1.siRNA micelleplexes-mediated glutamine metabolism re-engineering for vascular normalization-boosted photo-immunotherapy.
Yunfei YI ; Zhangwen PENG ; Yuanqi LIU ; Huisong HAO ; Liu YU ; Simin WEN ; Shengjie SUN ; Jianlin SHI ; Meiying WU ; Lin MEI
Acta Pharmaceutica Sinica B 2025;15(4):2237-2252
Among tumor microenvironment (TME), the entire metabolic characteristics of tumor-resident cells are reprogrammed to benefit the expansion of tumor cells, which count on glutamine in large part to fuel the tricarboxylic acid cycle for energy generation and anabolic metabolism support. Endothelial cells that are abducted by tumor cells to form a pathological tumor vascular network for constructing the hypoxic immunosuppressive TME, also rely on glutaminolysis as the "engine" of angiogenesis. Additionally, the glutamine metabolic preference benefits the polarization of TAMs towards pro-tumoral M2 phenotype as well. Herein, we developed a type of siRNA micelleplexes (MH@siGLS1) to reverse immunosuppressive TME by targeting glutaminolysis within tumor-resident cells for tumor vasculature normalization- and TAMs repolarization-enhanced photo-immunotherapy. Tumor cell starvation and antioxidant system destruction achieved by MH@siGLS1-mediated glutaminolysis inhibition could promote photodynamic therapy efficacy, which was available to trigger immunogenic cell death for adaptive antitumor immune responses. Meanwhile, glutaminolysis inhibition of tumor endothelial cells and TAMs could realize tumor vascular normalization and TAMs repolarization for antitumor immunity amplification. This study provides a unique perspective on cancer treatments by focusing on the interrelations of metabolic characteristics and the biofunctions of various cell types within TME.
2.Study on influencing factors and predictive model construction of cardiopulmonary complication after thoracoscopic surgery in stage Ⅰ-Ⅱ non-small cell lung cancer
Jianlin LI ; Sijin SUN ; Dali WANG
Tianjin Medical Journal 2025;53(6):583-588
Objective To construct a multivariable prediction model for assessing the risk of cardiopulmonary complication after thoracoscopic lobectomy in patients with stage Ⅰ-Ⅱ non-small cell lung cancer(NSCLC).Methods Clinical data of 600 patients with stage Ⅰ-Ⅱ NSCLC who underwent thoracoscopic lobectomy were retrospectively analyzed.Patients were divided into the complication group(84 cases)and the non-complication group(516 cases)based on the occurrence of postoperative complication within 7 days,including atelectasis,pulmonary embolism,respiratory failure,chylothorax,massive pleural effusion,hypoxemia and atrial fibrillation.Demographic characteristics,preoperative pulmonary function assessment,pathological features and perioperative indicators were collected.Multivariate Logistic regression analysis was used to identify independent risk factors influencing postoperative cardiopulmonary complication in patients and construct a predictive model.Internal validation was performed using the Bootstrap resampling method(1 000 iterations)to evaluate the discrimination,calibration and clinical decision-making value of the model.Results Multivariate Logistic regression analysis identified the following independent risk factors of postoperative cardiopulmonary complication,including age(OR=1.832,95%CI:1.537-2.183),history of chronic obstructive pulmonary disease(COPD)(OR=6.782,95%CI:2.685-17.130),Karnofsky performance status(KPS)score(OR=0.926,95%CI:0.888-0.965),the percentage of forced expiratory volume in the first second to the predictive value(FEV1%pred)(OR=0.906,95%CI:0.845-0.972),the percentage of diffusing capacity for carbon monoxide to the expected value(DLCO%pred)(OR=0.901,95%CI:0.832-0.975),intraoperative blood loss(OR=1.025,95%CI:1.014-1.036)and one-lung ventilation time(OR=1.057,95%CI:1.034-1.080).The area under the curve(AUC)of the combined diagnosis was 0.977(95%CI:0.965-0.989),with 96.4%sensitivity and 87.6%specificity.The Hosmer-Lemeshow test indicated excellent calibration(χ2=1.285,P=0.994).Decision curve analysis demonstrated significant clinical net benefit when the risk threshold probability ranged between 20%and 98%.Conclusion The multivariable prediction model for cardiopulmonary complication after thoracoscopic lobectomy in stage Ⅰ-Ⅱ NSCLC patients exhibits strong predictive performance.
