Background and purpose:BRCA1/2 plays an important role in maintaining the genome stability.Whether BRCA1/2 germline mutation could increase the tumor sensitivity to radiotherapy,thereby inducing secondary primary cancer after radiotherapy is unclear.This study aimed to investigate whether postoperative radiotherapy is a risk factor for the development of second primary cancer in triple-negative breast cancer(TNBC)patients with BRCA1/2 germline mutation.Methods:This research was based on a previously reported retrospective cohort,i.e.,the Fudan University Shanghai Cancer Center TNBC cohort.Between January 1,2007 and December 31,2014,a total of 292 female TNBC patients with BRCA1/2 mutation were enrolled.We performed logistic regression analysis in patients without BRCA1/2 germline mutation(n=261)and BRCA1/2 germline mutation patients(n=31),respectively,to assess the risk factors affecting the incidence of second primary cancer.We then performed interactive analysis on the above two analyses to evaluate the interactive effect between BRCA1/2 germline mutation and postoperative radiotherapy.P<0.05 indicates a statistically significant difference.The research was approved by Fudan University Shanghai Cancer Center TNBC Ethics Committee(050432-4-2108),and each patient provided written informed consent.Results:Logistic regression analysis in patients with BRCA1/2 germline mutations showed that postoperative radiotherapy significantly increased the risk of secondary primary disease compared to non-radiotherapy[odds ratio(OR)=2.475,95%confidence interval(CI):1.933-3.167,P<0.001].In patients without BRCA1/2 germline mutation,the effect of radiotherapy on the incidence of second primary tumor was not significant.There was a significant interaction between BRCA1/2 germline mutation and postoperative radiotherapy for the incidence of secondary primary cancer(OR=9.710,95%CI:0.320-295.250,P=0.193).Conclusion:Although statistical analysis results show that patients with BRCA1/2 germline mutations have an increased risk of developing a second primary tumor after postoperative radiotherapy compared to patients who have not received radiotherapy,there is no significant correlation between BRCA1/2 germline mutations and radiotherapy for the development of a second primary tumor.Therefore,patients with BRCA1/2 germline mutations who receive radiotherapy after surgery may not increase the risk of developing a second primary tumor.

Objective:To explore the effect of humanistic care combined with Morita therapy on anxiety state of hemodialysis patients.Methods:A self-controlled study was conducted on 54 patients with end-stage renal disease and anxiety who received maintenance hemodialysis in China-Japan Friendship Hospital from August 2020 to August 2022. All patients were treated with humanistic care nursing and Morita therapy for one month. The Self Rating Anxiety Scale (SAS) scores of the patients before and after the intervention were compaired. The comparison of quantitative data was conducted by paired t-test, and the comparison of qualitative data was conducted by χ2 test. The correlation between different factors and anxiety was analyzed by Spearman correlation analysis. Results:Among the 54 patients, there were 26 males and 28 females, aged (61.8±16.3) years (ranging from 29 to 88 years). The SAS score after the intervention (44.0±11.1) was lower than that before the intervention (51.9±8.5) ( t=5.395, P<0.001). The anxiety of patients was related to their age ( r=0.305), employment status ( r=0.270) and marital status ( r=0.397) (all P<0.05). The satisfaction of patients with care measures and nursing before and after the intervention was 45.6% and 87.7%, respectively ( χ2=5.720, P<0.05). Conclusion:After receiving combined humanistic care nursing and Morita therapy, patients in a state of anxiety could experience significant psychological improvement, which is conducive to the successful completion of hemodialysis treatment and enhances the quality of life for patients.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.

Objective:To evaluate the effect of resveratrol on radiation-induced myocardial injury in mice.Methods:A total of 80 C57BL/6 mice were randomly divided into the control group, resveratrol (Res) group, radiation (RT) group and radiation+resveratrol (RT+Res) group. In the RT group, mice were given with heart radiation and mice in the Res group were given with resveratrol by gavage for 3 months. Cardiac ultrasound was used to evaluate cardiac function at 3 months after cardiac radiation. The hearts of mice were collected for HE staining, immunofluorescence, TUNEL staining, Masson staining and Western blot to evaluate the expression of silent information regulator 1 (SIRT1), the level of oxidative stress, inflammatory response, apoptosis and the degree of fibrosis in myocardial tissues. Experimental data were expressed as Mean ± SD. Continous data were statistically analyzed by t-test. Results:After 3 months of irradiation, compared with the control group, the ejection fraction (EF) and fractional shortening (FS) of cardiac function were decreased, and myocardial degeneration and disorder, reactive oxygen species (ROS) and inflammatory levels (interleukin-1β, interleukin-6, tumor necrosis factor-α), myocardial apoptosis (TUNEL positive cell rate) and fibrosis were increased in the RT group. In the RT+Res group, the cardiac function was improved, the expression of SIRT1 was increased, and the levels of oxidative stress, inflammation, myocardial apoptosis and fibrosis were decreased.Conclusions:Resveratrol can reduce oxidative stress, inflammatory infiltration, apoptosis and fibrosis of myocardium in mice with radiation-induced myocardial injury, thereby improving cardiac structural abnormalities and cardiac dysfunction. This protective effect can be mediated by upregulation of SIRT1 expression.

