Programmed cell death protein-1(PD-1)/programmed cell death ligand-1(PD-L1)has been considered to be one of the most promising targets for tumor immunotherapy.At present,both monoclonal antibody drugs and small molecule inhibitors targeting PD-1/PD-L1 are facing bottlenecks.Numerous researchers have tried to explore different strategies to block the PD-L1/PD-L1 pathway,hoping to improve the effects of tumor immunotherapy.This review focuses on the degraders,bifunctional molecules and covalent inhibitors that target PD-L1,aiming to provide inspiring insights for the development of anti-PD-1/PD-L1 drugs.

Background: Total knee arthroplasty (TKA) is a common surgical procedure for patients with knee osteoarthritis. The patellar component plays a crucial role in knee biomechanics and can influence postoperative outcomes. This study aimed to investigate the relationship between radiological indices of patellar height and patient outcomes following TKA. Methods: A retrospective analysis was conducted on patients who underwent TKA for osteoarthritis. Radiographic measurements of patellar height, including the Insall-Salvati (IS) ratio, modified Blackburne-Peel (mBP) ratio, Caton-Deschamps ratio, and plateaupatellar angle (PPA), were obtained. Clinical outcomes were assessed using the Knee Society Score (KSS) and the Forgotten Joint Score-12 (FJS-12). Patient satisfaction and postoperative complications were also evaluated. Statistical analyses, including correlation analysis and multiple regression models, were performed to determine the association between radiological indices and patient outcomes. Results: The study included 330 cases that met the inclusion criteria. The analysis revealed significant correlations between different radiological indices of patellar height and patient outcomes. Lower postoperative PPA was correlated with worse KSS and range of motion scores. A decreased mBP ratio was associated with poorer FJS-12 responses and higher risks of dissatisfaction and patellar clunk or crepitus. Increased IS ratio was linked to a lower likelihood of incidental giving way of the knee. Advanced age was associated with reduced dissatisfaction and incidental giving way probabilities. Conclusions The findings of this study demonstrate that radiological indices of patellar height can predict patient outcomes following TKA. Assessing patellar height using various radiographic measurements provides valuable information for surgical planning and prognostic evaluation. Understanding the impact of patellar height on clinical outcomes can aid in optimizing TKA procedures and improving patient satisfaction. These findings emphasize the importance of considering patellar height as a predictive factor in TKA and highlight its potential role in guiding postoperative management and rehabilitation strategies.

Objective: Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms. Methods: A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations. Results: The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking. Conclusion Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.

Objective: Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms. Methods: A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations. Results: The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking. Conclusion Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.

Objective: Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms. Methods: A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations. Results: The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking. Conclusion Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.

Objective: Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms. Methods: A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations. Results: The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking. Conclusion Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.

Objective: Self-determination theory (SDT) deems that people have three causality orientations: autonomy orientation, control orientation, and impersonal orientation. Previous studies suggested that lower autonomy orientation or higher control and impersonal orientations may be associated with more addictive behaviors. Our study aimed to investigate if these associations exist in Internet gaming disorder (IGD), and if sensation seeking, anxiety, and depression could influence the associations between causality orientations and IGD symptoms. Methods: A total of 1,400 college students completed the Internet Gaming Disorder Scale, General Causality Orientation Scale, Brief Sensation Seeking Scale, Generalized Anxiety Disorder Scale, and Patient Health Questionnaire. Correlation, multiple linear regressions, structural equation model (SEM) analyses, and moderation analyses were conducted to explore the associations. Results: The control and impersonal orientations were positively associated with IGD symptoms, while the autonomy orientation was negatively associated with them. Moreover, SEM analyses showed that the autonomy-IGD relationship was totally mediated by anxiety and depression, the impersonal-IGD relationship was partially mediated by anxiety, and the control-IGD relationship was partially mediated by depression. Finally, the effects of causality orientations on IGD were moderated by sensation seeking. Conclusion Overall, autonomy orientation is linked to fewer gaming problems, whereas control and impersonal orientations are associated with more gaming problems. Moreover, the relationships between causality orientations and IGD symptoms are mediated by anxiety and depression and moderated by sensation seeking. Our findings inform theory on the motivations of gaming behaviors and may shed light on the prevention and intervention of IGD from the perspective of SDT.

