Objective:To study effect of STIL gene on proliferation and apoptosis of cervical cancer cells and its mechanism.Methods:Expressions of STIL mRNA and STIL protein in cervical cancer tissues,adjacent tissues,cervical cancer cell lines HeLa,SiHa,caski and human normal cervical epithelial cells HUCEC were calculated by RT-qPCR and Western blot.HeLa cells were divided into control(NC)group,si-NC group,si-STIL group,si-STIL+IL-6 group.CCK-8 and plate cloning assay were utilized to detect cell proliferation and cloning ability,and flow cytometry was used to analyze cell apoptosis rate.Western blot was used to detect IL-6,IL-6R and p-STAT3 proteins levels.sh-STIL stably transfected HeLa cells were subcutaneously inoculated into back of nude mice to investigate effect of inhibiting STIL expression on tumor formation.Results:STIL mRNA and protein expressions in cervical cancer tissues were significantly higher than adjacent tissues(P<0.05).STIL mRNA and protein expressions in HeLa,SiHa,and caski cells were significantly higher than HUCEC cells(P<0.05).Compared with si-NC group,cell absorbance,number of clones,and protein levels of IL-6,IL-6R and p-STAT3 in si-STIL group were significantly reduced(P<0.05),and apoptosis rate was significantly in-creased(P<0.05).Compared with si-STIL group,cell absorbance,number of clones and protein levels of IL-6,IL-6R and p-STAT3 in si-STIL+IL-6 group were significantly increased(P<0.05),and apoptotic rate was significantly reduced(P<0.05).Inhibiting STIL significantly inhibited tumor growth in vivo(P<0.05).Conclusion:STIL gene expression is up-regulated in cervical cancer,and inhi-biting STIL can inhibit proliferation and induce apoptosis of cervical cancer cells by inhibiting IL-6/STAT3 pathway.

Objective To explore the prognostic value of the coronary angiography-derived index of microcirculatory resistance(caIMR)for major adverse cardiovascular events(MACE)in patients with acute ST-segment elevation myocardial infarction(STEMI)after primary percutaneous coronary intervention(PCI).Methods Between September 2019 and March 2022,541 patients diagnosed with STEMI at the Affiliated Hospital of Xuzhou Medical University were enrolled.The caIMR was calculated using the FlashAngio system(Suzhou Rainmed Medical Technology Co.,Ltd.).The patients were divided into MACE and non-MACE groups according to the occurrence of MACE during hospitalization or follow-up,with MACE defined as all-cause mortality,heart failure readmission,and unplanned revascularization.COX regression analysis,receiver operating characteristic(ROC)curves,and Kaplan-Meier survival curves were used to evaluate the prognostic value of caIMR for STEMI patients after primary PCI.Results During the 1-year follow-up,61 patients(11.28％)experienced MACE.The patients in the MACE group had higher caIMR values than those in the non-MACE group.Multivariate COX analysis showed that caIMR was an independent risk factor for MACE.ROC curve analysis showed that caIMR predicted MACE with an area under the curve of 0.688,and the optimal cutoff value was 25.3 U.caIMR significantly increased the discriminant and reclassification indexes when added to a model with clinical risk factors.The patients were further divided into a low caIMR group(caIMR＜25 U,n=377)and a high caIMR group(caIMR ≥25 U,n=164).Kaplan-Meier curve showed that patients with caIMR≥25 U had a worse prognosis.Conclusions caIMR is an independent risk factor for poor prognosis after PCI in patients with STEMI,and patients with caIMR≥25 U had a worse prognosis.

Objective To explore the expression, correlation with clinicopathologic parameters, and clinical significance of MIS18 binding protein 1 (MIS18BP1) in bladder cancer. Methods TCGA and GEO databases were used to analyze the mRNA expression of MIS18BP1 in tumors and controls, and the results were verified via qRT-PCR. UALCAN online database was utilized in the analysis of the expression of MIS18BP1 and its correlation with clinicopathological parameters and the degree of immune cell infiltration. Immunohistochemistry was employed to analyze the expression of MIS18BP1 in bladder cancer and its relationship with clinicopathological features. The ROC curve was applied to evaluate the diagnostic value of MIS18BP1 mRNA in bladder cancer. Results Bioinformatics analysis and qRT-PCR results revealed the increased expression of MIS18BP1 mRNA in bladder cancer compared with that in the control group (P<0.05). Immunohistochemistry unveiled the significantly high positive rate of MIS18BP1 protein in bladder cancer (P<0.05) and its correlation with the clinical stage of tumors, depth of invasion, and lymph node metastasis (P<0.05). The immune infiltration analysis showed the association of MIS18BP1 with immune cell infiltration in bladder cancer. Conclusion The increased expression level of MIS18BP1 gene and protein in bladder cancer may regulate the development of bladder cancer by influencing immune cell infiltration.

