Objective To assess the potential role of disulfidptosis-related genes (DRGs) in pan-cancer on prognosis and immunity on the basis of bioinformatics approaches. Methods Pan-cancer RNA-seq data, mutation profiles, clinical information, TMB, MSI, stemness scores, and tumor and immune microenvironment data contained in TCGA and various open-source online databases, and multi-group R-language algorithms were used for comprehensive analysis. The expression levels of DRGs at the cellular level were experimentally validated using qPCR. Results LRPPRC, NCKAP1, NDUFS1, and NUBPL had a better prognosis in renal clear cell carcinoma (P<0.001), whereas SLC7A11, NCKAP1, and SLC3A2 had a worse prognosis in hepatocellular carcinoma (P<0.001). TME analysis showed that LRPPRC was negatively correlated with immune cells, stromal cells, and estimated scores in all tumor types. TMB analysis revealed the potential research value of DRGs for PD-1/PD-L1 therapy in pan-cancer. Drug sensitivity analysis showed that SLC7A11 (r=0.454), SLC3A2 (r=0.366), and NCKAP1 (r=0.455) were significantly associated with Kahalide F (P<0.01). Experimental validation demonstrated the overall higher expression levels of GYS1 and NCKAP1 than normal cells in lung adenocarcinoma, colon adenocarcinoma, esophageal squamous carcinoma, and hepatocellular carcinoma (P<0.05). Conclusion Pan-cancer analysis of DRGs indicates that DRGs may serve as important biomarkers for the diagnosis and prognosis of renal clear-cell carcinoma, lung adenocarcinoma, and hepatocellular carcinoma.

Objective:To explore the construction and validation of a nomogram model for predicting poor survival prognosis in patients with clear cell renal cell carcinoma（ccRCC）based on deep learning of pathological images.Methods:This study was an observational cohort study. The original pathological images and clinicopathological data（TCGA cohort）of 378 patients with ccRCC were obtained from the Cancer Genome Atlas Database（TCGA）for model training. A total of 301 patients with ccRCC who underwent surgical treatment at Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2010 to December 2020（Renji cohort）and 214 patients with ccRCC who underwent surgical treatment at the First People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2012 to December 2018（General cohort）were included for model validation. Their original pathological images and clinical pathological data were collected. A clustering-constrained attention and multi-instance learning method was used to accurately identify sub-regions of the images to classify and extract features of the pathological images. A deep learning-based disease-free survival prognosis prediction model（DL-DFS）was constructed through a weakly supervised learning strategy. The clinical pathological features and DL-DFS were further combined to construct a nomogram model for the clinical prognosis of ccRCC patients. Univariate and multivariate Cox regression analyses were employed to evaluate the independent risk factors for disease-free survival（DFS）. The efficacy of the predictive model were evaluated by the receiver operating characteristic curve（ROC）with area under the curve（AUC），respectively. Survival analysis was conducted using the Kaplan-Meier curve.Results:DL-DFS could accurately predict the DFS status of ccRCC patients in 5 years after surgery. Through ROC analysis in the training cohort，the AUC value reached 0.75（ P < 0.001）. In the Renji cohort and the General cohort，the AUC values were 0.65（ P < 0.001）and 0.81（ P < 0.001），respectively. Through Kaplan-Meier survival analysis，we found that DL-DFS could identify ccRCC patients with high survival risks. The hazard ratio in the training cohort was 3.86（95% CI 2.36-6.30， P < 0.001）. The hazard ratio in the Renji cohort and General cohort were 1.97（95% CI 1.03-3.80， P = 0.009）and 4.66（95% CI 1.80-12.06， P = 0.008），respectively. Univariate and multivariate Cox regression analyses indicated that DL-DFS risk score，tumor grade，and tumor stage could act as prognostic risk factors for patients with ccRCC（ P < 0.05）. Considering that age was a common prognostic risk factor for patients with renal cancer，a nomogram model was constructed by combining the DL-DFS risk score with patient age，tumor grade，and tumor stage. The AUC of this model for predicting the 5-year DFS of ccRCC patients after surgery was 0.87，which was significantly higher than that of DL-DFS（AUC = 0.74），tumor stage（AUC = 0.84），tumor grade（AUC = 0.72），and patient age（AUC = 0.56）in the TCGA cohort（all P<0.05）. In the Renji cohort and the General cohort，the AUC of the nomogram model were 0.78 and 0.86 respectively，which was significantly higher than that of DL-DFS（0.65 and 0.81），tumor stage（0.72 and 0.69），tumor grade（0.64 and 0.77），and patient age（0.56 and 0.63）. Conclusions:In this study a DL-DFS for ccRCC patients was constructed. Then a nomogram model was constructed by combining the DL-DFS risk value with patient age，tumor grade，and tumor stage. This nomogram model demonstrated superior predictive performance compared to DL-DFS alone in evaluating the DFS prognosis of ccRCC patients，which still needs to be further verified in prospective clinical studies.

