Objective:To investigate the risk factors and their warning effectiveness for postoperative intestinal barrier dysfunction (IBD) in patients with severe traumatic brain injury (sTBI).Methods:A retrospective cohort study was conducted to analyze the clinical data of 101 patients with sTBI admitted to Wuxi Branch of Zhongda Hospital Affiliated to Southeast University from May 2020 to February 2023, including 63 males and 38 females, aged 21-81 years [(53.4±14.2)years]. All the patients underwent emergency surgery. The patients were divided into IBD group ( n=67) and non-IBD group ( n=34) according to whether or not they had IBD after surgery. The gender, age, basic diseases (hypertension and diabetes), types of intracranial hematoma (subdural, epidural, and intracerebral hematoma), preoperative Glasgow Coma Scale (GCS), cerebral hernia, intraoperative initial intracranial pressure (iICP), operation time, removal of bone flap, treatment time in ICU, initiation time of enteral nutrition, and use of broad-spectrum antibiotics were recorded in the two groups. Univariate and multivariate binary Logistic regression analyses were conducted to assess the correlations between above-mentioned indicators and incidence of postoperative IBD in sTBI patients and determine the independent risk factors for sTBI. Receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to evaluate the warning effectiveness of each risk factor for IBD. Results:The results of the univariate analysis showed that preoperative GCS, cerebral hernia, intraoperative iICP, removal of bone flap, treatment time in ICU, initiation time of enteral nutrition, and use of broad-spectrum antibiotics were significantly correlated with the incidence of IBD in sTBI patients ( P<0.05 or 0.01), while there were no correlations of IBD with gender, age, basic diseases, types of intracranial hematoma and operation time ( P>0.05). The results of the multivariate binary Logistic regression analysis showed that preoperative GCS≤5 points ( OR=2.49, 95% CI 1.17, 5.32, P<0.05), intraoperative iICP>23 mmHg (1 mmHg=0.133 kPa)( OR=1.20, 95% CI 1.03, 1.39, P<0.05), and initiation time of enteral nutrition>24 hours ( OR=10.03, 95% CI 1.26, 80.21, P<0.05) were highly correlated with postoperative IBD in sTBI patients. The results of the ROC curve analysis showed that intraoperative iICP had the highest warning value (AUC=0.91, 95% CI 0.85, 0.96), followed by preoperative GCS (AUC=0.88, 95% CI 0.82, 0.95), and initiation time of enteral nutrition had the lowest warning value (AUC=0.78, 95% CI 0.69, 0.87). Conclusions:Preoperative GCS≤5 points, intraoperative iICP>23 mmHg, and initiation time of enteral nutrition>24 hours are independent risk factors for postoperative IBD in sTBI patients. The warning value of intraoperative iICP ranks the highest for postoperative IBD in sTBI patients, followed by preoperative GCS, with initiation time of enteral nutrition having the lowest warning value.

Objective:To predict the status of microvascular invasion (MVI) in intrahepatic cholangiocarcinoma (ICC) patients preoperatively based on the radiomics analysis of contrast-enhanced CT to provide imaging evidence for early identification of patients at high risk of recurrence.Methods:Clinical data of 40 ICC patients who underwent radical hepatectomy at Nanjing Drum Tower Hospital from January 2021 to May 2024 were retrospectively collected. Patients were divided into the MVI group ( n=8) and the non-MVI group ( n=32) according to the MVI status of the postoperative pathology report. Whether there were differences in each pathological index between the groups and the efficacy of radiomics analysis of contrast-enhanced CT for the preoperative prediction of MVI were analyzed. The regions of interest (ROI) were outlined on the arterial and venous phase images using the 3D Slicer software. Then, radiomics features were extracted from each ROI based on Python. Finally, the LASSO regression and glm function were used to screen radiomics features and establish a prediction model based on the R language. The established predictive model′s diagnostic efficacy, calibration, and net clinical benefit were evaluated using the receiver operating characteristic (ROC) curve, calibration curve, and decision curve analysis (DCA), respectively. Normally distributed measurement data were expressed as mean±standard deviation ( ± s) and compared using the t-test. Count data were expressed as frequency and compared using the chi-square test. Results:Patients in the MVI group had more poorly differentiated tumors and a significantly higher proportion of lymph node metastases ( P<0.05). The established radiomics prediction model included six features, 1 first-order statistical feature and 5 gray texture features. The area under the ROC curve was 0.87, the sensitivity was 75.0%, and the specificity was 90.6%. The calibration curve showed good agreement between the predicted MVI and actual MVI status, and the decision curve demonstrated that the model could provide a large net clinical benefit. Conclusion:Radiomics analysis of contrast-enhanced CT can identify the MVI status of ICC patients preoperatively and aid in clinical decision-making, providing vital evidence for individualized and precise treatment of ICC.

