Objective:To evaluate the efficacy and safety of sintilimab combined with bevacizumab in the second-line treatment of malignant pleural mesothelioma(MPM).Methods:This was a longitudinal study. Patients with MPM who had progressed after first-line treatment and were admitted to the Day-Care Outpatient Department of Medical Oncology, Ningguo People′s Hospital from February 2019 to February 2022 were included. General clinical data of the patients were collected at baseline. The patients were treated with the second-line treatment regimen of sintilimab (200 mg)+bevacizumab (15 mg/kg) on a 21-day cycle. Enhanced CT scans were performed every 3 cycles to evaluate the efficacy until tumor progression or death. Follow-up period ended in December 2023. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Efficacy was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), and the best response of each patient was recorded. The objective response rate (ORR) and disease control rate (DCR) were calculated. Adverse reactions were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), ranging from grade Ⅰto Ⅳ. Kaplan-Meier survival curves were used to analyze PFS and OS, and survival times were expressed as median values.Results:A total of 23 MPM patients were included, with the mean age of (55.04±13.27)years, 15 males, 8 females, 19 cases of epithelial type and 4 cases of non-epithelial type. The Eastern Cooperative Oncology Group (ECOG) performance status scores were 0-1 in 12 patients and 2 in 11 patients. There were 17 smokers and 6 non-smokers, 12 cases with PD-L1 positive and 11 cases with PD-L1 negative, and 6 cases with anti-angiogenic drugs and 17 cases without using anti-angiogenic drugs in the first-line treatment. Of the 23 patients, 1 achieved complete response (CR), 9 achieved partial response (PR), 7 had stable disease (SD), and 6 had progressive disease (PD). The ORR and DCR of the enrolled patients were 43.5% (10/23) and 73.9% (17/23), respectively. Kaplan-Meier survival analysis showed that the PFS of the enrolled patients was 7.50 (95% CI: 5.47-9.54) months, and the OS was 12.50 (95% CI: 1.07-23.93) months. The most common adverse reactions related to the treatment of sintilimab combined with bevacizumab were hypertension (14 cases (60.9%)), fatigue (10 cases (43.5%)), decreased appetite (8 cases (34.8%)), proteinuria (6 cases (26.1%)), pruritus (5 cases (21.7%)), constipation (4 cases (17.4%)) and nausea (3 cases (13.0%)), etc. Only 9 patients had grade Ⅲ adverse reactions (8 cases of hypertension and 1 case of nausea), and only 1 patient had grade Ⅳ adverse reaction (hypertension). Conclusion:Sintilimab combined with bevacizumab has some therapeutic effects on progressive MPM, and the adverse reactions are relatively mild.

Objective To explore and evaluate the adverse drug events(ADE)signals of thromboembolic events induced by cisplatin and carboplatin,and to provide references for clinical safety and rational use of drugs.Methods The cisplatin-and carboplatin-related thromboembolic adverse events reports were collected from the U.S.FDA Adverse Event Reporting System(FAERS)database with the reporting time range from the first quarter of 2004 to the fourth quarter of 2023.Thromboembolic ADR signals were detected using the reporting odds ratio(ROR)method,the medicines and healthcare products regulatory agency(MHRA)method,and the Bayesian confidence propagation neural network(BCPNN)method at the SMQ level and preferred term(PT)level.Results A total of 1 959 cisplatin-related thromboembolism events and 2 524 carboplatin-related thromboembolism events were reported.In terms of gender composition,after excluding reports with unspecified gender,the ratio of male to female was 1.69∶1 for cisplatin and 0.65∶1 for carboplatin.For cisplatin,triple signals were generated at the"thromboembolic events"SMQ level as well as its sub-levels"venous thromboembolic events",and dual signals were generated at the"arterial thromboembolic events"sub-level.However,for carboplatin,dual signals were generated at the"thromboembolic events"SMQ level,and three signals were generated only at the"venous thromboembolic events"sub-level.The PT hierarchy analysis of thromboembolic events revealed that except for"thrombotic microangiopathy"produced single signal,signals generated by cisplatin were all triple signals,among which"aortic thrombosis"(ROR 95%CI lower limit=72.59,IC-2SD=5.93)exhibited the strongest signal intensity.Different from cisplatin,except for"acute myocardial infarction","ischemic stroke",and"cerebral infarction",which generated dual signals,"aortic thrombosis",which generated a single signal,all the other signals produced by carboplatin were triple signals.Additionally,"venous occlusive liver disease"(ROR 95%CI lower limit=11.58,IC-2SD=3.35)displayed the strongest signal intensity.Among various types of thromboembolic events,both cisplatin-and carboplatin-related"pulmonary embolism"and"deep vein thrombosis"were reported the highest number,ranking first and second,respectively.Conclusions In this study,cisplatin and carboplatin were proven to increase the risk of thromboembolic adverse events.Cisplatin was associated with potential risks of"venous thromboembolism"and"arterial thromboembolism",while carboplatin was associated with"venous thromboembolism".Therefore,attention should be paid to the above risks during clinical use.