Objective:To explore the construction and validation of a nomogram model for predicting poor survival prognosis in patients with clear cell renal cell carcinoma（ccRCC）based on deep learning of pathological images.Methods:This study was an observational cohort study. The original pathological images and clinicopathological data（TCGA cohort）of 378 patients with ccRCC were obtained from the Cancer Genome Atlas Database（TCGA）for model training. A total of 301 patients with ccRCC who underwent surgical treatment at Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2010 to December 2020（Renji cohort）and 214 patients with ccRCC who underwent surgical treatment at the First People’s Hospital Affiliated to Shanghai Jiaotong University School of Medicine from January 2012 to December 2018（General cohort）were included for model validation. Their original pathological images and clinical pathological data were collected. A clustering-constrained attention and multi-instance learning method was used to accurately identify sub-regions of the images to classify and extract features of the pathological images. A deep learning-based disease-free survival prognosis prediction model（DL-DFS）was constructed through a weakly supervised learning strategy. The clinical pathological features and DL-DFS were further combined to construct a nomogram model for the clinical prognosis of ccRCC patients. Univariate and multivariate Cox regression analyses were employed to evaluate the independent risk factors for disease-free survival（DFS）. The efficacy of the predictive model were evaluated by the receiver operating characteristic curve（ROC）with area under the curve（AUC），respectively. Survival analysis was conducted using the Kaplan-Meier curve.Results:DL-DFS could accurately predict the DFS status of ccRCC patients in 5 years after surgery. Through ROC analysis in the training cohort，the AUC value reached 0.75（ P < 0.001）. In the Renji cohort and the General cohort，the AUC values were 0.65（ P < 0.001）and 0.81（ P < 0.001），respectively. Through Kaplan-Meier survival analysis，we found that DL-DFS could identify ccRCC patients with high survival risks. The hazard ratio in the training cohort was 3.86（95% CI 2.36-6.30， P < 0.001）. The hazard ratio in the Renji cohort and General cohort were 1.97（95% CI 1.03-3.80， P = 0.009）and 4.66（95% CI 1.80-12.06， P = 0.008），respectively. Univariate and multivariate Cox regression analyses indicated that DL-DFS risk score，tumor grade，and tumor stage could act as prognostic risk factors for patients with ccRCC（ P < 0.05）. Considering that age was a common prognostic risk factor for patients with renal cancer，a nomogram model was constructed by combining the DL-DFS risk score with patient age，tumor grade，and tumor stage. The AUC of this model for predicting the 5-year DFS of ccRCC patients after surgery was 0.87，which was significantly higher than that of DL-DFS（AUC = 0.74），tumor stage（AUC = 0.84），tumor grade（AUC = 0.72），and patient age（AUC = 0.56）in the TCGA cohort（all P<0.05）. In the Renji cohort and the General cohort，the AUC of the nomogram model were 0.78 and 0.86 respectively，which was significantly higher than that of DL-DFS（0.65 and 0.81），tumor stage（0.72 and 0.69），tumor grade（0.64 and 0.77），and patient age（0.56 and 0.63）. Conclusions:In this study a DL-DFS for ccRCC patients was constructed. Then a nomogram model was constructed by combining the DL-DFS risk value with patient age，tumor grade，and tumor stage. This nomogram model demonstrated superior predictive performance compared to DL-DFS alone in evaluating the DFS prognosis of ccRCC patients，which still needs to be further verified in prospective clinical studies.

