Objective:To investigate the efficacy of oral folic acid intervention in lung cancer patients with radiation esophagitis (RE) caused by concurrent chemoradiotherapy.Methods:In this randomized, controlled, single-center clinical trial, a total of 82 patients with stage N 2-N 3 lung cancer including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to October 2023 were prospectively included. All enrolled patients were randomly divided into the experimental group (folic acid group) and control group according to 1 vs. 1 of simple random method, and patients in both groups were required to receive radiation therapy for lung lesions and mediastinal metastatic lymph nodes [≥2 cycles of chemotherapy were completed during the same period of radiotherapy (≥40 Gy / 20 F) or targeted drugs were given simultaneously]. The severity of RE was evaluated using the modified common terminology criteria for adverse events criteria of the National Cancer Institute in both groups weekly at the onset of radiation esophagitis symptoms and thereafter until 1 week after the end of radiotherapy. Conventional treatment of RE was delivered according to the grading criteria of the Radiation Therapy Oncology Group. Patients in the folic acid group were given with folic acid tablets 30 mg/d orally at the beginning of radiotherapy until the end of radiotherapy, while those in the control group did not receive any drug intervention. The onset time, severity and duration of RE, and changes in the severity of esophageal toxicity after conventional treatment were recorded and analyzed. Serum folate value, serum vitamin B 12 value and homocysteine value were measured before and after radiotherapy. For continuous quantitative variables, independent sample t-test or independent sample rank-sum test was used for comparison among different groups. For categorical data, Chi-square test or Fisher's exact probability method was used for comparison among different groups. Results:During the observation period, no grade 4 or above RE was reported between two groups. The incidence of grade 0, 1, 2 and 3 RE in the folic acid and control groups was 10% (4/40) and 5% (2/41), 70% (28/40) and 42% (17/41), 15% (6/40) and 51% (21/41), 5% (2/40) and 2% (1/41), respectively. The differences were not statistically significant between two groups ( P=0.456). However, the incidence of grade 0-1 RE in the folic acid group was significantly higher than that in the control group ( Z=2.72, P=0.006). The median time of RE in the folic acid group and control group was 12 d (range 7-52 d) and 15 d (range 11-56 d) after the start of radiotherapy, respectively, with no statistically significant difference ( χ2=-0.75, P=0.456). However, median duration of the individual's most severe RE was 12 d (range 4-36 d) and 21 d (range 7-38 d) in the folic acid group and control groups, respectively, and the differences were statistically significant ( χ2=2.10, P=0.039). In the folic acid group, the grades of swallowing with pain and dysphagia were significantly declined after folic acid intervention, especially at 2 weeks after the occurrence of RE ( P=0.001, P=0.002). The remission rate of RE after 1 week in the folic acid group was higher than that in the control group, and the difference was statistically significant ( χ2=7.36, P=0.012). Conclusion:Oral intake of folic acid during concurrent chemoradiotherapy for lung cancer cannot reduce the incidence of RE, but it may reduce its severity, shorten the duration of the most severe RE in individuals, and have a certain protective effect.

