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.

BACKGROUND: In China, lung cancer remains the cancer with the highest incidence and mortality rate. Among early-stage lung adenocarcinomas (LUAD), the micropapillary (MPP) component is prevalent and typically exhibits high aggressiveness, significantly correlating with early metastasis, lymphatic infiltration, and reduced five-year survival rates. Therefore, the study is to explore the similarities and differences between MPP and non-micropapillary (non-MPP) components in malignant pulmonary nodules characterized by GGOs in early-stage LUAD, identify unique mutational features of the MPP component and analyze the relationship between the ZNF469 gene, a member of the zinc-finger protein family, and the prognosis of early-stage LUAD, as well as its correlation with immune infiltration. METHODS: A total of 31 malignant pulmonary nodules of LUAD were collected and dissected into paired MPP and non-MPP components using microdissection. Whole-exome sequencing (WES) was performed on the components of early-stage malignant pulmonary nodules. Mutational signatures analysis was conducted using R packages such as maftools, Nonnegative Matrix Factorization (NMF), and Sigminer to unveil the genomic mutational characteristics unique to MPP components in invasive LUAD compared to other tumor tissues. Furthermore, we explored the expression of the ZNF469 gene in LUAD using The Cancer Genome Atlas (TCGA) database to investigate its potential association with the prognosis. We also investigated gene interaction networks and signaling pathways related to ZNF469 in LUAD using the GeneMANIA database and conducted Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis. Lastly, we analyzed the correlation between ZNF469 gene expression and levels of immune cell infiltration in LUAD using the TIMER and TISIDB databases. RESULTS: MPP components exhibited a higher number of genomic variations, particularly the 13th COSMIC (Catalogue of Somatic Mutations in Cancer) mutational signature characterized by the activity of the cytidine deaminase APOBEC family, which was unique to MPP components compared to non-MPP components in tumor tissues. This suggests the potential involvement of APOBEC in the progression of MPP components in early-stage LUAD. Additionally, MPP samples with high similarity to APOBEC signature displayed a higher tumor mutational burden (TMB), indicating that these patients may be more likely to benefit from immunotherapy. The expression of ZNF469 was significantly upregulated in LUAD compared to normal tissue, and was associated with poor prognosis in LUAD patients (P<0.05). Gene interaction network analysis and GO/KEGG enrichment analysis revealed that COL6A1, COL1A1, COL1A2, TGFB2, MMP2, COL8A2 and C2CD4C interacted with ZNF469 and were mainly involved in encoding collagen proteins and participating in the constitution of extracellular matrix. ZNF469 expression was positively correlated with immune cell infiltration in LUAD (P<0.05). CONCLUSIONS The study has unveiled distinctive mutational signatures in the MPP components of early-stage invasive LUAD in the Asian population. Furthermore, we have identified that the elevated expression of mutated ZNF469 impacts the prognosis and immune infiltration in LUAD, suggesting its potential as a diagnostic and prognostic biomarker in LUAD.
Humans ; Lung Neoplasms/genetics* ; Adenocarcinoma of Lung/genetics* ; China ; Prognosis ; Transcription Factors

Objective To evaluate the analgesic effect of lidocaine gel cervical anaesthesia and tramadol uterine cavity injection anaesthesia in patients undergoing hysterosalpingography(HSG)and fallopian tube dredging.Methods A total of 109 infertile patients,who were admitted to the Affiliated Beijing Friendship Hospital of Capital Medical University of China between December 2021 and December 2022,were enrolled in this study.The patients were divided into anesthesia group and non-anesthesia group.For the patients of the anesthesia group,lidocaine gel cervical anaesthesia and tramadol uterine cavity injection anaesthesia were separately performed for HSG and fallopian tube dredging;while for the patients of the non-anesthesia group,no any anesthetic measure was given during the operation.The intraoperative,postoperative 0.5-hour and 24-hour visual analog scale(VAS)scores were analyzed.Results The intraoperative VAS score in the anesthesia group was lower than that in the non-anesthesia group,and the difference was statistically significant(P＜0.01).All patients of the anesthesia group could well tolerate and complete HSG and fallopian tube dredging procedure.Conclusion After the use of lidocaine gel cervical anaesthesia and tramadol uterine cavity injection anaesthesia,the patients have only mild pain during HSG and fallopian tube dredging procedure,the procedure becomes well tolerated,and the incidence of adverse reactions is also very low.(J Intervent Radiol,2024,33:651-666)