Objective:To evaluate the relationship of rotator cuff muscle function with shoulder abduction function after posterior superior rotator cuff tear via dynamic biomechanical study.Methods:By using the customized dynamic shoulder biomechanical testing system, seven freshly frozen cadaveric shoulders were used to stimulate shoulder abduction at 90° under four statuses: (1) intact rotator cuff with activation (normal rotator cuff group); (2) posterior superior rotator cuff tear with activation (posterior superior rotator cuff tear with activation group); (3) posterior superior rotator cuff tear with posterior superior rotator cuff deactivation (posterior superior rotator cuff tear with deactivation group); (4) none rotator cuff tissue above the geometric rotation center of the humeral head with deactivation (global tear group). The peak and stable value of middle deltoid force were used to evaluate biomechanical status in different rotator cuff tear conditions during shoulder abduction procedure. The peak subacromial pressure, average subacromial pressure, subacromial contact area, and subacromial force were used to evaluate subacromial pressed conditions under different rotator cuff tear conditions. The peak and stable ratio of glenohumeral contact force/middle deltoid force were used to evaluate shoulder stability under different rotator cuff tear conditions.Results:During dynamic abduction at 90°, the peak and stable value of middle deltoid force were (42.1±8.7)N and (29.9±7.4)N in normal rotator cuff group, (45.7±10.3)N and (30.5±7.2)N in posterior superior rotator cuff tear with activation group, and (48.4±13.4)N and (29.9±4.8)N in posterior superior rotator cuff tear with deactivation group (all P>0.05). But the peak and stable value of middle deltoid force were (69.7±9.7)N and (53.7±8.9)N in global tear group, significantly increased compared with other three groups (all P<0.05). The elevated middle deltoid force increased the subacromial contact pressure between glenohumeral head and acromion. The peak subacromial pressure, average subacromial pressure, subacromial contact area, and subacromial force were (0.40±0.05)MPa, (0.22±0.03)MPa, (7.71±5.09)mm 2, and (1.66±1.06)N respectively in normal rotator cuff group, (0.41±0.05)MPa, (0.26±0.07)MPa, (12.71±11.35)mm 2, and (2.93±2.46)N respectively in posterior superior rotator cuff tear with activation group, and (0.50±0.12)MPa, (0.26±0.07)MPa, (17.29±9.11)mm 2, and (4.09±1.46)N respectively in posterior superior rotator cuff tear with deactivation group (all P>0.05). However, the peak subacromial pressure, average subacromial pressure, subacromial contact area, and subacromial force were (3.64±1.70)MPa, (0.98±0.49)MPa, (47.63±11.91)mm 2, and (45.48±23.86)N respectively in global tear group, significantly higher than those in other three groups (all P<0.05). The peak and stable ratio of glenohumeral contact force/middle deltoid force were 2.24±0.30 and 2.46±0.13 in normal rotator cuff group, 2.21±0.19 and 2.52±0.08 in posterior superior rotator cuff tear with activation group, and 2.03±0.14 and 2.42±0.16 in posterior superior rotator cuff tear with deactivation group (all P>0.05). However, the peak and stable ratio of glenohumeral contact force/middle deltoid force were 1.40±0.14 and 1.52±0.41 in global tear group, significantly higher than those in other three groups (all P<0.05). No significant differences of the above parameters were observed in posterior superior rotator cuff tear with activation group, posterior superior rotator cuff tear with deactivation group and global tear group (all P>0.05). Conclusions:After posterior superior rotator cuff tear, rotator cuff muscle function does not affect the whole abduction function of shoulder. When the size of rotator cuff tear involves the whole superior humeral head rotation center, the normal abduction function of shoulder will be significantly impaired.

