Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

Objective To establish a rat model of Alzheimer's disease (AD) expressing human triple mutant amyloid precursor protein (APP) in the hippocampus, and to provide a model for the study of disease mechanisms and drug development. Methods Twenty-four 12-week-old SPF-grade female SD rats were randomly divided into a blank control group, a virus control group and an experimental group, with eight rats in each group; among them, the experimental group received a stereotaxic injection of adeno-associated virus (AAV) carrying the human triple mutant APP and NanoLuc luciferase genes into the hippocampus. In vivo imaging was used to observe viral expression in the brains of rats in each group, the novel object recognition test was used to assess the recognition memory of the rats in each group, real-time fluorescent quantitative PCR was used to detect the expression level of the APP gene, HE staining was used to examine the brain histopathology, Nissl staining was used to assess the hippocampal lesions, and immunohistochemistry was used to detect the deposition of amyloid β-protein (Aβ). Results In vivo imaging showed that reporter fluorescence was detected in the brains of rats in both experimental and virus control groups. Fluorescence quantitative PCR showed that the expression level of the APP gene was significantly increased in the brains of rats in the experimental group (P<0.01). Novel object recognition test revealed that the recognition memory of rats in the experimental group was significantly reduced compared with that of the blank control group (P<0.01). Six months after recombinant AAV virus infection, HE staining and Nissl staining of brain tissues showed that the number of neurons and Nissl bodies in the CA1 region of the hippocampus in the experimental group was reduced and disorganized; immuno-histochemistry testing of the CA1 region of the hippocampus and the pyramidal cell layer of the experimental group revealed prominent brown deposits, indicating Aβ protein deposition. Conclusion The rat model successfully established by stereotaxic injection and AAV-mediated delivery of human triple mutant APP gene exhibits typical AD features, providing a valuable animal model for studying AD pathology and developing drug therapies targeting Aβ protein deposition.

OBJECTIVES: To propose a hypothesis that aloe-emodin may inhibit scar tissue fibrosis through thrombospondin-1(THBS1)-PI3K-Akt pathway. METHODS: By cultivating fibroblasts derived from scar tissue after cleft palate surgery in humans, aloe emodin of different concentrations (10, 20, 30, 40 and 50 μmol/L) was added to the cells which activity was detected. At the same time, transcriptome sequencing was performed on scar tissue and cells, and bioinformatics methods were used to explore potential targets and signaling pathways of scar tissue fibrosis. RESULTS: Aloe-emodin had a concentration dependent inhibitory effect on fibroblast proliferation,with the 40 μmol/L concentration group showing the most significant effect. The results of tissue and cell sequencing indicated that differentially expressed genes were significantly enriched in extracellular matrix-receptor interaction pathway, and shared a common differential gene which was THBS1. The ORA analysis results indicated that differentially expressed genes, including THBS1, were significantly enriched in the PI3K-Akt signaling pathway. CONCLUSIONS Aloe emodin may inhibit the PI3K-Akt pathway by downregulating THBS1, thereby reducing the proliferation activity of fibroblasts derived from postoperative palatal scar tissue.
Thrombospondin 1/genetics* ; Humans ; Signal Transduction/drug effects* ; Fibroblasts/cytology* ; Proto-Oncogene Proteins c-akt/metabolism* ; Fibrosis ; Phosphatidylinositol 3-Kinases/metabolism* ; Cicatrix/metabolism* ; Cell Proliferation/drug effects* ; Anthraquinones/pharmacology* ; Cells, Cultured

