Objective:To analyze the changes and significance in clinical cardiac indicators of early cardiac myocardial dysfunction and cardiac substructure dose during conventional radiotherapy for N 2-N 3 non-small cell lung cancer (NSCLC) with mediastinal lymph node metastases. Methods:The data of 34 NSCLC patients with lymph node metastases in regions 4-8 admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to August 2023 were observed and analyzed. All patients were treated with volumetric modulated arc therapy with a prescribed dose of 60-70 Gy. Cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at 6 time points: within 1 week before radiotherapy ( t0); when the cumulative radiotherapy dose reaches 20 Gy ( t20), 40 Gy ( t40), 60 Gy ( t60) during radiotherapy; within 1 week after radiotherapy ( tp); 1 month after radiotherapy( tp1). Left ventricular global longitudinal strain (LVGLS) and left atrial global longitudinal strain (LAGLS) were assessed at 4 time points: t0, t40, tp and tp1, respectively. The changes in cardiac indicators at different time points during radiotherapy and their correlation with substructure doses were analyzed using analysis of variance, linear regression analysis, and Pearson correlation. Results:The correlation between cardiac substructure dose and mean heart dose (MHD) in the study cohort in the descending order was as follows: left ventricle ( B=0.43, P<0.001), right ventricle ( B=0.37, P=0.002), left atrium ( B=0.16, P<0.001), and right atrium ( B=0.15, P=0.001). There were significant differences in the changes of LVGLS and LAGLS across different time points ( F=3.13, P=0.029; F=17.18, P<0.001). At 1 month after radiation, LAGLS was significantly decreased compared to pre-radiation levels ( P=0.009), whereas no significant difference was observed in LVGLS ( P=1.000). No significant differences were observed in the changes of cTnT and NT-proBNP across different time points (all P>0.05). Significant correlations were identified between cTnT and right ventricle mean dose at t40 ( r=0.38, P=0.025), as well as between NT-proBNP and right atrium mean dose at t60 and tp ( r=0.54, P=0.001; r=0.41, P=0.016). Conclusions:At present, there is no significant difference between the sensitive serum markers of myocardial injury and LVGLS in detecting early myocardial injury. LAGLS may hold substantial clinical value. There is uncertainty about radiation injury and repair of various cardiac substructures.

Objective:To analyze the changes and significance in clinical cardiac indicators of early cardiac myocardial dysfunction and cardiac substructure dose during conventional radiotherapy for N 2-N 3 non-small cell lung cancer (NSCLC) with mediastinal lymph node metastases. Methods:The data of 34 NSCLC patients with lymph node metastases in regions 4-8 admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to August 2023 were observed and analyzed. All patients were treated with volumetric modulated arc therapy with a prescribed dose of 60-70 Gy. Cardiac troponin T (cTnT) and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were measured at 6 time points: within 1 week before radiotherapy ( t0); when the cumulative radiotherapy dose reaches 20 Gy ( t20), 40 Gy ( t40), 60 Gy ( t60) during radiotherapy; within 1 week after radiotherapy ( tp); 1 month after radiotherapy( tp1). Left ventricular global longitudinal strain (LVGLS) and left atrial global longitudinal strain (LAGLS) were assessed at 4 time points: t0, t40, tp and tp1, respectively. The changes in cardiac indicators at different time points during radiotherapy and their correlation with substructure doses were analyzed using analysis of variance, linear regression analysis, and Pearson correlation. Results:The correlation between cardiac substructure dose and mean heart dose (MHD) in the study cohort in the descending order was as follows: left ventricle ( B=0.43, P<0.001), right ventricle ( B=0.37, P=0.002), left atrium ( B=0.16, P<0.001), and right atrium ( B=0.15, P=0.001). There were significant differences in the changes of LVGLS and LAGLS across different time points ( F=3.13, P=0.029; F=17.18, P<0.001). At 1 month after radiation, LAGLS was significantly decreased compared to pre-radiation levels ( P=0.009), whereas no significant difference was observed in LVGLS ( P=1.000). No significant differences were observed in the changes of cTnT and NT-proBNP across different time points (all P>0.05). Significant correlations were identified between cTnT and right ventricle mean dose at t40 ( r=0.38, P=0.025), as well as between NT-proBNP and right atrium mean dose at t60 and tp ( r=0.54, P=0.001; r=0.41, P=0.016). Conclusions:At present, there is no significant difference between the sensitive serum markers of myocardial injury and LVGLS in detecting early myocardial injury. LAGLS may hold substantial clinical value. There is uncertainty about radiation injury and repair of various cardiac substructures.

