Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective To establish a reliable prediction model for radiation pneumonitis(RP)based on multi-regional radiomics analysis of localizable CT images.Methods A retrospective analysis was conducted on 185 patients who received radiotherapy from January 2021 to June 2023 in the Department of Radiotherapy,Xuzhou Cancer Hospital.Patients were classified as having RP or not based on imaging combined with clinical diagnosis.Three regions of interest(ROI)were defined in the localizable CT images:Lung,Lung-PTV and PTV,and their radiomics features were extracted.After feature screening using methods such as Mann-Whitney Utest,recursive feature elimination,and Lasso,a prediction model was established using support vector machine classification algorithm.The model performance was validated using 6 evaluation metrics:the area under the receiver operating characteristic curve(AUC),accuracy,specificity,sensitivity,positive predictive value,and negative predictive value.Results The prediction model consisted of 7 radiomics features.The clinical model of target-to-lung ratio,PTV model,Lung model,and Lung-PTV model achieved AUC values of 0.535,0.801,0.672,and 0.706 in the test set,respectively.The AUC value and accuracy of PTV model reached 0.843 and 0.775 in the training set,while 0.801 and 0.750 in the test set.PTV model was superior to Lung model,Lung-PTV model,and clinical model in predictive performance.The AUC values of the combined PTV+(Lung-PTV)model in the training and test sets were 0.867 and 0.806,respectively,higher than those of PTV model and Lung-PTV model.Conclusion The predictive ability of the prediction models constructed from radiomics features in different ROI for symptomatic RP varies.The radiomics prediction model using PTV as ROI exhibits superior predictive performance,and the combined multi-regional radiomics model can further improve the predictive ability for RP.

Objectives:To explore whether short-course radiotherapy (SCRT)-based total neoadjuvant therapy (TNT) combined with PD-1 inhibitors could further promote tumor regression and improve the prognosis.Methods:This is a prospective, multicenter, two-arm randomized controlled, seamless phase Ⅱ/Ⅲ trial for proficient mismatch repair or microsatellite stable (pMMR/MSS) locally advanced rectal cancer (LARC). Eligible patients were randomly assigned to the iTNT (TNT+PD-1) group or the TNT group. Patients in the TNT group received SCRT (5 Gy×5) followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX chemotherapy, with the iTNT group receiving SCRT followed by the same regime in combination with 4 cycles of Sintilimab. Total mesorectal excision (TME) surgery or watch and wait (W&W) was performed after neoadjuvant therapy and then 2 cycles of same regimen as before were recommended. The primary endpoints are the complete response (CR) rate for phase Ⅱ trial and 3-year disease-free survival (DFS) for phase Ⅲ trial. A total of 588 patients will be enrolled for the phase Ⅱ/Ⅲ trial. Short-term efficacy and safety data from the initial 100 treated patients were analyzed as planned.Results:From 2022-8-31 to 2023-5-24 the initial 100 patients were enrolled from 10 hospitals in China, 76.0%(76/100) patients were male, and the median age was 61 years (21-74 years). More patients had tumors located in the lower rectum (78.0%, 78/100), staged T3-4 (97.0%, 97/100) and N1-2 (93.0%, 93/100), and about half of the tumors invaded the mesorectal fascia (52.0%, 52/100) and with extramural vascular invasion (51.0%, 51/100). Analyses were performed according to the per-protocal (PP) set. All patients in the iTNT group ( n=52) and the TNT group ( n=48) completed SCRT; The 4-cycle chemotherapy±Sintilimab completion rates were 86.5% and 100.0% in the iTNT and TNT groups, respectively. In the iTNT group, 82.7% (43/52), 11.5% (6/52), and 5.8% (3/52) of the patients received 4, 3, and 2 cycles of PD-1 inhibitor. After TNT, 68 patients underwent radical surgery and 15 patients achieved cCR and adopted W&W. The pathological complete response (pCR) rates were 48.5% (16/33) and 17.1% (6/35) in the iTNT and TNT groups, with CR rates of 50.0% (25/50) and 26.1% (12/46), respectively. The incidence of treatment-related grade 3-4 adverse events was 26.9% (14/52, iTNT group) and 18.8% (9/48, TNT group), with thrombocytopenia and leukopenia being the most common. Among patients receiving immunotherapy, grade 3 immunotherapy-related adverse events occurred in 2 (3.8%, 2/52) patients: one case was pancreatitis, another case was hepatitis combined with myositis and myocarditis. Conclusion:The preliminary results show that SCRT-based TNT combined with PD-1 inhibitors could further improve the CR rate for LARC without unexpected serious adverse events.