Objective:To investigate the specific expressions of Delta like non-canonical Notch ligand 1 ( DLK1) and Maternally expressed gene 3 ( MEG3) in POU class 1 homeobox 1 (POU1F1) spectrum pituitary tumors and their correlation with prognosis. Methods:A retrospective case-control study method was adopted. A total of 167 patients with POU1F1 lineage pituitary adenomas who were diagnosed and underwent pituitary adenoma resection at Tangshan People′s Hospital from April 2021 to April 2023 were collected as the research subjects. There were 98 males and 69 females with an average age of (63.05±7.51) years, ranging from 52 to 82 years. They were divided into good prognosis group ( n=111) and poor prognosis group ( n=56) according to postoperative follow-up. A multiple linear regression analysis was performed to examine the relationships between the levels of DLK1 mRNA and MEG3 mRNA and the immune function indicators (Complement 3/Complement 4/Immunoglobulin M/Immunoglobulin A). Multivariate Logistic regression analysis was used to investigate the correlation between DLK1 mRNA and MEG3 mRNA levels and poor prognosis of patients. The odds ratio (OR) of multivariate Logistic regression analysis was calculated. RCS model was used to analyze the dose-response relationship between DLK1 mRNA and MEG3 mRNA and poor prognosis of pituitary tumor resection in POU1F1 spectrum patients. The measurement data following a normal distribution were presented as mean±standard deviation ( ± s), and the t-test was used for comparison between groups. The count data were presented as the number of cases and percentages (%), and the chi-square test was used for comparison between groups. Results:Before treatment, the levels of DLK1 mRNA and MEG3 mRNA in the serum of patients in the good prognosis group were 0.142±0.047 and 0.075±0.024 respectively, and after treatment, they were 0.019±0.003 and 0.577±0.067 respectively. Before treatment, the levels of DLK1 mRNA and MEG3 mRNA in the serum of patients in the poor prognosis group were 0.109±0.035 and 0.067±0.016 respectively, and after treatment, they were 0.057±0.011 and 0.298±0.047 respectively. Before and after treatment the level of DLK1 mRNA in the good prognosis group was significantly lower than that in the poor prognosis group, and the level of MEG3 mRNA in the good prognosis group was significantly higher than that in the poor prognosis group ( P< 0.05). Moreover, the serum DLK1 mRNA and MEG3 mRNA of patients after treatment were significantly different from those before treatment ( P<0.05). The levels of adrenocorticotropin (ACTH), growth hormone, prolactin, complement 3, mean visual field defect and weighted visual field index in the good prognosis group were (42.15±4.68) ng/L, (13.47±2.17) ng/L, (8.28±1.76) ng/L, (1.38±0.34) g/L, (5.26±1.15) dB, (89.14±17.23)%. In the poor prognosis group, there were (56.64±6.42) ng/L, (18.06±3.11) ng/L, (11.49±2.93) ng/L, (1.12±0.45) g/L and (7.96±1.52) dB, (73.65±15.28)%, and there was statistical significance in the above indexes between the two groups ( P< 0.05). There was no independent correlation between the expression of DLK1 mRNA and MEG3 mRNA and immune function indexes (Complement 3/Complement 4、IgM、IgA) ( P>0.05). There was an independent positive correlation between high level of DLK1 mRNA and poor prognosis ( OR=0.521, 95% CI: 0.466-0.738), and a stable correlation between low level of MEG3 mRNA and poor prognosis ( OR=0.761, 95% CI: 0.526-0.883). There is a negative nonlinear dose-response relationship between MEG3 and risk of poor prognosis, and a positive nonlinear dose-response relationship between DLK1 and risk-poor prognosis. The area under ROC curve (AUC) of DLK1 mRNA and MEG3 mRNA for predicting poor prognosis were 0.685(0.504-0.797) and 0.710 (0.611-0.806), respectively. Conclusion:There are significant differences between serum DLK1 mRNA and MEG3 mRNA after treatment and before treatment. DLK1 mRNA were positively nonlinear independent correlated with poor prognosis, and MEG3 mRNA was negatively nonlinear independent correlated with poor prognosis.