Objective:To investigate the correlations of urinary adverse reactions with dose to the bladder and urethra during external pelvic irradiation for locally advanced cervical cancer.Methods:This study retrospectively collected relevant dosimetric parameters and urinary symptoms, such as frequent, urgent, and painful urination, from locally advanced cervical cancer patients treated with external pelvic irradiation in the Department of Oncology, Affiliated Hospital of Guizhou Medical University. The dosimetric parameters examined in this study included the maximum, minimum, and mean doses to bladder and urethra (i.e., Dmax, Dmin and Dmean), mean doses received in an area of 0.1, 1, and 2 cm 3 around the planning target volume, D0.1 cm 3, D1 cm 3, D2 cm 3, and percentages of irradiated volumes in the whole organ volume under doses of 5, 10, 15, 20, 25, 30, 35, 40, 45, 50 Gy, V5 Gy, V10 Gy, V15 Gy, V20 Gy, V25 Gy, V30 Gy, V35 Gy, V40 Gy, V45 Gy, V50 Gy. Then the correlations between urinary symptoms and these dosimetric parameters were analyzed using the independent-sample t-test and the Logistic regression model. Results:The median volumes of bladder and urethra were 294.8 and 4.71 cm 3, respectively. Patients were divided into two groups based on the median division. The univariate analysis showed that urethral Dmax, Dmin, Dmean, V5 Gy, V10 Gy, V15Gy, V20 Gy, V25 Gy, V30 Gy, V35 Gy, V40 Gy, V45 Gy and V50 Gy correlated with urinary complications ( t = 14.30, 21.65, 32.19, 33.36, 16.62, 17.91, 21.52, 20.11, 12.27, 37.25, 30.18, 36.24 and 21.98, P<0.05). The multivariate analysis further indicates that urethral D2 cm 3, V20 Gy, V40 Gy and Bladder V40 Gy, D1 cm 3, D2 cm 3 were independent predictors of grade 2 urinary adverse reactions ( P<0.05). Conclusions:This study reported the correlations of relevant dosimetric parameters of urethra with urinary toxicity during external pelvic irradiation. It holds that urethral D2 cm 3, V20 Gy and V40 Gy should be restricted to minimize the risks of grade 2 urinary complications.

Objective:To analyze the characteristics, diagnosis, and treatment of pulmonary infections related to bronchobiliary fistula (BBF), and to enhance the understanding of this disease.Methods:A total of 33 patients with pulmonary infections related to BBF hospitalized at the Third Affiliated Hospital of Naval Medical University from January 2011 to January 2024 were included in this study. The clinical retrospective case series research method was used to collect and analyze the clinical data of the included patients, including age, clinical manifestations, laboratory tests, imaging studies, bronchoscopy, cholangiography, and treatment.Results:The age of the 33 patients was (51.4±7.9) years. The most common symptoms were coughing and biliary sputum (33/33, 100.0%), followed by fever (23/33, 69.7%). Other common symptoms included chest tightness, dyspnea, chest pain and hemoptysis. Bilirubin tests on sputum were performed in seven cases and on pleural effusions in four cases, and all were positive. Imaging studies revealed pneumonia in all patients, which was adjacent to the diaphragm. All patients had pleural effusion, with additional common findings included subphrenic effusion, liver abscesses, bile duct dilation, and gas in the bile duct. Bronchoscopy was performed on six patients, all of whom exhibited golden yellow biliary secretions. The presence of BBF was confirmed through percutaneous transhepatic cholangiography (6/10), T-tube cholangiography (3/6), and endoscopic retrograde cholangiopancreatography (5/18) in some patients. All patients received anti-infective therapy and supportive treatment. Among the 33 patients, 18(54.5%) cases underwent endoscopic nasobiliary drainage, 12(36.4%) percutaneous transhepatic biliary drainage, 19(57.6%) thoracentesis, 17(51.5%) subphrenic effusion drainage, five (15.2%) liver abscess drainage, 13(39.4%) abdominal paracentesis, and six (18.2%) brochosopic embolization of bronchial fistula. Only three patients underwent surgical intervention when non-surgical treatments failed.Conclusions:The clinical manifestations of pulmonary infections related to BBF are complex. When patients with hepatobiliary diseases present with coughing and biliary sputum, BBF should be highly suspected. Early diagnosis can be achieved through bilirubin testing of sputum or pleural effusion. The main treatments are biliary drainage or percutaneous puncture drainage and other non-surgical treatments. Surgical treatment could be considered only after the failure of non-surgical treatments.

