[摘 要] 目的：评估放疗作为原位疫苗的联合治疗模式在晚期软组织肉瘤（STS）患者中的有效性和安全性。方法：回顾性分析2020年12月至2024年9月期间在南京大学医学院附属鼓楼医院肿瘤中心接受联合治疗模式的12例晚期STS患者的临床资料。12例患者均接受了联合治疗。放疗主要以大分割为主。靶向治疗：安罗替尼10例、阿帕替尼2例。免疫治疗以PD-1抗体为主。主要研究终点为疾病控制率（DCR），次要研究终点为客观有效率（ORR）及安全性。结果：接受联合治疗的12例STS患者中有0例CR，4例PR，7例SD，1例PD。ORR为33%，DCR为91.7%，其中靶病灶的DCR为100%。12例患者中，9例出现Ⅰ~Ⅱ级不良反应。最常发生的血液学不良反应是贫血（6例）、肝功能检查结果异常（3例）。最常发生的非血液学不良反应是尿蛋白（5例）、高血压（4例）、甲状腺功能异常（3例）、厌食（3例）、恶心呕吐（2例）；仅2例发生Ⅲ级血液毒性，有1例发生Ⅲ级气胸。结论：放疗作为原位疫苗的联合治疗模式在晚期STS患者中展现出较高的DCR，且未出现严重不良反应。该联合治疗模式具有良好的有效性与安全性。

Objective:To explore the efficacy and safety of tislelizumab combined with zanubrutinib in the treatment of refractory diffuse large B-cell lymphoma (DLBCL).Methods:A prospective observational study was conducted. A total of 10 patients with refractory DLBCL admitted to Beijing Chaoyang District Third Ring Cancer Hospital, a specialist medical consortium of Cancer Hospital Chinese Academy of Medical Sciences from November 2020 to February 2023 were prospectively collected. All the 10 refractory DLBCL patients at least received first-line systemic therapy containing rituximab; and they were given tislelizumab 200 mg, intravenous infusion, on day 1 and zanubrutinib 160 mg, orally, twice a day, day 1-day 21, with 21 days as 1 cycle; 6 patients received second-line therapy and 4 patients received ≥ third-line therapy. Subsequent regimens were added with rituximab (375 mg/m 2, intravenous infusion on day 1). The primary endpoint will be reached 12 months after enrollment if there was no disease progression or other events that were scheduled to withdraw from the study. The therapeutic efficacy was summarized at the end of the follow-up in March 2023. Kaplan-Meier method was used to make survival analysis and the adverse reactions were summed up. Results:There were 6 males and 4 females, all at stage Ⅲ-Ⅳ; and age [ M ( Q1, Q3)] was 55 years (50 years, 69 years). All 10 patients completed 90 cycles of treatment with tislelizumab and zanubrutinib, with the cycle number of 8 cycles (2 cycles, 24 cycles). The follow-up time was 19 months (11 months, 28 months); 4 cases achieved complete remission, 3 cases achieved partial remission and 1 case had the stable disease. The progression-free survival was 8.5 months (1.3 months, 27.0 months); the median remission duration time and median overall survival time were not reached. Treatment-related adverse reactions included 2 cases of neutropenia, 1 case of anemia, and 1 case of elevated alanine aminotransferase and aspartate aminotransferase, all of which were grade 1-2. Conclusions:Tislelizumab combined with zanubrutinib has good clinical efficacy and safety in the treatment of refractory DLBCL.