Objective To establish a reliable prediction model for radiation pneumonitis(RP)based on multi-regional radiomics analysis of localizable CT images.Methods A retrospective analysis was conducted on 185 patients who received radiotherapy from January 2021 to June 2023 in the Department of Radiotherapy,Xuzhou Cancer Hospital.Patients were classified as having RP or not based on imaging combined with clinical diagnosis.Three regions of interest(ROI)were defined in the localizable CT images:Lung,Lung-PTV and PTV,and their radiomics features were extracted.After feature screening using methods such as Mann-Whitney Utest,recursive feature elimination,and Lasso,a prediction model was established using support vector machine classification algorithm.The model performance was validated using 6 evaluation metrics:the area under the receiver operating characteristic curve(AUC),accuracy,specificity,sensitivity,positive predictive value,and negative predictive value.Results The prediction model consisted of 7 radiomics features.The clinical model of target-to-lung ratio,PTV model,Lung model,and Lung-PTV model achieved AUC values of 0.535,0.801,0.672,and 0.706 in the test set,respectively.The AUC value and accuracy of PTV model reached 0.843 and 0.775 in the training set,while 0.801 and 0.750 in the test set.PTV model was superior to Lung model,Lung-PTV model,and clinical model in predictive performance.The AUC values of the combined PTV+(Lung-PTV)model in the training and test sets were 0.867 and 0.806,respectively,higher than those of PTV model and Lung-PTV model.Conclusion The predictive ability of the prediction models constructed from radiomics features in different ROI for symptomatic RP varies.The radiomics prediction model using PTV as ROI exhibits superior predictive performance,and the combined multi-regional radiomics model can further improve the predictive ability for RP.

Objective To explore the effect of disposable electronic soft mirror and conventional repeatable soft mirror on the renal function and prostaglandin E2(PGE2),5-hydroxytryptamine(5-HT)levels in patients with upper ureteral calculi and analyze the factors influencing recurrence after retrograde intrarenal surgery(RIRS).Methods 114 patients with upper ureteral calculi from March 2022 to March 2023 were selected and randomly divided into two groups,with 57 cases forming the observation group and 57 cases forming the control group.The observation group was administrated with RIRS via disposable electronic soft mirror,while the control group accepted RIRS via conventional repeatable soft mirror.The two groups were compared in the aspect of surgical data.Patients'serum renal function indicators[blood urea nitrogen(BUN),creatinine(Cr),cystatin C(CysC)],PGE2 and 5-HT levels were tested preoperative and postoperative 24 h.Postoperative complications and recurrence were compared between the two groups after 6 months follow-up.The patients were grouped according to whether there was recurrence or not.The medical records of recurrence group and non-recurrence group were collected,and the risk factors of recurrence were analyzed statistically.Results There was no sxtatistically significant difference between the observation group and the control group in terms of surgical time,intraoperative bleeding,one-time stone removal rate,and hospital stay(P>0.05).After operation both groups saw much higher levels of BUN,Cr,CysC,PGE2 and 5-HT than they did before the operation(P<0.05),but no significant difference in the aforementioned indicators was seen between the two groups either before or after the operation(P>0.05).The incidence of complications and recurrence rate of the observation group were 3.51%and 15.79%respectively,seeing no big difference from 12.28%and 21.05%of the control group(P>0.05).The body mass index(BMI),postoperative residual calculi and urinary tract infections in the recurrence team were remarkably higher than those in the non recurrence team(P<0.05).The results of multivariate Logistic regression analysis showed that after adjusting for confounding factors such as gender,age,course of disease,maximum diameter of calculi,number of calculi,location of calculi,and surgical method,postoperative residual calculi and postoperative urinary tract infections were independent risk factors for postoperative recurrence of upper ureteral calculi after RIRS(P<0.05).Conclusion Both disposable electronic soft endoscopy and conventional repeatable soft endoscopy can achieve satisfactory results in the treatment of upper ureteral calculi,both can impact the renal function and serum PGE2,5-HT levels in patients to a certain extent,and both present a risk of recurrence after surgery.Residual postoperative calculi and postoperative urinary tract infections are independent risk factors inducing recurrence of upper ureteral calculi after RIRS.

