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: The available evidence regarding the benefits of percutaneous coronary intervention (PCI) on patients receiving dialysis with coronary artery disease (CAD) is limited and inconsistent. This study aimed to evaluate the association between PCI and clinical outcomes as compared with medical therapy alone in patients undergoing dialysis with CAD in China. METHODS: This multicenter, retrospective study was conducted in 30 tertiary medical centers across 12 provinces in China from January 2015 to June 2021 to include patients on dialysis with CAD. The primary outcome was major adverse cardiovascular events (MACE), defined as a composite of cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. Secondary outcomes included all-cause death, the individual components of MACE, and Bleeding Academic Research Consortium criteria types 2, 3, or 5 bleeding. Multivariable Cox proportional hazard models were used to assess the association between PCI and outcomes. Inverse probability of treatment weighting (IPTW) and propensity score matching (PSM) were performed to account for potential between-group differences. RESULTS: Of the 1146 patients on dialysis with significant CAD, 821 (71.6%) underwent PCI. After a median follow-up of 23.0 months, PCI was associated with a 43.0% significantly lower risk for MACE (33.9% [ n  = 278] vs . 43.7% [ n  = 142]; adjusted hazards ratio 0.57, 95% confidence interval 0.45-0.71), along with a slightly increased risk for bleeding outcomes that did not reach statistical significance (11.1% vs . 8.3%; adjusted hazards ratio 1.31, 95% confidence interval, 0.82-2.11). Furthermore, PCI was associated with a significant reduction in all-cause and cardiovascular mortalities. Subgroup analysis did not modify the association of PCI with patient outcomes. These primary findings were consistent across IPTW, PSM, and competing risk analyses. CONCLUSION This study indicated that PCI in patients on dialysis with CAD was significantly associated with lower MACE and mortality when comparing with those with medical therapy alone, albeit with a slightly increased risk for bleeding events that did not reach statistical significance.
Humans ; Percutaneous Coronary Intervention/methods* ; Male ; Female ; Coronary Artery Disease/drug therapy* ; Retrospective Studies ; Renal Dialysis/methods* ; Middle Aged ; Aged ; China ; Proportional Hazards Models ; Treatment Outcome

Ulcerative colitis(UC)is a chronic im-mune-mediated disease characterized by diffuse mucosal inflammation and clinical symptoms of ab-dominal pain,diarrhea,mucopurulent bloody stool and tenesmus.Due to its complex etiology,difficult treatment and poor prognosis,UC has been listed as one of the modern refractory diseases by the World Health Organization.MicroRNAs(microR-NAs)regulate various biological processes such as cell growth,differentiation,and development by regulating gene expression.Studies have shown that miRNA is involved in the pathogenesis of UC through various pathways such as intestinal muco-sal barrier homeostasis disorder,intestinal flora im-balance and excessive differentiation of immune cells,and is expected to become a new target for clinical treatment of UC.In order to better under-stand the role of miRNA in the pathogenesis of UC and provide new research directions for the treat-ment of UC,this article reviews the correlation be-tween miRNA and the pathogenesis of UC,the po-tential of miRNA as a biomarker of UC,and the treatment strategies of miRNA in UC in recent years.

Thyroglossal duct papillary carcinoma is extremely rare in clinical practice.This article reports a case of a thyroglossal duct cyst complicated by thyroid papillary carcinoma,while also reviewing the relevant literature.It summarizes the clinical manifestations,imaging characteristics,and pathological features of thyro-glossal duct papillary carcinoma and discusses the relationship between thyroglossal duct cysts,malignant trans-formation of thyroglossal duct cysts,and thyroid papillary carcinoma.

Myelodysplastic syndrome(MDS)is a malignant clonal disease with high heterogeneity in cytogenetics and molecular genetics,and the risk of progression to acute myeloid leukemia(AML)is extremely high.Transforming growth factor-β(TGF-β)is closely related to the pathogenesis of MDS.It is a key executor of immune homeostasis and immune tolerance,and can inhibit the expansion and function of many components of immune system.TGF-β signaling pathway can regulate hematopoietic cells and immune cells in microenvironment,inhibit their normal biological functions,and thus accelerate the progression of MDS.This study reviews regulatory effects of TGF-β signaling pathway on MDS blood cells,T lymphocytes,natural killer cells and macrophages in recent years,and provides a new perspective for the pathogenesis and treatment of MDS.

