Objective:To investigate the value of biparametric-MRI (bpMRI) based peritumoral radiomics for preoperative prediction of extraprostatic extension (EPE) in prostate cancer (PCa).Methods:In this cross-sectional study, consecutive bpMRI of patients undergoing prostatectomy for PCa were retrospectively collected from the First Medical Center (center 1) and the Third Medical Center (center 2) of Chinese PLA General Hospital. A total of 274 patients were finally enrolled. Patients at center 1 from January 2020 to December 2022 were randomly divided into a training set (149 cases) and an internal validation set (63 cases) by stratified random sampling. Patients at center 2 from January 2023 to March 2024 were assigned to the external test set (62 cases). Patients were categorized into EPE-positive group and EPE-negative group according to pathological assessment postoperatively. In the training set, there were 49 cases in EPE-positive group and 100 cases in EPE-negative group. In the internal validation set, there were 26 cases in EPE-positive group and 37 cases in EPE-negative group. In the external test set, there were 22 cases in EPE-positive group and 40 cases in EPE-negative group. Axial T 2WI and apparent diffusion coefficient (ADC) images were manually annotated to obtain index lesion regions of interest (ROIs), with the peritumoral ROIs subsequently delineated by semi-automatic segmentation technique. Radiomics features were extracted from intra-tumoral, peri-tumoral, and intra-tumoral plus peri-tumoral ROIs. The training set data was employed to select and optimize features to build the radiomics models. The logistic regression analysis was used to develop radiomics, clinical, and integrated models. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC) in the external test set, and compared by the DeLong test. The sensitivity and specificity were compared by the exact McNemar test. Results:In the external test set, the peri-tumoral radiomics model based on bpMRI showed the highest performance in evaluating EPE, with an AUC of 0.739 (95% CI 0.611-0.842), which was identified as the optimal radiomics model. EPE grade ( OR=6.151, 95% CI 3.371-11.226, P<0.001) was incorporated into the clinical model, with an AUC of 0.780 (95% CI 0.657-0.875) in the external test set. The integrated model had an AUC of 0.817 (95% CI 0.698-0.904) in the external test set. There was no statistically significant difference in comparisons of AUCs among the three models (all P>0.05). The sensitivity of the integrated model (68.2%) showed no significant difference from those of the clinical model and the optimal radiomics model (77.3% and 86.4%, respectively; P=0.500 and P=0.289). However, the specificity of the integrated model (85.0%) was significantly higher than those of the clinical model (67.5%, P=0.016) and the optimal radiomics model (50.0%, P<0.001). Conclusion:A bpMRI-based peritumoral radiomics integrating clinical model demonstrates high performance for preoperative prediction of EPE in PCa.

BACKGROUND:Degeneration of nucleus pulposus cells is a key component of intervertebral disc degeneration.Ferroptosis,a novel form of programmed cell death,is closely associated with the onset and progression of intervertebral disc degeneration;however,its precise mechanisms remain unclear.OBJECTIVE:To establish an oxidative stress model in vitro by inducing ferroptosis in nucleus pulposus cells using tert-butyl hydroperoxide and to investigate the mechanisms of tert-butyl hydroperoxide-induced ferroptosis in nucleus pulposus cells,thereby elucidating the role of ferroptosis in the pathogenesis of intervertebral disc degeneration.METHODS:Nucleus pulposus cells were treated with varying concentrations of tert-butyl hydroperoxide(0,25,50,100,and 200 μmol/L),and cell morphology and viability were assessed using fluorescence microscopy and the cell counting kit-8 assay.Interventions with 100 μmol/L tert-butyl hydroperoxide,10 μmol/L RSL3,or dimethylsulfoxide were applied to nucleus pulposus cells,and cell proliferation was evaluated using the EdU assay.The expression levels of ferroptosis-related proteins(glutathione peroxidase 4,ferritin heavy chain 1,PTGS2,and ACSL4)and intervertebral disc degeneration marker proteins(matrix metalloproteinase 13 and Col2A)were analyzed via western blot and immunofluorescence.Additionally,reactive oxygen species and lipid peroxidation levels were quantified using the reactive oxygen species detection kit and C11-BODIPY probe.Mitochondrial morphological changes were observed under transmission electron microscopy.RESULTS AND CONCLUSION:(1)tert-Butyl hydroperoxide treatment significantly reduced the viability and proliferation of nucleus pulposus cells.(2)tert-Butyl hydroperoxide induced typical ferroptosis-related morphological changes in nucleus pulposus cells.(3)tert-Butyl hydroperoxide exposure led to a decrease in the expression of ferroptosis-suppressing proteins glutathione peroxidase 4 and ferritin heavy chain 1,while increasing the expression of ferroptosis-promoting factors ACSL4 and PTGS2.(4)tert-Butyl hydroperoxide elevated intracellular reactive oxygen species production and lipid peroxidation levels in nucleus pulposus cells.(5)Transmission electron microscopy revealed ferroptosis-specific mitochondrial changes in nucleus pulposus cells treated with tert-butyl hydroperoxide,including contraction,reduced cristae,and increased membrane density.(6)tert-Butyl hydroperoxide treatment also resulted in the increased expression of matrix metalloproteinase 13 and decreased expression of Col2A in nucleus pulposus cells.In conclusion,tert-butyl hydroperoxide induces ferroptosis in nucleus pulposus cells,contributing to the development of intervertebral disc degeneration.This process may represent a key pathological mechanism in intervertebral disc degeneration and offers potential targets for developing novel therapeutic strategies.

