridium hathewayi,Propionibacterium,Allistipes,Bacteroides salanitiphilus,and Dyella was associated with a reduced risk of liver cirrhosis.The cML-MA analysis revealed statistical significance for Mitsuokella,Clostridium L2-50,Marvinbryantia,Coprococcus,and Dyella,indicating a strong correlation between these five gut microbiota species and liver cirrhosis.The heterogeneity and horizontal pleiotropy for 16 bacterial clusters showed P＞0.05,suggesting an absence of heterogeneity and horizontal pleiotropy,and the leave-one-out analysis did not identify any abnormal single nucleotide polymorphism.Conclusion This research reveals an association between 16 gut microbiota and liver cirrhosis in the East Asian population,with 5 of these gut microbiota demonstrating a significant correlation with liver cirrhosis,and offering new genetic insights for the prevention and treatment of liver cirrhosis.

Objective To investigate the factors influencing international normalized ratio (INR)>3.0 in patients undergoing warfarin anticoagulation therapy after mechanical heart valve replacement. Methods A retrospective analysis was performed on the clinical data of patients who underwent mechanical heart valve replacement surgery and received warfarin anticoagulation therapy at West China Hospital of Sichuan University from January 1, 2011 to June 30, 2022. Based on the discharge INR values, patients were divided into two groups: an INR≤3.0 group and an INR>3.0 group. The factors associated with INR>3.0 at the time of discharge were analyzed. Results A total of 8901 patients were enrolled, including 3409 males and 5492 females, with a median age of 49.3 (43.5, 55.6) years. The gender, body mass index (BMI), New York Heart Association (NYHA) cardiac function grading, INR, glutamic oxaloacetic transaminase, and preoperative prothrombin time (PT) were statistically different between the two groups (P<0.05). Multivariate logistic regression analysis revealed that lower BMI, preoperative PT>15 s, and mitral valve replacement were independent risk factors for INR>3.0 at discharge (P<0.05). Conclusion BMI, preoperative PT, and surgical site are factors influencing INR>3.0 at discharge in patients undergoing warfarin anticoagulation therapy after mechanical heart valve replacement. Special attention should be given to patients with lower BMI, longer preoperative PT, and mitral valve replacement to avoid excessive anticoagulation therapy.

Objective To explore the association between gut microbiota and liver cirrhosis in East Asian populations by using Mendelian randomization(MR)methods.Methods Genome wide association study(GWAS)datasets on gut microbiota were obtained from National GeneBank Big Data Platform and GWAS datasets on liver cirrhosis were obtained from IEU Open GWAS database,by using gut microbiota as the exposure factor and liver cirrhosis as the outcome variable.Inverse variance weighted(IVW)method was adopted as the main analytical method,with the constrained maximum likelihood and model averaging(cML-MA)method as a secondary analysis method,to verify the causal relationship between gut microbiota and liver cirrhosis.The robustness of the results were further validated through sensitivity analysis and leave-one-out analysis.Results The primary IVW analysis preliminarily identified 16 gut microbiota species associated with liver cirrhosis.An increased abundance of Clostridium L2-50,Marvinbryantia,Sulfate-reducing bacteria,Treponema socranskii,Coprococcus,Ruminococcaceae,Sanguinibacter,Vibrio funis,Thermanaerovibrio,and Mitsuokella was found to elevate the risk of liver cirrhosis.Conversely,an increased abundance of Desulfovibrio,Clostridium hathewayi,Propionibacterium,Allistipes,Bacteroides salanitiphilus,and Dyella was associated with a reduced risk of liver cirrhosis.The cML-MA analysis revealed statistical significance for Mitsuokella,Clostridium L2-50,Marvinbryantia,Coprococcus,and Dyella,indicating a strong correlation between these five gut microbiota species and liver cirrhosis.The heterogeneity and horizontal pleiotropy for 16 bacterial clusters showed P＞0.05,suggesting an absence of heterogeneity and horizontal pleiotropy,and the leave-one-out analysis did not identify any abnormal single nucleotide polymorphism.Conclusion This research reveals an association between 16 gut microbiota and liver cirrhosis in the East Asian population,with 5 of these gut microbiota demonstrating a significant correlation with liver cirrhosis,and offering new genetic insights for the prevention and treatment of liver cirrhosis.