ObjectiveTo explore the efficacy-driving mechanism of Danhong injection （DHI） in the treatment of stable angina pectoris （SAP） based on the composition-activity relationship of target modules and clarify the pharmacological effects of DHI. MethodAccording to the angina frequency （AF） in the Seattle Angina Questionnaire （SAQ） that was obtained in the previous clinical trial， the patients before and after DHI treatment were grouped based on efficacy. The transcriptomic data of the patients before treatment and in the best efficacy group 30 days post-treatment were selected as the data source， and then weighted gene co-expression network analysis （WGCNA） was employed to construct the co-expression network. Relevant modules in the network were identified and associated with clinical features. In addition， the On-modules （Z value below 0） were identified by Zsummary. The topological indicators such as density， centrality， and clustering coefficient were adopted to explore the dynamics of DHI efficacy at the network level and module level， respectively. In addition， the driver genes were screened by the personalized network control （PNC） algorithm. Finally， rat H9C2 cells were used to establish the model of hypoxia/reoxygenation （H/R）， which was used to confirm the potential therapeutic target of DHI for SAP and provide a scientific basis for revealing the therapeutic mechanism of DHI. ResultWe identified 19 modules in the best efficacy group of DHI for SAP， and the comparison between day 0 and day 30 revealed 12 On-modules. The changes of network topological indicators at the network and module levels confirmed the correlation between the best efficacy of DHI treatment and topological dynamics. Finally， the driver genes， Klotho and fibroblast growth factor 22 （FGF22）， in DHI treatment of SAP were verified by the H9C2 cell model of H/R. ConclusionBased on clinical transcriptome data， this study determined the composition-activity relationship of target modules of DHI for SAP， which provided a scientific basis for deciphering the efficacy-driven mechanism of DHI for SAP.

Objective: To explore the combined effect of health literacy and nonsuicidal selfinjury on suiciderelated behaviors in junior middle school students, so as to provide reference for suicide prevention. Methods: During May to June 2023, a selffilling questionnaire survey was conducted among 7 367 junior middle school students selected by the methods of multistage stratified cluster sampling combined with conventient sampling in Chongqing. And a binary Logistic regression model was established to analyze the association of health literacy and NSSI with suiciderelated behaviors. Results: The detection rates of suicidal ideation, suicide planning, and suicide attempt among junior middle school students were 27.99%, 9.84%, and 4.64%, and the detection rate of NSSI was 38.03%, the rates of possessing total health literacy, functional health literacy, interactive health literacy, and critical health literacy were 62.68%, 66.51%, 54.24%, and 72.65%, respectively. Binary Logistic regression analyses showed that the absence of total health literacy and the three dimensions of health literacy and NSSI were positively correlated with suicidal ideation, suicide planning, and suicide attempt in junior middle school students (OR=1.42-10.30), and there were combined effects (OR=7.43-18.71) (P<0.05). Conclusions Lack of health literacy or the presence of NSSI and their coexistence increase the risk of suiciderelated behaviors, and health literacy level should be improved in junior middle school students to reduce NSSI and thereby prevent suiciderelated behaviors.

Background::Breast cancer is ranked among the most prevalent malignancies in the Chinese female population. However, comprehensive reports detailing the latest epidemiological data and attributable disease burden have not been extensively documented.Methods::In 2018, high-quality cancer surveillance data were recorded in 700 population-based cancer registries in China. We extracted data on female breast cancers (International Classification of Diseases, Tenth Revision [ICD-10]: C50) and estimated the incidence and mortality in 2022 according to the baseline data and corresponding trends from 2010 to 2018. Pathological types were classified according to the ICD for Oncology, 3rd Edition codes. Disability-adjusted life years (DALYs) were calculated as the sum of the years of life lost (YLLs) and years lived with disability (YLDs).Results::In 2022, approximately 357,200 new female breast cancer cases and 75,000 deaths occurred in China, accounting for 15.59% and 7.94% of total new cancer cases and deaths, respectively. The age-standardized incidence rate (ASIR) was 33.04 per 100,000. When analyzed by pathological type, the ASIRs for papillary neoplasms, invasive breast carcinoma, rare and salivary gland-type tumors, and other types were 1.13, 29.79, 0.24, and 1.88 per 100,000, respectively. The age-standardized mortality rate (ASMR) was 6.10 per 100,000. A total of 2,628,000 DALYs were found to be attributable to female breast cancer in China, comprising 2,278,300 YLLs and 349,700 YLDs. The ASIR, ASMR, and age-standardized rate (ASR) for DALYs in urban areas were consistently higher than those in rural areas. We observed a four-fold increase in the ASIR and ASR for DALYs and an eight-fold increase in the ASMR among females over 55 years compared with those aged under 55 years.Conclusion::These data provide invaluable insights into the latest epidemiology of female breast cancer in China and highlight the urgency for disease prevention and control strategy formulation.