3.Study on influencing factors and predictive model construction of cardiopulmonary complication after thoracoscopic surgery in stage Ⅰ-Ⅱ non-small cell lung cancer
Jianlin LI ; Sijin SUN ; Dali WANG
Tianjin Medical Journal 2025;53(6):583-588
Objective To construct a multivariable prediction model for assessing the risk of cardiopulmonary complication after thoracoscopic lobectomy in patients with stage Ⅰ-Ⅱ non-small cell lung cancer(NSCLC).Methods Clinical data of 600 patients with stage Ⅰ-Ⅱ NSCLC who underwent thoracoscopic lobectomy were retrospectively analyzed.Patients were divided into the complication group(84 cases)and the non-complication group(516 cases)based on the occurrence of postoperative complication within 7 days,including atelectasis,pulmonary embolism,respiratory failure,chylothorax,massive pleural effusion,hypoxemia and atrial fibrillation.Demographic characteristics,preoperative pulmonary function assessment,pathological features and perioperative indicators were collected.Multivariate Logistic regression analysis was used to identify independent risk factors influencing postoperative cardiopulmonary complication in patients and construct a predictive model.Internal validation was performed using the Bootstrap resampling method(1 000 iterations)to evaluate the discrimination,calibration and clinical decision-making value of the model.Results Multivariate Logistic regression analysis identified the following independent risk factors of postoperative cardiopulmonary complication,including age(OR=1.832,95%CI:1.537-2.183),history of chronic obstructive pulmonary disease(COPD)(OR=6.782,95%CI:2.685-17.130),Karnofsky performance status(KPS)score(OR=0.926,95%CI:0.888-0.965),the percentage of forced expiratory volume in the first second to the predictive value(FEV1%pred)(OR=0.906,95%CI:0.845-0.972),the percentage of diffusing capacity for carbon monoxide to the expected value(DLCO%pred)(OR=0.901,95%CI:0.832-0.975),intraoperative blood loss(OR=1.025,95%CI:1.014-1.036)and one-lung ventilation time(OR=1.057,95%CI:1.034-1.080).The area under the curve(AUC)of the combined diagnosis was 0.977(95%CI:0.965-0.989),with 96.4%sensitivity and 87.6%specificity.The Hosmer-Lemeshow test indicated excellent calibration(χ2=1.285,P=0.994).Decision curve analysis demonstrated significant clinical net benefit when the risk threshold probability ranged between 20%and 98%.Conclusion The multivariable prediction model for cardiopulmonary complication after thoracoscopic lobectomy in stage Ⅰ-Ⅱ NSCLC patients exhibits strong predictive performance.
4.Conceptual analysis of health literacy in children and adolescents with unintentional injury
Ping TANG ; Jingmin SUN ; Qunfeng LU ; Wenjuan TANG ; Jianlin JI
Chinese Journal of Child Health Care 2024;32(1):73-78
【Objective】 To clarify the concept of health literacy among children and adolescents with accidental injuries through literature review and analysis. 【Methods】 A systematic search was conducted across multiple databases, including China National Knowledge Infrastructure, Wanfang database, VIP database, China Biomedical literature database, PubMed, CINAHL, and PscyINFO database. The literature was analyzed using Rodgers′ evolutionary concept analysis method. 【Results】 A total of 56 articles were included. The health literacy of children and adolescents with accidental injuries comprised three conceptual attributes:cognition, emotion and behavior. The influencing factors included children′s demographic factors, family and school related factors and social related factors. The result can be beneficial to reduce the occurrence of injury events, save family economic expenditure and alleviate the burden on social medical resources. However, there is currently a lack of specific measurement tools for assessing health literacy in this population, as the existing evaluation items are drawn from general health literacy scales. 【Conclusions】 The concept of health literacy among children and adolescents with accidental injuries is multifaceted and evolving. Future research should focus on exploring the characteristics of health literacy among children and adolescents of different ages and regions from their own perspectives. Additionally, efforts should be made to refine the concept and develop specialized measurement tools to facilitate further studies in this area.