OBJECTIVE To understand the drug resistance among the acquired immune deficiency syndrome(AIDS)population who failed in the antiviral therapy from 2022 to 2023 and analyze the molecular network.METHODS The plasma specimens were collected from the population with viral load no less than 1000 cps/ml who received antiviral therapy for more than 6 months in Aksu area from 2022 to 2023,which were delivered to Aksu Regional Center for Disease Control and Prevention for test.MEGA5 and the Stanford University drug resistance database were employed to determine the subtypes and drug resistance after the sequences of human immunodefi-ciency virus type Ⅰ polymerase gene region(HIV-1pol)were obtained,and the molecular network was established by HIV-trace.RESULTS Totally 648 sequences of HIV-1pol region were obtained,CRF07_BC(97.69％)was the major subtype,and the drug resistance rate was 58.33％;the drug resistance rates to non-nucleoside reverse transcriptase inhibitor(NNRTI),nucleoside reverse transcriptase inhibitor(NRTI)and protease inhibitor(PI)were 51.70％,19.75％and8.64％,respectively.The univariate analysis showed that year(x2=6.341),age(x2=18.455)and route of infection(x2=14.061)had remarkable effects on the drug resistance among the population with failed ART(P＜0.05).Multivariate regression analysis indicated that the drug resistance rate was higher in 2022 than in 2023(95％CI:1.132 to 2.191),and the drug resistance rate was higher among the population aged less than 60 years old than among the population more than 6 years old(95％CI:3.647 to 70.268,95％CI:1.435 to 8.235,95％CI:1.061 to 6.164,re-spectively).With 1.5％of the genetic distance set as the threshold,the molecular network was established,the network access rate was 49.07％,77.14％of the clusters had drug-resistant mutation sites,and the male population was at higher risk of network access than the female population.CONCLUSIONS The drug resistance rate is relatively high among the AIDS population with failed ART,and the drug-resistant strains appear in clusters in the molecular network.It is neces-sary to further strengthen the monitoring of drug resistance and improve the quality of the follow-up so as to reduce the occurrence of drug resistance and transmission of virulent strains.

OBJECTIVE To understand the drug resistance among the acquired immune deficiency syndrome(AIDS)population who failed in the antiviral therapy from 2022 to 2023 and analyze the molecular network.METHODS The plasma specimens were collected from the population with viral load no less than 1000 cps/ml who received antiviral therapy for more than 6 months in Aksu area from 2022 to 2023,which were delivered to Aksu Regional Center for Disease Control and Prevention for test.MEGA5 and the Stanford University drug resistance database were employed to determine the subtypes and drug resistance after the sequences of human immunodefi-ciency virus type Ⅰ polymerase gene region(HIV-1pol)were obtained,and the molecular network was established by HIV-trace.RESULTS Totally 648 sequences of HIV-1pol region were obtained,CRF07_BC(97.69％)was the major subtype,and the drug resistance rate was 58.33％;the drug resistance rates to non-nucleoside reverse transcriptase inhibitor(NNRTI),nucleoside reverse transcriptase inhibitor(NRTI)and protease inhibitor(PI)were 51.70％,19.75％and8.64％,respectively.The univariate analysis showed that year(x2=6.341),age(x2=18.455)and route of infection(x2=14.061)had remarkable effects on the drug resistance among the population with failed ART(P＜0.05).Multivariate regression analysis indicated that the drug resistance rate was higher in 2022 than in 2023(95％CI:1.132 to 2.191),and the drug resistance rate was higher among the population aged less than 60 years old than among the population more than 6 years old(95％CI:3.647 to 70.268,95％CI:1.435 to 8.235,95％CI:1.061 to 6.164,re-spectively).With 1.5％of the genetic distance set as the threshold,the molecular network was established,the network access rate was 49.07％,77.14％of the clusters had drug-resistant mutation sites,and the male population was at higher risk of network access than the female population.CONCLUSIONS The drug resistance rate is relatively high among the AIDS population with failed ART,and the drug-resistant strains appear in clusters in the molecular network.It is neces-sary to further strengthen the monitoring of drug resistance and improve the quality of the follow-up so as to reduce the occurrence of drug resistance and transmission of virulent strains.

