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 detect mutated genes in thyroid cancer using next-generation sequencing(NGS)Panel and analyze genes associated with the prognosis of thyroid cancer.METHODS Samples from 90 newly diagnosed thyroid cancer patients who underwent surgical treatment at Jilin Cancer Hospital from January 2020 to January 2023 were collected.DNA and RNA were extracted from tissue samples and subjected to high-throughput sequencing.Mutated genes were identified,and their correlation with the patients'AJCC TNM staging and prognosis of thyroid cancer was analyzed.RESULTS Several gene mutations,including FN1,SLC34A2,FABP4,SNCA,MATN2,and EIF2AK1,were detected in thyroid cancer.Among them,FN1 mutation was positively correlated with later stages of the AJCC TNM staging,which is closely associated with prognosis.CONCLUSION FN1 gene mutation may serve as a potential genetic biomarker for predicting the prognosis of thyroid cancer.

Objective To investigate the relationship between glycoprotein synthase kinase-3 (GSK-3β) and mitochondrial cleavage protein (Drp-1) during diabetes mellitus-caused antagonization of cardioprotection induced by sevoflurane postconditioning in rats.Methods Clean-grade healthy male Sprague-Dawley rats,weighing 250-300 g,were used in this study.Diabetes mellitus was induced by high-fat and high-sucrose diet and intraperitoneal streptozotocin 30 g/kg.Forty rats with diabetes mellitus were divided into 5 groups (n =8 each) using a random number table method:ischemia-reperfusion (I/R) group,sevoflurane postconditioning group (SP group),sevoflurane postconditioning plus Drp1 inhibitor Mivi-1 group (SM group),sevoflurane postconditioning plus GSK-3β inhibitor SB216763 group (SB group) and sevoflurane postconditioning plus Mivi-1 plus SB216763 group (SMB group).Myocardial I/R was induced by 30 min occlusion of the left anterior descending branch of the coronary artery followed by 120 min reperfusion.The rats inhaled 2.5％ sevoflurane for 10 min starting from 5 min before reperfusion in SP,SM,SB and SBM groups.Mivi-1 1.2 mg/kg was injected via the caudal vein at 15 min before reperfusion in group SM.SB216763 0.2 mg/kg was injected via the caudal vein at 5 min before reperfusion in group SB.Mivi-1 1.2 mg/kg and SB216763 0.2 mg/kg were injected via the caudal vein at 15 and 5 min before reperfusion,respectively,in group SMB.Blood samples were collected from the abdominal aorta at 120 min of reperfusion for determination of serum cardiac troponin Ⅰ (cTnⅠ) concentrations.The rats were sacrificed and myocardial specimens were obtained from the apex for determination of the cell apoptosis (by TUNEL) and expression of caspase-3 (by Western blot),and apoptotic index (AI) was calculated.Results Compared with group I/R,no significant change was found in caspase-3 expression,AI or serum cTnⅠ concentrations (P＞0.05),and the pathological changes of myocardium were comparable in group SP,and the expression of caspase-3 was significantly down-regulated,and AI and serum cTnⅠ concentration were decreased (P＜0.05),and the pathological changes of myocardium were significantly attenuated in SM,SB and SMB groups.Compared with group SP,the expression of caspase-3 was significantly down-regulated,AI and serum cTnⅠ concentrations were decreased (P＜0.05),and the pathological changes of myocardium were significantly attenuated in SM,SB and SMB groups.Compared with group SMB or group SB,the expression of caspase-3 was significantly down-regulated,AI and serum cTnI concentrations were decreased (P＜0.05),and the pathological changes of myocardium were significantly attenuated in group SMB.Conclusion It is not a single regulatory relationship between GSK-3β and Drp-1 in the pathophysiological process of diabetes mellitus-caused antagonization of cardioprotection induced by sevoflurane postconditioning in rats.