Objective:To analyze the characteristics, diagnosis, and treatment of pulmonary infections related to bronchobiliary fistula (BBF), and to enhance the understanding of this disease.Methods:A total of 33 patients with pulmonary infections related to BBF hospitalized at the Third Affiliated Hospital of Naval Medical University from January 2011 to January 2024 were included in this study. The clinical retrospective case series research method was used to collect and analyze the clinical data of the included patients, including age, clinical manifestations, laboratory tests, imaging studies, bronchoscopy, cholangiography, and treatment.Results:The age of the 33 patients was (51.4±7.9) years. The most common symptoms were coughing and biliary sputum (33/33, 100.0%), followed by fever (23/33, 69.7%). Other common symptoms included chest tightness, dyspnea, chest pain and hemoptysis. Bilirubin tests on sputum were performed in seven cases and on pleural effusions in four cases, and all were positive. Imaging studies revealed pneumonia in all patients, which was adjacent to the diaphragm. All patients had pleural effusion, with additional common findings included subphrenic effusion, liver abscesses, bile duct dilation, and gas in the bile duct. Bronchoscopy was performed on six patients, all of whom exhibited golden yellow biliary secretions. The presence of BBF was confirmed through percutaneous transhepatic cholangiography (6/10), T-tube cholangiography (3/6), and endoscopic retrograde cholangiopancreatography (5/18) in some patients. All patients received anti-infective therapy and supportive treatment. Among the 33 patients, 18(54.5%) cases underwent endoscopic nasobiliary drainage, 12(36.4%) percutaneous transhepatic biliary drainage, 19(57.6%) thoracentesis, 17(51.5%) subphrenic effusion drainage, five (15.2%) liver abscess drainage, 13(39.4%) abdominal paracentesis, and six (18.2%) brochosopic embolization of bronchial fistula. Only three patients underwent surgical intervention when non-surgical treatments failed.Conclusions:The clinical manifestations of pulmonary infections related to BBF are complex. When patients with hepatobiliary diseases present with coughing and biliary sputum, BBF should be highly suspected. Early diagnosis can be achieved through bilirubin testing of sputum or pleural effusion. The main treatments are biliary drainage or percutaneous puncture drainage and other non-surgical treatments. Surgical treatment could be considered only after the failure of non-surgical treatments.