Objective To compare the safety and clinical efficacy of lesion removal combined with percutaneous pedicle screw fixation with classical posterior lesion removal in the treatment of lumbar brucelli spondylitis(LBS)by unilateral biportal endoscopic technique with transforaminal lumbar interbody fusion(UBE-LIF)technique.Methods The clinical data of 32 patients with LBS admitted by the Department of Spine and Orthopedics of Gansu Provincial Hospital of Traditional Chinese Medicine from January 2020 to January 2022 were retrospectively analyzed,and the clinical data of the 32 LBS patients were divided into 15 cases in the UBE-LIF group and 17 cases in the posterior group.The general data,surgery-related indexes,and postoperative pathological HE staining of the two groups were recorded and analyzed.The patients'clinical recovery was assessed according to their erythrocyte sedimentation rate(ESR)and C-reactive protein(CRP),low back pain visual analogue score(VAS),Japanese Orthopaedic Association(JOA)score,and Oswestry Dysfunction Index(ODI)preoperative,1 week after surgery,1,3,6 months and 1 year after surgery.Lumbar lordosis angle(LL)and intervertebral space height(DH)were measured by imaging before surgery and at the last follow-up,and intervertebral bone graft fusion was assessed using Suk grading criteria.Results Both groups successfully completed the operation and no serious postoperative complications occurred.There were no significant differences in gender,age,surgical segment,operation time,preoperative ESR and CRP,preoperative VAS,JOA score and ODI index,preoperative LL and DH(P＞0.05).The intraoperative blood loss,postoperative drainage,postoperative getting out of bed,and postoperative hospital stay in UBE-LIF group were significantly lower than those in the posterior group(P＜0.001).Pathological examination of diseased tissues was performed during surgery,all of which was consistent with brucellosis changes.Patients in both groups were followed up for 12-18 months,with an average of 14.8 months.The VAS,JOA score,and ODI index at all postoperative time points in the two groups were significantly improved compared with the preoperative period(P＜0.05).The difference between the two groups was significantly greater than that in the postoperative group:VAS score was lower in UBE-LIF group than in the posterior group(P＜0.01),CRP in both groups was higher than that in the preoperative group,and the elevation level was significantly lower in UBE-LIF group than in the posterior group(P＜0.001).There was no significant difference in ESR between the two groups compared with that before surgery(P＞0.05).There were no significant differences in VAS,JOA score,ODI index,CRP or ESR between the remaining time points after surgery(P＞0.05).At the last follow-up,imaging examination showed that the overall fusion rate of intervertebral bone graft in UBE-LIF group was 93.3％and 94.1％in the posterior group,without significant difference(x2=0.246,P=0.884).LL and DH were significantly improved in both groups compared with preoperative ones(P＜0.01),and the two groups did not significantly differ before and after surgery(P＞0.05).Conclusion Both surgical treatments for LBS are safe effect.Compared with posterior lesion removal bone graft fusion internal fixation,UBE-LIF technology combined with percutaneous pedicle screw internal fixation has the advantages of clear intraoperative vision,less blood loss,faster early postoperative recovery,and shorter postoperative hospital stay,and thus is a feasible surgical method for the minimally invasive treatment of LBS.

Background Arsenic, cobalt, barium, and other individual metal exposure have been confirmed to be associated with the incidence of kidney stones. However, there are few studies on the association between mixed metal exposure and kidney stones, especially in occupational groups. Objective To investigate the association between mixed metal exposure and kidney stones in an occupational population from a metal smelting plant. Methods A questionnaire survey was conducted to collect sociodemographic characteristics, medical history, and lifestyle information of 1158 mixed metal-exposed workers in a metal smelting plant in Guangdong Province from July 2021 to January 2022. Midstream morning urine samples were collected from the workers, the concentrations of 18 metals including lithium, vanadium, chromium, manganese, cobalt, nickel, copper, zinc, arsenic, selenium, strontium, molybdenum, cadmium, cesium, barium, tungsten, titanium, and lead were measured by inductively coupled plasma mass spectrometry, and the urinary mercury levels were measured by cold atomic absorption spectroscopy. Based on predetermined inclusion criteria, a total of 919 mixed metal-exposed workers were included in the study, including 117 workers in the kidney stone group and 802 workers in the non-kidney stone group. With a detection rate of urinary metals greater than 80% as entry criterion, 16 eligible metals were finally included for further analysis. Parametric or non-parametric methods were used to compare the differences between continuous or categorical variables of the non-kidney stone group and the kidney stone group. Logistic regression models were constructed to explore the association between individual metal exposures and kidney stones. Weighted quantile sum (WQS) regression models were used to evaluate the association between mixed metal exposure and kidney stones, as well as the weights of each metal on kidney stones. Then Bayesian kernel machine regression (BKMR) models were used to explore the overall effect of mixed metal exposure on renal calculi and the potential interactions between metals. Results We found that there were significant differences in sex, age, length of service, and body mass Index (BMI) between the non-kidney stone group and the kidney stone group (P<0.05). The urinary concentrations of molybdenum and barium in the kidney stone group were higher than those in the non-kidney stone group, and the differences were statistically significant (P<0.05). The logistic regression models demonstrated that urinary cobalt, arsenic, molybdenum, and barium were positively correlated with the risk of kidney stones (P_trend<0.05). The WQS regression models showed that the mixed exposure to vanadium, cobalt, arsenic, molybdenum, and barium was positively associated with the risk of kidney stones (P<0.05). Among them, molybdenum, arsenic, and barium accounted for 0.391, 0.337, and 0.154, respectively. The BKMR results revealed a positive association between metal mixture exposure and the risk of kidney stones (P<0.05). When other metals were fixed at the 25th, 50th, or 75th percentile, arsenic, molybdenum, cobalt, and barium exhibited significant positive effects on the risk of kidney stones (P<0.05), while vanadium showed a significant negative effect (P<0.05). The interaction analysis demonstrated interactions between barium and cobalt, as well as between vanadium and cobalt (P<0.05). Conclusion In the occupational population of this smelter, occupational mixed metal exposure could increase the risk of kidney stones, and the main metals are molybdenum, arsenic, barium, and cobalt.