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 investigate the changes in the structural parameters and mechanical properties of the necrotic femoral head and compare the effects of core decompression and hone grafting with those of bone cement filling on the mechanical properties and pre-vention of articular surface collapse of the necrotic femoral head.Methods Thirty-two fresh human femoral heads were collected from patients who underwent total hip arthroplasty at our hospital between June 2020 and January 2022.The femoral heads were divided into four groups:8 femoral neck fractures(TFF group),8 osteonecrosis of the femoral head(ONFH group),8 osteonecrosis of the femoral head treated with cement percutaneous injection(CPI group),and 8 osteonecrosis of the femoral head treated with core decompression and bone graft(CDBG group).Cement filling or core decompression was performed under radiographic guidance.All samples were scanned and three-dimensionally reconstructed using micro-CT.The spatial heterogeneity of the femoral head was observed,and the bone morphometric parameters of each region of interest were calculated.Mechanical analysis was performed to evaluate the femoral head parameters of dis-placement and stress in vitro.Results Bone microarchitecture and morphometry in necrotic femoral heads were markedly altered.The biomechanical properties of the necrotic zone in the femoral head were markedly weakened.After the necrotic area was filled with bone cement,the biomechanical properties of the necrotic zone of the femoral head increased significantly.In addition,after core decompres-sion and bone grafting in the necrotic area,the biomechanical properties increased significantly in the necrotic zone of the femoral head.Conclusion Bone cement filling or bone grafting in the necrotic area can change the biomechanical mechanism of the femoral head,improve the load-supporting ability,and prevent femoral head collapse.Cement filling may be a practical approach for the treatment of osteonecrosis of the femoral head that can be useful for practicing orthopedists.

With the advancement of technology,artificial intelligence technologies represented by natural language processing had developed rapidly.Compared with previous generations of large language models,the accuracy of GPT-4 had been significantly improved,and its application scope continued to expand.This article started from the perspective of GPT-4 technology,combined with relevant policies for the construction of national smart hospitals and the importance of psychiatric hospitals,analyzed and elaborated on three application scenarios of GPT-4 in the construction of smart hospitals for mental health,included smart healthcare,smart service and smart management;And designed the architectures of the smart hospital systems;Subsequently,the problems of GPT-4 in the construction of smart psychiatric hospitals were elaborated,and countermeasures were proposed.

BACKGROUND: Primary malignant bone tumors are uncommon, and their epidemiological features are rarely reported. We aimed to study the incidence and death characteristics of bone tumors from 2000 to 2015. METHODS: Population-based cancer registries submitted registry data to National Central Cancer Registry of China (NCCRC). The data collected from 501 local cancer registries in China were assessed using NCCRC screening methods and criteria. Incidence and mortality rates of primary bone tumor were stratified by age group, gender, and area. Age-standardized incidence and mortality rates were adjusted using the Chinese standard population in 2000 and Segi's world population. The annual percentage change (APC) in rate was calculated using the Joinpoint Regression Program. RESULTS: Data from 368 registries met quality control criteria, of which 134 and 234 were from urban and rural areas, respectively. The data covered 309,553,499 persons. The crude incidence, age-standardized incidence, and crude mortality rates were 1.77, 1.35, and 1.31 per 100,000, respectively. Incidence and mortality rates were higher in males than those in females; they showed downward trends, with declines of 2.2% and 4.8% per year, respectively, and the rates in urban areas were lower than those in rural areas. Significant declining trends were observed in urban areas. Stable trends were seen in rural areas during 2000 to 2007, followed by downward trends. Age-specific incidence and mortality rates showed stable trends in the age group of 0 to 19 years, and downward trends in the age group elder than 19 years. CONCLUSIONS The incidence and mortality rates of primary malignant bone tumors in rural areas were higher compared to those in urban areas. Targeted prevention measures are required to monitor and control bone tumor incidence and improve the quality of life of affected patients. This research can provide a scientific basis for the prevention and control of bone tumors, as well as basic information for follow-up research.
Adolescent ; Adult ; Child ; Child, Preschool ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Young Adult ; China/epidemiology* ; Incidence ; Quality of Life ; Bone Neoplasms/mortality* ; East Asian People

Objective To investigate the effect of genistein on the proliferation,migration and invasion of prostate cancer cells and its molecular mechanism.Methods Prostate cancer LNCaP and CWR22RV1 cells were divided into the control group(conventional culture)and the experimental group(50μmol/L genistein treatment).The effect of genistein on the proliferation of prostate cancer cells were analyzed by MTT assay.The effect of genistein on the migration and invasion of prostate cancer cells were analyzed by cell scratch assay and Transwell assay.The protein levels of epithelial interstital transformation(EMT)intermediate markers E-Cadherin,N-Cadherin,Vimentin,and tumor stem cell markers CD44 and Oct-4 were detected by Western blot assay.Results MTT assay showed that genistein could inhibit the proliferation of prostate cancer cells.The scratch closure rates of LNCaP and CWR22RV1 cells were significantly reduced in the experimental group compared with those in the control group,and the number of cells passing through the Transwell membrane was significantly reduced(P＜0.05).Western blot assay showed that genistein could down-regulate the expression levels of N-Cadherin,Vimentin,CD44 and Oct4 in prostate cancer cells,and up-regulate the expression of E-Cadherin in epithelial cells(P＜0.01).Conclusion Genistein reduces the dryness of prostate cancer cells by inhibiting the EMT process,thus reducing the proliferation,migration and invasion of prostate cancer cells.