The medical electron linear accelerator(LINAC)has the characteristics of complex system structure,many core components and high precision control requirements,which puts forward higher requirements for product quality control and regulation.This study puts forward the main points of field inspection through the analysis of the technical characteristics and production risk of LINAC,combined with the requirements of the good manufacturing practice of medical devices.It has certain reference significance for quality management personnel and field inspectors.

With the encouragement of policies and the rapid development of the biopharmaceutical industry,the number of software as medical device(SaMD)registration applications in Shanghai has continued to increase in recent years,and this paper summarizes the GMP nonconformities found in the field inspection of SaMD in Shanghai from 2020 to 2023,and the results show that nearly 70%of the problems were found in the software development process.Through in-depth analysis,this paper proposes the corresponding countermeasures for the problems found in the five most common stages such as software requirements,software design,software testing,software defect management and software configuration management,combined with the characteristics of software development.These suggested measures have certain reference significance for medical device software development and quality control personnel,and technical reviewer and inspectors.

Objective To investigate the clinical efficacy of staged individualized surgical method for treating neuromuscular origin severe clubfoot complicating complex lower limb deformity.Methods Ten ca-ses of neurogenic severe clubfoot deformity treated in the Affiliated Hospital of Guizhou Medical University from May 2021 to June 2023 were collected as the research subjects.In the first stage,the soft-tissue release,tendon transfer combined with Ilizarov technique were adopted to correct the clubfoot deformity,and in the second stage,according to the patients' postoperative gait and the degree of lower limb deformity,the patients were given individualized and appropriate osteotomy assisted by the increase of Ilizarov external frame length-ening,supra-ankle osteotomy,and distal femoral osteotomy.The clinical results of treatment in the patients were observed.The American Orthopaedic Association Division of Foot and Ankle Surgery (AOFAS) scores and visual analog scale (VAS) scores were compared between before operation and 1,3,6,12 and 18 months after operation.The lower extremity biodynamic line related imaging parameters were compared between be-fore and 18 months after operation.Results All patients successfully completed the surgery without nerve or vascular injury during and after operation and there were no serious complications such as pinhole or incision infection.All patients were followed up for 16-24 months.The ankle joint AOFAS score at each time point after operation was increased compared with the physical examination before operation (P<0.05),and the VAS score was decreased compared with the physical examination before operation (P<0.05).The lower ex-tremity biodynamic line related imaging parameters at 18 months after operation were significantly improved compared with before operation (P<0.05).Conclusion Adopting the staged individualized surgical method for the treatment of neuromuscular origin severe clubfoot complicating complex deformity of the lower limbs could achieve more satisfactory and relatively ideal therapeutic effect.

Objective To explore the relationship of serum micro ribonucleic acid(miR)-124,miR-134 and CT regional assessment grading of pia mater collateral,core infarct volume and prognosis in patients with acute ischemic stroke.Methods A total of 192 patients with acute ischemic stroke(observation group)and 100 healthy volunteers(control group)were selected.The serum miR-124 and miR-134 were compared between the two groups.At the same time,the serum miR-124,miR-134 and the score of pia mater collateral in CT region of patients with different clinical characteristics in the observation group were analyzed.Results The relative expression levels of serum miR-124 and miR-134 in the observation group were significantly higher than those in the control group(P＜0.05).The relative expression serum miR-124 and miR-134 in patients with core infarct volume≥50 mL in the observation group were significantly higher than those in patients with core infarct volume＜50 mL(P＜0.05).In the observation group,the score of pia mater collateral in CT region of patients with core infarct volume ≥50 mL was significantly lower than that of patients with core infarct volume＜50 mL(P＜0.05).The relative expression levels of serum miR-124 and miR-134 were positively correlated with the core infarct volume(r=0.378 and 0.466,P＜0.05),and the score of pia mater collateral in CT region was negatively correlated with the core infarct volume(r=-0.463,P＜0.05).The relative expression levels of serum miR-124 and miR-134 in patients with poor prognosis were significantly higher than those in patients with good prognosis(P＜0.05),while the score of pia mater collateral in CT region was significantly lower than that in patients with good prognosis(P＜0.05).Conclusion The serum miR-124 and miR-134 in patients with acute ischemic stroke are up-regulated,and miR-124 and miR-134 are positively correlated with the core infarct volume,while the score of pia mater collateral in CT region is negatively correlated with the core infarct volume.At the same time,miR-124,miR-134,and the score of pia mater collateral in CT region may be related to the prognosis of patients.