Objective:To analyze the clinical characteristics of long-term survival patients with advanced non-small cell lung cancer (NSCLC) treated with chemotherapy combined with primary tumor radiotherapy, and to establish a Nomogram prognostic model, aiming to provide a certain reference for making a decision about the treatment of advanced NSCLC.Methods:A retrospective analysis was made on the data of 260 NSCLC patients who participated in two prospective clinical studies from January 2003 to May 2012 and the data of 138 NSCLC patients admitted to the Affiliated Cancer Hospital of Guizhou Medical University from January 2014 to August 2020. The former 260 cases were used as a training set and the latter 138 cases were used as the validation set. The overall survival (OS) of ≥ 18 months was defined as long-term survival (LTS). The clinical characteristics of LTS patients were compared with those with OS less than 18 months. The clinical characteristics and treatment-related parameters between the two types of patients were compared using the χ2 test. A multivariate analysis was made using logistic regression, and a nomogram model was built using RStudio. Results:The median OS of the training set was 13.4 months (95% CI: 11.9-14.9), with 1-, 2-, and 3-year OS rates of 55.4%, 19.1%, and 11.9%, respectively. In the training set, 87 cases had LTS and were classified as the LTS group, while 173 cases had OS less than 18 months and were classified as the non-LTS group. The univariate analysis showed that the prognostic factors affecting LST included the KPS score, T status, the number of metastatic organs, the number of metastatic lesions, brain metastasis, bone metastasis, the number of chemotherapy cycles, the biologically effective dose (BED) to the primary tumor, hemoglobin level, platelet count, plasma D-dimer, fibrinogen level, lactate dehydrogenase, and lung immune prognostic index (LIPI; χ2=4.72-12.63, P < 0.05). The multivariable analysis showed that the independent prognostic factors of LTS included a number of chemotherapy cycles ≥ 4, BED ≥ 70 Gy, platelets ≤ 220×10 9/L, D-dimer ≤ 0.5 mg/L, and a good LIPI score ( P= 0.002, 0.036, 0.005, 0.008, and 0.002). A nomogram model was established using the meaningful parameters obtained in the multivariable analysis, determining that the training and validation sets had a consistency index (C-index) of 0.750 and 0.727, respectively. As shown by the analytical result of the corrected curves, for the advanced NSCLC patients treated with thoracic radiotherapy, their LTS probability predicted using the nomogram prognostic model was highly consistent with their actual LTS probability. Both the analytical result of the receiver operating characteristic (ROC) curves and the decision curve analysis (DCA) result showed that the composite prediction model was more beneficial than a single prediction model. Conclusions:For patients with advanced NSCLC treated with thoracic radiotherapy, the independent prognostic factors of LTS included the number of chemotherapy cycles, BED, platelet count, pre-chemotherapy D-dimer, and LIPI score. The Nomogram prognostic model built based on these prognostic factors is a convenient, intuitive, and personalized prediction model used to screen patients who can benefit from thoracic radiotherapy.

Objective:To compare the efficacy and safety of vildagliptin tablets (the generic drug) manufactured by Qilu Pharmaceutical Co., Ltd. and vildagliptin tablets (the original drug) manufactured by Novartis Pharmaceutical Co., Ltd. in the treatment of type 2 diabetes mellitus (T2DM) in third round of national centralized volume-based procurement.Methods:The study design was a multicenter retrospective cohort study. The study subjects were T2DM patients treated with vildagliptin tablets at the Outpatient Department of Zhuhai People′s Hospital, Zhongshan City People′s Hospital, Jiangmen Central Hospital, and General Hospital of Southern Theater Command of PLA from January 2020 to December 2021. Using the hospital electronic medical record system, medical records in outpatients who met the inclusion criteria were collected, and relevant clinical data were extracted. The patients were divided into generic drug group and original drug group. To exclude the interference of confounding factors, the propensity score matching method was used. The efficacy evaluation index was the magnitude of hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) reductions within one year after administration. Generalized linear regression model was used to analyze the influencing factors for the magnitude of HbA1c and FPG reduction. The safety evaluation index was the incidence of adverse events within one year of drug use.Results:A total of 4 511 patients with T2DM who were treated with vildagliptin tablets were collected from 4 hospitals, including 3 039 in the generic drug group and 1 472 in the original drug group. After treatment, the HbA1c and FPG in patients of the 2 groups decreased compared with those before treatment. The magnitude of HbA1c and FPG reductions in patients of the generic drug group were not significantly different from those in the original drug group [0.50 (0.05, 2.30)% vs. 0.90 (-0.10, 1.70)%, Z=0.235, P=0.814; 0.59 (-0.40, 2.20) mmol/L vs. 1.00 (-0.61, 2.32) mmol/L, Z=0.421, P=0.674]. The results of generalized linear regression model analysis showed that the therapeutic drugs did not affect the magnitude of HbA1c and FPG reductions ( P=0.627, P=0.478). Compared with the original drug group, the incidences of adverse events and hypoglycemia in the generic drug group were not statistically significant [1.6‰ (5/3 039) vs. 2.7‰ (4/1 472), P=0.721; 0.7 ‰ (2/3 039) vs. 0.7 ‰ (1/1 472), P=1.000]. Conclusion:The efficacy and safety of generic vildagliptin tablets manufactured by Qilu Pharmaceutical Co., Ltd. were generally consistent with those of the original drug in the treatment of T2DM.