Approximately 140 million people worldwide are homozygous carriers of APOE4 (ε4), a strong genetic risk factor for late onset familial and sporadic Alzheimer's disease (AD), 91% of whom will develop AD at earlier age than heterozygous carriers and noncarriers. Susceptibility to AD could be reduced by targeted editing of APOE4, but a technical basis for controlling the off-target effects of base editors is necessary to develop low-risk personalized gene therapies. Here, we first screened eight cytosine base editor variants at four injection stages (from 1- to 8-cell stage), and found that FNLS-YE1 variant in 8-cell embryos achieved the comparable base conversion rate (up to 100%) with the lowest bystander effects. In particular, 80% of AD-susceptible ε4 allele copies were converted to the AD-neutral ε3 allele in human ε4-carrying embryos. Stringent control measures combined with targeted deep sequencing, whole genome sequencing, and RNA sequencing showed no DNA or RNA off-target events in FNLS-YE1-treated human embryos or their derived stem cells. Furthermore, base editing with FNLS-YE1 showed no effects on embryo development to the blastocyst stage. Finally, we also demonstrated FNLS-YE1 could introduce known protective variants in human embryos to potentially reduce human susceptivity to systemic lupus erythematosus and familial hypercholesterolemia. Our study therefore suggests that base editing with FNLS-YE1 can efficiently and safely introduce known preventive variants in 8-cell human embryos, a potential approach for reducing human susceptibility to AD or other genetic diseases.
Humans ; Apolipoprotein E4/genetics* ; Cytosine ; Mutation ; Blastocyst ; Heterozygote ; Gene Editing ; CRISPR-Cas Systems

We reviewed and developed an indicator system framework for assessing teaching effect of laparoscopic simulation training through literature research, expert consultation, analytic hierarchy process and factor analysis. We also made an empirical study on the constructed index system. The system included 3 domains (A1: evaluation of laparoscopic simulator; A2: operation evaluation of experimental animals; A3: evaluation of clinical practice), 10 second-level indicators and 23 third-level indicators for assessing teaching effect of laparoscopic simulation training. The indicator system framework has good internal consistency (Cronbach α= 0.968) and external consistency (>0.72). The empirical study found that: in the results of A1-A3 in the first level indicator, the score of the experienced group was significantly higher than that of the inexperienced group ( P<0.05). In the evaluation results of the 10 secondary indicators in the secondary indicators B1-B10, the score of the experienced group was significantly higher than that of the inexperienced group ( P<0.01). For the first time, we have established and evaluated a comprehensive evaluation indicator system which is reliable and effective and can be used for further evaluation of teaching effect of laparoscopic simulation training. The following empirical studies have verified the effectiveness and practicability of the evaluation system.