Objective To study the treatment effect of cinnamaldehyde on Aspergillus fumigatus biofilm(BF) in vitro .Meth‐ods The models of A .fumigatus BF were established in vitro ;the minimum inhibitory concentration(MIC) on A .fumigatus was measured .The crystal violet assay and scanning electron microscopy were employed to determined the treatment effect of A .fumiga‐tus biofilm under varying concentrations of cinnamaldehyde .Results BF models were established successfully in vitro .MIC value of A .fumigatus of cinnamaldehyde was 256 μg/mL ;The biofilm biomass in serially increasing concentrations of cinnamaldehyde(1 MIC ,1/2 MIC ,1/4 MIC)were 0 .81 ± 0 .11 ,1 .13 ± 0 .18 and 1 .59 ± 0 .11 respectively .Compared to untreated control group(2 .18 ± 0 .15) ,difference achieved statistical significance(P<0 .05) .SEM studies revealed the deformity of three‐dimensional structures of biofilms treated with sub‐MICs of cinnamaldehyde .Conclusion Cinnamaldehyde has significant antifungal activity against Aspergil‐lus fumigatus ,sub‐MICs could disrupt the mature biofilm in vitro .

Objective To evaluate the in vitro antifungal activity of Cinnamaldehyde in combination with Voriconazole (VRC) against clinically isolated Aspergillus fumigatus strains. Methods According to the Clinical and Laboratory Stan?dards Institute (CLSI) M38-A2 document,the minimal inhibitory concentrations (MIC) of Cinnamaldehyde and VRC alone or in combination against 42 clinical Aspergillus fumigatus isolates were determined by both microdillution method and check?board method respectively. The MIC50, MIC90, MICG and MICs distribution were compared between single drug and both in combination. The concentration-accumulative curve was drawn and fractional inhibitory concentration index (FICI) was cal?culated to evaluate the interaction between two test agents. Results The values of MIC50, MIC90 and MICG were significant?ly decreased (P<0.001) when combination of the two drugs than those of their single use, with their MIC distribution concen?tration-accumulative curves shifted to the left. The value of FICI of Cinnamaldehye-VRC combination ranged from 0.187 5 to 1.5. Sixteen strains (38.10%) of them showed the synergistic effect, 19 strains (45.23%) showed additive effect, and 7 strains (16.67%) showed an unrelated effect, and no antagonist effect on tested Aspergillus fumigatus strains in vitro. Conclu?sion Cinnamaldehye in combination with VRC mainly shows a combined synergic and additive inhibitory effect on Asper?gillus fumigatus isolates, and this combination appears to be more active against the test strains, which are less susceptible to voriconazole.

OBJECTIVETo investigate changes in renal function, urine N-acetyl-beta-D-glucosaminidase enzyme (N-AG),liver function, myocardial enzymes, the pathology of renal damage and the mechanism of acute renal failure (ARF) associated with fish gall bladder poisoning.

METHODSEleven patients with acute fish gall bladder poisoning were consecutively admitted to our hospital from September 1997 to October 1999. Renal function, urine N-AG enzyme, liver function, and myocardial enzymes were assayed before and after treatment. One patient consented to a kidney biopsy and the pathology of renal damage was observed under light and electron microscopes.

RESULTSAll patients had multiple organ dysfunction syndrome (MODS) and 11 patients suffered from ARF. Ten patients had liver dysfunction, ten patients had poisonous myocarditis, and 8 patients had gastrointestinal dysfunction. Renal function, urine N-AG enzyme, liver function, and myocardial enzymes were significantly improved after treatment compared with those of before treatment (P < 0.05). Kidney biopsy showed that the main damage site was the proximal renal tubule. All eleven patients recovered and were discharged from the hospital.

CONCLUSIONSIngestion of fish gall bladder leads to kidney damage, as well as liver, heart and gastrointestinal tract injury. The mechanism of acute renal function failure is the serious tubular damage, confirming the location of kidney damage. Necrosis of the proximal tubules plays an important role in the development of ARF. Immediate hemodialysis is the most effective treatment.

Adult ; Aged ; Animals ; Female ; Fishes ; Foodborne Diseases ; etiology ; Gallbladder ; Humans ; Male ; Middle Aged ; Multiple Organ Failure ; etiology

Objective:To find valid indicator to differentiate random test of MMPI-2.Methods:According to four coincidence indicators of MMPI-2 of 1278 psychiatric cases (male, 623; female,555), including VRIN,│F-Fb│,VRIN+│F-Fb│,F+Fb+│F-Fb│,differentiate random test of MMPI-2 were studied.Results:VRIN+-F-Fb-,-F-Fb-were the best indexes. VRIN was a fine index. F+Fb+ and│F-Fb│were poor.Conclusions:It is not good to use one coincidence indicator, but it can eliminate 91.50% of random test if the four coincidence indicators are used together.