Objective To evaluate MRI and clinicopathological prognostic factors in predicting disease-free survival(DFS)of stage ⅢC1p cervical cancer patients.Methods A total of 102 stage ⅢC1p cervical cancer patients who underwent surgical treatment were selected.Based on survival status,stage ⅢC1p cases were divided into two subgroups:progression group and no progression group.The influencing factors of clinicopathological indexes and MRI features on prognosis in the two groups were analyzed.Results The results of the univariate analysis showed that squamous cell carcinoma antigen(SCC-Ag)level,T stage and location of lymph node metastasis(LNM)were correlated with the prognosis of stage ⅢC1p cervical cancer patients(P<0.05).Multivariate analysis results showed that late T stage,SCC-Ag>13 ng/mL,and LNM location≥3 were the high risk factors affecting the 3-year DFS decline in stage ⅢC1p cervical cancer patients.Conclusion SCC-Ag,T stage,and LNM location are independent risk factors for 3-year DFS in stage ⅢC1p cervical cancer patients.

Background::Programmed death 1 (PD-1) blockade plus chemotherapy has become the new first-line standard of care for patients with advanced non-small-cell lung cancer (NSCLC). Yet not all NSCLC patients benefit from this regimen. This study aimed to investigate the predictors of PD-1 blockade plus chemotherapy in untreated advanced NSCLC.Methods::We integrated clinical, genomic, and survival data from 287 patients with untreated advanced NSCLC who were enrolled in one of five registered phase 3 trials and received PD-1 blockade plus chemotherapy or chemotherapy alone. We randomly assigned these patients into a discovery cohort ( n = 125), a validation cohort ( n = 82), and a control cohort ( n = 80). The candidate genes that could predict the response to PD-1 blockade plus chemotherapy were identified using data from the discovery cohort and their predictive values were then evaluated in the three cohorts. Immune deconvolution was conducted using transcriptome data of 1014 NSCLC patients from The Cancer Genome Atlas dataset. Results::A genomic variation signature, in which one or more of the 15 candidate genes were altered, was correlated with significantly inferior response rates and survival outcomes in patients treated with first-line PD-1 blockade plus chemotherapy in both discovery and validation cohorts. Its predictive value held in multivariate analyses when adjusted for baseline parameters, programmed cell death ligand 1 (PD-L1) expression level, and tumor mutation burden. Moreover, applying both the 15-gene panel and PD-L1 expression level produced better performance than either alone in predicting benefit from this treatment combination. Immune landscape analyses revealed that tumors with one or more variation in the 15-gene panel were associated with few immune infiltrates, indicating an immune-desert tumor microenvironment.Conclusion::These findings indicate that a 15-gene panel can serve as a negative prediction biomarker for first-line PD-1 blockade plus chemotherapy in patients with advanced NSCLC.

Objective:To investigate the effect of guided imagery relaxation therapy on pain self-efficacy and quality of life in patients with gynecological malignant tumor.Methods:A total of 94 gynecological malignant tumor patients were assigned to study group and control group by random digits table method with 47 cases each, the control group received routine nursing, while the study group carried out guided imagery relaxation therapy for 4 weeks. The pain degree, pain self-efficacy and quality of life was assessed by Chinese version of Brief Pain Inventory (BPI-C), Chronic Pain Self-efficacy Scale (CPSS) and Quality of Life Questionnaire-core 30 (QLQ-C30), before and 4-week after intervention.Results:Compared to the control group, the scores of pain right now, pain at worst in the 24 hours, pain on the average of BPI-C and symptom scales, single items of QLQ-C30 were (3.76±0.54), (4.37±1.39), (3.63±0.73), (32.40±8.69), (34.34±5.81) points in the study group, and (4.18±0.93), (5.18±1.75), (4.23±0.97), (37.72±6.37), (38.54±6.84) points in the control group, the differences were statistically significant( t values were 2.415-3.287, all P <0.05). The scores of self-efficacy for pain management, self-efficacy for physical function, self-efficacy for coping with symptoms, total CPSS total scale and function scales, global QOL scale were (17.43±5.50), (27.25±4.40), (29.76±6.46), (74.44±9.21), (72.73±17.74), (64.02±11.03) points in the study group, and (14.68±3.53), (22.60±4.01), (24.87±4.03), (62.14±7.10), (65.60±13.89), (57.23±15.60) points in the control group, the differences were statistically significant( t values were 2.105-7.036, P <0.05 or 0.01). Conclusions:Guided imagery relaxation therapy can alleviate cancerous pain and promote pain self-efficacy and quality of life of patients with gynecological malignant tumor.