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 efficacy of oral folic acid intervention in lung cancer patients with radiation esophagitis (RE) caused by concurrent chemoradiotherapy.Methods:In this randomized, controlled, single-center clinical trial, a total of 82 patients with stage N 2-N 3 lung cancer including small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) admitted to the Affiliated Cancer Hospital of Guizhou Medical University from June 2022 to October 2023 were prospectively included. All enrolled patients were randomly divided into the experimental group (folic acid group) and control group according to 1 vs. 1 of simple random method, and patients in both groups were required to receive radiation therapy for lung lesions and mediastinal metastatic lymph nodes [≥2 cycles of chemotherapy were completed during the same period of radiotherapy (≥40 Gy / 20 F) or targeted drugs were given simultaneously]. The severity of RE was evaluated using the modified common terminology criteria for adverse events criteria of the National Cancer Institute in both groups weekly at the onset of radiation esophagitis symptoms and thereafter until 1 week after the end of radiotherapy. Conventional treatment of RE was delivered according to the grading criteria of the Radiation Therapy Oncology Group. Patients in the folic acid group were given with folic acid tablets 30 mg/d orally at the beginning of radiotherapy until the end of radiotherapy, while those in the control group did not receive any drug intervention. The onset time, severity and duration of RE, and changes in the severity of esophageal toxicity after conventional treatment were recorded and analyzed. Serum folate value, serum vitamin B 12 value and homocysteine value were measured before and after radiotherapy. For continuous quantitative variables, independent sample t-test or independent sample rank-sum test was used for comparison among different groups. For categorical data, Chi-square test or Fisher's exact probability method was used for comparison among different groups. Results:During the observation period, no grade 4 or above RE was reported between two groups. The incidence of grade 0, 1, 2 and 3 RE in the folic acid and control groups was 10% (4/40) and 5% (2/41), 70% (28/40) and 42% (17/41), 15% (6/40) and 51% (21/41), 5% (2/40) and 2% (1/41), respectively. The differences were not statistically significant between two groups ( P=0.456). However, the incidence of grade 0-1 RE in the folic acid group was significantly higher than that in the control group ( Z=2.72, P=0.006). The median time of RE in the folic acid group and control group was 12 d (range 7-52 d) and 15 d (range 11-56 d) after the start of radiotherapy, respectively, with no statistically significant difference ( χ2=-0.75, P=0.456). However, median duration of the individual's most severe RE was 12 d (range 4-36 d) and 21 d (range 7-38 d) in the folic acid group and control groups, respectively, and the differences were statistically significant ( χ2=2.10, P=0.039). In the folic acid group, the grades of swallowing with pain and dysphagia were significantly declined after folic acid intervention, especially at 2 weeks after the occurrence of RE ( P=0.001, P=0.002). The remission rate of RE after 1 week in the folic acid group was higher than that in the control group, and the difference was statistically significant ( χ2=7.36, P=0.012). Conclusion:Oral intake of folic acid during concurrent chemoradiotherapy for lung cancer cannot reduce the incidence of RE, but it may reduce its severity, shorten the duration of the most severe RE in individuals, and have a certain protective effect.

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.

Emerging research suggests a potential association of progression of Alzheimer's disease(AD)with al-terations in synaptic currents and mitochondrial dynamics.However,the specific associations between these pathological changes remain unclear.In this study,we utilized Aβ42-induced AD rats and primary neural cells as in vivo and in vitro models.The investigations included behavioural tests,brain magnetic resonance imaging(MRI),liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)analysis,Nissl staining,thioflavin-S staining,enzyme-linked immunosorbent assay,Golgi-Cox staining,trans-mission electron microscopy(TEM),immunofluorescence staining,proteomics,adenosine triphosphate(ATP)detection,mitochondrial membrane potential(MMP)and reactive oxygen species(ROS)assess-ment,mitochondrial morphology analysis,electrophysiological studies,Western blotting,and molecular docking.The results revealed changes in synaptic currents,mitophagy,and mitochondrial dynamics in the AD models.Remarkably,intervention with Dengzhan Shengmai(DZSM)capsules emerged as a pivotal element in this investigation.Aβ42-induced synaptic dysfunction was significantly mitigated by DZSM intervention,which notably amplified the frequency and amplitude of synaptic transmission.The cognitive impairment observed in AD rats was ameliorated and accompanied by robust protection against structural damage in key brain regions,including the hippocampal CA3,primary cingular cortex,prelimbic system,and dysgranular insular cortex.DZSM intervention led to increased IDE levels,augmented long-term potential(LTP)amplitude,and enhanced dendritic spine density and length.Moreover,DZSM intervention led to favourable changes in mitochondrial parameters,including ROS expression,MMP and ATP contents,and mitochondrial morphology.In conclusion,our findings delved into the realm of altered synaptic currents,mitophagy,and mitochondrial dynamics in AD,concurrently highlighting the therapeutic potential of DZSM intervention.