Objective:To investigate the prognostic factors for the risk of prolonged postoperative ileus (PPOI) after colorectal cancer resection.Methods:The clinical data of 896 patients undergoing radical colorectal cancer resection at Affiliated Hospital of Qingdao University between Jan 2016 and Dec 2022 were retrospectively analyzed. Patients were divided into PPOI group (59 cases) and non-PPOI group (837 cases) according to whether PPOI happened after surgery. Potential prognostic factors for the risk of developing PPOI were analyzed by univariate and multivariate Logistic regression. The receiver operating characteristic curve analysis was performed to assess the predictive power of potential prognosis factors.Results:Fifty-nine patients (6.5%) developed PPOI after radical colorectal cancer resection. Univariate and multifactorial logistic regression analyses showed that diabetes mellitus ( OR=2.360, P=0.018), preoperative albumin level <35 g/L ( OR=2.196, P=0.036), postoperative epidural analgesia ( OR=2.399, P=0.007), open surgery ( OR=3.413, P=0.001), and ICU hospitalization ≥ 48 h ( OR=6.134, P<0.001) were independent prognostic factors for PPOI. Combining the above prognostic factors to construct the receiver operating characteristic curve yielded an area under the curve of 0.806 (95% CI: 0.698-0.838), with an accuracy, sensitivity and specificity of 73.9%, 74.0%, 72.9%, respectively. Conclusion:Diabetes mellitus, preoperative albumin level, postoperative epidural analgesia, open surgery, and ICU hospitalization ≥ 48 h were risk factors for PPOI after radical colorectal cancer resection.

Objective To evaluate the value of a machine learning-based biparametric magnetic resonance imaging(bpMRI)radiomics model in predicting clinically significant prostate cancer(csPCa)in the transitional zone.Methods A retrospective analysis was con-ducted on 507 cases in two medical centers.All patients underwent prostate MRI examinations before surgery,with complete patho-logical data.The case distribution was as follows:256 cases of csPCa,97 cases of clinically insignificant prostate cancer(ciPCa),and 154 cases of benign prostatic hyperplasia(BPH).Using the R language,the data from Center One was randomly divided into training and test groups at a ratio of 7∶3,and the data from Center Two as an independent external validation group.The image features from T2 WI and diffusion weighted imaging(DWI)were extracted,and the least absolute shrinkage and selection operator(LASSO)was used to reduce dimensionality and filter features.Two datasets were constructed based on T2 WI features alone and combined T2 WI and DWI features.Six prediction models were established using random forest(RF),logistic regression(LR),and support vector machine(SVM).The efficacy of six models of T2 WI features and combined T2 WI and DWI features in the diagnosis of prostate dis-eases through receiver operating characteristic(ROC)curve,area under the curve(AUC),and decision curve analysis(DCA)were compared and evaluated.Results In the training group,feature screening identified 7 and 8 features from the T2WI single sequence and the T2WI with DWI dual sequence for csPCa prediction in the transitional zone.The results showed that the T2WI with DWI dual sequence RF model had the highest AUC performance.The AUC of the training,test,and validation groups were 0.950,0.866,and 0.818,respectively.The test group accuracy was 0.805,sensitivity was 0.690,and specificity was 0.920;the validation group accu-racy was 0.726,sensitivity was 0.661,and specificity was 0.793.DCA showed that within a wide probability threshold range,the T2 WI with DWI dual sequence RF model had the greatest net benefit.Conclusion Based on the bpMRI radiomics model,non-invasive prediction of csPCa in the transitional zone can be achieved before surgery,which helps to make clinical diagnosis and treatment decisions.