Objective To compare the diagnostic accuracies of deep convolutional neural network (CNN) and dermatologists for pigmented nevus and seborrheic keratosis.Methods CNN network ResNet-50 was trained with 5 094 dermoscopic images of pigmented nevus and seborrheic keratosis using transfer learning,so as to establish a CNN two-classification model.Then,this model was applied to the automatic classification of 30 dermoscopic images of pigmented nevus and 30 dermoscopic images of seborrheic keratosis.Meanwhile,in combination with clinical photos of skin lesions,95 experienced dermatologists who had received dermoscopy training gave their diagnosis for the above 60 dermoscopic images.The diagnostic accuracies were compared between the two methods,and misclassified images were further analyzed.Results The CNN automatic classification model had the diagnostic accuracies of 100％ (30/30)and 76.67％ (23/30) for pigmented nevus and seborrheic keratosis respectively,and the total accuracy was 88.33％ (53/60).The average diagnostic accuracies of 95 dermatologists were 82.98％ (25.8/30) and 85.96％ (24.9/30) for pigmented nevus and seborrheic keratosis respectively,and the total accuracy was 84.47％ (50.7/60).There were no significant differences in the diagnostic accuracies for pigmented nevus or seborrheic keratosis between the CNN automatic classification model and 95 dermatologists (x2 =0.38,P ＞ 0.05).The dermoscopic images misclassified by CNN were divided into 3 categories:special-type lesions with high pigment content and marked keratosis,typical skin lesions with interference factors,and typical skin lesions without definite reasons for misclassification.Conclusions The performance of CNN automatic classification model is similar to that of experienced dermatologists in the two classification of pigmented nevus and seborrheic keratosis.The reasons for misclassification by CNN still need to be explored by dermatologists and professionals in artificial intelligence.

Objective To assess the value of transesophageal echocardiography (TEE) in left atrial appendage (LAA) closer with Amplatzer Cardiac Plug (ACP).Methods Consecutive 32 atrial fibrillation patients (CHADS2≥1) with high risk bleeding underwent LAA occlusion with ACP LAA occlusion device under the guidance of TEE.Measurements of LAA anchoring area diameter (AAD) and LAA anatomical orifice diameter (AOD) including maximum,minimum values,and LAA depth on 2 dimentional TEE (2D TEE) were conducted before closer device implantation.The outcomes of LAA occlusion were analyzed.Results Among 32 patients,27 cases achieved successful LAA occlusion,including 2 cases with peripheral leakage ≤5 mm,and 5 cases failed occlusion.Among 5 failed closed patients,3 cases with LAA AAD≥ 30 mm,1 case with LAA of short depth,and 1 case with anatomical variation of LAA of low position that access sheath could not be positioned in the LAA.LAA AAD maximum,minimum and LAA depth were (25.9±4.9)mm,(20.0±3.8)mm,(31.0±5.6)mm,respectively,and LAA AOD maximum,minimum diameters were (26.2±6.2)mm,(19.4±4.3)mm,respectively.Among 10 cases with LAA AAD≥30 mm,7 cases achieved successful LAA occlusion,but 3 cases failed.The implanted device diameter was (26.4±3.8)mm,and device compression rate was (7.6±5.5)%.The coefficient of correlation between device diameter and large LAA AAD and AOD is 0.770 and 0.717,respectively.There was no complication but 1 case with pericardial effusion.Conclusions Two dimentional TEE measurements of LAA have clinical guiding significance in the selection of proper size of ACP LAA occluder.The AAD of 2D TEE has the good correlation with ACP occluder′s size,the AADs are important factors which affect the success of LAA occlusion.