Objective:To understand the mastery of occupational hygienic knowledge and the implementing of occupational health protection measures in the group which were exposed to the procedure of manufacture and use in glass fiber company, and to explore the feasibility of the prevention of the skin injury by occupational health education in glass fiber workers.Methods:We selected 257 on-the-job employees as the research object in a ceramic enterprise in Nanjing from June 2018 to August 2019, with the method of cluster random sampling. According to Solomon's design, the intervention group in which we took measures with health education was divided into RG 1 (O 1XO 2) and RG 3 (XO 5) group, and the control group where we didn't take any intervention was divided into RG 2 (O 3-O 4) and RG 4 (-O 6) group. The intervention effect of health education on the occupational protection of glass fiber workers was evaluated by the results of questionnaire. Results:After training, the average score of occupational health knowledge in the intervention group was 27.34 points higher than that before training, the intervention index was 1.42, 23.62-27.73 points higher than the control glass fiber workers and 33.62-35.52 points higher than the control glass non-glass fiber workers; Compared with the control group, the positive attitude rate of fiber glass workers in the intervention group increased by 13.28%, 13.51%, 11.68% and 11.48%, and the intervention indexes were 1.18, 1.17, 1.14 and 1.15, which was corresponding to using protective cream, wearing gloves, wearing working clothes, washing hands and bathing after work, respectively; Compared with the control group, the implementation rate of occupational protection measures which were represented by wearing gloves、washing hands and bathing for glass fiber workers in the intervention group increased by 29.25% and 7.27% respectively, and the intervention indexes were 1.43 and 1.08 respectively; The skin injury rate of fiberglass workers in the intervention group was reduced by 11.43% comparing to the control group, the intervention index was 1.67.Conclusion:According to the occupational health education of fiberglass workers, it improves the mastery of occupational health knowledge, positive atti-tude rate and the implementation rate of occupational protection measures, meanwhile, it reduces the skin injury rate of the intervention objects to a certain extent.

Objective:To understand the mastery of occupational hygienic knowledge and the implementing of occupational health protection measures in the group which were exposed to the procedure of manufacture and use in glass fiber company, and to explore the feasibility of the prevention of the skin injury by occupational health education in glass fiber workers.Methods:We selected 257 on-the-job employees as the research object in a ceramic enterprise in Nanjing from June 2018 to August 2019, with the method of cluster random sampling. According to Solomon's design, the intervention group in which we took measures with health education was divided into RG 1 (O 1XO 2) and RG 3 (XO 5) group, and the control group where we didn't take any intervention was divided into RG 2 (O 3-O 4) and RG 4 (-O 6) group. The intervention effect of health education on the occupational protection of glass fiber workers was evaluated by the results of questionnaire. Results:After training, the average score of occupational health knowledge in the intervention group was 27.34 points higher than that before training, the intervention index was 1.42, 23.62-27.73 points higher than the control glass fiber workers and 33.62-35.52 points higher than the control glass non-glass fiber workers; Compared with the control group, the positive attitude rate of fiber glass workers in the intervention group increased by 13.28%, 13.51%, 11.68% and 11.48%, and the intervention indexes were 1.18, 1.17, 1.14 and 1.15, which was corresponding to using protective cream, wearing gloves, wearing working clothes, washing hands and bathing after work, respectively; Compared with the control group, the implementation rate of occupational protection measures which were represented by wearing gloves、washing hands and bathing for glass fiber workers in the intervention group increased by 29.25% and 7.27% respectively, and the intervention indexes were 1.43 and 1.08 respectively; The skin injury rate of fiberglass workers in the intervention group was reduced by 11.43% comparing to the control group, the intervention index was 1.67.Conclusion:According to the occupational health education of fiberglass workers, it improves the mastery of occupational health knowledge, positive atti-tude rate and the implementation rate of occupational protection measures, meanwhile, it reduces the skin injury rate of the intervention objects to a certain extent.

Objective:To investigate the risk factors for Gleason score upgrading after radical prostatectomy in clinical low-risk prostate cancer patients aged≥65 years.Methods:A total of 485 clinical low-risk prostate cancer patients aged≥65 years at five centers of the national multi-center PC-follow database from January 2015 to March 2019 were retrospectively analyzed.Data including age at diagnosis, prostate-specific antigen(PSA), MRI prostate imaging, puncture Gleason score, operation method, puncture method, positive incision margin and capsule penetration were collected.Differences in Gleason scores before and after operation were compared, and the risk factors for Gleason score upgrading after radical resection were evaluated by univariate and multivariate Logistic regression analysis.Results:Of 485 patients with a puncture Gleason score of 3+ 3=6, 261(53.8%)cases had postoperative pathological upgrading, in whom 228(87.4%)cases had Gleason score upgrading of 7, 22(8.4%)had Gleason score upgrading of 8, and 11(4.2%)had Gleason score upgrading of 9 or more.The rate of Gleason score upgrading was elevated with increased preoperative PSA levels, positive pelvic MRI, and higher positive rates of puncture biopsy.The incidences of postoperative capsule penetration(27.2% vs.12.5%, P<0.001)and positive incision margin(25.2% vs.17.4%, P=0.036)had statistically significant differences between the pathologically upgraded group and the pathologically non-upgraded group.Multivariate analysis showed that preoperative PSA level, percentage of positive puncture biopsies, biopsy Gleason score and pelvic MRI were independent predictors of prostate cancer. Conclusions:For clinical low-risk prostate cancer patients aged≥65 years with high risk factors for Gleason score upgrading, repeated biopsies should be carried out when necessary and the treatment plan should be adjusted accordingly.

