Th17/Treg balance and macrophage polarization ratio in lower extremity arteriosclerosis obliterans

Objective:To explore the balance of peripheral blood T helper 17 cells/regulatory T cell(Th17/Treg)ratio and the polarization ratio of M1 and M2 macrophages in lower extremity arteriosclerosis obliterans(ASO).Methods:A rat model of lower extremity ASO was established,and blood samples from patients with lower extremity ASO before and after surgery were obtained.ELISA was used to detect interleukin 6(IL-6),IL-10,and IL-17.Real-time RCR and Western blot analyses were used to detect Foxp3,IL-6,IL-10,and IL-17 expression.Moreover,flow cytometry was applied to detect the Th17/Treg ratio and M1/M2 ratio.Results:Compared with the control group,the iliac artery wall of ASO rats showed significant hyperplasia,and the concentrations of cholesterol and triglyceride were significantly increased(P<0.01),indicating the successful establishment of ASO.Moreover,the levels of IL-6 and IL-17 in ASO rats were pronouncedly increased(P<0.05),while the IL-10 level was significantly decreased(P<0.05).In addition to increased IL-6 and IL-17 levels,the mRNA and protein levels of Foxp3 and IL-10 in ASO rats were significantly decreased compared with the control group.The Th17/Treg and M1/M2 ratios in the ASO group were markedly increased(P<0.05).These alternations were also observed in ASO patients.After endovascular surgery(such as percutaneous transluminal angioplasty and arterial stenting),all these changes were significantly improved(P<0.05).Conclusions:The Th17/Treg and M1/M2 ratios were significantly increased in ASO,and surgery can effectively improve the balance of Th17/Treg,and reduce the ratio of M1/M2,and the expression of inflammatory factors.

Unraveling colorectal cancer prevention:The vitamin D-gut flora-immune system nexus

Colorectal cancer(CRC)is one of the most common cancers diagnosed in the world.Although environmental and genetic factors play a major role in the pathogenesis of CRC,extensive research has suggested that vitamin D may play a pivotal role in the development of CRC.Vitamin D,primarily obtained through sunlight exposure,dietary sources,and supplements,has long been recognized for its essential functions in maintaining health,including immune regulation.This article delves into the intricate relationship between vitamin D,the immune system,gut flora,and the prevention of CRC.It presents a synthesis of epidemiological data,experimental studies,and clinical trials,highlighting the mechanisms by which vitamin D influences immune cell function,cytokine production,and inflammation.By enhancing the immune system’s surveillance and antitumor activity,vitamin D may offer a promising avenue for CRC prevention.Furthermore,this comprehensive review delves into the prospective clinical applications of vitamin D supplementation and delineates the forthcoming avenues of research in this dynamic domain.Additionally,the paper tentatively outlines a spectrum of prophylactic impacts of vitamin D on CRC,emphasizing its significant potential in reducing CRC risk through shedding light on its mechanisms,encompassing antineoplastic mechanisms,influences on the immune system,and modulation of the gut microbiome.

Combining machine and deep transfer learning for mediastinal lymph node evaluation in patients with lung cancer

Background The prognosis and survival of patients with lung cancer are likely to deteriorate with metastasis.Using deep-learning in the detection of lymph node metastasis can facilitate the noninvasive calculation of the likelihood of such metastasis,thereby providing clinicians with crucial information to enhance diagnostic precision and ultimately improve patient survival and prognosis.Methods In total,623 eligible patients were recruited from two medical institutions.Seven deep learning models,namely Alex,GoogLeNet,Resnet18,Resnet101,Vgg16,Vgg19,and MobileNetv3(small),were utilized to extract deep image histological features.The dimensionality of the extracted features was then reduced using the Spearman correlation coefficient(r≥0.9)and Least Absolute Shrinkage and Selection Operator.Eleven machine learning methods,namely Support Vector Machine,K-nearest neighbor,Random Forest,Extra Trees,XGBoost,LightGBM,Naive Bayes,AdaBoost,Gradient Boosting Decision Tree,Linear Regression,and Multilayer Perceptron,were employed to construct classification prediction models for the filtered final features.The diagnostic performances of the models were assessed using various metrics,including accuracy,area under the receiver operating characteristic curve,sensitivity,specificity,positive predictive value,and negative predictive value.Calibration and decision-curve analyses were also performed.Results The present study demonstrated that using deep radiomic features extracted from Vgg16,in conjunction with a prediction model constructed via a linear regression algorithm,effectively distinguished the status of mediastinal lymph nodes in patients with lung cancer.The performance of the model was evaluated based on various metrics,including accuracy,area under the receiver operating characteristic curve,sensitivity,specificity,positive predictive value,and negative predictive value,which yielded values of 0.808,0.834,0.851,0.745,0.829,and 0.776,respectively.The validation set of the model was assessed using clinical decision curves,calibration curves,and confusion matrices,which collectively demonstrated the model's stability and accuracy.Conclusion In this study,information on the deep radiomics of Vgg16 was obtained from computed tomography images,and the linear regression method was able to accurately diagnose mediastinal lymph node metastases in patients with lung cancer.