Objective:To explore the clinical changes in levels of the new clinical marker serum hepatitis B virus (HBV) pregenomic RNA (pgRNA) in patients with chronic hepatitis B (CHB) with long-term antiviral therapy.Methods:100 CHB cases who were initially treated with nucleos(t)ide analogues (NAs) at Peking University First Hospital were included. The levels of alanine aminotransferase (ALT), HBV DNA, hepatitis B e-antigen (HBeAg), and hepatitis B surface antigen (HBsAg) during the follow-up period were measured. The TaqMan-based real-time quantitative PCR method was used to detect serum HBV pgRNA levels. The independent sample t-test and Mann-Whitney U test were used to compare continuous variables between groups, while Pearson's χ2 test and Fisher's exact test were used to compare categorical variables. Results:HBV pgRNA levels decreased significantly in patients who developed virological responses at 48 weeks ( n = 54) during subsequent treatment compared to those who did not ( n = 46). The HBV pgRNA level was lower in HBeAg-positive patients than in HBeAg-negative patients ( P < 0.05 or P < 0.01). Patients with higher HBV DNA and HBeAg-positivity levels at baseline had a higher HBV pgRNA level following antiviral therapy. There was no statistically significant difference in HBV pgRNA levels in patients with different HBV pgRNA levels at baseline after antiviral therapy. There was no correlation between serum HBV pgRNA and HBsAg at baseline, but there was a correlation after long-term antiviral therapy, while there was a weak correlation between HBV pgRNA and HBsAg at the fifth and ninth years of antiviral therapy ( r = 0.262, P = 0.031; r = 0.288, P = 0.008). Conclusion:HBV pgRNA levels were higher with higher HBV activity in CHB patients with long-term antiviral therapy.

Objective To investigate the value of multiparametric magnetic resonance imaging(MRI)texture analysis based on T2 weighted image(T2WI),diffusion weighted imaging(DWI),and dynamic contrast enhanced-MRI(DCE-MRI)in predicting the axillary lymph node status of small-sized invasive ductal carcinoma(IDC)of the breast.Methods A retrospective analysis was conducted on the medical records of 139 patients with newly diagnosed IDC,who were treated at Taizhou Central Hospital from January 2018 to June 2023.Based on the postoperative pathological results,the patients were divided into two groups:85 cases without axillary lymph node metastasis and 54 cases with axillary lymph node metastasis.All patients underwent preoperative MRI examination,including sequences such as T2WI,DWI,and DCE-MRI.After delineating the region of interest(ROI)on the slice with the largest tumor diameter in each sequence,texture analysis was performed using Firevoxel software,which yielded five major parameters,including mean,standard deviation,skewness,kurtosis,and entropy.Univariate analysis was employed to evaluate the effectiveness of each parameter in distinguishing the axillary lymph node status.Variables that showed significant results in the univariate analysis were then included in binary Logistic regression analysis to explore the relationship between these parameters and lymph node metastasis status.Receiver operating characteristic(ROC)curves were plotted,and the area under the curve(AUC)was calculated.Results Significant differences were observed between the two groups in the entropy and mean values of the ROI delineated on the DCE-MRI sequence,as well as the skewness of the T2WI(P<0.001).Among these texture parameters,the entropy of the DCE-MRI sequence showed the highest AUC value of 0.719 in the univariate analysis.Multivariate analysis of the selected parameters yielded an optimal diagnostic model,with an AUC of 0.769 in differentiating lymph node metastasis from non-metastasis.Conclusion Texture analysis of small-sized breast cancer based on multiparametric MRI can effectively predict the preoperative axillary lymph node status of breast cancer.