Objective:To evaluate the efficacy and safety of sintilimab combined with bevacizumab in the second-line treatment of malignant pleural mesothelioma(MPM).Methods:This was a longitudinal study. Patients with MPM who had progressed after first-line treatment and were admitted to the Day-Care Outpatient Department of Medical Oncology, Ningguo People′s Hospital from February 2019 to February 2022 were included. General clinical data of the patients were collected at baseline. The patients were treated with the second-line treatment regimen of sintilimab (200 mg)+bevacizumab (15 mg/kg) on a 21-day cycle. Enhanced CT scans were performed every 3 cycles to evaluate the efficacy until tumor progression or death. Follow-up period ended in December 2023. The primary endpoints were progression-free survival (PFS) and overall survival (OS). Efficacy was evaluated according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST), and the best response of each patient was recorded. The objective response rate (ORR) and disease control rate (DCR) were calculated. Adverse reactions were graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE), ranging from grade Ⅰto Ⅳ. Kaplan-Meier survival curves were used to analyze PFS and OS, and survival times were expressed as median values.Results:A total of 23 MPM patients were included, with the mean age of (55.04±13.27)years, 15 males, 8 females, 19 cases of epithelial type and 4 cases of non-epithelial type. The Eastern Cooperative Oncology Group (ECOG) performance status scores were 0-1 in 12 patients and 2 in 11 patients. There were 17 smokers and 6 non-smokers, 12 cases with PD-L1 positive and 11 cases with PD-L1 negative, and 6 cases with anti-angiogenic drugs and 17 cases without using anti-angiogenic drugs in the first-line treatment. Of the 23 patients, 1 achieved complete response (CR), 9 achieved partial response (PR), 7 had stable disease (SD), and 6 had progressive disease (PD). The ORR and DCR of the enrolled patients were 43.5% (10/23) and 73.9% (17/23), respectively. Kaplan-Meier survival analysis showed that the PFS of the enrolled patients was 7.50 (95% CI: 5.47-9.54) months, and the OS was 12.50 (95% CI: 1.07-23.93) months. The most common adverse reactions related to the treatment of sintilimab combined with bevacizumab were hypertension (14 cases (60.9%)), fatigue (10 cases (43.5%)), decreased appetite (8 cases (34.8%)), proteinuria (6 cases (26.1%)), pruritus (5 cases (21.7%)), constipation (4 cases (17.4%)) and nausea (3 cases (13.0%)), etc. Only 9 patients had grade Ⅲ adverse reactions (8 cases of hypertension and 1 case of nausea), and only 1 patient had grade Ⅳ adverse reaction (hypertension). Conclusion:Sintilimab combined with bevacizumab has some therapeutic effects on progressive MPM, and the adverse reactions are relatively mild.