Objective:To analyze the mutation spectrum and regional distribution of susceptibility pathogenic genes in Chinese chronic pancreatitis (CP) patients.Methods:A retrospective analysis was conducted on 1 758 sporadic CP patients who underwent gene sequencing for pathogenic mutations of four major susceptibility genes ( SPINK1, PRSS1, CTRC, and CFTR) at the First Affiliated Hospital of Naval Medical University from December 2010 to November 2022. Pathogenic mutations of four major susceptibility genes were detected by using the next-generation sequencing, and both known and novel pathogenic mutations were validated by Sanger sequencing. The ethnic and regional distributions of pathogenic mutations across different ethnic groups were compared. The ArcMap 10.7 software was used to provide the distribution map of common CP pathogenic mutations in China, and regional differences of these mutations were assessed. According to seven major geographical regions in China, we also evaluated the enrichment differences of CP pathogenic mutations in North China region, Northeast China region, East China region, Central China region, South China region, Southwest China region, and Northwest China region. Results:Among 1 758 CP patients, 50.23% (883/1 758) carried pathogenic mutations, and the SPINK1 pathogenic mutations were most predominated (39.31%). Among them, c.194+2T>C mutations accounted for 94.21% of all SPINK1 mutations. 32.59% (573/1 758) of patients carried single heterozygous mutation of one susceptibility gene, and 4.61% carried homozygous mutation of SPINK1 c.194+2T>C. There was no statistically significant difference on the overall pathogenic mutation carrying rate between Han and ethnic minority patients, whereas the mutation carrying rate of SPINK1 c.194+2T>C was significantly higher among Han patients than among ethnic minorities (37.48% vs 20.00%, P<0.05). Among 31 provinces and cities, the mutation carrying rate of CP patients in Tianjin, Guangdong, Yunnan, Hubei and Anhui were all higher than 60.00%. The SPINK1 mutations accounted for the highest proportion of pathogenic mutations across all provinces (33.33% to 61.54%), and SPINK1 c.194+2T>C was the most prevalent mutation. The mutation carrying rate of SPINK1 c.194+2T>C was higher than 40.00% in Jilin, Liaoning, Tianjin, Anhui, Jiangxi, Hubei, Henan, and Guangdong. Distribution analysis of seven geographic regions showed that the overall carrying rate of pathogenic mutations in North China region was significantly lower than that in Central China region (represented by Henan, Hubei, and Hunan; 38.38% vs 58.15%), and the differences were statistically significant ( P<0.05). Additionally, although the carrying rate of SPINK1 c.194+2T>C was highest in Central (41.85%) and Northeast China region (38.78%), no significant differences were found among different regions. Conclusions:Genetic factors was the main etiology of CP in China, with SPINK1 c.194+2T>C mutations being most prevalent. The carrying rates of common susceptibility genes of CP were highest in Central China region as well as SPINK1 c.194+2T>C mutation.