Accuracy of multi-echo Dixon sequence in quantification of hepatic steatosis in Chinese children and adolescents

BACKGROUND Nonalcoholic fatty liver disease(NAFLD) is currently the outstanding cause of chronic liver disease in children and adolescents, especially in overweight and obese groups. Liver biopsy is the reference standard to diagnose NAFLD but invasive, thus it is not the best choice in clinical diagnosis and follow-up.Magnetic resonance(MR) is widely used in clinical trials to noninvasively quantify liver fat content in adults and children in foreign countries. While currently, it is rarely used in Chinese children and adolescents. We postulated that quantifying hepatic steatosis by MR could be extended to children and adolescents in China.AIM To investigate the accuracy of MR imaging(MRI) in quantifying liver fat with MR spectroscopy(MRS) as a reference. A secondary goal was to assess the prevalence of NAFLD in overweight and obese Chinese children and adolescents.METHODSThere were 86 children and adolescents enrolled in this study, including 65 overweight and obese children and 21 healthy children. The participants underwent MRI and MRS. MRI and MRS were performed using multi-echo Dixon and HISTO sequences, respectively, to calculate hepatic proton density fat fraction(PDFF). Hepatic steatosis was diagnosed using MRS-PDFF > 5% as the threshold. Spearman's analysis was used to evaluate the correlation between MRI and MRS. The agreement between these two methods was assessed by BlandAltman analysis.RESULTS The MRI-PDFF in the MRS region of interest and the entire liver was 9.9% ±10.3% with a range of 0.3%-39.9%, and 10.6% ± 9.4% with a range of 1.9%-38.9%,respectively. The MRS-PDFF was 9.1% ± 10.0%, with a range of 0.5%-37.8%. The incidence of hepatic steatosis detected by MRS-PDFF was 46.5%(40/86) of all participants, all of whom belonged to the overweight and obese group.Spearman's analysis indicated an excellent correlation between multi-echo Dixon and MRS(r > 0.9, P < 0.01). Bland-Altman analysis also demonstrated a good agreement between these two methods.CONCLUSION Multi-echo Dixon shows an excellent correlation and agreement with MRS in quantifying liver fat content and could be a potential tool to detect hepatic steatosis in Chinese children and adolescents.

Effect of PPARγagonist(rosiglitazone)on the secretion of Th2 cytokine in asthma mice

Objective: To explore the effect of PPAR γ agonist(rosiglitazone) on the secretion of Th2 cytokines and the proportion of immune cell subsets in asthma mice,Methods: Ovalbumin(OVA)-sensitized mice were used to build asthma models,Those mice were divided into the normal control group,model group and rosiglitazone group,Differences of the changes in lung histopathology of mice in the three group were observed through hematoxylin and eosin(HE) strain,and the numbers of the total cells,eosinophils and neutrophils in BALF of mice in the three groups were compared,ELISA and real-time PCR were employed to detect the protein levels of interleukin(IL)-5,IL-13,IL-4 and IL-10 and m RNA level,respectively,Flow cytometry number was implied to analyze the proportion of immune cell subsets in peripheral blood of mice,Results: Compared with the mice in the control group,and mice of the model group,the infiltration of inflammatory cells in BALF increased,bronchial smooth muscle became thickened,a large amount of collagen deposited,the secretion of Th2 cytokine increased significantly,the ratio of regulatory T cells(Treg) decreased,the ratio of T17 cells rose distinctly; while in mice of the rosiglitazone group,the changes of their lung histopathology were improved obviously,the number of infiltration of inflammatory cells declined,the thickened smooth muscle relieved,the deposition of collagen decreased,the secretion of Th2 cytokine was inhibited,the ratio of Treg went up,and the increased of the ratio of T17 cells was inhibited but still not return to normal level,Conclusions: Rosiglitazone can regulate the proportion of Treg and Th17 cells and inhibit the secretion of Th2 cytokines,which inhibit the airway inflammatory response for asthma mice effectively.