5.Titanium cable tensioning ring fixation for distal tibiofibular syndesmosis injury
Jianlin SUN ; Zuoming YANG ; Bin WANG ; Xiaoming ZHAO ; Quanyong ZHAO ; Mengyan LI ; Xin LI
Chinese Journal of Orthopaedic Trauma 2024;26(10):858-864
Objective:To evaluate the titanium cable tensioning ring fixation in the treatment of distal tibiofibular syndesmosis (DTS) injury.Methods:A retrospective study was conducted to analyze the 108 patients with DTS injury who had undergone surgical treatment from January 2021 to January 2023 at Department of Traumatology, The Second Hospital of Tangshan. There were 68 males and 40 females with an age of (40.1±13.0) years. According to the fixation methods used, the patients were divided into a Titanium cable group and an Endobutton plate group. The Titanium cable group of 53 cases was subjected to fixation with a titanium cable tensioning ring while the Endobutton plate group of 55 cases to fixation with an Endobutton plate. The 2 groups were compared in terms of the anterior and posterior tibiofibular spaces on the transverse CT images at 1 week and 12 months postoperatively, as well as the Baird-Jackson scores of ankle joint function at 6 and 12 months postoperatively.Results:There was no statistically significant difference in the preoperative general data between the 2 groups, indicating comparability ( P > 0.05). There was no statistically significant difference in the comparison of the anterior and posterior tibiofibular spaces on the transverse CT images at 1 week postoperatively ( P > 0.05). The anterior and posterior tibiofibular spaces on the transverse CT images at 12 months postoperatively in the Endobutton plate group [(3.60±0.59) mm and 4.58 (4.38, 4.89) mm] were significantly greater than those in the Titanium cable group [(3.34±0.53) mm and 4.36 (4.13, 4.67) mm] ( P < 0.05). There was no statistically significant difference in the Baird-Jackson ankle function scores at 6 and 12 months postoperatively between the 2 groups ( P > 0.05). Conclusions:In the treatment of DTS injury, fixation with titanium cable tensioning ring can achieve as good therapeutic effects as fixation with Endobutton plate. However, the former may have certain advantages in surgical operation and long-term reduction loss.
6.Effect of Dapagliflozin combined with insulin treatment on blood glucose index and pancreatic β-cell function in overweight/obese type 2 diabetes mellitus patients with different disease durations
Yan ZHANG ; Yuli LU ; Miao MIAO ; Yongqi FU ; Xiaolong LI ; Dianjing SUN ; Jianlin GENG
Chinese Journal of Diabetes 2024;32(12):898-902
Objective To investigate the effects of Dapagliflozin combined with insulin treatment on blood glucose index and pancreatic β-cell function in overweight/obese type 2 diabetes mellitus(T2DM) patients with different disease durations. Methods A total of 288 patients with impaired pancreatic function who were treated from June 2019 to June 2020 were selected. They were divided into three groups,short duration group (≤10 years group,n=95),medium duration group (10~20 years group,n=96) and long duration group (≥20 years group,n=97). Three groups of patients were treated with Dapagliflozin in addition to the regular insulin therapy for 6 months. Clinical efficacy,blood glucose indices,pancreatic β-cell function and complications during the treatment period were compared among the three groups. Results After treatment,there was a significant decrease in the values of three groups including WC,FPG,2 hPG,HbA1c,TC,TG,LDL-C,BMI,FIns and HOMA-IR(P<0.05). Meanwhile,HDL-C,C-P,HOMA-β and HOMA-IS values showed a significant increase(P<0.05). After treatment,WC,FPG,2 hPG,HbA1c,TC,TG,LDL-C,FIns and HOMA-IR increased in turn(P<0.05),while HDL-C,C-P,HOMA-β and HOMA-IS decreased in turn in ≤10 years group,10~20 years group,≥20 years group(P<0.05). The BMI of 10~20 years group was lower than that of ≤10 years group and ≥20 years group (P<0.05),while the BMI of ≥20 years group was higher than that of ≤10 years group (P<0.05). Conclusions In overweight/obese T2DM patients with different DM durations,Dapagliflozin combined with insulin treatment shows a significant advantage in lowering blood glucose indices and improving pancreatic β-cell function,especially for patients with a shorter disease duration.
7.Effect of Dapagliflozin combined with insulin treatment on blood glucose index and pancreatic β-cell function in overweight/obese type 2 diabetes mellitus patients with different disease durations
Yan ZHANG ; Yuli LU ; Miao MIAO ; Yongqi FU ; Xiaolong LI ; Dianjing SUN ; Jianlin GENG
Chinese Journal of Diabetes 2024;32(12):898-902
Objective To investigate the effects of Dapagliflozin combined with insulin treatment on blood glucose index and pancreatic β-cell function in overweight/obese type 2 diabetes mellitus(T2DM) patients with different disease durations. Methods A total of 288 patients with impaired pancreatic function who were treated from June 2019 to June 2020 were selected. They were divided into three groups,short duration group (≤10 years group,n=95),medium duration group (10~20 years group,n=96) and long duration group (≥20 years group,n=97). Three groups of patients were treated with Dapagliflozin in addition to the regular insulin therapy for 6 months. Clinical efficacy,blood glucose indices,pancreatic β-cell function and complications during the treatment period were compared among the three groups. Results After treatment,there was a significant decrease in the values of three groups including WC,FPG,2 hPG,HbA1c,TC,TG,LDL-C,BMI,FIns and HOMA-IR(P<0.05). Meanwhile,HDL-C,C-P,HOMA-β and HOMA-IS values showed a significant increase(P<0.05). After treatment,WC,FPG,2 hPG,HbA1c,TC,TG,LDL-C,FIns and HOMA-IR increased in turn(P<0.05),while HDL-C,C-P,HOMA-β and HOMA-IS decreased in turn in ≤10 years group,10~20 years group,≥20 years group(P<0.05). The BMI of 10~20 years group was lower than that of ≤10 years group and ≥20 years group (P<0.05),while the BMI of ≥20 years group was higher than that of ≤10 years group (P<0.05). Conclusions In overweight/obese T2DM patients with different DM durations,Dapagliflozin combined with insulin treatment shows a significant advantage in lowering blood glucose indices and improving pancreatic β-cell function,especially for patients with a shorter disease duration.