OBJECTIVE To explore the influence of Zingiber officinale and processed Z. officinale on pharmacodynamic indexes and intestinal flora on gastric ulcer rats with spleen -stomach deficiency and cold type before and after processing with sand . METHODS The SD rats were randomly divided into normal group ，model group ，positive control group （Compound tianqi weitong capsule 0.45 g/kg），Z. officinale high-dose（15.0 g/kg）and low -dose（7.5 g/kg）groups，processed Z. officinale high- dose（15.0 g/kg）and low -dose（7.5 g/kg）groups，with 10 rats in each group . The rat model of gastric ulcer with spleen -stomach deficiency and cold type was established by intragastric administration of vinegar （day 1-10）and absolute ethanol （day 11）. Administration groups were given relevant liquid intragastrically ，and normal group and model group were given water intragastrically（day 5-10）. One hour after intragastric administration of absolute ethanol ，blood was taken from the femoral artery of rats ，the serum contents of motilin （MTL），gastrin（GAS），epidermal growth factor （EGF）as well as 4 items of blood coagulation [activated partial thromboplastin time （APTT），prothrombin time （PT），thrombin time （TT），fibrinogen（FIB）] were detect. The ulcer index and inhibition rate of ulcer in gastric tissue were calculated . The pathological changes of gastric tissue were observed，and the number and area of erosions were recorded . The diversity of gut microbiota in fecal samples of rats was detected . RESULTS Compared with model group ，the contents of MTL （except for processed Z. officinale low-dose group ），GAS（except for processed Z. officinale low-dose group ），EGF（except forofficinale groups） and FIB （except for Z. officinale groups），inhibitory rate of ulcer （only positive control group ）were all increased significantly （P＜0.05）. APTT（except for Z. officinale groups），PT（only processed Z. officinale high- dose group ），TT（except for Z. officinale groups），ulcer index （except for Z. officinale groups），the number （except for Z. officinale groups）and area of erosions （except for Z. officinale groups）were shortened and decreased significantly （P＜0.05）； improvement effects of processed Z. officinale were better than those of the same dose of Z. officinale on EGF ，4 items of blood coagulation（except for PT ，TT，FIB of processed Z. officinale low-dose group ），ulcer index （except for processed Z. officinale low-dose group ）and inhibitory rate of ulcer （P＜0.05）. Compared with model group ，α diversity indexes as ACE ，Shannon and Simpson of intestinal microorganisms in rats were increased significantly in processed Z. officinale group；the relative abundance of Proteobacteria was decreased significantly in processed Z. officinale group，while that of Bacteroidetes was increased significantly （P＜0.05）； the relative abundance of Limosilactobacillus was decreased significantly in Z. officinale group （P＜0.05）. CONCLUSIONS Z. officinale and processed Z. officinale can improve the symptoms of spleen -stomach deficiency and cold ，and enhance gastrointestinal function by increasing the content of GAS and MTL . Processed Z. officinale can significantly inhibit gastric ulcer of spleen -stomach deficiency and cold type ，which is related to the promotion of mucosal protection and repair ，improvement of coagulation functionand adjustment of gut microbiotadisorder .