Objective:To investigate the value of biparametric-MRI (bpMRI) based peritumoral radiomics for preoperative prediction of extraprostatic extension (EPE) in prostate cancer (PCa).Methods:In this cross-sectional study, consecutive bpMRI of patients undergoing prostatectomy for PCa were retrospectively collected from the First Medical Center (center 1) and the Third Medical Center (center 2) of Chinese PLA General Hospital. A total of 274 patients were finally enrolled. Patients at center 1 from January 2020 to December 2022 were randomly divided into a training set (149 cases) and an internal validation set (63 cases) by stratified random sampling. Patients at center 2 from January 2023 to March 2024 were assigned to the external test set (62 cases). Patients were categorized into EPE-positive group and EPE-negative group according to pathological assessment postoperatively. In the training set, there were 49 cases in EPE-positive group and 100 cases in EPE-negative group. In the internal validation set, there were 26 cases in EPE-positive group and 37 cases in EPE-negative group. In the external test set, there were 22 cases in EPE-positive group and 40 cases in EPE-negative group. Axial T 2WI and apparent diffusion coefficient (ADC) images were manually annotated to obtain index lesion regions of interest (ROIs), with the peritumoral ROIs subsequently delineated by semi-automatic segmentation technique. Radiomics features were extracted from intra-tumoral, peri-tumoral, and intra-tumoral plus peri-tumoral ROIs. The training set data was employed to select and optimize features to build the radiomics models. The logistic regression analysis was used to develop radiomics, clinical, and integrated models. The predictive performance was assessed by the area under the receiver operating characteristic curve (AUC) in the external test set, and compared by the DeLong test. The sensitivity and specificity were compared by the exact McNemar test. Results:In the external test set, the peri-tumoral radiomics model based on bpMRI showed the highest performance in evaluating EPE, with an AUC of 0.739 (95% CI 0.611-0.842), which was identified as the optimal radiomics model. EPE grade ( OR=6.151, 95% CI 3.371-11.226, P<0.001) was incorporated into the clinical model, with an AUC of 0.780 (95% CI 0.657-0.875) in the external test set. The integrated model had an AUC of 0.817 (95% CI 0.698-0.904) in the external test set. There was no statistically significant difference in comparisons of AUCs among the three models (all P>0.05). The sensitivity of the integrated model (68.2%) showed no significant difference from those of the clinical model and the optimal radiomics model (77.3% and 86.4%, respectively; P=0.500 and P=0.289). However, the specificity of the integrated model (85.0%) was significantly higher than those of the clinical model (67.5%, P=0.016) and the optimal radiomics model (50.0%, P<0.001). Conclusion:A bpMRI-based peritumoral radiomics integrating clinical model demonstrates high performance for preoperative prediction of EPE in PCa.