Objective To explore and evaluate the adverse drug events(ADE)signals of thromboembolic events induced by cisplatin and carboplatin,and to provide references for clinical safety and rational use of drugs.Methods The cisplatin-and carboplatin-related thromboembolic adverse events reports were collected from the U.S.FDA Adverse Event Reporting System(FAERS)database with the reporting time range from the first quarter of 2004 to the fourth quarter of 2023.Thromboembolic ADR signals were detected using the reporting odds ratio(ROR)method,the medicines and healthcare products regulatory agency(MHRA)method,and the Bayesian confidence propagation neural network(BCPNN)method at the SMQ level and preferred term(PT)level.Results A total of 1 959 cisplatin-related thromboembolism events and 2 524 carboplatin-related thromboembolism events were reported.In terms of gender composition,after excluding reports with unspecified gender,the ratio of male to female was 1.69∶1 for cisplatin and 0.65∶1 for carboplatin.For cisplatin,triple signals were generated at the"thromboembolic events"SMQ level as well as its sub-levels"venous thromboembolic events",and dual signals were generated at the"arterial thromboembolic events"sub-level.However,for carboplatin,dual signals were generated at the"thromboembolic events"SMQ level,and three signals were generated only at the"venous thromboembolic events"sub-level.The PT hierarchy analysis of thromboembolic events revealed that except for"thrombotic microangiopathy"produced single signal,signals generated by cisplatin were all triple signals,among which"aortic thrombosis"(ROR 95%CI lower limit=72.59,IC-2SD=5.93)exhibited the strongest signal intensity.Different from cisplatin,except for"acute myocardial infarction","ischemic stroke",and"cerebral infarction",which generated dual signals,"aortic thrombosis",which generated a single signal,all the other signals produced by carboplatin were triple signals.Additionally,"venous occlusive liver disease"(ROR 95%CI lower limit=11.58,IC-2SD=3.35)displayed the strongest signal intensity.Among various types of thromboembolic events,both cisplatin-and carboplatin-related"pulmonary embolism"and"deep vein thrombosis"were reported the highest number,ranking first and second,respectively.Conclusions In this study,cisplatin and carboplatin were proven to increase the risk of thromboembolic adverse events.Cisplatin was associated with potential risks of"venous thromboembolism"and"arterial thromboembolism",while carboplatin was associated with"venous thromboembolism".Therefore,attention should be paid to the above risks during clinical use.

Objective:To characterize the biomechanics of distal dynamic locking and distal static locking of proximal femur bionic nails (PFBN) in fixation of intertrochanteric fractures by a finite element analysis.Methods:The CT image data from the hip to the upper tibia from an adult male volunteer were used to establish a three-dimensional model of the femur by Mimics 20.0 and Geomagic 2013 which was processed further into a model of Evans type I intertrochanteric fracture by software NX 12.0. With reference to the internal fixation parameters commonly used, 4 models of PFBN fixation were established: distal single transverse nail dynamic locking (model A), single oblique nail dynamic locking (model B), single nail static locking (model C) and double nail dynamic locking (model D). Abaqus 6.14 software was used to load and analyze the internal fixation stresses and displacements of fracture ends.Results:Under a 2100N loading, the peak stress was located upon the main nail in the 4 models. The smallest peak stress upon the main nail was in Model D (161.9 MPa), decreased by 15.9% compared with model A (192.5 MPa), by 15.6% compared with model B (191.9 MPa), and by 0.9% compared with model C (163.3 MPa). The peak stress upon the fixation screw was the largest in model A (95.3 MPa), the smallest in model B (91.5 MPa), and 91.5 MPa and 92.2 MPa in models C and D, respectively. The overall displacements of the implants, in a descending order, were 10.14 mm in model A, 10.10 mm in model B, 10.09 mm in model C, and 10.05 mm in model D. Similarly, the displacements of fracture ends were 0.125 mm in model A, 0.121 mm in model B, 0.110 mm in model C, and 0.098 mm in model D.Conclusion:Compared with dynamic locking, distal static locking of PFBN provides a better mechanical stability and reduces stress concentration upon internal fixation.