8.The effectiveness and safety of concurrent chemoradiotherapy combined with nimotuzumab for patients with inoperable esophageal squamous cell carcinoma
Lichen DAI ; Jianfeng HUANG ; Lijun HU ; Jia WU ; Jianlin WANG ; Qinghong MENG ; Fei SUN ; Qiuhua DUAN ; Jingping YU
Chinese Journal of Radiological Medicine and Protection 2023;43(3):182-188
Objective:To evaluate the effectiveness and safety of concurrent chemoradiotherapy combined with nimotuzumab in the treatment of patients with inoperable esophageal squamous cell carcinoma (ESCC).Methods:A retrospective analysis was conducted on the clinical data of 503 patients with inoperable ESCC who underwent concurrent chemoradiotherapy in the Department of Radiation Oncology, Changzhou No. 2 People′s Hospital Affiliated to Nanjing Medical University and Department of Radiation Oncology, Affiliated Hospital of Jiangnan University from 2014 to 2020. Among these patients, 69 received concurrent chemoradiotherapy combined with nimotuzumab (the combined therapy group) and 434 received concurrent chemoradiotherapy alone (the concurrent chemoradiotherapy group). Patients of both groups were matched at a ratio of 1∶2 using the propensity score matching (PSM) method. As a result, 168 patients were determined for clinical analysis, including 61 in the combined therapy group and 107 in the concurrent chemoradiotherapy group. The short-term efficacy and adverse reactions of both groups were compared. The overall survival (OS) curves and progression-free survival (PFS) curves were plotted using the Kaplan-Meier method for the Log-rank test.Results:The two groups showed no statistical difference ( P > 0.05) in clinical baseline characteristics after the PSM. The objective response rate (ORR) of the combined therapy group was significantly higher than that of the concurrent chemoradiotherapy group with statistically significant differences (85.2% vs. 71.0%, χ2 = 4.33, P = 0.037). There was no statistical difference (98.4% vs. 91.6%, P > 0.05) in the disease control rate (DCR) between the two groups. The combined therapy group had median PFS of 28.07 months and 1-, 3-, and 5-year PFS ratios of 78.2%, 37.5% and 29.1%, respectively. The concurrent chemoradiotherapy group had mPFS of 19.54 months and 1-, 3-, and 5-year PFS ratios of 72.9%, 28.3% and 21.3%, respectively. Both groups showed statistically significant differences in PFS ( χ2 = 4.49, P = 0.034). The combined group had median OS of 34.93 months and 1-, 3-, and 5-year OS ratios of 88.5%, 46.8% and 37.4%, respectively. The concurrent chemoradiotherapy group had mOS of 24.30 months and 1-, 3-, and 5-year OS ratios of 81.3%, 35.2% and 28.0%, respectively. Both groups showed statistically significant differences in OS (χ 2= 5.11, P = 0.024), but did not show statistical differences ( P > 0.05) in the severity degree of each adverse effect during the treatment. Conclusions:Concurrent chemoradiotherapy combined with nimotuzumab can improve the ORR and prolong the PFS and OS of patients with inoperable ESCC compared with concurrent chemoradiotherapy alone. Furthermore, combining with nimotuzumab does not increase adverse effects and can be tolerated by patients with high safety.