ObjectiveTo explore the distribution characteristics of traditional Chinese medicine （TCM） syndrome elements of macroangiopathy in patients with type 2 diabetes mellitus （T2DM） and the key elements of occurrence， development and progression of disease. MethodsA multicenter cross-sectional study was conducted to enroll 445 T2DM patients from five hospitals， and according to the presence or absence of macroangiopathy， the patients were divided into a T2DM group （120 cases） and a diabetic macroangiopathy （DM） group （325 cases）. Patients in DM group were divided into grade Ⅰ， Ⅱ， Ⅲ and Ⅳ according to the peripheral vascular color Doppler ultrasound results and the vascular anomalies classification standard. The general data including gender， age， duration of T2DM and body mass index （BMI） were collected， and the data of four examinations were obtained for syndrome differentiation. According to the diagnostic criteria of TCM syndrome elements， the patients can be divided into 9 patterns including qi deficiency， blood deficiency， yin deficiency， yang deficiency， qi stagnation， blood stasis， excess heat， and excess cold. The general data and distribution of TCM syndrome elements were compared between the two groups. The distribution of TCM syndrome elements in different vascular anomalies grades in the DM group was analyzed. Logistic regression analysis was used to explore the influence of various TCM syndrome elements on the occurrence of macroangiopathy in T2DM. ResultsThere was no significant difference in gender and BMI between groups （P＞0.05）. The age and duration of diabetes in the DM group were older and longer than those in the T2DM group （P＜0.01）. With the increase of age and prolonged course of disease， the severity of diabetic macroangiopathy increases gradually （P＜0.05 or P＜0.01）. There was no significant difference in BMI and course of disease among the different TCM syndrome elements （P＞0.05）. The average age of patients with blood stasis syndrome was the oldest （P＜0.05）. There was significant difference in gender distribution between the excess heat syndrome and yin deficiency syndrome （P＜0.05）. A total of 240 TCM syndrome elements were extracted from the T2DM group， while 731 TCM syndrome elements extracted from the DM group. The top two high-frequency syndrome elements in the two groups were qi deficiency and yin deficiency， with a frequency of larger than 50%. The distribution of phlegm-damp syndrome and blood-stasis syndrome were significantly higher in the DM group than in the T2DM group （P＜0.01）. There were significant differences in the distribution of qi deficiency syndrome， yin deficiency syndrome， phlegm-damp syndrome， blood stasis syndrome， and excess heat syndrome among different grades of vascular anomalies （P＜0.01）； qi deficiency and yin deficiency were both high-frequency TCM syndrome elements in patients at grades 0 to Ⅲ； phlegm-damp syndrome increased in frequency with the progression of the disease from grades 0 to Ⅳ， and the frequency of blood stasis syndrome showed an overall upward trend. The frequency of phlegm-dampness syndrome increased from grades 0 to Ⅳ with the progression of the disease， and the frequency of blood stasis syndrome showed an overall upward trend. Logistic regression analysis showed that phlegm-damp syndrome and blood stasis syndrome were important TCM syndrome elements related to the vascular anomalies degree of macrovascular disease in T2DM （P＜0.05 or P＜0.01）. ConclusionQi deficiency and yin deficiency are the basic TCM syndrome elements throughout the whole process of T2DM and diabetic macrovascular disease. Phlegm-damp and blood stasis are related to the degree of vascular anomalies in diabetic macrovascular disease and are the key TCM syndrome elements in the progression of macroangiopathy in T2DM.