This study details a rare instance of a high fibula fracture, classified as a Bosworth fracture. A 54-year-old male presented with pain and restricted movement in his right ankle after a sprain that occurred 10 hours ago. After initial assessments he was diagnosed as a right ankle fracture with posterior dislocation, a proximal right fibula fracture, and an injury to the right lower tibiofibular joint. According to Lauge-Hansen classification this was a type IV injury charactered by pronation-external rotation. Attempts at manual reduction were unsuccessful. Further evaluation using CT scans with three-dimensional reconstruction showed a separation and dislocation at the lower tibiofibular joint, with the distal fibula interlocked with the posterolateral tibia. Additionally, comminuted fractures of the medial and posterior malleoli showed significant displacement and misalignment, leading to persistent ankle dislocation. Immediate calcaneal traction and symptomatic treatment were applied. On the third day of admission a reevaluation indicated successful reduction of the dislocated ankle and tibiofibular joint. Surgery was then performed with favorable outcome. Follow-up X-rays at one and a half years after surgery demonstrated bony heal of the fractures with normal ankle joint space and functionality. Bosworth fractures involving pronation-external rotation are notably less common than those with posterior-external rotation. When manual reduction proves ineffective, applying continuous calcaneal traction with gradual tension can help unlock fibular dislocation, thereby expediting surgical intervention.

Objective:To investigate the status quo of psychological contracts and influencing factors among members of the "1+N" family doctor teams in Shenzhen and to explore the impact of psychological contracts on job burnout.Methods:This cross-sectional study was conducted from September 30 to October 31, 2022 among 361 members of 92 family doctor teams from 92 community health service centers which provided family doctor team service in Shenzhen city. A self-designed general information questionnaire, an employee psychological contract questionnaire (including organizational responsibility and personal responsibility dimensions), and a job burnout scale (including emotional exhaustion, depersonalization, and personal accomplishment dimensions) were used in the study. T-tests, one-way ANOVA, Pearson correlation analysis, and multiple linear regression analysis were used to analyze the influencing factors of psychological contracts and job burnout.Results:Among 361 respondents, there were 299 females (82.8%) and 62 males (17.2%), and a higher proportion of general practitioners (37.5%, 129/361) and nurses (41.8%, 151/361). The total score of psychological contracts among the 361 respondents was (141.6±19.5), with organizational responsibility scoring (70.6±11.2) and personal responsibility scoring (71.0±9.3). On the job burnout scale, emotional exhaustion scored (17.89±6.82), depersonalization scored (6.51±2.54), and personal accomplishment scored (30.95±5.70). General practitioners scored lower in organizational responsibility and personal responsibility compared to other members ( F=7.341,3.119, all P<0.05), and higher in emotional exhaustion and depersonalization ( F=7.637, 2.415, all P<0.05). Members with≤5 years of work experience scored lower in personal responsibility and personal accomplishment ( F=3.656, 4.205, all P<0.05). Correlation analysis showed that scores of organizational responsibility and personal responsibility were negatively correlated with levels of emotional exhaustion and depersonalization ( r=-0.618, -0.526, all P<0.01), ( r=-0.404, -0.393, all P<0.01), and positively correlated with personal accomplishment ( r=0.500, 0.558, all P<0.01). Multiple linear regression analysis indicated that organizational responsibility negatively affected emotional exhaustion and depersonalization ( β=-0.554, -0.274, all P<0.01), and positively affected personal accomplishment ( β=0.172, P<0.05). Personal responsibility positively affected personal accomplishment ( β=0.404, P<0.01). Conclusions:The study demonstrates that general practitioners in family doctor teams in Shenzhen city have lower psychological contract levels and are more prone to emotional exhaustion and depersonalization; members with≤5 years of work experience have lower personal responsibility and accomplishment. The results indicate that enhancing organizational responsibility can reduce job burnout of members in family doctor teams.