BACKGROUND:Degeneration of nucleus pulposus cells is a key component of intervertebral disc degeneration.Ferroptosis,a novel form of programmed cell death,is closely associated with the onset and progression of intervertebral disc degeneration;however,its precise mechanisms remain unclear.OBJECTIVE:To establish an oxidative stress model in vitro by inducing ferroptosis in nucleus pulposus cells using tert-butyl hydroperoxide and to investigate the mechanisms of tert-butyl hydroperoxide-induced ferroptosis in nucleus pulposus cells,thereby elucidating the role of ferroptosis in the pathogenesis of intervertebral disc degeneration.METHODS:Nucleus pulposus cells were treated with varying concentrations of tert-butyl hydroperoxide(0,25,50,100,and 200 μmol/L),and cell morphology and viability were assessed using fluorescence microscopy and the cell counting kit-8 assay.Interventions with 100 μmol/L tert-butyl hydroperoxide,10 μmol/L RSL3,or dimethylsulfoxide were applied to nucleus pulposus cells,and cell proliferation was evaluated using the EdU assay.The expression levels of ferroptosis-related proteins(glutathione peroxidase 4,ferritin heavy chain 1,PTGS2,and ACSL4)and intervertebral disc degeneration marker proteins(matrix metalloproteinase 13 and Col2A)were analyzed via western blot and immunofluorescence.Additionally,reactive oxygen species and lipid peroxidation levels were quantified using the reactive oxygen species detection kit and C11-BODIPY probe.Mitochondrial morphological changes were observed under transmission electron microscopy.RESULTS AND CONCLUSION:(1)tert-Butyl hydroperoxide treatment significantly reduced the viability and proliferation of nucleus pulposus cells.(2)tert-Butyl hydroperoxide induced typical ferroptosis-related morphological changes in nucleus pulposus cells.(3)tert-Butyl hydroperoxide exposure led to a decrease in the expression of ferroptosis-suppressing proteins glutathione peroxidase 4 and ferritin heavy chain 1,while increasing the expression of ferroptosis-promoting factors ACSL4 and PTGS2.(4)tert-Butyl hydroperoxide elevated intracellular reactive oxygen species production and lipid peroxidation levels in nucleus pulposus cells.(5)Transmission electron microscopy revealed ferroptosis-specific mitochondrial changes in nucleus pulposus cells treated with tert-butyl hydroperoxide,including contraction,reduced cristae,and increased membrane density.(6)tert-Butyl hydroperoxide treatment also resulted in the increased expression of matrix metalloproteinase 13 and decreased expression of Col2A in nucleus pulposus cells.In conclusion,tert-butyl hydroperoxide induces ferroptosis in nucleus pulposus cells,contributing to the development of intervertebral disc degeneration.This process may represent a key pathological mechanism in intervertebral disc degeneration and offers potential targets for developing novel therapeutic strategies.

Background::Artificial intelligence (AI) technology represented by deep learning has made remarkable achievements in digital pathology, enhancing the accuracy and reliability of diagnosis and prognosis evaluation. The spatial distribution of CD3 + and CD8 + T cells within the tumor microenvironment has been demonstrated to have a significant impact on the prognosis of colorectal cancer (CRC). This study aimed to investigate CD3 CT (CD3 + T cells density in the core of the tumor [CT]) prognostic ability in patients with CRC by using AI technology. Methods::The study involved the enrollment of 492 patients from two distinct medical centers, with 358 patients assigned to the training cohort and an additional 134 patients allocated to the validation cohort. To facilitate tissue segmentation and T-cells quantification in whole-slide images (WSIs), a fully automated workflow based on deep learning was devised. Upon the completion of tissue segmentation and subsequent cell segmentation, a comprehensive analysis was conducted.Results::The evaluation of various positive T cell densities revealed comparable discriminatory ability between CD3 CT and CD3-CD8 (the combination of CD3 + and CD8 + T cells density within the CT and invasive margin) in predicting mortality (C-index in training cohort: 0.65 vs. 0.64; validation cohort: 0.69 vs. 0.69). The CD3 CT was confirmed as an independent prognostic factor, with high CD3 CT density associated with increased overall survival (OS) in the training cohort (hazard ratio [HR] = 0.22, 95% confidence interval [CI]: 0.12–0.38, P <0.001) and validation cohort (HR = 0.21, 95% CI: 0.05–0.92, P = 0.037). Conclusions::We quantify the spatial distribution of CD3 + and CD8 + T cells within tissue regions in WSIs using AI technology. The CD3 CT confirmed as a stage-independent predictor for OS in CRC patients. Moreover, CD3 CT shows promise in simplifying the CD3-CD8 system and facilitating its practical application in clinical settings.

