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

Objective:To observe the effect of Tongguan Liqiao(opening orifices)needling plus tongue pressure resistance feedback training in treating post-stroke deglutition disorders. Methods:A prospective randomized controlled trial was conducted.A total of 120 patients with post-stroke deglutition disorders were divided into a control group and an observation group using the random number table method,with 60 cases in each group.Both groups were treated with routine treatments.The control group was treated with additional tongue pressure resistance feedback training,and the observation group was treated with additional Tongguan Liqiao needling based on the same intervention in the control group.After 4 weeks of treatment,the clinical efficacy was evaluated,and the complications that occurred during treatment were summarized.The FUJISHIMA Ichiro food intake level scale(FILS)and the swallowing quality of life questionnaire(SWAL-QOL)were scored before treatment and after 4 weeks of treatment. Results:The total effective rate of the observation group was higher than that of the control group(P<0.05).After 4 weeks of treatment,the FILS and SWAL-QOL scores in both groups were higher than those before treatment,and the scores in the observation group were higher than those in the control group(P<0.05).There was no statistical difference in the complication occurrence between the two groups(P>0.05). Conclusion:On the basis of routine treatments,Tongguan Liqiao needling plus tongue pressure resistance feedback training has a better effect in the treatment of post-stroke deglutition disorders.This method can effectively improve the swallowing function of patients,improve the quality of life,and is safe.

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.

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 protective effect and mechanism of hydroxysafflor yellow A (HSYA) on severe acute pancreatitis (SAP) related lung injury.Methods:Fifty mice were randomly (random number) divided into five groups: the sham-operated group, SAP group and different doses (20, 40 and 80 mg/kg) of HSYA pretreatment group. Mice were pretreated with HSYA 24 h before SAP induction, pancreatic and lung tissues were isolated for histopathological examination at 72 h after modeling, and bronchoalveolar lavage fluid (BALF) was collected for biochemical analysis. Results:Compared with the sham-operated group, serum amylase activity, lung injury pathological score and BALF protein concentration in the SAP group were significantly increased [(2120.44 ± 354.50) U/L vs. (226.72 ± 20.84) U/L; (6.91 ± 0.28) vs. (0.53±0.18); (2563.25±348.22) μg/mL vs. (345.62±56.35) μg/mL, all P<0.05]. Inflammatory factors tumor necrosis factor (TNF)-α and interleukin (IL)-6 levels and myeloperoxidase (MPO) activity were increased [(120.5±14.25) pg/mL vs. (31.5±4.82) pg/mL; (214.72±10.62) pg/mL vs. (39.26±5.66) pg/mL; (4.52±0.34) U/mg vs. (1.03±0.17) U/mg]. Compared with the SAP group, HSYA pretreatment significantly attenuated SAP-related pancreatic and lung tissue damage and the activities of the inflammatory factors TNF-α, IL-6 and MPO in BALF. In addition, HSYA promoted the expression of the antioxidant protein heme oxygenase-1 and blocked the activation of the NF-κB signaling pathway. Conclusions:HSYA exerts anti-inflammatory and antioxidant activities to inhibit SAP-related lung injury, which indicated that HSYA may be a potential therapeutic drug for SAP-induced lung injury.

In recent years, with the wide application of magnetic resonance imaging (MRI) equipment in clinical practice, the quality of the equipment causes adverse events, which put pressure on manufacturers, at the same time, it puts forward higher requirements for medical device supervisors. In order to help the medical device supervisors to clarify the key points of verification, this paper analyzes the main risk points in the production process of the product according to the medical device good manufacturing practice(GMP), and puts forward the suggestions for field verification, which has practical significance for the submission of verification efficiency.
Commerce ; Magnetic Resonance Imaging

Objective:To investigate the diagnostic performance of repeat biopsy 68Ga-PSMA PET/CT to distinguish between benign and malignant prostate disease. Methods:The clinical data and medical imaging of thirty-nine patients underwent repeat prostate biopsy were analyzed respectively in this study. The median age of patients was 65 years (range 46-81 years), the median PSA level was 11.0ng/ml (range 5.4-49.8 ng/ml), f/tPSA was 0.15(0.01-16.50)ng/ml, prostate volume was 43.80(7.79-108.63)ml, and PSA density was 0.24(0.09-2.31)ng/ml 2. All patients underwent pre-biopsy 68Ga-PSMA PET/CT and the standard transrectal ultrasound-guided systematic prostate biopsy. Based on the biopsy results, 68Ga-PSMA PET/CT images of all patients were visually and semi-quantitatively analyzed. By visual analysis, 68Ga-PSMA uptake in prostate was defined as focal, multimodal and inhomogeneous, and then the detection rate of prostate cancer in each subgroup was analyzed. The value of the ROC curve in the diagnosis of prostate cancer was analyzed based on the SUV max of prostate cancer(SUV max), tumor-to-normal-prostate background(SUV T/BGp)as semi-quantitative parameters of 68Ga-PSMA PET/CT. Results:Prostate cancer was detected in 18 patients (46.2%) and 12 patients (30.8%) had clinically significant disease. There were 11, 5 and 2 patients with prostate cancer respectively in men with a focal (12 patients), multifocal(7 patients) and inhomogeneous (20 patients) 68Ga-PSMA uptake. The ROC analysis revealed a SUV max 5.3 and SUV T/BGp1.8 as an optimal cut-off level to distinguish between non-prostate cancer and prostate cancer in 68Ga-PSMA PET/CT, the sensitivity and specificity were 100.0% and 85.7% for SUV max (AUC=0.979), 83.3% and 90.5% for SUV T/BGp (AUC=0.915). Conclusions:Pre-biopsy 68Ga-PSMA PET/CT could help to distinguish between benign and malignant prostate disease before repeat prostate biopsy and detect the foci of prostate cancer.