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.

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.

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.

【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.

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.

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.

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.

BACKGROUND: Management of gastric leak after sleeve gastrectomy (SG) is challenging due to its unpredictable outcomes. We aimed to summarize the characteristics of SG leaks and analyze interventions and corresponding outcomes in a real-world setting. METHODS: To retrospectively review of 15,721 SG procedures from 2010 to 2020 based on a national registry. A cumulative sum analysis was used to identify a fitting curve of gastric leak rate. The Kaplan-Meier method and log-rank tests were performed to calculate and compare the probabilities of relevant outcomes. The logistic regression analysis was conducted to determine the predictors of acute leaks. RESULTS: A total of 78 cases of SG leaks were collected with an incidence of 0.5% (78/15,721) from this registry (6 patients who had the primary SG in non-participating centers). After accumulating 260 cases in a bariatric surgery center, the leak rate decreased to a stably low value of under 1.17%. The significant differences presented in sex, waist circumference, and the proportion of hypoproteinemia and type 2 diabetes at baseline between patients with SG leak and the whole registry population ( P = 0.005, = 0.026, <0.001, and = 0.001, respectively). Moreover, 83.1% (59/71) of the leakage was near the esophagogastric junction region. Leakage healed in 64 (88.9%, 64/72) patients. The median healing time of acute and non-acute leaks was 5.93 months and 8.12 months, respectively. Acute leak (38/72, 52.8%) was the predominant type with a cumulative reoperation rate >50%, whereas the cumulative healing probability in the patients who required surgical treatment was significantly lower than those requring non-surgical treatment ( P = 0.013). Precise dissection in the His angle area was independently associated with a lower acute leak rate, whereas preservation ≥2 cm distance from the His angle area was an independent risk factor. CONCLUSIONS Male sex, elevated waist circumference, hypoproteinaemia, and type 2 diabetes are risk factors of gastric leaks after SG. Optimizing surgical techniques, including precise dissection of His angle area and preservation of smaller gastric fundus, should be suggested to prevent acute leaks.
Humans ; Male ; Retrospective Studies ; Diabetes Mellitus, Type 2/complications* ; Obesity, Morbid ; Anastomotic Leak/epidemiology* ; Gastrectomy/methods* ; Reoperation/methods* ; Registries ; Laparoscopy/methods* ; Treatment Outcome

Objective:To study the effects of poly adenosine diphosphate ribose polymerase (PARP) inhibitors niraparib and pamiparib on the radiosensitivity of breast cancer cell lines MCF-7 and MDA-MB-436, and to explore its mechanism.Methods:MCF-7 and MDA-MB-436 cells were divided into control group, niraparib group, pamiparib group, radiation group, combination group treated with niraparib and radiation, and combination group treated with pamiparib and radiation, respectively. The effects of drugs on cell proliferation and radiosensitivity were measured by CCK-8 assay and colony formation assay, respectively. The effect of drugs combined with radiation on cell cycle and apoptosis were detected by flow cytometry. Immunofluorescence method was used to detect the changes of γ-H2AX focal number of cells. The expressions of FANCG, Bax and Bcl-2 mRNA and protein were detected by qPCR and Western blot, respectively.Results:Both niraparib and pamiparib inhibited the proliferation of breast cancer cells MCF-7 and MDA-MB-436 in a time-dose dependent manner. With the increase of irradiation dose, D0, Dq, SF2 value of MCF-7 and MDA-MB-436 cells decreased, and SER D0 and SER Dq value increased. Compared with control group, the percentages of cells in G 2/M phase were increased ( tMCF-7=41.66, 44.08, P<0.05; t436=24.69, 18.91, P<0.05), the percentage of cells in G 0/G 1 phase were decreased ( tMCF-7=8.67, 29.61, P<0.05; t436=26.39, 29.12, P<0.05), and the cell apoptosis rate was significantly increased ( tMCF-7=11.17, 11.71, P<0.05; t436=42.68, 15.89, P<0.05) in the combination group. Compared with control group, the number of γ-H2AX foci of MCF-7 cells in the radiation group and combination group treated with niraparib and radiation increased significantly at 2 h after irradiation ( t=8.89, 21.72, P<0.05). At 24 h after irradiation, the number of γ-H2AX foci basically returned to normal level in the radiation group but remained at a higher level in the combination group ( t=8.82, P<0.05). Compared with control group, the expressions of FANCG and Bcl-2 mRNA decreased ( tFANCG=14.07, P<0.05; tBcl-2=29.21, P<0.05), the expression of Bax mRNA increased ( t=8.90, P<0.05), and the expression of FANCG and Bcl-2 proteins decreased ( tFANCG=7.09, P<0.05; tBcl-2=10.24, P<0.05), while the expression of Bax protein increased ( t=2.90, P<0.05) in the combination group. Conclusions:PARP inhibitors niraparib and pamiparib can increase the radiosensitivity of breast cancer MCF-7 and MDA-MB-436 cells probably through down-regulating the expression of FANCG in FA-BRCA pathway, up-regulating apoptosis-related genes and inhibiting DNA damage repair.

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.