Objective:To summarize the experience of robot-assisted enucleation of tumors located in uncinate process of pancreas.Methods:This is a retrospective case series study. The clinical data of patients with robot-assisted enucleation of tumors located in the uncinate process of pancreas at the Department of Gastroenterology and Pancreatic Surgery,Zhejiang Provincial People′s Hospital from June 2019 to December 2023 were retrospectively analyzed. A total of 16 cases were enrolled,including 10 males and 6 females,with an age( M(IQR)) of 56(21)years (range: 28 to 77 years),and body mass index of 22.4(2.3)kg/m 2 (range:19.8 to 25.6 kg/m 2). Follow-up was asked every 6 to 12 months after the first 3-month postoperative follow-up through out-patient service or via telephone. Results:In total 16 cases,there were 11 cases with pancreatic enucleation,and 5 cases with resection of the uninate process. The operation time was 70(60) minutes (range: 40 to 165 minutes),and the blood loss was 30(13)ml (range: 10 to 80 ml). The rate of pancreatic fistula was 5/16. The length of stay was 8(6)days (range: 5 to 33 days). The pathological finding included non-functional neuroendocrine tumor( n=3),insulinoma( n=2),introductal papillary mucinous neoplasm ( n=5),solid pseudopapillary neoplasm ( n=2),mucinous cystadenoma ( n=1),serous cystadenoma ( n=2),pseudocyst ( n=1). Follow-up as of March 12, 2024, the follow-up time was 16(12)months (range: 3 to 41 months). All patients had no new onset diabetes and no dyspepsia. Conclusion:Robot-assisted surgical system can be used for local resection of uncinate process tumors of pancreas,and the quality of life of patients can be improved.

Objective:To summarize the experience of robot-assisted enucleation of tumors located in uncinate process of pancreas.Methods:This is a retrospective case series study. The clinical data of patients with robot-assisted enucleation of tumors located in the uncinate process of pancreas at the Department of Gastroenterology and Pancreatic Surgery,Zhejiang Provincial People′s Hospital from June 2019 to December 2023 were retrospectively analyzed. A total of 16 cases were enrolled,including 10 males and 6 females,with an age( M(IQR)) of 56(21)years (range: 28 to 77 years),and body mass index of 22.4(2.3)kg/m 2 (range:19.8 to 25.6 kg/m 2). Follow-up was asked every 6 to 12 months after the first 3-month postoperative follow-up through out-patient service or via telephone. Results:In total 16 cases,there were 11 cases with pancreatic enucleation,and 5 cases with resection of the uninate process. The operation time was 70(60) minutes (range: 40 to 165 minutes),and the blood loss was 30(13)ml (range: 10 to 80 ml). The rate of pancreatic fistula was 5/16. The length of stay was 8(6)days (range: 5 to 33 days). The pathological finding included non-functional neuroendocrine tumor( n=3),insulinoma( n=2),introductal papillary mucinous neoplasm ( n=5),solid pseudopapillary neoplasm ( n=2),mucinous cystadenoma ( n=1),serous cystadenoma ( n=2),pseudocyst ( n=1). Follow-up as of March 12, 2024, the follow-up time was 16(12)months (range: 3 to 41 months). All patients had no new onset diabetes and no dyspepsia. Conclusion:Robot-assisted surgical system can be used for local resection of uncinate process tumors of pancreas,and the quality of life of patients can be improved.

Background:Circular RNAs(circRNAs)are covalently closed single-stranded RNAs with multiple biological functions.CircRNA.0007127 is derived from the carbon catabolite repression 4-negative on TATA-less(CCR4-NOT)complex subunit 2(CNOT2),which was found to regulate tumor cell apoptosis through caspase pathway.Methods:Potential circRNA.0007127 target microRNAs(miRNAs)were analyzed by miRanda,TargetScan,and RNAhybrid software,and the miRNAs with binding sites for apoptosis-related genes were screened.The roles of circRNA.0007127 and its downstream target,microRNA(miR)-513a-5p,were validated by quantitative real-time polymerase chain reaction(qPCR),flow cytometry,mitochondrial membrane potential,immunofluorescence,western blot,and caspase-8(CASP8)protein activity in vitro in H2O2-induced K-562 cells.The circRNA.0007127-miR-513a-5p and CASP8-miR-513a-5p interactions were verified by luciferase reporter assays.Results:Silencing circRNA.0007127 decreased cell apoptosis by inhibiting CASP8 pathway activation in K-562 cells.Compared with the control group,the expression of CASP8 was reduced by 50％and the 43-kD fragment of CASP8 protein was significantly reduced(P≤0.05).The luciferase reporting assay showed that circRNA.0007127 combined with miR-513a-5p or CASP8,with extremely significant differences(P≤0.001).The overexpression of miR-513a-5p inhibited the gene expression level of CASP8 in a human myeloid leukemia cell model(75％change)and the level of a 43-kD fragment of CASP8 protein(P≤0.01).The rescue experiment showed that cotransfection with circRNA.0007127 small-interfering RNA(siRNA)and the miR-513a-5p inhibitor increased CASP8 gene expression and the apoptosis rate,suggesting that the miR-513a-5p inhibitor is a circRNA.0007127 siRNA antagonist.Conclusions:CircRNA.0007127 regulates K-562 cell apoptosis through the miR-513a-5p/CASP8 axis,which can serve as a novel powerful molecular target for K-562 cells.