Cryptotanshinone increases the sensitivity of liver cancer to sorafenib by inhibiting the STAT3/Snail/ epithelial mesenchymal transition pathway

Objective:Sorafenib resistance has been a major factor limiting its clinical use as a targeted drug in liver cancer.The present study aimed to investigate whether cryptotanshinone can enhance the sensitivity of liver cancer and reduce the resistance to sorafenib.Methods:Sorafenib-resistant cells were established based on HepG2 and Huh7 cell lines.And the anti-tumor effect of sorafenib combined with cryptotanshinone on the sorafenib-resistant cells was verified by MTT,colony formation,transwell assays and tumor growth xenograft model.Moreover,the effects of the combined treatment on the expression of phosphorylated(p)-STAT3,as well as epithelial mesenchymal transition(EMT)and apoptosis related proteins of cells were evaluated by western blot analysis.Results:It was identified that cryptotanshinone inhibited the viability of both HepG2 and Huh7 cells in a dose-and time-dependent manner,and decreased p-STAT3 expression rather than total STAT3 expression at a concentration of 40μmol/L.In the sorafenib-resistant cells,sorafenib in combination with cryptotanshinone markedly inhibited cell viability,invasion and migration compared with sorafenib alone.In contrast,increased p-STAT3 level by colivelin led to the inhibition of the synergistic effect of cryptotanshinone and sorafenib not only on cell viability,but also on EMT and apoptosis,suggesting that cryptotanshinone and sorafenib may act by downregulating STAT3 signaling.Further,the inhibition of carcinogenicity effect was also verified in xenografted tumor models.Conclusion:The present results indicated that cryptotanshinone could synergize with sorafenib to inhibit the proliferative,invasive,and migratory abilities of sorafenib-resistant cells by downregulating STAT3 signaling.

Helicobacter pylori infection with atrophic gastritis: An independent risk factor for colorectal adenomas

BACKGROUND The significance of Helicobacter pylori(H.pylori)infection and atrophic gastritis(AG)in the prevalence of colorectal adenomas has been examined in a limited number of studies.However,these studies reported disputed conclusions.AIM To investigate whether H.pylori infection,AG,and H.pylori-related AG increase the risk of colorectal adenomas.METHODS This retrospective cross-sectional study included 6018 health-check individuals.The relevant data for physical examination,laboratory testing,13C-urea breath testing,gastroscopy,colonoscopy and histopathological examination of gastric and colorectal biopsies were recorded.Univariate and multivariate logistic regression analyses were performed to determine the association between H.pylori-related AG and colorectal adenomas.RESULTS Overall,1012 subjects(16.8%)were diagnosed with colorectal adenomas,of whom 143(2.4%)had advanced adenomas.Among the enrolled patients,the prevalence of H.pylori infection and AG was observed as 49.5%(2981/6018)and 10.0%(602/6018),respectively.Subjects with H.pylori infection had an elevated risk of colorectal adenomas(adjusted odds ratio[OR]of 1.220,95%confidence interval(CI):1.053-1.413,P=0.008)but no increased risk of advance adenomas(adjusted OR=1.303,95%CI:0.922-1.842,P=0.134).AG was significantly correlated to an increased risk of colorectal adenomas(unadjusted OR=1.668,95%CI:1.352-2.059,P<0.001;adjusted OR=1.237,95%CI:0.988-1.549,P=0.064).H.pylori infection accompanied by AG was significantly associated with an increased risk of adenomas(adjusted OR=1.491,95%CI:1.103-2.015,P=0.009)and advanced adenomas(adjusted OR=1.910,95%CI:1.022-3.572,P=0.043).CONCLUSION H.pylori-related AG was associated with a high risk of colorectal adenomas and advanced adenomas in Chinese individuals.