Objective:To compare the efficacy and safety of vildagliptin tablets (the generic drug) manufactured by Qilu Pharmaceutical Co., Ltd. and vildagliptin tablets (the original drug) manufactured by Novartis Pharmaceutical Co., Ltd. in the treatment of type 2 diabetes mellitus (T2DM) in third round of national centralized volume-based procurement.Methods:The study design was a multicenter retrospective cohort study. The study subjects were T2DM patients treated with vildagliptin tablets at the Outpatient Department of Zhuhai People′s Hospital, Zhongshan City People′s Hospital, Jiangmen Central Hospital, and General Hospital of Southern Theater Command of PLA from January 2020 to December 2021. Using the hospital electronic medical record system, medical records in outpatients who met the inclusion criteria were collected, and relevant clinical data were extracted. The patients were divided into generic drug group and original drug group. To exclude the interference of confounding factors, the propensity score matching method was used. The efficacy evaluation index was the magnitude of hemoglobin A1c (HbA1c) and fasting plasma glucose (FPG) reductions within one year after administration. Generalized linear regression model was used to analyze the influencing factors for the magnitude of HbA1c and FPG reduction. The safety evaluation index was the incidence of adverse events within one year of drug use.Results:A total of 4 511 patients with T2DM who were treated with vildagliptin tablets were collected from 4 hospitals, including 3 039 in the generic drug group and 1 472 in the original drug group. After treatment, the HbA1c and FPG in patients of the 2 groups decreased compared with those before treatment. The magnitude of HbA1c and FPG reductions in patients of the generic drug group were not significantly different from those in the original drug group [0.50 (0.05, 2.30)% vs. 0.90 (-0.10, 1.70)%, Z=0.235, P=0.814; 0.59 (-0.40, 2.20) mmol/L vs. 1.00 (-0.61, 2.32) mmol/L, Z=0.421, P=0.674]. The results of generalized linear regression model analysis showed that the therapeutic drugs did not affect the magnitude of HbA1c and FPG reductions ( P=0.627, P=0.478). Compared with the original drug group, the incidences of adverse events and hypoglycemia in the generic drug group were not statistically significant [1.6‰ (5/3 039) vs. 2.7‰ (4/1 472), P=0.721; 0.7 ‰ (2/3 039) vs. 0.7 ‰ (1/1 472), P=1.000]. Conclusion:The efficacy and safety of generic vildagliptin tablets manufactured by Qilu Pharmaceutical Co., Ltd. were generally consistent with those of the original drug in the treatment of T2DM.