Objective:To investigate the establishment and application value of a radio-mics prediction model for lymph node metastasis of gallbladder carcinoma based on dual-phase enhanced computed tomography (CT).Methods:The retrospective cohort study was conducted. The clinicopathological data of 194 patients with gallbladder carcinoma who were admitted to the First Affiliated Hospital of Xi'an Jiaotong University from January 2012 to December 2020 were collected. There were 70 males and 124 females, aged (64±10)years. All patients underwent curative-intent resection of gallbladder carcinoma. A total of 194 patients were randomly divided into 156 cases in training set and 38 cases in test set according to the ratio of 8:2 based on random number method in R software. The training set was used to establish a diagnostic model, and the test set was used to validate the diagnostic model. After the patients undergoing CT examination, image analysis was performed, radiomics features were extracted, and a radiomics model was established. Based on clinicopathological data, a nomogram prediction model was established. Observation indicators: (1) lymph node dissection and histopathological examination results; (2) establishment and characteristic analysis of a radiomics prediction model; (3) analysis of influencing factors for lymph node metastasis of gallbladder carcinoma; (4) establishment of a nomogram prediction model for lymph node metastasis; (5) comparison of the predictive ability between the radiomics prediction model and nomogram prediction model for lymph node metastasis. Measurement data with normal distribution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range). Count data were expressed as absolute numbers, and comparison between groups was performed by the chi-square test. Univariate analysis was conducted by the chi-square test, and multivariate analysis was performed by the Logistic regression model forward method. The receiver operating characteristic curve was drawn, and the area under curve, decision curve, confusion matrix were used to evaluate the predictive ability of prediction models. Results:(1) Lymph node dissection and histopathological examination results. Of the 194 patients, 182 cases underwent lymph node dissection, with the number of lymph node dissected as 8(range, 1?34) per person and the number of positive lymph node as 0(range, 0?11) per person. Postoperative histopathological examination results of 194 patients: 122 patients were in stage N0, with the number of lymph node dissected as 7(range, 0?27) per person, 48 patients were in stage N1, with the number of lymph node dissected as 8(range, 2?34) per person and the number of positive lymph node as 1(range, 1?3) per person, 24 patients were in stage N2, with the number of lymph node dissected as 11(range, 2?20) per person and the number of positive lymph node as 5(range, 4?11) per person. (2) Establishment and characteristic analysis of a radiomics prediction model. There were 107 radiomics features extracted from 194 patients, including 18 first-order features, 14 shape features and 75 texture features. According to the intra-group correlation coefficient and absolute median difference of each radiomics feature, mutual information, Select K-Best, least absolute shrinkage and selection operator regression were conducted to further reduce dimensionality. By further combining 5 different machine learning algorithms including random forest, gradient boosting secession tree, support vector machine (SVM), K-Nearest Neighbors and Logistic regression, the result showed that the Select K-Best_SVM model had the best predictive performance after analysis, with the area under receiver operating characteristic curve as 0.76 in the test set. (3) Analysis of influencing factors for lymph node metastasis of gallbladder carcinoma. Results of univariate analysis showed that systemic inflammation response index, carcinoembryonic antigen (CEA), CA19-9, CA125, radiological T staging and radiological lymph node status were related factors for lymph node metastasis of patients with gallbladder cancer ( χ2=4.20, 11.39, 5.68, 11.79, 10.83, 18.58, P<0.05). Results of multivariate analysis showed that carcinoembryonic antigen, CA125, radiological T staging (stage T3 versus stage T1?2, stage T4 versus stage T1?2), radiological lymph node status were independent influencing factors for lymph node metastasis of patients with gallbladder carcinoma [ hazard ratio=2.79, 4.41, 5.62, 5.84, 3.99, 95% confidence interval ( CI) as 1.20?6.47, 1.81?10.74, 1.50?21.01, 1.02?33.31, 1.87?8.55, P<0.05]. (4) Establishment of a nomogram prediction model for lymph node metastasis. A nomogram prediction model was established based on the 4 independent influencing factors for lymph node metastasis of gallbladder carcinoma, including CEA, CA125, radiological T staging and radiological lymph node status. The concordance index of the nomogram model was 0.77 (95% CI as 0.75?0.79) in the training set and 0.73 (95% CI as 0.68?0.72) in the test set, respectively. (5) Comparison of the predictive ability between the radiomics predic-tion model and nomogram prediction model for lymph node metastasis. The receiver operating characteristic curve showed that the areas under the curve of Select K-Best_SVM radiomics model were 0.75 (95% CI as 0.74?0.76) in the training set and 0.76 (95% CI as 0.75?0.78) in the test set, respectively. The areas under the curve of nomogram prediction model were 0.77 (95% CI as 0.76?0.78) in the training set and 0.70 (95% CI as 0.68?0.72) in the test set, respectively. The decision curve analysis showed that Select K-Best_SVM radiomics model and nomogram prediction model had a similar ability to predict lymph node metastasis. The confusion matrix showed that Select K-Best_SVM radiomics model had the sensitivity as 64.29% and 75.00%, the specificity as 73.00% and 59.09% in the training set and test set, respectively. The nomogram had the sensitivity as 51.79% and 50.00%, the specificity as 80.00% and 72.27% in the training set and test set, respectively. Conclusion:A dual-phase enhanced CT imaging radiomics prediction model for lymph node metastasis of gallbladder carcinoma is successfully established, and its predictive ability is good and consistent with that of nomogram.

