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 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 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 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 analyze the mediastinal displacement of target volume in the postoperative radiotherapy (PORT) process for non-small cell lung cancer (NSCLC) and the value of mid-term evaluation.Methods:For 100 patients with postoperativeN 2 stage NSCLC, R 1-2 and any N staging, bone anatomy was utilized to measure the change of the first and second CT localization on the same level. Statistical analysis were performed using the WilCoxon, Kruskal-Wallis and χ2 tests. The cut-off values were calculated with the receiver operating characteristic (ROC) curve. Results:Among the included patients, in the PORT process, the mediastinal displacement in the x (front and rear), Y (left and right) and Z (upper and lower) directions were 0.04-0.53 cm, 0.00-0.84 cm and 0.00-1.27 cm, respectively, and the order of mediastinal displacement distance wasz > Y> X,respectively. According to the ROC curve calculation, the cut-off values were 0.263, 0.352 and 0.405, respectively, which were greater than the cut-off values in 25 cases (25%), 30 cases (30%) and 30 cases (30%), respectively. There was significant difference in the three-dimensionalmediastinal displacement ( P=0.007, <0.001 and<0.001). The mediastinal displacement in thex, Y and Z directions had no statistical significance regarding resection site ( P=0.355, 0.239 and 0.256) and operation mode ( P=0.241, 0.110 and 0.064). Comparative analysis of modified whole group mediastinal shift> and cut-off values, medium-simulation (m-S) and the originally planned radiotherapy shown that there was no significant difference in the incidence of radiation esophagitis (RE) and radiation pneumonitis in PORT patients (all P>0.05); however, the incidence of ≥grade 3 RE in the modified plan after m-S was significantly lower than that in the originally planned PORT patients, which were 0 and 7%, respectively ( P<0.001). Conclusions:Mediastinal displacement exists in the PORT process of N 2 or/and R 1-2 cases after radical operation of NSCLC, and obvious movement occurs in 20%-30% of patients. Relocating and modifying the target volume and radiotherapy plan in the middle of the PORT process is beneficial to quality assurance and quality control.

Objective:To investigate the implication of micro RNA-21(miR-21) in Endostar combined with X-ray irradiation of cardiac fibroblasts (CF).Methods:Rat CFs were used in this experiment and been divided into the blank control group, 10 Gy X-ray irradiation group, Endostar group, 10 Gy X-ray+ Endostar group, 10 Gy X-ray+ Endostar+ NC mimic group (negative control 1), 10 Gy X-ray+ Endostar+ miR-21 mimic group, 10 Gy X-ray+ Endostar+ NC inhibitor group (negative control 2) and 10 Gy X-ray+ Endostar+ miR-21 inhibitor group. The proliferation of CF was determined by Methyl thiazolyl tetrazolium (MTT) assay. The expression level of Collagen Ⅰ protein was analyzed by Western blot. The expression levels of Collagen Ⅰ and miR-21 mRNA were assayed by real-time quantitative polymerase chain reaction (q-PCR).Results:In the 10 Gy X-ray+ Endostar+ miR-21 mimic group, the CF proliferation, Collagen Ⅰ and miR-21 mRNA were increased significantly compared with those in the blank control group, 10 Gy X-ray+ Endostar group, and negative control group 1 (all P<0.05). In the 10 Gy X-ray+ Endostar+ miR-21 inhibitor group, the CF proliferation and expression levels of Collagen Ⅰ mRNA were decreased significantly compared with those in the blank control group, 10 Gy X-ray+ Endostar group and negative control group 2(all P<0.05). Conclusions:The CF proliferation and Collagen Ⅰ expression are increased when the expression level of miR-21 gene is simulated. When inhibiting the expression of miR-21 gene, the CF proliferation and Collagen Ⅰ expression are reduced.