Objective To explore the mechanism of Marsdenia tenacissima in the treatment of breast cancer through network pharmacology and experimental verification.Methods Literature retrieval was conducted to obtain the active components of Marsdenia tenacissima.The SwissTargetPrediction database was used to predict the potential targets of these active components.Targets of breast cancer were obtained from GeneCards,GEPIA2,OMIM,PharmGKB and TTD databases.The intersection targets were obtained,and a Marsdenia tenacissima-breast cancer-targets network was constructed using Cytoscape 3.9.0 software.The core targets were identified through protein-protein interaction(PPI)network analysis,followed by GO and KEGG pathway enrichment analysis to screen relevant signaling pathways.Molecular docking validation was performed for the top 10 key targets and major active components.The human breast cancer cell line MDA-MB-231 was treated with Marsdenia tenacissima injection in vitro.Cell proliferation ability was detected by CCK-8 assay and colony formation assay.Cell apoptosis was detected by Calcein-AM/PI staining and flow cytometry.Cell migration ability was detected by Transwell assay.Western blot experiment was used to validate the PI3K-AKT signaling pathway.Results Totally 37 active components and 276 potential targets against breast cancer were screened from Marsdenia tenacissima,including 11alpha-O-Benzoyl-12beta-O-acetyl tenacigenin B,Caffeic acid,Drevogenin A and Kaempferol.25 core targets were screened by PPI network such as AKT1,EGFR,TNF,CTNNB1 and IL-6,which mainly affected the estrogen signaling pathway,ErbB signaling pathway,HIF-1 signaling pathway and PI3K-AKT signaling pathway,etc.The molecular docking results showed that the main active components of Marsdenia tenacissima exhibited good binding activities with the core targets AKT1,ALB,CASP3,ESR1 and TNF.The results of in vitro experiments showed that Marsdenia tenacissima injection could inhibit the proliferation and migration ability of MDA-MB-231 cells(P<0.01,P<0.001)and induce apoptosis(P<0.001),as well as inhibit the activation of PI3K-AKT signaling pathway(P<0.05,P<0.01).Conclusion Marsdenia tenacissima may exert its anti-breast cancer effects through multiple targets and pathways,and the mechanism may be related to the inhibition of PI3K-AKT signaling pathway.

Objective:To study the morphologic features of the fusion site of proximal tibial epiphysis in normal adults and analyze its potential clinical value based on Mimics three-dimensional (3D) reconstruction.Methods:CT images of knee joint of 68 patients without obvious abnormalities of lower limbs were retrospectively analyzed in electronic database of our hospital from June 2020 to June 2021, including 41 males and 27 females. The mean age of the patients was 38.7±8.4 years (range, 25-55 years), and the mean body mass index (BMI) was 25.3±4.0 kg/m 2 (range, 18.75-41.8 kg/m 2). Mimics 3D reconstruction technique was used to reconstruct the 3D model of the proximal tibia and epiphyseal fusion site. The relationship between the surface area of epiphyseal fusion site and age and BMI was studied, and the changes of cortical thickness and density at epiphyseal fusion site were also explored. Results:The fusion site of adult epiphyseal reconstructed by Mimics 3D reconstruction is a complex wavy surface structure in 3D space. The surface area of the epiphyseal fusion site was 2,994.7±645.3 mm 2 (range, 1,704.0-4,650.0 mm 2) obtained by 3-Matic Research 12.0. The fusing area of male epiphysis was 3 269.3±533.9 mm 2 than that of female 2,577.6±578.7 mm 2, the difference was statistically significant ( t=5.06, P<0.001). However, there was no significant correlation between the epiphyseal fusion site surface area and age ( R2=0.02, P=0.268) and BMI ( R2=0.04, P=0.125). Mimics software was used to obtain the CT values of bone cortex at the epiphysis line and the distal end of the epiphysis line at 10 mm and 20 mm levels as 451.059±74.953 Hu, 1,018.412±125.732 Hu and 1,414.162±107.848 Hu, respectively. The thickness of bone cortex was 1.814±0.090 mm, 2.511±0.089 mm and 3.189±0.185 mm at 10 mm and 20 mm layers of epiphysis line and distal epiphysis line, respectively. Conclusion:In this study, Mimics 3D reconstruction technique was used to visualize the fusion site of the proximal tibial epiphysis in normal adults. The epiphyseal fusion site of adult is a undulating plate-like structure, and the cortical bone density of epiphyseal fusion site is low and thin, theoretically, it is easy to fracture under indirect violence.