Objective:To explore the effects of prenatal dexamethasone (DEX), postnatal pulmonary surfactant (PS) and respiratory support on the lung fluid clearance in premature rabbits at gestational age (GA) of 25-28 d (full term: 31 d) and their relationship with dynamic compliance of respiratory system (Cdyn), pulmonary morphology and other parameters.Methods:In our previous publications, premature rabbits were divided into four groups according to the intervention strategy: control group, PS-only group, DEX-only group and DEX+PS group in which data of several parameters including wet-to-dry lung weight ratio (W/D), Cdyn and volume density of alveoli (Vv) were retrieved and the lung tissue sections were scanned to recalculate the ratio of perivascular sheath to vascular sectional area (S/V) and lung injury scores-edema (LIS-E). W/D, LIS-E, S/V and Vv were adjusted for birth weight (BW) (divided by BW, represented as W/D/BW, LIS-E/BW, S/V/BW and Vv/BW) and mean Cdyn (Cdyn-m) was adopted. Based on the grouping of previous studies, the intervention groups in this study were divided as DEX group and non-DEX group, and PS group and non-PS group to analyze the influence of DEX and PS on the above parameters. Two independent samples t-test, one-way analysis of variance, LSD test, Kruskal-Wallis H test, Mann-Whitney U test and Pearson correlation analysis were used for statistical analysis. Results:A total of 196 newborn rabbits receiving mechanical ventilation after birth were included in this study. (1) Effects of DEX: compared with the non-DEX group, the DEX group showed increased W/D/BW (489±69 vs 421±113, t=－2.09), LIS-E/BW (188±57 vs 138±55, t=－2.61) and Vv/BW (20.1±4.9 vs 14.2±4.7, t=－3.60), but decreased S/V (0.33±0.23 vs 0.51±0.25, t=2.23) and S/V/W/D (0.05±0.03 vs 0.07±0.04, t=2.22) at 25 d of gestation; at 26 d of gestation, W/D/BW (472±76 vs 303±44, t=－8.75), LIS-E/BW (189±63 vs 106±36, t=－5.23), Cdyn-m [(0.16±0.07) vs (0.05±0.03) ml/(kg?cmH 2O), 1 cmH 2O=0.098 kPa; t=－7.29] and Vv/BW increased (22.4±5.0 vs 12.2±3.8, t=－7.46), while S/V (0.23±0.19 vs 0.62±0.38, t=4.10), S/V/BW (15.7±12.4 vs 25.7±17.3, t=2.20), S/V/W/D (0.03±0.03 vs 0.08±0.05, t=3.92) and propensity scores decreased [(12.5±1.2) vs (15.1±1.2) scores, t=7.00]; at 27 d of gestation, Cdyn-m increased [(0.23±0.12) vs (0.16±0.07) ml/(kg?cmH 2O), t=－2.43], but S/V (0.32±0.23 vs 0.57±0.39, t=2.57) and S/V/W/D decreased (0.05±0.04 vs 0.09±0.06, t=2.55); at 28 d of gestation, W/D/BW (270±64 vs 162±33, t=－8.09), LIS-E/BW (72±32 vs 35±20, t=－5.17), S/V (0.90±0.60 vs 0.59±0.48, t=－2.81), S/V/BW (34.0±23.6 vs 15.2±12.7, t=－3.77) and Vv/BW increased (16.9±4.3 vs 9.2±2.9, t=－8.04); the differences were all statistically significant (all P<0.05). (2) Effects of PS: compared with the non-PS group, the PS group had decreased LIS-E/BW at 25, 26 and 27 d of gestation, increased Cdyn-m and Vv/BW at 25 and 27 d of gestation and higher propensity scores at 25 d of gestation (all P<0.05). (3) The correlation between gestational age and each index: gestational age was positively correlated with S/V ( r=0.31, P<0.05), but negatively correlated with W/D/BW and LIS-E/BW ( r=－0.73 and－0.63, both P<0.05). Conclusions:The pharmacological action of prenatal DEX on lung fluid clearance is mainly confined to preterm rabbits at the GA of 28 d which is supported by mechanical ventilation. Prenatal treatment with DEX and/or postnatal PS can improve the early respiratory function in preterm rabbits between GA of 25-27 d, but had no substantial impact on lung fluid clearance. The GA-related lung maturation appears to play a crucial role, in comparison with medications, in lung fluid clearance.