Objective To analyze the co-expressed genes in blood lipid metabolism,hyperlipidemia and tacrolimus metabolism and their correlation with blood lipid levels in kidney transplant recipients.Methods Co-expressed genes were screened from Comparative Toxicogenomic Database(CTD).Baseline data of 25 kidney transplant recipients were collected.The expression levels of ATP binding cassette subfamily A member 1(ABCA1),peroxisome proliferator activated receptor γ(PPAR-γ)and glycosylphosphatidylinositol anchored high density lipoprotein binding protein 1(GPIHBP1)were measured.All recipients were followed up.The concentrations of fasting blood glucose,glycosylated hemoglobin,triglyceride,total protein,albumin,globulin,cholesterol,high-density lipoprotein,low-density lipoprotein and tacrolimus blood concentration were collected at postoperative 1,3,6 and 12 months,and the incidence of hyperlipidemia in the recipients was analyzed.The correlation between ABCA1,GPIHBP1,PPAR-γ and clinical indexes was assessed.The diagnostic effiiciency of related indexes for hyperlipidemia after kidney transplantation was evaluated.Results Three co-expressed genes including ABCA1,PPAR-γ and GPIHBP1 were screened.ABC Al was positively correlated with cholesterol level at postoperative 6 months and tacrolimus blood concentration at postoperative 3 months,whereas negatively correlated with fasting blood glucose level at postoperative 3 months(all P＜0.05).GPIHBP1 was negatively correlated with preoperative cholesterol and triglyceride levels,whereas positively correlated with tacrolimus blood concentration at postoperative 3 months(all P＜0.05).PPAR-γ was negatively correlated with preoperative globulin and low-density lipoprotein levels(both P＜0.05).ABCA1,GPIHBP1 and PPAR-γ combined with preoperative globulin and blood glucose level at postoperative 1 and 6 months after operation yielded high diagnostic effiiciency for hypertriglyceridemia after kidney transplantation(AUC=0.900).ABCA1,GPIHBP1 and PPAR-γ combined with tacrolimus blood concentrations at postoperative 1 and 6 months and blood glucose level at postoperative 6 months had high diagnostic effiiciency for hypercholesterolemia after kidney transplantation(AUC=0.931).Conclusions ABCA1,GPIHBP1 and PPAR-γ are correlated with blood lipid level and tacrolimus blood concentration after kidney transplantation to different degrees.No definite evidence has been supported for predicting hyperlipidemia after kidney transplantation.Immunity improvement and rational blood glucose management may be beneficial factors for hyperlipidemia control.

Objective To explore the plasma-activated medium(PAM)produced by low temperature plasma(LTP)on the proliferation and angiogenesis of human umbilical vein endothelial cells(HUVECs)so as to provide theoretical basis for the future use of PAM to promote wound healing and inhibit tumor angiogenesis.Methods HUVECs were selected as the in vitro research model.The PAM-containing medium after LTP treatment for different time points(0 s,15 s,30 s,45 s,60 s,and 75 s)was used for intervention.The influence of PAM on HUVECs viability was assessed using the MTT assay and cell cycle analysis.The effects of PAM on angiogenesis were examined through angiogenesis experiments.Intracellular levels of reactive oxygen species(ROS)were measured using fluorescence probes.A melanoma mouse model was established,and CD31 expression was detected by immunohistochemistry.Results As the treatment time increased,the intracellular levels of ROS also elevated.PAM derived from LTP exhibited a bidirectional effect on angiogenesis in HUVECs.Compared to the control group(0 s),low-dose treatments(15 s and 30 s)enhanced HUVECs viability,while high-dose treatments(45 s,60 s,and 75 s)significantly decreased cell viability(P＜0.05).The proportion of HUVECs in the S phase was significantly increased in the PAM-15 s and PAM-30 s groups,but markedly decreased in the PAM-45 s,PAM-60 s,and PAM-75 s groups,with statistically significant differences(P＜0.05).The HUVECs tube formation ability was enhanced in the 15 s and 30 s PAM groups,but diminished in the PAM-45 s,PAM-60 s,and PAM-75 s groups,characterized by the decreased numbers of vascular nodes,intersections,meshes,and branching points(P＜0.05).After PAM treatment in the melanoma mouse model,the control group exhibited widespread distribution of CD31 in tumor tissue,while the PAM-5 min and PAM-10 min groups displayed reduced distribution of CD31.Conclusion Short-term exposure to PAM enhances HUVECs proliferation and angiogenesis,whereas prolonged exposure suppresses cell viability and inhibits angiogenesis.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.

Objective To explore the feasibility of radiomics features combined with different machine learning methods based on CT scans to predict lymphovascular and perineural invasion in patient with gastric cancer.Methods A total of 142 patients with gas-tric cancer lymphovascular confirmed by operative pathological examination were retrospectively selected.Among all patients,there were 96 positive cases and 46 negative cases.Among 137 patients with perineural invasion,there were 76 positive cases and 61 nega-tive cases.The 3D-Slicer package was used for delineation,and the Pyradiomics package was used to extract radiomics features.All data were randomly divided into training set and test set in an 8∶2 ratio.Intraclass correlation coefficient(ICC),Pearson correla-tion analysis,least absolute shrinkage and selection operator(LASSO)algorithm were used for feature selection.Support vector machine(SVM),K-nearest neighbor(KNN),decision tree(DT),random forest(RF),extreme tree(ET),extreme gradient boosting(XGBoost),and LightGBM were used to compare the models of lymphovascular and perineural invasion,respectively.Receiver operating characteris-tic(ROC)curve and area under the curve(AUC)were used to evaluate the predictive performance of these models.Results The lymphovascular group AUC of SVM,KNN,DT,RF,ET,XGBoost,and LightGBM in the training set were 0.926,0.753,1.000,0.999,1.000,1.000,and 0.917,and the AUC in the test set were 0.894,0.692,0.456,0.678,0.753,0.650,and 0.650,respectively.The perineural invasion group AUC of SVM,KNN,DT,RF,ET,XGBoost,and LightGBM in the training set were 0.864,0.794,1.000,1.000,1.000,1.000,and 0.866,and the AUC in the test set were 0.861,0.706,0.700,0.672,0.731,0.667,and 0.678,respectively.Conclusion Based on venous phase CT radiomics features combined with machine learning methods,it is feasible to predict lymphovascu-lar and perineural invasion of gastric cancer preoperatively.Among the variousmachine learning methods,SVM shows the best predictive performance for lymphovascular and perineural invasion in patient with gastric cancer.