【Objective】 To explore the different expressions of TP53, P16 and K-ras in gallbladder high-grade intraepithelial neoplasia and early carcinoma, and establish their mutation random forest prediction model. 【Methods】 We retrospectively analyzed the clinicopathological data of 71 patients who underwent cholecystectomy at The First Affiliated Hospital of Xi’an Jiaotong University from January 2013 to December 2018, including 20 cases of chronic cholecystitis, 28 cases of gallbladder high-grade intraepithelial neoplasia, and 23 cases of early gallbladder carcinoma. The immunohistochemical SP method was conducted to detect the expressions of TP53, P16 and K-ras in the gallbladder pathological tissues; the correlation between the above genes and clinicopathological data was analyzed. A random forest prediction model of each gene mutation was established based on the clinicopathological data and gene expression. 【Results】 The positive expressions of TP53, P16 and K-ras were related to the gallbladder with cholecystolithiasis or polyps and gallbladder pathological tissue type. The positive rates of the three genes in the gallbladder polyps were significantly higher than those in the cholecystolithiasis group (P<0.05). The positive rates of the three genes in the latter two groups of gallbladder high-grade intraepithelial neoplasia and early gallbladder carcinoma were significantly higher than those in the chronic cholecystitis (P<0.05), while there was no statistical difference between the latter two groups (P>0.05). The mutations of TP53, P16 and K-ras had a certain correlation (χ²=6.285, 19.595, 4.070, r=0.298, 0.525, 0.239, P<0.05). TP53, P16 and K-ras mutation prediction models based on random forest had good accuracy (AUC=77.42%, 80.06%, 71.75%, accuracy=76.06%, 76.06%, 67.61%). 【Conclusion】 TP53, P16 and K-ras gene mutations promote the transformation of chronic cholecystitis to gallbladder carcinoma. The mutation prediction model based on random forest has a good accuracy, which can provide an important reference for carcinogenesis and early diagnosis of gallbladder carcinoma.

Objective:To examine a survival prognostic model applicable for patients with intrahepatic cholangiocarcinoma (ICC) based on Bayesian network.Methods:The clinical and pathological data of ICC patients who underwent curative intent resection in ten Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected.A total of 516 patients were included in the study. There were 266 males and 250 females.The median age( M( Q R)) was 58(14) years.One hundred and sixteen cases (22.5%) with intrahepatic bile duct stones,and 143 cases (27.7%) with chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis.The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.One-year survival prediction models based on tree augmented naive Bayesian (TAN) and na?ve Bayesian algorithm were established by Bayesialab software according to different variables,a nomogram model was also developed based on the independent predictors.The receiver operating characteristic curve and the area under curve (AUC) were used to evaluate the prediction effect of the models. Results:The overall median survival time was 25.0 months,and the 1-,3-and 5-year cumulative survival rates was 76.6%,37.9%,and 21.0%,respectively.Univariate analysis showed that gender,preoperative jaundice,pathological differentiation,vascular invasion,microvascular invasion,liver capsule invasion,T staging,N staging,margin,intrahepatic bile duct stones,carcinoembryonic antigen,and CA19-9 affected the prognosis(χ 2=5.858-54.974, all P<0.05).The Cox multivariate model showed that gender,pathological differentiation,liver capsule invasion, T stage,N stage,intrahepatic bile duct stones,and CA19-9 were the independent predictive factors(all P<0.05). The AUC of the TAN model based on all 19 clinicopathological factors was 74.5%,and the AUC of the TAN model based on the 12 prognostic factors derived from univariate analysis was 74.0%,the AUC of the na?ve Bayesian model based on 7 independent prognostic risk factors was 79.5%,the AUC and C-index of the nomogram survival prediction model based on 7 independent prognostic risk factors were 78.8% and 0.73,respectively. Conclusion:The Bayesian network model may provide a relatively accurate prognostic prediction for ICC patients after curative intent resection and performed superior to the nomogram model.