Objective:To explore the potential mechanism of PD-1 inhibitor P on RIMI from the perspective of immune microenvironment.Methods:To establish a mouse model of radiation-induced myocardial injury (RIMI), twenty C57BL/6 mice were randomly divided into 4 groups, 5 in each group. Group A was the healthy control group; Group B was the PD-1 inhibitor group; Group C was the simple irradiation group, with a heart irradiation of 15 Gy; Group D was the irradiation+ PD-1 inhibitor group. One month after irradiation, the mice were anesthetized and sacrificed. The morphological changes of myocardial tissues were observed by HE staining. The myocardial fibrosis was assessed by Masson staining. CD 3+ , CD 3+ CD 4+ , CD 3+ CD 8 lymphocyte subsets and cytokines (IL-4, IL-6, IL-17A, TNF-α, TGF-β 1 and INF-γ) levels were determined by flow cytometry. The apoptosis rate of myocardial cells was detected by TUNE. Results:One month after irradiation, there was no obvious myocardial fibrosis in group B, and collagen fibers were distributed in the interstitium of myocardial cells in groups C and D. Semi-quantitative analysis results showed that the myocardial collagen volume fraction (CVF) of groups A, B, C and D were (1.97±0.36)%, (2.83±1.03)%, (5.39±0.77)% and (7.72±1.43)%, respectively. The CVF between group A and group B was similar ( P=0.314), and the differences in CVF between the other groups were statistically significant (all P<0.05). Compared with group A, the absolute value and percentage of CD 3+ T lymphocytes were significantly increased in groups B, C and D (all P<0.01). The values in group D were significantly higher than those in group B and group C (all P<0.01); The absolute value and percentage of CD 3+ CD4 T lymphocytes were similar among four groups (all P>0.05); The absolute value and percentage of CD 3+ CD 8 T lymphocytes in group D were significantly higher than those in groups A, B and C (all P<0.001). The expression levels of IL-6, IL-17A, and TGF-β 1 in group D were significantly higher compared with those in groups A, B and C (all P<0.001). The apoptotic index was gradually increased in four groups, and the differences in apoptotic index among four groups were statistically significant (all P<0.001). Conclusion:PD-1 inhibitors can aggravate RIMI by promoting myocardial immune inflammatory response.

Objective:To analyze the radiotherapy-related factors affecting the survival of non-small cell lung cancer (NSCLC) patients complicated with malignant pleural effusion (MPE)(MPE-NSCLC).Methods:From 2007 to 2019, 256 patients pathologically diagnosed with MPE-NSCLC received primary treatment. Among them, 117 cases were enrolled in this study. All patients were divided into two groups according to the radiation dose (<63 Gy and≥63 Gy). Propensity score matching (PSM) was performed to further adjust the confounding factors (Calipers value=0.1). The impact of radiotherapy-related factors on the overall survival (OS) was analyzed by Kaplan—Meier method, log-rank test and Cox’s regression model. Results:Primary tumor radiotherapy significantly prolonged the OS ( P<0.001). The radiation dose escalation (36.0-44.1 Gy, 45.0-62.1 Gy, 63.0-71.1 Gy) of primary tumor significantly prolonged the OS ( P<0.001). The corresponding median OS were 5, 13 and 18 months, respectively. Before the PSM, univariate analysis suggested that radiation dose ≥63 Gy, gross tumor volume (GTV)<157.7 cm 3 and stations of metastatic lymph node (S-mlN)≤5 were significantly associated with better OS (all P<0.05) and T 4N 3 was significantly associated with worse OS ( P=0.018). After the PSM, univariate analysis indicated that radiation dose ≥63 Gy was significantly associated with better OS ( P=0.013) and S-mlN ≤5 had a tendency to prolong the OS ( P=0.098). Prior to the PSM, multivariate analysis showed that radiation dose ≥63 Gy was an independent favorable factor of OS ( HR=0.566, 95% CI 0.368-0.871, P=0.010) and GTV<157.7 cm 3 had a tendency to prolong the OS ( HR=0.679, 95% CI 0.450-1.024, P=0.065). After the PSM, multivariate analysis revealed that radiation dose ≥63 Gy was still an independent favorable factor of OS ( HR=0.547, 95% CI 0.333~0.899, P=0.017). No ≥grade 4 radiation toxicity occurred. The incidence rates of grade 3 radiation esophagitis and pneumonitis were 9.4% and 5.1%, respectively. Conclusion:For MPE-NSCLC, radiotherapy dose of primary tumor may play a key role in improving OS on the basis of controllable MPE.