Relative peripheral refraction and its role in myopia onset in teenage students

AIM:To characterize peripheral refraction and its relationship with myopia development in a selected group of male teenage Chinese students.METHODS:This 2-year prospective cohort study randomly enrolled 85 non-myopic boys(age,14-16 y)from the Experimental Class of Air Force in China.Cycloplegic peripheral refraction was examined at 0°,±10°,and±20°along the horizontal visual field in the right eye at the baseline and 2-year follow-up.RESULTS:The incidence of myopia at the 2-year followup was 15.29%(13/85).The baseline central refraction(CR)and peripheral refraction at±10°were significantly lower in students who developed myopia than in those who did not(P<0.05).Relative peripheral refraction(RPR)did not differ between students with and without myopia(P>0.05).At the 2-year follow-up,the RPR at±10°and 20°nasal was significantly more hyperopic in the myopic group than in the non-myopic group.Multiple linear regression analysis indicated that the change in CR was significantly correlated with the changes in RPR at 20°nasal,10°nasal,and 20°temporal.Multivariate Logistic regression analysis indicated that the baseline CR[odds ratio(OR):0.092,95%confidence interval(CI):0.012-0.688,P=0.020]and the baseline RPR at 10°nasal(OR:0.182,95%CI:0.042-0.799,P=0.024)were significantly correlated with incident myopia(Omnibus test,χ=10.20,P=0.006).CONCLUSION:CR change is significantly correlated with changes in RPR,and students who develop myopia have more relative peripheral hyperopia.More baseline CR and relative peripheral hyperopia at 10°nasal are protective of myopia onset.

RING finger and WD repeat domain 3 regulates proliferation and metastasis through the Wnt/β-catenin signalling pathways in hepatocellular carcinoma

BACKGROUND Hepatocellular carcinoma(HCC)exhibits high invasiveness and mortality rates,and the molecular mechanisms of HCC have gained increasing research interest.The abnormal DNA damage response has long been recognized as one of the important factors for tumor occurrence and development.Recent studies have shown the potential of the protein RING finger and WD repeat domain 3(RFWD3)that positively regulates p53 stability in response to DNA damage as a therapeutic target in cancers.AIM To investigate the relationship between HCC and RFWD3 in vitro and in vivo and explored the underlying molecular signalling transduction pathways.METHODS RFWD3 gene expression was analyzed in HCC tissues and adjacent normal tissues.Lentivirus was used to stably knockdown RFWD3 expression in HCC cell lines.After verifying the silencing efficiency,Celigo/cell cycle/apoptosis and MTT assays were used to evaluate cell proliferation and apoptosis.Subsequently,cell migration and invasion were assessed by wound healing and transwell assays.In addition,transduced cells were implanted subcutaneously and injected into the tail vein of nude mice to observe tumor growth and metastasis.Next,we used lentiviral-mediated rescue of RFWD3 shRNA to verify the phenotype.Finally,the microarray,ingenuity pathway analysis,and western blot analysis were used to analyze the regulatory network underlying HCC.RESULTS Compared with adjacent tissues,RFWD3 expression levels were significantly higher in clinical HCC tissues and correlated with tumor size and TNM stage(P<0.05),which indicated a poor prognosis state.RFWD3 silencing in BEL-7404 and HCC-LM3 cells increased apoptosis,decreased growth,and inhibited the migration in shRNAi cells compared with those in shCtrl cells(P<0.05).Furthermore,the in vitro results were supported by the findings of the in vivo experiments with the reduction of tumor cell invasion and migration.Moreover,the rescue of RFWD3 shRNAi resulted in the resumption of invasion and metastasis in HCC cell lines.Finally,gene expression profiling and subsequent experimental verification revealed that RFWD3 might influence the proliferation and metastasis of HCC via the Wnt/β-catenin signalling pathway.CONCLUSION We provide evidence for the expression and function of RFWD3 in HCC.RFWD3 affects the prognosis,proliferation,invasion,and metastasis of HCC by regulating the Wnt/β-catenin signalling pathway.