9.Effects of niraparib on the radiosensitivity of human esophageal cancer cells and its mechanism
Fuzhen ZHAO ; Yue FENG ; Zhaoming MA ; Lijun HU ; Fei SUN ; Jianlin WANG ; Jingping YU
Chinese Journal of Radiation Oncology 2023;32(8):718-724
Objective:To evaluate the effect of niraparib, the poly (ADP-ribose) polymerase (PARP) inhibitor, on the radiosensitivity of esophageal squamous cell carcinoma (ESCC) and to preliminarily investigate its mechanism.Methods:Human esophageal squamous cell carcinoma cells ECA-109 and KYSE-150 were divided into the control, niraparib, single irradiation, combined (niraparib+irradiation) groups. Cell proliferation was measured by CCK-8 assay. The changes of cell survival rate were detected by colony formation assay. The changes of cell cycle and apoptosis were analyzed by flow cytometry. The number of γH2AX foci was detected by immunofluorescence, and the expression levels of PARP-1, cleaved-PARP, RAD51, mitogen-activated protein kinase (MAPK) [extracellular signal-regulated kinase 1 and 2 (ERK1/2) ] and p-MAPK (ERK1/2) proteins were determined by Western blot. All data were expressed as Mean±SD. Data between two groups conforming to normal distribution through the normality test were subject to independent sample t-test and multiple groups were analyzed using one-way ANOVA. Results:In human ESCC cells ECA-109 and KYSE-150, the proliferation of ESCC cells was significantly inhibited by niraparib combined with irradiation, and the values of average lethal dose (D 0), quasi-threshould dose(D q), survival fraction after 2 Gy irradiation (SF 2) in the combined group were decreased compared with those in the single irradiation group. The effect of irradiation alone on apoptosis of ECA-109 and KYSE-150 cells was limited. Compared to single irradiation group, irradiation combined with niraparib further increased the apoptosis rate in ESCC cells ( P=0.015, P=0.006). In ECA-109 cells, G 2/M phase arrest was significantly increased in combined group compared with irradiation alone group ( P<0.001). In ECA-109 cells, the number of γH2AX foci in combined group was higher than that in the single irradiation group after 2 h, and showed a significantly slower decay of γH2AX foci ( P<0.001). Moreover, niraparib combined with irradiation enhanced the radiation-induced cleavage of PARP-1 and down-regulated the expression of Rad51 and p-MAPK(ERK1/2). Conclusion:Niraparib can increase the radiosensitivity of esophageal cancer cells by inhibiting cell proliferation, promoting cell apoptosis, inhibiting the repair of DNA damage and regulating the MARK-ERK signaling pathway.
10.Reliability and validity of General Burnout Scale in multiple populations
Jin WANG ; Xiaoman LIU ; Yanyan SUN ; Jianlin LOU ; Fang YUAN ; Daoyuan SUN ; Ruijie LING ; Dan YU ; Shuang LI
Journal of Environmental and Occupational Medicine 2023;40(4):382-388
Background As one of the common tools for job burnout assessment, Maslach Burnout Inventory-General Survey (MBI-GS), its reliability and validity across different populations in China have not been examined yet. Objective To evaluate the reliability and validity of General Burnout Scale (GBS) by multiple occupational groups through the translation and preliminary test of MBI-GS. Methods Based on the Special Project of Occupational Hazards in Key Populations led by the Institute of Occupational Health and Poison Control, China CDC, key occupational groups in five typical industries were selected by multi-stage stratified cluster sampling, including teachers, firefighters, manufacturing workers, medical staff, and traffic police. Confirmatory factor analysis (CFA) was used to evaluate the construct validity of GBS by single-factor, two-factor, and three-factor structure models. The model fitness was assessed by ratio of the chi-square statistic to the respective degrees of freedom (χ2/ν), root mean square error of approximation (RMSEA), goodness-of-fit index (GFI), comparative fit index (CFI), and parsimony-adjusted non-normed fit index (PNFI). Spearman correlation analysis was used to calculate the criterion validity of GBS with occupational stress, depressive symptoms, and sleep disorders. Cronbach's α coefficient and composite reliability (CR) coefficient were used to evaluate the internal consistency reliability of GBS. Results A total of 3485 subjects were surveyed in this study, 3375 valid questionnaires were recovered with a valid response rate of 96.84%. The results of CFA showed that in the adjusted three-factor structure model of GBS (exhaustion, cynicism, and professional efficacy), the χ2/ν < 4, the RMSEA ranged from 0.032 to 0.069, the GFI > 0.90, the CFI > 0.90, and the PNFI > 0.70, which illustrated a good fitness than that of the single- or the two-factor structure models in different occupational groups. The Spearman correlation analysis results showed that occupational stress, depressive symptoms, and sleep disorders were positively correlated with exhaustion and cynicism dimensions, and negatively correlated with professional efficacy dimension of the GBS, with the

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