ObjectiveTo explore the efficacy and safety of bevacizumab combined with preoperative chemotherapy for colorectal cancer patients with liver metastases.MethodsClinical data of 89 colorectal cancer patients with liver metastases admitted and treated in Sun Yat-sen University Cancer Center between May 2009 and August 2013 were retrospectively analyzed. The informed consents of all patients were obtained and the local ethical committee approval was received. According to the first-line chemotherapy regimens, the patients were divided into the bevacizumab combined with preoperative chemotherapy group (bevacizumab group,n=32) and the simple preoperative chemotherapy group (the chemotherapy group,n=57). Among the patients in the bevacizumab group, 24 were males and 8 were females with the age ranging from 29 to 74 years old and the median of 59 years old, 22 were with colon cancer and 10 were with rectal cancer. Among the patients in the chemotherapy group, 42 were males and 15 were females with the age ranging from 28 to 74 years old and the median of 57 years old, 42 were with colon cancer and 15 were with rectal cancer. The progression-free survival, response rate, resection rate and conversion rate of liver metastases and adverse effect incidence of preoperative therapy in two groups were observed and compared. The rates were compared using Chi-square test, and the survival analysis was conducted using Kaplan-Meier method and Log-rank test.ResultsThe median progression-free survival was 16 months in the bevacizumab group and 13 months in the chemotherapy group, and no significant difference was observed in the progression-free survival rate between two groups (χ2=0.030,P>0.05). The response rate, resection rate and conversion rate of liver metastases were respectively 59%(19/32), 69%(22/32) and 53%(17/32) in the bevacizumab group and 39%(22/57), 54%(31/57) and 40%(23/57) in the chemotherapy group, and no signiifcant differences were observed (χ2=3.561, 1.755, 0.983;P>0.05). The overall incidence of adverse events was 12%(4/32) in the bevacizumab group with 2 cases of neutropenia, 1 case of hand-foot syndrome and 1 case of gradeⅢ gums bleeding, while the overall incidence of adverse events was 9%(5/57) in the chemotherapy group with 3 cases of thrombocytopenia, 1 case of neutropenia and 1 case of liver function impairment. And no signiifcant difference was observed between two groups (χ2=0.313, P>0.05).ConclusionsBevacizumab combined with preoperative chemotherapy is safe and has potential curative effect to prolong the disease-free survival for colorectal cancer patients with liver metastases.

OBJECTIVETo explore the clinicopathological characteristics, efficacy, and prognostic factors for patients with rectal gastrointestinal stromal tumor(GIST).

METHODSClinicopathological and follow-up data of 61 patients with rectal GIST in our department from January 1990 to October 2012 were analyzed retrospectively and pathology specimens were reviewed. Kaplan-Meier method was used to calculate the survival. Univariate analysis and multivariate analysis were performed to investigate the influencing factors of prognosis with Log-rank test and Cox regression model.

RESULTSThere were 42 male and 19 female patients with a median age of 59 years old. Eighteen cases(29.5%) were confirmed preoperatively as GIST by biopsy and 46 cases were diagnosed as GIST by first pathological examination. Fifteen cases(24.6%) were revised as GIST after re-examination of specimes among whom 14 cases had been diagnosed as leiomyoma or sarcoma, and 1 as neurolemmoma. Tumor location was above peritoneal reflection in 12 cases(19.7%) and below peritoneal reflection in 49(80.3%). Fifty-two patients underwent surgery, including 21 extended resections(lymph nodes clearance and combined organs resection simultaneously) and 31 local resections(tumor rejection or partial resection of rectal wall). Eleven patients received preoperative imatinib(400 mg/d). Forty-one cases received imatinib therapy after operation or biopsy diagnosis, including 25 cases who received palliative treatment for postoperative recurrence. Median follow-up time was 55(6 to 391) months and follow-up longer than 2 years was carried out in 46 patients. Overall survival rates of 1-, 2-, 3- , 5-year were 98%, 95.6%, 86.0% and 73.7% respectively. There were no significant differences between local resection group(96.4%, 92%, 83.3% and 77.3%) and extended resection group (100%, 94.7%, 89.50% and 82.6%)(χ(2)=0.004, P=0.947). Univariate analysis showed that survival was only associated with recurrence and metastasis (χ(2)=4.292, P=0.038). Multivariate Cox analysis showed postoperative survival was not associated with any factors(all P>0.05). The 3-year survival rate of patients with postoperative recurrence or metastasis receiving imatinib therapy was better as compared to those who did not received imatinib(82.7% vs. 71.4%).