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 study the relationship between endoplasmic reticulum stress (ERS) and apoptotic protein and myocardial pathological changes in rats after endostar combined with low-dose X-ray irradiation.Methods:Forty SD rats were evenly divided into four groups: control group (intraperitoneal injection of equal volume physiological saline, once per day, 14 d), endostar group (intraperitoneal injection of endostar 6 mg/kg, once per day, 14 d), irradiation group (15 Gy divided into 3 times X-ray irradiation) and combination group (intraperitoneal injection of endostar after irradiation at the same dose and time as the endostar group). At 1 and 6 months after treatment, myocardial tissues of rats were prepared for HE staining and Masson staining to observe the myocardial histological changes. TUNEL assay was used to detect myocardial cell apoptosis, and ImageJ software was utilized to calculate myocardial collagen volume fraction (CVF). The expression levels of ERS and apoptotic protein glucose-regulated protein 78 (GRP78), protein kinase-like endoplasmic reticulum kinases (PERK), CCAAT/enhancer binding protein homologous protein (CHOP) and cysteine-containing aspartate-specific protease-12 (Caspase-12) were detected by Western blot. One-way ANOVA was conducted using GraphPad Prism 8.0.1 software, and comparison between two groups was conducted using t-test. Results:At 6 months after treatment, the myocardial interstitium in the irradiation and combination groups was widened, showing strip-like or reticular fibrosis changes, and the myocardial interstitium had diffuse collagen fiber deposition. Compared with the control group, CVF was increased significantly (both P<0.01). At 1 and 6 months after treatment, the apoptotic index of myocardial cells in the combination group was significantly higher than that in the control group ( P<0.05, <0.001). At 1 and 6 months after treatment, the expression levels of GRP78 protein in the irradiation and combination groups were increased (all P<0.01), and the expression levels of PERK and CHOP proteins in the combination group were increased compared to those in the control group (both P<0.05). At 6 months after treatment, the expression levels of PERK and CHOP proteins in the irradiation group were increased compared to those in the control group (both P<0.05). Compared with the control group, Caspase-12 expression levels at 1 and 6 months after treatment were increased in the endostar, irradiation and combination groups (all P<0.05). Conclusions:The expression levels of ERS and apoptotic proteins are related to cardiac injury caused by irradiation in rats. After low-dose X-ray combined with endostar treatment, ERS is aggravated and myocardial apoptosis is increased.

Objective:To explore the characteristics of failure patterns of three-dimensional radiotherapy combined with first-line drug therapy for primary tumors of stage Ⅳ non-small cell lung cancer(NSCLC)and investigate the influence of radiotherapy-related factors.Methods:708 patients newly-diagnosed with stage Ⅳ NSCLC from March 2003 to July 2020 were selected. Chi-square test was used for univariate analysis of failure patterns. Kaplan-Meier method, Log-rank test and Cox regression model were employed for multivariate analysis. Results:The incidence of first-line treatment failure in 708 cases was 71.2%, and the incidence of treatment failure was 22.7%, 28.8%, 13.3%, and 6.4% for ≤6 months, >6-12 months, >12-24 months, and>24 months, respectively, and the median survival time was 7.2, 13.4, 22.2, and 37.6 months, which was significantly different( χ2=226.013, P<0.001). The incidence of recurrence failure(RF)was 21.3%.There was no significant difference in the incidence of RF between oligometastasis(OM)and non-oligometastasis(NOM). The incidence of DF was 66.3% and the order of incidence was brain>bone>lung>pleural cavity>liver>distant lymph nodes>adrenal gland>other sites, occurring in approximately 1/2 of AM and 1/3 of PSM cases. Metastatic status, time to treatment failure, pathological type, gender, combined treatment intensity were the independent influencing factors for predicting prognosis. Conclusions:The failure pattern of radiotherapy for primary tumors of stage Ⅳ NSCLC is different from that of first-line drug therapy, with significantly lower local failure and predominantly metastatic failure. The incidence of brain metastasis is the highest. The later time to treatment failure, the longer the overall survival(OS). OM, female, non-squamous cell carcinoma, late treatment failure, 4-6 cycles of chemotherapy over the same period ≥63 Gy are the independent prognostic factors for prolonging survival.