Objective To observe the relationship between functional connectivity(FC)of frontoparietal network(FPN)and cognitive function in patients with cerebral small vessel disease(CSVD)using resting-state functional MRI(rs-fMRI).Methods rs-fMRI of 50 CSVD patients with cognitive impairment(CI group),65 CSVD patients with normal cognition(NC group)and 60 healthy controls(HC group),as well as outcomes of neuropsychological tests were retrospectively analyzed.Brain regions with different FC of FPN were compared among 3 groups and between each 2 groups.Partial correlation analysis was used to evaluate the correlations of FC of brain regions value being statistically different between CI and NC groups and cognitive scores.Results Significant differences of FC in bilateral cingulate gyrus,left middle frontal gyrus,right supramarginal gyrus,right inferior parietal lobule and right medial superior frontal gyrus were found among groups(FWE correction,all P＜0.05).Compared with NC group,FC of left cingulate gyrus decreased,of right inferior frontal gyrus and right medial superior frontal gyrus increased in CI group(FWE correction,all P＜0.05).The decreased FC value of left cingulate gyrus was negatively correlated with clock drawing test score in CSVD patients(r=-0.159,P=0.049).Conclusion CSVD patients with or without CI had extensive abnormal FC of FPN,and the left cingulate gyrus was associated with patient's cognitive function.

Biology-guided radiotherapy (BgRT) is a novel technique of external beam radiotherapy, combining positron emission tomography-computed tomography (PET-CT) with a linear accelerator (LINAC). The key innovation is to utilize PET signals from tracers in tumor tissues for real-time tracking and guiding beamlets. Compared with a traditional LINAC system, a BgRT system is more complex in hardware design, software algorithm, system integration and clinical workflow. RefleXion Medical has developed the world's first BgRT system. Nevertheless, its actively advertised function, PET-guided radiotherapy, is still in the research and development phase. In this review study, we presented a number of issues related to BgRT, including its technical advantages and potential challenges.
Positron Emission Tomography Computed Tomography ; Radiotherapy Planning, Computer-Assisted/methods* ; Algorithms ; Particle Accelerators ; Biology ; Radiotherapy, Image-Guided/methods* ; Radiotherapy Dosage

Objective To investigate the safety and efficacy of photodynamic therapy (PDT) for malignant obstruction of the biliary tract. Methods We retrospectively analyzed the clinical data of patients with malignant biliary obstruction treated by PDT in our medical center. On the basis of different treatment plans, the patients were categorized into the photodynamic only group and the combined treatment group, in which additional interventional operations, targeted therapy, or immunotherapy were arranged. The alterations in liver function, duration of biliary patency, and postoperative complications that occurred within one month were closely monitored in both groups. Results A total number of 19 patients were enrolled in this study. The technical success rate of PDT was 100%. The deterioration of liver function was not observed in any patients within one month after PDT. Within a maximum of 17.7 months follow-up, the patency rates of the biliary tract were 100.0%, 89.5%, 72%, and 64% at 1, 3, 6, and 12 months after the procedure, respectively. The mean biliary patency time was 6.9±0.8 months (95%CI: 5.2-8.7 months). Specifically, the biliary patency times for Bismuth type Ⅲ and Ⅳ were 7.5±1.1 and 6.1±1.3 months, respectively. The biliary patency time was around 3.3±0.7 months in the photodynamic only group and 7.9±0.9 months in the combined treatment group (P=0.017). Conclusion PDT for Bismuth Ⅲ-Ⅳ malignant biliary obstruction is safe and effective. Moreover, the period of biliary patency is greatly extended when PDT is combined with systemic therapy.