Objective:To investigate the effects of gelatin methacrylate anhydride (GelMA) hydrogel loaded with small extracellular vesicles derived from human umbilical cord mesenchymal stem cells (hUCMSCs-sEVs) in the treatment of full-thickness skin defect wounds in mice.Methods:This study was an experimental study. hUCMSCs-sEVs were extracted by ultracentrifugation, their morphology was observed through transmission electron microscope, and the expression of CD9, CD63, tumor susceptibility gene 101 (TSG101), and calnexin was detected by Western blotting. The human umbilical vein endothelial cells (HUVECs), the 3 rd and 4 th passages of human epidermal keratinocytes (HEKs) and human dermal fibroblasts (HDFs) were all divided into blank control group (routinely cultured) and hUCMSC-sEV group (cultured with the cell supernatant containing hUCMSCs-sEVs). The cell scratch test was performed and the cell migration rates at 6, 12, and 24 h after scratching were calculated, the cell Transwell assay was performed and the number of migration cells at 12 h after culture was calculated, and the proportion of proliferating cells was detected by 5-acetylidene-2'-deoxyuridine and Hoechst staining at 24 h after culture, with sample numbers being all 3. The simple GelMA hydrogel and the GelMA hydrogel loaded with hUCMSCs-sEVs (hereinafter referred to as hUCMSC-sEV/GelMA hydrogel) were prepared. Then the micromorphology of 2 kinds of hydrogels was observed under scanning electron microscope, the distribution of hUCMSCs-sEVs was observed by laser scanning confocal microscope, and the cumulative release rates of hUCMSCs-sEVs at 0 (immediately), 2, 4, 6, 8, 10, and 12 d after soaking hUCMSC-sEV/GelMA hydrogel in phosphate buffer solution (PBS) were measured and calculated by protein colorimetric quantification ( n=3). Twenty-four 6-week-old male C57BL/6J mice were divided into PBS group, hUCMSC-sEV alone group, GelMA hydrogel alone group, and hUCMSC-sEV/GelMA hydrogel group according to the random number table, with 6 mice in each group, and after the full-thickness skin defect wounds on the back of mice in each group were produced, the wounds were performed with PBS injection, hUCMSC-sEV suspenson injection, simple GelMA coverage, and hUCMSC-sEV/GelMA hydrogel coverage, respectively. Wound healing was observed on post injury day (PID) 0 (immediately), 4, 8, and 12, and the wound healing rates on PID 4, 8, and 12 were calculated, and the wound tissue was collected on PID 12 for hematoxylin-eosin staining to observe the structure of new tissue, with sample numbers being both 6. Results:The extracted hUCMSCs-sEVs showed a cup-shaped structure and expressed CD9, CD63, and TSG101, but barely expressed calnexin. At 6, 12, and 24 h after scratching, the migration rates of HEKs (with t values of 25.94, 20.98, and 20.04, respectively), HDFs (with t values of 3.18, 5.68, and 4.28, respectively), and HUVECs (with t values of 4.32, 19.33, and 4.00, respectively) in hUCMSC-sEV group were significantly higher than those in blank control group ( P<0.05). At 12 h after culture, the numbers of migrated HEKs, HDFs, and HUVECs in hUCMSC-sEV group were 550 ±23, 235 ±9, and 856 ±35, respectively, which were significantly higher than 188 ±14, 97 ±6, and 370 ±32 in blank control group (with t values of 22.95, 23.13, and 17.84, respectively , P<0.05). At 24 h after culture, the proportions of proliferating cells of HEKs, HDFs, and HUVECs in hUCMSC-sEV group were significantly higher than those in blank control group (with t values of 22.00, 13.82, and 32.32, respectively, P<0.05). The inside of simple GelMA hydrogel showed a loose and porous sponge-like structure, and hUCMSCs-sEVs was not observed in it. The hUCMSC-sEV/GelMA hydrogel had the same sponge-like structure, and hUCMSCs-sEVs were uniformly distributed in clumps. The cumulative release rate curve of hUCMSCs-sEVs from hUCMSC-sEV/GelMA hydrogel tended to plateau at 2 d after soaking, and the cumulative release rate of hUCMSCs-sEVs was (59.2±1.8)% at 12 d after soaking. From PID 0 to 12, the wound areas of mice in the 4 groups gradually decreased. On PID 4, 8, and 12, the wound healing rates of mice in hUCMSC-sEV/GelMA hydrogel group were significantly higher than those in the other 3 groups ( P<0.05); the wound healing rates of mice in GelMA hydrogel alone group and hUCMSC-sEV alone group were significantly higher than those in PBS group ( P<0.05). On PID 8 and 12, the wound healing rates of mice in hUCMSC-sEV alone group were significantly higher than those in GelMA hydrogel alone group ( P<0.05). On PID 12, the wounds of mice in hUCMSC-sEV/GelMA hydrogel group showed the best wound epithelization, loose and orderly arrangement of dermal collagen, and the least number of inflammatory cells, while the dense arrangement of dermal collagen and varying degrees of inflammatory cell infiltration were observed in the wounds of mice in the other 3 groups. Conclusions:hUCMSCs-sEVs can promote the migration and proliferation of HEKs, HDFs, and HUVECs which are related to skin wound healing, and slowly release in GelMA hydrogel. The hUCMSC-sEV/GelMA hydrogel as a wound dressing can significantly improve the healing speed of full-thickness skin defect wounds in mice.