Objective:To compare the biomechanical properties of triangular supporting fixation and Gamma nail fixation for intertrochanteric fractures of the femur.Methods:The femoral CT imaging data provided by a healthy adult male volunteer aged 40 years, height 172 cm, and weight 75 kg were used to reconstruct the femur model using Mimics 21.0 software and Geomagics 2013 software. Evans type I intertrochanteric fracture models were established using UG12.0 software, and Gamma nail and triangular supporting intramedullary nail models were reconstructed to simulate intertrochanteric fracture internal fixation, respectively. In Abaqus software, two internal fixation models of Gamma nail and triangular supporting intramedullary nail in standing state are simulated, and the stress peaks of the main nail, fixation screw and bone substance were collected, also the stress peak of supporting screw of the triangular supporting intramedullary nail is obtained. Additionally, the maximum displacement of the fracture model fixed by Gamma nail and triangular supporting intramedullary nail is measured.Results:Under the load of 1 200 N, the peak stress of the two fracture internal fixation models was located in the main nail, in which the peak stress of the triangular supporting intramedullary nail was 233.73 MPa, which was 11.9% lower than that of the Gamma nail (265.21 MPa); the peak stress of the fixation screw was located in the contact area between the pressure screw and the main nail, which was 23.2% lower in triangular supporting intramedullary nail than that of the Gamma nail (138.86 MPa vs. 180.75 MPa); the peak stress of the bone model was located in the medial cortex of the femur, which was 61.67 MPa and 32.38 MPa, respectively, 47.5% lower in the triangular supporting intramedullary nail than that of the Gamma nail; the peak stress of the supporting screw in the triangular supporting intramedullary nail was 92.04 MPa. The maximum displacement of the fracture model fixed with triangular supporting intramedullary nail was 17.34 mm, which was 10.5% less than the maximum displacement of the fracture model fixed with Gamma nail (19.37 mm). Conclusion:Compared with Gamma nail, triangular supporting intramedullary nail fixation can significantly improve the stability of intertrochanteric fractures and stress distribution as well as reduce stress peak and stress concentration area, which is helpful to improve the efficacy of intertrochanteric fractures.

Objective To analyze the etiology and therapeutic measures of acute pancreatitis (AP) within 5 years in Huangshan region by single center analysis.Methods The clinical data of patients with acute pancreatitis from January 2013 to December 2017 were retrospectively analyzed.Results A total of 394 cases were enrolled,including 170 cases of male and 224 cases of female.Causes of acute pancreatitis included 112 cases of gallstones,21 cases of common bile duct stones,12 cases of gallstones combined with common bile duct stones,8 cases of hyperlipidemia,and 237 cases of other reasons.For the types of treatment,266 cases had conservative treatment,93 cases had laparoscopy,15 cases had EST,16 cases had laparoscopy combined with EST,and 5 cases had open surgery.The average hospital stay was 15.9 days.Conclusion Biliary disease is the main reason for acute pancreatitis,and conservative and surgical treatments are the important therapeutic measures.

Objective To analyze the etiology and therapeutic measures of acute pancreatitis (AP) within 5 years in Huangshan region by single center analysis.Methods The clinical data of patients with acute pancreatitis from January 2013 to December 2017 were retrospectively analyzed.Results A total of 394 cases were enrolled,including 170 cases of male and 224 cases of female.Causes of acute pancreatitis included 112 cases of gallstones,21 cases of common bile duct stones,12 cases of gallstones combined with common bile duct stones,8 cases of hyperlipidemia,and 237 cases of other reasons.For the types of treatment,266 cases had conservative treatment,93 cases had laparoscopy,15 cases had EST,16 cases had laparoscopy combined with EST,and 5 cases had open surgery.The average hospital stay was 15.9 days.Conclusion Biliary disease is the main reason for acute pancreatitis,and conservative and surgical treatments are the important therapeutic measures.