CONCLUSIONSRectal GIST are more common in the lower rectum. Surgery is the main treatment for rectal GIST. Local complete resection is the mainstay treatment. Extensive resection and lymph node clearance may not improve survival. Imatinib can improve the prognosis of patients with recurrence or metastasis.

Benzamides ; Female ; Gastrointestinal Stromal Tumors ; therapy ; Humans ; Imatinib Mesylate ; Male ; Neoplasm Recurrence, Local ; Piperazines ; Prognosis ; Pyrimidines ; Rectal Neoplasms ; pathology ; therapy ; Retrospective Studies ; Survival Rate

Objective To explore the clinicopathological characteristics, efficacy, and prognostic factors for patients with rectal gastrointestinal stromal tumor (GIST). Methods Clinicopathological and follow-up data of 61 patients with rectal GIST in our department from January 1990 to Oc tober 2012 were analyzed retrospectively and pathology specimens were reviewed. Kaplan-Meier method was used to calculate the survival. Univariate analysis and multivariate analysis were performed to investigate the influencing factors of prognosis with Log-rank test and Cox regression model. Results There were 42 male and 19 female patients with a median age of 59 years old. Eighteen cases (29.5%) were confirmed preoperatively as GIST by biopsy and 46 cases were diagnosed as GIST by first pathological examination. Fifteen cases (24.6%) were revised as GIST after re-examination of specimes among whom 14 cases had been diagnosed as leiomyoma or sarcoma, and 1 as neurolemmoma. Tumor location was above peritoneal reflection in 12 cases (19.7%) and below peritoneal reflection in 49 (80.3%). Fifty-two patients underwent surgery, including 21 extended resections(lymph nodes clearance and combined organs resection simultaneously) and 31 local resections (tumor rejection or partial resection of rectal wall). Eleven patients received preoperative imatinib(400 mg/d). Forty-one cases received imatinib therapy after operation or biopsy diagnosis, including 25 cases who received palliative treatment for postoperative recurrence. Median follow-up time was 55 (6 to 391) months and follow-up longer than 2 years was carried out in 46 patients. Overall survival rates of 1-, 2-, 3-, 5-year were 98%, 95.6%, 86.0%and 73.7%respectively. There were no significant differences between local resection group (96.4%, 92%, 83.3%and 77.3%) and extended resection group (100%, 94.7%, 89.50%and 82.6%) (χ2=0.004, P=0.947). Univariate analysis showed that survival was only associated with recurrence and metastasis (χ2=4.292, P=0.038). Multivariate Cox analysis showed postoperative survival was not associated with any factors (all P>0.05). The 3-year survival rate of patients with postoperative recurrence or metastasis receiving imatinib therapy was better as compared to those who did not received imatinib (82.7%vs. 71.4%). Conclusions Rectal GIST are more common in the lower rectum. Surgery is the main treatment for rectal GIST. Local complete resection is the mainstay treatment. Extensive resection and lymph node clearance may not improve survival. Imatinib can improve the prognosis of patients with recurrence or metastasis.