Objective:To evaluate the reliability and validity of different quantitative methods based on CT images to evaluate the proportion of shoulder glenoid defect.Methods:Four shoulder joint specimens with no trauma, osteoarthritis or deformity were used, including 2 females and 2 males; the average age of death was 58±10 years old; all the specimens were prepared with a standard method with no bone defect occurring before preparation. A glenoid bone defect model was established with each specimen being cut into four defect gradient defects of approximately 8%, 16%, 24%, and 32% in proportion in sequence. A total of 16 samples were obtained. Physical photography and CT image reconstruction were performed on the 16 samples respectively. A total of 8 quantitative methods were used to quantify bone defects, which were surface area method, superimposed circle method, Barchilon method, Pico method, Shaha method, Griffith method, Sugaya method, and Giles method. Intraclass correlation (ICC) using a consistency model was used to evaluate reliability. Paired t-test was used to evaluate validity, with the physical measurement of the specimens using the surface area method as the reference standard. Result:The consistency ICC of each quantitative method was greater than 0.9, and all had high reliability. Combining the results of all bone defect gradients and imaging images, the surface area method had the best validity, which was 0.83%±0.75%; the Barchilon method came second, which was 0.91%±0.93%; the superimposed circle method and the Pico method had good validity, which were 0.99%±0.87% and 1.27%±1.09%, respectively; the Shaha method, the Griffith method, and the Sugaya method had poor validity, which were 6.11%±1.56%, 5.06%±1.35%, and 6.02%±1.61%, respectively; the Giles method had the worst validity, which was 8.40%±3.08%. Conclusion:In clinical practice, surface area method and superimposed circle method are the most reliable to quantify the proportion of bone defect if they can be performed. Otherwise, linear measurement of Barchilon method is the favored method while PICO method is the favored method for angle measurement.

Objective:To investigate the clinical benefit and application value of the Da Vinci robotic surgical system through bilateral axillary areolar approach in cervical lymph node dissection in obese thyroid carcinoma patients.Methods:The clinical data of 117 patients with thyroid cancer admitted to the thyroid and breast surgery Department of the 960th Hospital of the Chinese PLA Joint Logistic Support Force from January 2018 to June 2023 were retrospectively analyzed. There were 55 males and 62 females, aged from 17 to 64 years, with an average age of (36.05±8.77) years. According to body mass index (BMI), patients were divided into normal group (18.5 kg/m 2≤BMI< 24 kg/m 2, n=60) and obese group (BMI≥28 kg/m 2, n=57). Gender, age, BMI, operation time, postoperative drainage fluid volume, tumor diameter, central lymph node dissection and number of metastasis, cervical lymph node dissection and number of metastasis, postoperative hospital stay, postoperative aesthetic satisfaction score and surgical complications of the two groups were analyzed. SPSS 26.0 statistical software was used to analyze the data. Results:All of patients completed the operation successfully, and neither group was transferred to open surgery. The BMI of obese group was higher than that of normal group [(31.35±3.08) kg/m 2vs (22.53±0.82) kg/m 2, t=20.97, P<0.05]. The maximum tumor diameter in the obese group was greater than that in the normal group [(13.81±10.70) mm vs (10.42±5.53) mm, t=2.17, P<0.05]. There were no significant differences in operation time, number of central lymph node dissection and metastasis, number of cervical lymph node dissection and metastasis and postoperative complications between the two groups ( P>0.05). Conclusions:Utilization of the Da Vinci robotic surgical system via the BABA approach demonstrates both safety and feasibility in obese patients with thyroid carcinoma undergoing lateral cervical lymph node dissection. Importantly, this technique does not increase the risk of surgical complications, thus providing a novel alternative for lateral cervical lymph node dissection in obese thyroid carcinoma patients.

AIM: To observe the clinical efficacy of multi -glycoside of tripterygium wilfordii (GTW) on diabetic nephropathy. METHODS: Fifty-one patients with diabetic kidney disease (DKD) with a history of GTW dosing admitted to the outpatient clinic of Yijishan Hospital affiliated to Wannan Medical College from June 2019 to October 2022 were selected as study subjects, and were followed up regularly to observe the changes in laboratory indexes before and after GTW dosing and adverse drug reactions after 6 months of treatment. The t-test, Mann-Whitney U-test or χ