Objective:To establish a nomogram model for predicting positive resection margins after prostate cancer surgery, and to perform the corresponding verification, in order to predict the risk of positive resection margins after surgery.Methods:A total of 2 215 prostate cancer patients from The First Affiliated Hospital of Naval Medical University, Hospital, Peking University First Hospital, Peking University Third Hospital, Peking University, and First Affiliated Hospital of Xi′an Jiaotong University were included in the PC-follow database from 2015 to 2018, and a simple random sampling method was used. They were divided into 1 770 patients in the modeling group and 445 patients in the verification group. In the modeling group, the age (<60 years, 60 to 70 years, >70 years), PSA (<4 ng/ml, 4-10 ng/ml, 11-20 ng/ml, >20 ng/ml), pelvic MRI (negative, suspicious, positive), clinical stage of the tumor (T 1-T 2, ≥T 3), percentage of positive needles (≤33%, 34%-66%, >66%), Gleason score of biopsy pathology (≤6 points, 7 points, ≥8 points). Univariate and multivariate logistic analysis were performed to screen meaningful indicators to construct a nomogram model. The model was used for validation in the validation group. Results:The results of multivariate analysis showed that preoperative PSA level ( OR=2.046, 95% CI 1.022 to 4.251, P=0.009), percentage of puncture positive needles ( OR=1.502, 95% CI 1.136 to 1.978, P=0.002), Gleason score of puncture pathology ( OR=1.568, 95% CI 1.063 to 2.313, P=0.028), pelvic MRI were correlated ( OR=1.525, 95% CI 1.160 to 2.005, P=0.033). Establish a nomogram model for independent predictors of positive margin of prostate cancer. The area under the receiver operating characteristic (ROC) curve of the validation group is 0.776. The area under the ROC curve of the preoperative PSA level, percentage of puncture positive needles, puncture pathology Gleason score, pelvic MRI, postoperative pathology Gleason score were 0.554, 0.615, 0.556, 0.522, and 0.560, respectively. The difference between the nomogram model and other indicators was statistically significant ( P<0.05). Conclusions:The constructed nomogram model has higher diagnostic value than the preoperative PSA level, percentage of puncture positive needles, Gleason score of puncturing pathology, pelvic MRI, and postoperative pathological Gleason score in predicting positive margin.

Objective:To summarize the effect of thoracoscopy for infants with double aortic arch malformation.Methods:The clinical data of 10 infants with double aortic arch malformation from January 2015 to May 2019 were retrospectively summarized, including 7 boys and 3 girls aged from 2 hours to 8 months, 9 with right arch dominance and 1 with left arch dominance. MRI examination was performed at 35 weeks before birth to understand the relationship between vascular ring and trachea and esophagus. Postnatal surgery was performed when trachea compression exceeded one third, and selective operation was performed around six months after birth if the compression was less than one third.Results:All the 10 cases underwent thoracoscopic surgery, and 1 case underwent thoracotomy because oxygen saturation could not be maintained. The operation time was 80-135 minutes, with an average of 100 minutes. Intraoperative bleeding was about 5-10 ml. Postoperative ventilator support time was 4-14 days. 1 patient was cured and discharged except that he gave up treatment for economic reasons. Postoperative follow-up period was 1-6 months. No difficulty in eating, no difficulty in breathing required tracheal stenosis surgery again. 4 patients needed ventilator support for more than 7 days, 2 patients developed pneumothorax and were cured after drainage. One patient presented hoarseness.Conclusion:Prenatal examination can improve the diagnosis rate of double aortic arch deformity, early intervention follow-up in pediatric surgery can reduce the incidence of related complications in children, and thoracoscopic surgery is feasible to correct the deformity, with small trauma and Less bleeding.