人Ⅰ期肺腺癌及癌旁组织蛋白质双向电泳图谱的差异分析(英文)

Objective:The aim of this study was to establish reproducible two-dimensional electrophoretic assay used for profiling and identification of differentially expressed proteins in human stage Ⅰ lung adenocarcinoma and paired normal tumor-adjacent tissue.Methods:The proteins from 12 human stage Ⅰ lung adenocarcinoma tissues and normal tumor-adjacent tissues were separated using isoelectric focusing electrophoresis(the first dimension) and the subsequent homogeneous SDS-polyacrylamide gel electrophoresis(SDS-PAGE)(the second dimension).The differentially expressed proteins were determined with PDQuest image analysis software,and identified using matrix-assisted laser desorption/ionization time of flight mass spectrometry(MALDI-TOF-MS) and database searching.Results:The well-reproducible 2-DE gel patterns of human stage Ⅰ lung adenocarcinoma and normal tumor-adjacent tissues were profiled and 26 differentially expressed proteins uncovered.Nine of these 26 protein spots were cut out from the preparation gels and determined with MALDI-TOF-MS.Searching against the protein database,four candidate proteins were identified.They were 60S acidic ribosomal protein P2,Cathepsin B1,Apolipoprotein A-I precursor,and La 4.1 protein.Conclusion:In this study,high reproducible 2-DE gel protein images of human stage Ⅰ lung adenocarcinoma and paired normal tumor-adjacent tissues were achieved successfully,and 4 differentially expressed proteins were revealed.These data will be helpful for screen of early biomarker and study of molecular mechanisms of human lung adenocarcinoma.

Feature selection and machine learning approach for carotid atherosclerosis in asymptomatic adults

Objective:The presence of carotid atherosclerosis reflects the overall atherosclerotic load and may predict cardiovascular and cerebrovascular accidents.Studies have reported risk factors for carotid atherosclerosis.However,few practical models have been established to predict carotid atherosclerosis risk.Thus,this study was conducted to investigate important features of carotid atherosclerosis and to propose a machine learning-based method for predicting carotid atherosclerosis in asymptomatic adults.Methods:Cross-sectional study was conducted using routine medical check-up data of individuals from January 2019 to January 2020.Pearson’s correlation analysis was performed to correlate the features.Then,features were selected by python’s feature-selection library and analyzed through three algorithms.Multiple machine learning algorithms,including Decision Tree,Random Forest and Logistic Regression(LR)were used to predict the risk of carotid atherosclerotic plaques and compared their precision,accuracy,recall,F1-score and area under the curve.Results:A total of 150 individuals were enrolled in this study,30(20%)of them were found with carotid atherosclerotic plaques.Sex,age,body mass index,total cholesterol,Systolic blood pressure(SBP),and carbohydrate antigen 724(CA724)were independently correlated to carotid atherosclerosis.Pepsinogen Ⅰ and pepsinogen Ⅱ serum levels had no correlations with Carotid intima-media thickness and pulse wave velocity.SBP,diastolic blood pressure age,low-density lipoprotein,Pepsinogen I,pepsinogen II,body mass index,Waist,CA724,and Uric Acid contribute to the cumulative importance of 0.9,and SBP was the most crucial feature for carotid atherosclerosis.LR algorithm has the precision(0.92),values of recall(0.91),F1(0.9),and area under the curve(0.95),and showed the optimal performance to predict the presence or absence of carotid atherosclerosis in asymptomatic adults.The code for analysis in this article was uploaded to GitHub(https://github.com/ganbingliangyi/machine-learning).Conclusions:SBP was the most crucial feature in ranking features,the LR algorithm showed the optimal performance to predict the presence or absence of carotid atherosclerosis in asymptomatic adults.

Preoperative diagnosis of malignant pulmonary nodules in lung cancer screening with a radiomics nomogram