Objective:To analyze the mutation spectrum and regional distribution of susceptibility pathogenic genes in Chinese chronic pancreatitis (CP) patients.Methods:A retrospective analysis was conducted on 1 758 sporadic CP patients who underwent gene sequencing for pathogenic mutations of four major susceptibility genes ( SPINK1, PRSS1, CTRC, and CFTR) at the First Affiliated Hospital of Naval Medical University from December 2010 to November 2022. Pathogenic mutations of four major susceptibility genes were detected by using the next-generation sequencing, and both known and novel pathogenic mutations were validated by Sanger sequencing. The ethnic and regional distributions of pathogenic mutations across different ethnic groups were compared. The ArcMap 10.7 software was used to provide the distribution map of common CP pathogenic mutations in China, and regional differences of these mutations were assessed. According to seven major geographical regions in China, we also evaluated the enrichment differences of CP pathogenic mutations in North China region, Northeast China region, East China region, Central China region, South China region, Southwest China region, and Northwest China region. Results:Among 1 758 CP patients, 50.23% (883/1 758) carried pathogenic mutations, and the SPINK1 pathogenic mutations were most predominated (39.31%). Among them, c.194+2T>C mutations accounted for 94.21% of all SPINK1 mutations. 32.59% (573/1 758) of patients carried single heterozygous mutation of one susceptibility gene, and 4.61% carried homozygous mutation of SPINK1 c.194+2T>C. There was no statistically significant difference on the overall pathogenic mutation carrying rate between Han and ethnic minority patients, whereas the mutation carrying rate of SPINK1 c.194+2T>C was significantly higher among Han patients than among ethnic minorities (37.48% vs 20.00%, P<0.05). Among 31 provinces and cities, the mutation carrying rate of CP patients in Tianjin, Guangdong, Yunnan, Hubei and Anhui were all higher than 60.00%. The SPINK1 mutations accounted for the highest proportion of pathogenic mutations across all provinces (33.33% to 61.54%), and SPINK1 c.194+2T>C was the most prevalent mutation. The mutation carrying rate of SPINK1 c.194+2T>C was higher than 40.00% in Jilin, Liaoning, Tianjin, Anhui, Jiangxi, Hubei, Henan, and Guangdong. Distribution analysis of seven geographic regions showed that the overall carrying rate of pathogenic mutations in North China region was significantly lower than that in Central China region (represented by Henan, Hubei, and Hunan; 38.38% vs 58.15%), and the differences were statistically significant ( P<0.05). Additionally, although the carrying rate of SPINK1 c.194+2T>C was highest in Central (41.85%) and Northeast China region (38.78%), no significant differences were found among different regions. Conclusions:Genetic factors was the main etiology of CP in China, with SPINK1 c.194+2T>C mutations being most prevalent. The carrying rates of common susceptibility genes of CP were highest in Central China region as well as SPINK1 c.194+2T>C mutation.

Objective:To investigate the relationship between pancreatic fibrotic marker transforming growth factor-β(TGF-β) and platelet derived growth factor-BB(PDGF-BB) and serum glycated hemoglobin (HbA1c) levels in patients with type 3c diabetes mellitus secondary to chronic pancreatitis(CP-T3cDM).Methods:The clinical data of 39 patients with CP-T3cDM admitted to the Department of Gastroenterology of the First Affiliated Hospital of Naval Medical University between February 2018 and August 2020 were collected, and the patients' age, gender, body mass index, duration of chronic pancreatitis and diabetes mellitus, smoking history, alcohol consumption history, serum HbA1c level at admission, degree of pancreatic atrophy, morphology of the main pancreatic duct, and treatment of diabetes mellitus were recorded. Serum TGF-β and PDGF-BB were detected by ELISA. Patients were divided into high and low level group according to the median TGF-β and PDGF-BB levels, respectively. Clinical characteristics of patients were compared between the TGF-β and PDGF-BB high and low level group. The correlation between TGF-β, PDGF-BB and HbA1c was analyzed by Spearman's correlation analysis.Results:A total of 39 CP-T3cDM patients were included; 35 were male and 4 were female. The age of first onset of chronic pancreatitis was (42±14) years old, and the duration of diabetes mellitus was 24(4, 36) months. The serum HbA1c level was (7.8±1.6)%, and the serum TGF-β and PDGF-BB levels were 20.5(10.5, 43.1) and 647.5(276.9, 1349.2)pg/ml, respectively. The serum HbA1c levels of patients in the high-level group of serum TGF-β and PDGF-BB were significantly higher than those in the corresponding low-level group [8.6%(7.4%, 9.9%) vs 6.7%(6.2%, 7.8%) and 8.6%(7.4%, 9.6%) vs 6.7%(6.1%, 7.8%), respectively] , and the difference was statistically different (both P value <0.01), while none of other indicators showed statistically significant differences between both groups. The correlation analysis showed that the levels of TGF-β and PDGF-BB were significantly positively correlated with HbA1c level ( r=0.45, 0.53, both P value <0.01). Conclusions:Increased pancreatic fibrosis in patients with CP-T3cDM was an important factor contributing to elevated blood glucose level. Patients with higher serum pancreatic fibrotic factors exhibited a significant increase in HbA1c level.