Objective To explore the clinicopathological characteristics, efficacy, and prognostic factors for patients with rectal gastrointestinal stromal tumor (GIST). Methods Clinicopathological and follow-up data of 61 patients with rectal GIST in our department from January 1990 to Oc tober 2012 were analyzed retrospectively and pathology specimens were reviewed. Kaplan-Meier method was used to calculate the survival. Univariate analysis and multivariate analysis were performed to investigate the influencing factors of prognosis with Log-rank test and Cox regression model. Results There were 42 male and 19 female patients with a median age of 59 years old. Eighteen cases (29.5%) were confirmed preoperatively as GIST by biopsy and 46 cases were diagnosed as GIST by first pathological examination. Fifteen cases (24.6%) were revised as GIST after re-examination of specimes among whom 14 cases had been diagnosed as leiomyoma or sarcoma, and 1 as neurolemmoma. Tumor location was above peritoneal reflection in 12 cases (19.7%) and below peritoneal reflection in 49 (80.3%). Fifty-two patients underwent surgery, including 21 extended resections(lymph nodes clearance and combined organs resection simultaneously) and 31 local resections (tumor rejection or partial resection of rectal wall). Eleven patients received preoperative imatinib(400 mg/d). Forty-one cases received imatinib therapy after operation or biopsy diagnosis, including 25 cases who received palliative treatment for postoperative recurrence. Median follow-up time was 55 (6 to 391) months and follow-up longer than 2 years was carried out in 46 patients. Overall survival rates of 1-, 2-, 3-, 5-year were 98%, 95.6%, 86.0%and 73.7%respectively. There were no significant differences between local resection group (96.4%, 92%, 83.3%and 77.3%) and extended resection group (100%, 94.7%, 89.50%and 82.6%) (χ2=0.004, P=0.947). Univariate analysis showed that survival was only associated with recurrence and metastasis (χ2=4.292, P=0.038). Multivariate Cox analysis showed postoperative survival was not associated with any factors (all P>0.05). The 3-year survival rate of patients with postoperative recurrence or metastasis receiving imatinib therapy was better as compared to those who did not received imatinib (82.7%vs. 71.4%). Conclusions Rectal GIST are more common in the lower rectum. Surgery is the main treatment for rectal GIST. Local complete resection is the mainstay treatment. Extensive resection and lymph node clearance may not improve survival. Imatinib can improve the prognosis of patients with recurrence or metastasis.

Objective:To investigate the expressions of Mfn2(mitofusin 2) in non-small-cell lung cancer (NSCLC) tissues and non-cancerous lung tissues,and analyze its relationship with clinicopathological characteristics of lung carcinomas.Methods:The expressions of Mfn2 mRNA and protein in 92 cases of NSCLC tissues and 27 cases of non-cancerous lung tissues were detected by in situ hybridization and immunohistochemical methods. Results:The positive rates of Mfn2 mRNA and protein in pulmonary squamous cell carcinoma were higher than those in adenocarcinoma (83.33% and 89.58% vs 56.82% and 65.91%), respectively. The positive rates of Mfn2 mRNA and protein in NSCLC were higher than those in the non-cancerous lung tissues (25.93% and 29.63%) . The difference was statistically significant among the three groups (P<0.001 and P<0.01). The expressions of Mfn2 mRNA and protein in well-differentiated (93.75% and 100%) and moderately-differentiated NSCLC (91.67% and 91.67%) were higher than those in poor-diffe-rentiated NSCLC (21.43% and 42.86%). The difference was significant (P<0.001). The expressions of Mfn2 mRNA and protein had no correlation with the gender, age, tumor size, TNM stage and lymph node metastasis (P>0.05). The expression of Mfn2 mRNA was consistent with that of Mfn2 protein in NSCLC.Conclusion:Mfn2 was involved in the initiation and progression of lung cancer, and the expression of Mfn2 was related to the histological types of lung cancer and its differentiation degree.

Objective To investigate the expression of hyperplasia suppressor gene(HSG)/mitofusin 2 (Mfn2)and P21 WAF1 in non-small cell lung cancer(NSCLC).Methods The expression of(HSG/Mfn2)and P21 WAF1 was detected in 92 cases of NSCLC samples by immunohistochemistry(SP).Results The absorptance value of the expression of HSG/Mfn2 in squamous cell carcinoma,adenocarcinoma,and non-cancer tissue were 15.06±2.73,12.21±2.96 and 10.36±3.60,respectively(P<0.05),and they were associated with tumor differentiation.The absorptanee valtue of the expression of P21 WAF1 in squamous cell carcinoma,adenocarcinoma,and non-cancer tissue were 3.16±0.98,3.44±0.22,0.06±0.32.The expression of P21 WAF1 in squamous cell carcinoma and adenocarcinoma Was higher than that in non-cancer tissue(P<0.05),and was closely associated with tumor differ-entiation and lymph node metastasis.Conclusion HSG/Mfn2,P21WAF1 is closely related to the pathogenesis and development of lung cancer.There is positive correlation between the HSG/Mfn2 and P2l WAF1 in lung cancer.