Immune factors play an important role in recurrent spontaneous abortion(RSA),and immune imbalance affects embryo implantation,growth,and development.There is currently no consensus on the etiology and pathogenesis of RSA caused by immune factors.Based on the theory of latent toxic in TCM and combined with the pathological mechanism of the dynamic changes of immune abnormal substances in the body,this article proposed that latent toxic is the key cause of RSA caused by immune factors.Furthermore,it expounded the pathogenic characteristics of latent toxic:combination of heat and blood stasis hidden in the womb,and latent toxic plays a role in embryo formation under qi deficiency conditions.It is established that latent toxin stagnation in the membrane is the pathogenic mechanism.Moreover,this article revealed the variable pathological changes such as the blockage of the inner membrane system and the outer membrane system.Treatment should be based on the basic methods of tonifying qi and nourishing blood,tonifying kidney to secure the Thoroughfare Vessel,clearing heat and cooling blood,promoting blood circulation and removing blood stasis.This article could provide a theoretical basis for TCM syndrome differentiation and treatment of RSA caused by immune factors.

Inflammatory bowel disease(IBD)is a disease characterized by chronic,recurrent intestinal inflammation,includ-ing Crohn's disease(CD)and ulcerative colitis(UC).Etiology and pathogenesis of IBD are unknown,and the treatment is difficult.In recent years,immunocellular therapy represented by regulatory T(Treg)cell therapy and dendritic cell(DC)therapy has developed rapidly in the field of immune-related disease treatment,and some progress has also been made in the treatment of IBD.This review will introduce application and progression of Treg cell therapy and DC therapy in IBD treatment.

[Objective]To investigate the effect and mechanism of Shuxuetong and its main component hirudin on the apoptosis of cerebellar granule neurons(CGNs)in Sprague-Dawley(SD)rats.[Methods]CGNs incubated in vitro for 7 days were divided into survival control group or 25 K group(cultured in medium containing 25 mmol/L KCL)and apopto-sis group or 5 K group(cultured in medium containing 5 mmol/L KCL).CGNs were separately treated with proportionally diluted and different concentrations of Shuxuetong(1/50,1/40,1/30,1/20 and 1/10)and the corresponding different con-centrations of hirudin(2,2.5,3.34,5 and 10 U/mL).Hoechst staining was performed to analyze the apoptosis.Western blot was used to detect the expression levels of Cleaved Caspase-3,Bim and VEGF.[Results]Hoechst staining showed that 5 K group had a higher apoptosis rate than 25 K group.In 25 K group,there was no significant change in the apoptosis rate between neurons treated with different concentrations of Shuxuetong and hirudin,but significant changes was found in 5 K group and the higher the concentration,the lower the apoptosis rate.Western blot results revealed that,compared with control neurons in 5 K group,Shuxuetong injection and hirudin treatments resulted in a decrease of Cleaved Caspase-3 and Bim expression,but an increase of VEGF protein.[Conclusions]Shuxuetong and its main component hirudin inhibits the apoptosis of CGNs through suppressing proapoptotic BH3-only protein Bim.