Objective:To explore the effect of metformin during pregnancy on pregnancy outcomes of women with polycystic ovary syndrome (PCOS) complicated with euglycemia and hyperinsulinemia.Methods:One hundred and thirty PCOS pregnant patients complicated with euglycemia and hyperinsulinemia admitted to the Second Affiliated Hospital of Chongqing Medical University from January 2017 to December 2019 were selected and divided into two groups, the treatment group was treated with metformin during pregnancy, and the control group was treated with lifestyle intervention. Pregnancy outcomes, pregnancy complications, delivery complications, first cesarean section rate, length, gestational age, weight, and blood glucose of the newborn were compared.Results:The incidence of early pregnancy loss (23.8% vs 6.0%, P=0.040), embryo damage(23.8% vs 4.5%, P=0.001), and premature rupture of membrane(21.3% vs 8.1%, P=0.047) in the treatment group were lower than those in the control group. There were no statistically significant differences in pregnancy complications, first cesarean section rate, length, weight, and blood glucose of the newborn and other adverse pregnancy outcomes ( P>0.05). Conclusion:Metformin therapy during pregnancy in PCOS patients can effectively reduce the incidence of early pregnancy loss, embryo damage , and premature rupture of membrane, improve pregnancy outcomes, and have no effect on the length, weight, and blood glucose of the newborn, with high safety and no obvious adverse events.

Objective: To summarize the incidence and characteristics of postoperative complications after laparoscopic pancreaticoduodenectomy(LPD), and to share our experience on management of complications. Methods: The clinical data of 320 LPD performed by a single team in Sir Run Run Shaw Hospital and Zhejiang Provincial People′s Hospital between September 2012 and September 2017 were retrospectively analyzed, among which there were 196 males and 124 females with age of (60.2±11.6) years old.There were 306 patients who underwent standard LPD, and 14 patients who underwent extended LPD. The patients were divided into 2 groups of former 160 LPD and later 160 LPD according to the time order. By analyzing the differences of clinical outcomes between the two groups, especially focusing on the incidence of postoperative complications.The experience on management of complications was concluded. The prior surgical history of latter group was significantly higher than the former group(30.0%(48/160)vs. 18.8%(30/160), χ²=5.49, P=0.019), and the rest of baseline characteristics remained the comparable (P>0.05). For resectable lesions, LPD was performed by "No back" approach, following the principle of "From distal to cephalad, from ventral to dorsal, and from left to right" . As for the borderline resectable patients, LPD was performed by "Easy first" strategy. Student t test, χ² test or Fisher test was used to analyzed the data between the two groups respectively. Results: Of 320 LPD patients, 306 cases underwent standard LPD, 14 cases underwent LPD with resection of other organs.There were 278 LPD cases who followed "No back" approach, and 42 cases who followed "Easy first" strategy because of difficulty in creating the retro-pancreatic tunnel. And the overall morbidity was 32.2%(103/320) with reoperation rate of 5.3%(17/320). The perioperative mortality was 0.6%(2/320). The operation time of latter group was ((346.6±48.8)minutes), which was shorter than that of former group((358.0±54.4)minutes)(t=1.97, P=0.048). The blood loss of former and latter group remained comparable((207.9±135.8)ml vs.(189.6±121.4)ml, P=0.205). However, in subgroup analysis, the patients with blood loss less <200 ml of latter group decreased significantly from 59.4%(95/160) to 47.5%(76/160)(χ²=4.53, P=0.033). The overall morbidity of latter group was 28.8%(46/160), indicated a decrease from 35.6%(57/160) of former group without significant difference(P=0.188). Moreover, Grade A/B/C pancreatic fistula rate, Grade A/C bile leakage rate, Grade B/C postoperative hemorrhage rate of the later group tended to decrease, although they also didn′t reach a significant difference. However, the abdominal infection rate decreased significantly(χ²=3.93, P=0.047). The length of hospital stay remained comparable(P=0.156). Conclusions The most common complications after LPD were postoperative hemorrhage and pancreatic fistula. With specialized team and accumulated experience, the morbidity can decrease progressively by analyzing the leading cause and improving the technical skills.