Objective:To evaluate the related factors of gallstones related gallbladder intraepithelial neoplasia(GBIN) and establish the prediction models for gallstones related GBIN.Methods:The clinicopathological data of 750 patients who underwent cholecystectomy for gallstones at Department of Hepatobiliary Surgery of the First Affiliated Hospital of Xi′an Jiaotong University from January 2013 to December 2018 and the postoperative pathological examination showed chronic cholecystitis or GBIN were analyzed retrospectively,including 150 cases of gallstones with GBIN and 600 cases of gallstones with chronic cholecystitis.There were 264 males and 486 females with age of (51.3±14.5) years (range: 18 to 90 years).The related factors for gallstones related GBIN were screened by χ 2 test and Logistic regression model,and the prediction models were established based on independent related factors and internal validation was conducted.The original data were randomly divided into a training cohort(526 cases) and a validation cohort(224 cases) at a ratio of 7∶3,and the nomogram and tree augmented na?ve Bayes were conducted to establish the prediction model for gallstones related GBIN.The consistency index(C-index),calibration chart,area under the receiver operating characteristic curve(AUC) and confusion matrix were used to evaluate the prediction performance of the two models. Results:Univariate analysis showed that age,gallstones history(years),gallbladder size,whether the gallbladder mucosa smooth or not,whether the gallbladder wall thickened or not,gallstones diameter,and number of gallstones were related factors for the occurrence of gallstones related GBIN (χ2=19.957,8.599,9.724,9.301,8.341,15.288,9.169,all P<0.05).Multivariate analysis showed that age ( OR=2.23,95% CI:1.50-3.31, P<0.01),gallbladder size ( OR=2.11,95% CI:1.17-3.80, P=0.013),whether the gallbladder mucosa smooth or not ( OR=1.80,95% CI:1.13-2.88, P=0.014),gallstones diameter( OR=2.98,95% CI:1.71-5.21, P<0.01),and number of gallstones ( OR=2.14,95% CI:1.34-3.42, P<0.01) were independent related factors for the occurrence of gallstones related GBIN; the C-index of the nomogram in training cohort and validation cohort were 0.708 and 0.696,respectively.The AUC of the two models in training cohort were 70.60% and 70.73%,and in validation cohort were 68.14% and 67.47%,respectively.The accuracy of the two models in training cohort were 69.96% and 70.72%,and in validation cohort were 66.96% and 67.41%,respectively. Conclusion:Age,gallbladder size,whether the gallbladder mucosa smooth or not,gallstones diameter and number of gallstones are independent related factors for the occurrence of gallstones related GBIN,and the nomogram and tree augmented na?ve Bayes prediction models based on the above factors can be used to predict the occurrence of GBIN.

Objective:To examine a survival prognostic model applicable for patients with intrahepatic cholangiocarcinoma (ICC) based on Bayesian network.Methods:The clinical and pathological data of ICC patients who underwent curative intent resection in ten Chinese hepatobiliary surgery centers from January 2010 to December 2018 were collected.A total of 516 patients were included in the study. There were 266 males and 250 females.The median age( M( Q R)) was 58(14) years.One hundred and sixteen cases (22.5%) with intrahepatic bile duct stones,and 143 cases (27.7%) with chronic viral hepatitis.The Kaplan-Meier method was used for survival analysis.The univariate and multivariate analysis were implemented respectively using the Log-rank test and Cox proportional hazard model.One-year survival prediction models based on tree augmented naive Bayesian (TAN) and na?ve Bayesian algorithm were established by Bayesialab software according to different variables,a nomogram model was also developed based on the independent predictors.The receiver operating characteristic curve and the area under curve (AUC) were used to evaluate the prediction effect of the models. Results:The overall median survival time was 25.0 months,and the 1-,3-and 5-year cumulative survival rates was 76.6%,37.9%,and 21.0%,respectively.Univariate analysis showed that gender,preoperative jaundice,pathological differentiation,vascular invasion,microvascular invasion,liver capsule invasion,T staging,N staging,margin,intrahepatic bile duct stones,carcinoembryonic antigen,and CA19-9 affected the prognosis(χ 2=5.858-54.974, all P<0.05).The Cox multivariate model showed that gender,pathological differentiation,liver capsule invasion, T stage,N stage,intrahepatic bile duct stones,and CA19-9 were the independent predictive factors(all P<0.05). The AUC of the TAN model based on all 19 clinicopathological factors was 74.5%,and the AUC of the TAN model based on the 12 prognostic factors derived from univariate analysis was 74.0%,the AUC of the na?ve Bayesian model based on 7 independent prognostic risk factors was 79.5%,the AUC and C-index of the nomogram survival prediction model based on 7 independent prognostic risk factors were 78.8% and 0.73,respectively. Conclusion:The Bayesian network model may provide a relatively accurate prognostic prediction for ICC patients after curative intent resection and performed superior to the nomogram model.