Objective:To evaluate the accuracy and practicability of hepatocellular carcinoma prediction score (PAGE-B) and modified hepatocellular carcinoma prediction score (mPAGE-B) in predicting the development of hepatocellular carcinoma in patients with hepatitis B virus (HBV)-associated liver cirrhosis and received nucleos(t)ide analogue (NA) treatment.Methods:From June 2009 to December 2014, at Department of Hepatology, the First Affiliated Hospital of Fujian Medical University, the clinical data of 707 patients with HBV-associated liver cirrhosis and received NA treatment were retrospectively collected, and the patients were followed up. The risk factors of development of hepatocellular carcinoma were analyzed. PAGE-B (including platelet count, age, gender), mPAGE-B (including platelet count, age, gender and albumin), Child-Turcotte-Pugh (CTP) score and aspartate aminotransferase to platelet ratio index (APRI) were compared in area under receiver operator characteristic curve (AUROC) for predicting the occurrence of hepatocellular carcinoma within 5 years. Risk stratification analysis was carried out for mPAGE-B and PAGE-B. Multivariate Cox regression analysis, receiver operator characteristic curve, Mann-Whitney U test and Kaplan-Meier method were used for statistical analysis. Results:The age of 707 patients was (46.7±12.2) years old, including 567 males (80.2%) and 140 females (19.8%). The positive rate of hepatitis B e antigen was 56.4% (399/707). The scores of PAGE-B, mPAGE-B, CTP and APRI were 15.90±4.24, 12.39±3.58, 6.88±2.15 and 1.80 (0.85, 3.79), respectively. The overall follow up time was (38.14±20.97) months and the incidence of hepatocellular carcinoma was 8.1% (57/707). The results of multivariate Cox regression analysis showed that advanced age, low platelet count and quantitative reduction of HBV DNA were independent risk factors of development of hepatocellular carcinoma (Wald=20.44, 5.64 and 9.25; HR(95% confidence interval (95% CI) 1.056(1.031 to 1.081), 0.994(0.989 to 0.999) and 0.769(0.649 to 0.911); P<0.001, =0.018 and 0.002). The AUROCs (95% CI) of PAGE-B, mPAGE-B, CTP score and APRI for predicting the occurrence of hepatocellular carcinoma within 5 years were 0.708 (0.639 to 0.778), 0.724 (0.657 to 0.778), 0.576 (0.500 to 0.652) and 0.516 (0.443 to 0.589), respectively. There were no statistically significant differences in AUROCs for predicting the occurrence of hepatocellular carcinoma within 5 years between mPAGE-B and PAGE-B, between APRI and CTP score (both P>0.05). The AUROC for predicting the occurrence of hepatocellular carcinoma within 5 years of CTP score was less than those of PAGE-B and mPAGE-B, and the differences were statistically significant ( Z=3.00 and 3.79; P=0.003, <0.001). The AUROC for predicting the occurrence of hepatocellular carcinoma within 5 years of APRI was less than those of PAGE-B and mPAGE-B, and the differences were statistically significant ( Z=4.75 and 5.46, both P<0.001). There were 51 cases (7.2%), 394 cases (55.7%) and 262 cases (37.1%) in the low-risk (<10) group, medium-risk (10 to 17) group and high-risk (>17) group as assessed by PAGE-B. The incidence of hepatocellular carcinoma was 0(0/51), 4.8% (19/394) and 14.5% (38/262), respectively the annual average incidence of hepatocellular carcinoma was 0, 1.6% and 5.5%, respectively, the 5-year cumulative incidence of hepatocellular carcinoma was 0, 7.3% and 31.3%, respectively. The 5-year cumulative incidence of hepatocellular carcinoma of high-risk group was higher than those of medium-risk group and low-risk group (log-rank test=19.27, P<0.001). There were 97 cases (13.7%), 246 cases (34.8%) and 364 cases (51.5%) in the low-risk group (<9), medium-risk group (9 to 12) and high-risk group (>12) as assessed by mPAGE-B. The incidence of hepatocellular carcinoma was 2.1% (2/97), 3.7% (9/246) and 12.6%(46/364), the annual average incidence of hepatocellular carcinoma was 0.6%, 1.1% and 4.7%, respectively, the 5-year cumulative incidence of hepatocellular carcinoma was 2.4%, 5.1% and 26.7%, respectively. The 5-year cumulative incidence of hepatocellular carcinoma of high-risk group was higher than those of medium-risk group and low-risk group (log-rank test value=18.64, P<0.001). Conclusions:Both PAGE-B and mPAGE-B can predict the occurrence of hepatocellular carcinoma within 5 years in patients with HBV-associated liver cirrhosis treated with antiviral therapy, identify liver cirrhotic patients at high risk of development of hepatocellular carcinoma and guide clinicans to use more efficient screening strategies.

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.

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.