Objective To investigate the feasibility of using contrast-enhanced T1WI radiomics in predicting the pathological grade in rectal adenocarcinoma.Methods The MRI and pathological data of 127 patients with rectal adenocarcinoma were analyzed retrospectively.ITK-SNAP software was used to manually draw region of interest(ROI)in rectal cancer on axial T,WI enhanced images.The radiomics features were extracted by the Pyradiomics software from ROI.The task was divided into two parts:task 1("high & non-high"group)predicted the high-differentiation and moderate/low-differentiation of the tumor;task 2("moderate & low"group)predicted the tumor's moderate-differentiation and low-differentiation in"non-high"group.Maximum relevance and minimum redundancy(mRMR)method was used to screen features.The five methods including least absolute shrinkage and selection operator(LASSO),logistic regression(LR),naive Bayes(NB),random forest(RF),and support vector machine(SVM)were used to build the models,and the efficiency of each model was evaluated and compared.Results In task 1,the area under the curve(AUC)of five methods were 0.86,0.90,0.59,1.00,0.99 in the training cohort and 0.71,0.62,0.53,0.67,0.64 in the testing cohort.In task 2,the AUC of five methods in the training cohort were 0.93,0.85,0.67,0.92,0.89,and in the testing cohort were 0.86,0.80,0.50,0.78,0.71.The models constructed by LASSO in both tasks were the dominant models,the AUC of the fusion model in the testing cohort which combined with age,gender and the dominant Radiomics score(Radscore)was 0.80[95％confidence interval(CI)0.63-0.96]in task 1,and the accuracy,sensitivity and specificity were 78.94％,77.78％,and 79.31％respectively.They were 0.89(95％CI 0.74-1.00),90.00％,95.65％,and 71.43％,respectively in task 2.The calibration curves showed that the fusion models had a good goodness of fit.Conclusion Based on the establishment of two dichotomous models,the radiomics based on the contrast-enhanced T1 WI is feasible in predicting the high,moderate and low differentiation degree of rectal adenocarcinoma.

Objective To investigate the epidemiological characteristics and mutation spectrum of monogenic diseases in Chinese population through a large-scale,multicenter carrier screening.Methods This study was conducted among a total of 33 104 participants(16 610 females)from 12 clinical centers across China.Carrier status for 223 genes was analyzed using high-throughput sequencing and different PCR methods.Results The overall combined carrier frequency was 55.58%for 197 autosomal genes and 1.84%for 26 X-linked genes in these participants.Among the 16 669 families,874 at-risk couples(5.24%)were identified.Specifically,584 couples(3.50%)were at risk for autosomal genes,306(1.84%)for X-linked genes,and 16 for both autosomal and X-linked genes.The most frequently detected autosomal at-risk genes included GJB2(autosomal recessive deafness type 1A,393 couples),HBA1/HBA2(α-thalassemia,36 couples),PAH(phenylketonuria,14 couples),and SMN1(spinal muscular atrophy,14 couples).The most frequently detected X-linked at-risk genes were G6PD(G6PD deficiency,236 couples),DMD(Duchenne muscular dystrophy,23 couples),and FMR1(fragile X syndrome,17 couples).After excluding GJB2 c.109G>A,the detection rate of at-risk couples was 3.91%(651/16 669),which was lowered to 1.72%(287/16 669)after further excluding G6PD.The theoretical incidence rate of severe monogenic birth defects was approximately 4.35‰(72.5/16 669).Screening for a battery of the top 22 most frequent genes in the at-risk couples could detect over 95%of at-risk couples,while screening for the top 54 genes further increased the detection rate to over 99%.Conclusion This study reveals the carrier frequencies of 223 monogenic genetic disorders in the Chinese population and provides evidence for carrier screening strategy development and panel design tailored to the Chinese population.In carrier testing,genetic counseling for specific genes or gene variants can be challenging,and the couples need to be informed of these difficulties before testing and provided with options for not screening these genes or gene variants.