Background:Lung cancer is the most commonly diagnosed cancer worldwide.Its survival rate can be significantly improved by early screening.Biomarkers based on radiomics features have been found to provide important physiological information on tumors and considered as having the potential to be used in the early screening of lung cancer.In this study,we aim to establish a radiomics model and develop a tool to improve the discrimination between benign and malignant pulmonary nodules.Methods:A retrospective study was conducted on 875 patients with benign or malignant pulmonary nodules who underwent computed tomography(CT)examinations between June 2013 and June 2018.We assigned 612 patients to a training cohort and 263 patients to a validation cohort.Radiomics features were extracted from the CT images of each patient.Least absolute shrinkage and selection operator(LASSO)was used for radiomics feature selection and radiomics score calculation.Multivariate logistic regression analysis was used to develop a classification model and radiomics nomogram.Radiomics score and clinical variables were used to distinguish benign and malignant pulmonary nodules in logistic model.The performance of the radiomics nomogram was evaluated by the area under the curve(AUC),calibration curve and Hosmer-Lemeshow test in both the training and validation cohorts.Results:A radiomics score was built and consisted of 20 features selected by LASSO from 1288 radiomics features in the training cohort.The multivariate logistic model and radiomics nomogram were constructed using the radiomics score and patients’age.Good discrimination of benign and malignant pulmonary nodules was obtained from the training cohort(AUC,0.836;95%confidence interval[CI]:0.793-0.879)and validation cohort(AUC,0.809;95%CI:0.745-0.872).The Hosmer-Lemeshow test also showed good performance for the logistic regression model in the training cohort(P=0.765)and validation cohort(P=0.064).Good alignment with the calibration curve indicated the good performance of the nomogram.Conclusions:The established radiomics nomogram is a noninvasive preoperative prediction tool for malignant pulmonary nodule diagnosis.Validation revealed that this nomogram exhibited excellent discrimination and calibration capacities,suggesting its clinical utility in the early screening of lung cancer.

Pericyst may be a new pharmacological and therapeutic target for hydatid disease

Background Most hydatid cysts with calcified walls are biologically and clinically silent and inactive. Transforming growth factor-beta 1 （TGF-β1） plays a critical role in the calcification process of cells. The aim of this study was to assess the effect of modulating TGF-β1 signaling on the calcification of hydatid cysts. Methods Pericyst cells isolated from hepatic hydatid cysts were cultured with osteogenic media. These cells were assessed for alkaline phosphatase activity and mineralization capacity using Alizarin Red staining. Cells were also treated with recombinant human TGF-β1 and TGF-β inhibitor, and the expression profiles of osteoblast markers （RUNX2, osterix, and osteocalcin） were analyzed using Western blotting. The effects of inhibiting TGF-β1 signaling on calcification of pericyst walls were assessed using different doses of TGF-β inhibitor for 7 weeks in a preclinical disease model of liver cystic echinococcosis. Results Cells within the pericyst displayed high levels of alkaline phosphatase activity and mineralized nodule formation, as induced by osteogenic media. These activities, as well as expression profiles of osteoblast markers （RUNX2, osterix, and osteocalcin） could be inhibited by addition of recombinant human TGF-β1 （rhTGF-β1） and enhanced by TGF-β inhibitor. In the animal model of cystic echinococcosis, inhibition of TGF-β1 signaling increased calcification of the pericyst wall, which was associated with decreased cyst load index and lower viability of protoscoleces. Conclusions Cells within the pericysts adopt an osteoblast-like phenotype and have osteogenic potential, inhibition of TGF-β1 signaling increases hydatid cyst calcification. Pharmacological modulation of calcification in pericysts may be a new therapeutic target in the treatment of hydatid disease.

Association between peroxisome proliferator-activated receptor γ gene polymorphism and susceptibility to northwest dryness syndrome

OBJECTIVE:To investigate the relationship between gene polymorphism of peroxisome proliferator-activated receptor(PPAR) and susceptibility to northwest dryness syndrome(NDS).METHODS:The polymorphisms of 11 PPARl51, rs13γ7 gene oci rs10510418, rs1263353640,rs17036188, rs2921190, rs4135247, rs4135275,rs4135283, rs6768587, rs709156, and rs7615916 were detected in 249 patients with NDS and 260 patients with non-NDS(control group) by using Snapshot single-nucleotide polymorphism typing technology.RESULTS:All locus detections were in accordance with Hardy-Weinberg equilibrium test.Compared with the control group, rs2921190 genotype frequency showed statistical difference in the NDS group(P < 0.05).Two-two comparison result showed that CC genotype frequency in the NDS group was higher than that in the control group.CT and TT genotype distribution frequencies showed differences between the two groups.The rare allele frequency in the NDS group was lower than that of the control group(P < 0.01).Multi-factor logistic regression analysis showed that the age and genotype entered the regression equation.The subjects in the age bracket 30-55 and 45-45 were1.796 and 1.561 times likely, respectively, than those in other age brackets to contract NDS,.The patients with CC genotype was only 0.524 times likely than those with CT/TT genotype to suffer from NDS.CONCLUSION:PPARsm was correlated γw gene rs2921190 polymorphiith the susceptibility to NDS.