Alzheimer's disease (AD) is a neurodegenerative disease with clinical hallmarks of progressive cognitive impairment. Synergistic effects of the Aβ-Tau cascade reaction are tightly implicated in AD pathology, and microglial NLRP3 inflammasome activation drives neuronal tauopathy. However, the underlying mechanism of how Aβ mediates NLRP3 inflammasome remains unclear. Herein, we determined that oligomeric Aβ (o-Aβ) bound to microglial Kv2.1 and promoted Kv2.1-dependent potassium efflux to activate NLRP3 inflammasome resulting in neuronal tauopathy by using Kv2.1 inhibitor drofenine (Dfe) as a probe. The underlying mechanism has been intensively investigated by assays with Kv2.1 knockdown in vitro (si-Kv2.1) and in vivo (AAV-ePHP-si-Kv2.1). Dfe deprived o-Aβ of its capability to promote microglial NLRP3 inflammasome activation and neuronal Tau hyperphosphorylation by inhibiting the Kv2.1/JNK/NF-κB pathway while improving the cognitive impairment of 5×FAD-AD model mice. Our results have highly addressed that the Kv2.1 channel is required for o-Aβ-driven microglial NLRP3 inflammasome activation and neuronal tauopathy in AD model mice and highlighted that Dfe as a Kv2.1 inhibitor shows potential in the treatment of AD.

Objective To explore the repair effect and mechanism of human amniotic mesenchymal stem cells(hAMSCs)on endometrial injury.Methods hAMSCs were isolated using a two-enzyme digestion and then cultured.The third-passage(P3)cells were harvested to detect the surface markers by flow cytometry and to identify their trilineage differentiation potentials.Eighteen nulliparous female SD rats(8～9 weeks old,weighing 250～280 g)were randomly divided into 3 groups(n=6):normal control group,model group,and hAMSCs group.A rat model of intrauterine adhesions(IUA)was established in SD rats by using curettage combined with lipopolysaccharide(LPS)infection.In 2 weeks after modeling,the hAMSCs group received a bilateral uterine horn transplantation of 0.2 mL hAMSCs(1.0×10? cells/mL),while the model group received a same volume of PBS into both uterine horns.All rats were sacrificed in 2 weeks after transplantation.HE and Masson staining was used to observe endometrial thickness and gland number as well as endometrial fibrosis area.RT-qPCR and Western blotting were performed to detect the mRNA and protein levels of TGF-β1,Smad3,Smad7,epithelial-mesenchymal transition(EMT)markers(E-cadherin,Vimentin),fibrosis factor α-SMA,and endometrial estrogen receptor(ER)and progesterone receptor(PR)in endometrial tissues.Results The obtained cells were identified as hAMSCs due to the characteristics of surface markers and differentiation potentials.Compared with the normal control group,the model group showed decreased endometrial thickness,reduced gland number,increased fibrosis area,and enhanced mRNA and protein levels of fibrosis-related factors TGF-β1,Smad3,Vimentin,and α-SMA(P<0.01),while down-regulation of fibrosis-inhibiting molecule Smad7,the EMT marker E-cadherin,and endometrial receptors ER and PR at both mRNA and protein levels(P<0.01).hAMSCs transplantation increased endometrial thickness and gland number,decreased fibrosis area,and down-regulated mRNA expression of the aforementioned fibrosis-related factors(P<0.01),and up-regulated the mRNA expression levels of Smad7,E-cadherin,ER,and PR(P<0.01).The hAMSCs group also exhibited obviously down-regulated protein levels of TGF-β1,Smad3,and α-SMA(P<0.05),while enhanced protein levels of Smad7 and PR(P<0.05).Conclusion Intrauterine transplantation of hAMSCs can promote the repair of endometrial injury,and inhibits endometrial EMT and fibrosis through the TGF-β1/Smad7 signaling pathway.

Objective To observe the clinical efficacy of Tongyuan acupuncture in the treatment of acute gouty arthritis.Methods A total of 126 cases of patients with definitive diagnosis of acute gouty arthritis admitted to the wards and outpatient clinics of Guangzhou Nansha District Hospital of Traditional Chinese Medicine from November 2023 to June 2024 were selected as the study subjects.The patients were randomly divided into observation group and control group according to the random number table method,with 63 cases in each group.The control group was given health training and conventional treatment,while the observation group was given Tongyuan acupuncture on the basis of treatment in the control group.Patients in both groups were treated for 14 consecutive days.After two weeks of treatment,the clinical efficacy of the two groups was evaluated.The changes in the clinical symptom scores,the Visual Analogue Scale(VAS)scores of pain,the levels of musculoskeletal ultrasonography(synovial proliferation,blood flow signals,and joint fluid)before and after the treatment were observed in patients of both groups.The changes of blood uric acid(UA),erythrocyte sedimentation rate(ESR),C-reactive protein(CRP),tumor necrosis factor α(TNF-α),and interleukin 1(IL-1)before and after treatment were compared between the two groups.Results(1)The total effective rate was 95.24%(60/63)in the observation group and 84.13%(53/63)in the control group.The efficacy of the observation group was superior to that of the control group,the difference being statistically significant(P<0.05).(2)After treatment,the clinical symptom scores and VAS scores of the patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(3)After treatment,the serum UA,ESR,and CRP levels of patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(4)After treatment,the TNF-α and IL-1 levels of patients in the two groups were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).(5)After treatment,the musculoskeletal ultrasound indicators of the two groups of patients were improved significantly(P<0.05),and the improvement in the observation group was significantly superior to that in the control group,the difference being statistically significant(P<0.05).Conclusion Tongyuan acupuncture in the treatment of acute gouty arthritis can significantly improve the clinical symptoms of patients,reduce the level of patients'blood UA and inflammatory factor.

Objective:To investigate the clinical and genetic features of patients with ACTL6B gene variations, and to report novel pathogenic variations of the ACTL6B gene, summarize the clinical phenotypes and genotypes of the gene. Methods:The clinical phenotypes and genotypes of a infant with developmental epileptic encephalopathy carrying the ACTL6B gene variations, who visited the Department of Neurology, Capital Institute of Pediatrics-Peking University Teaching Hospital on March 12, 2021 were analyzed. The phenotypes and genotypes of patients carrying the ACTL6B gene variations reported in the literature were also summarized and analyzed. Results:The proband was a 2-month-old male presented with convulsive seizures, development delay, dystonia, and cherry erythema in the fundus. The whole exome sequencing of his family showed that he carried compound heterozygous variation c.937-2A>G(p.?), c.11delG(p.G4Afs *86) which derived from his parents respectively. These 2 genotypes had not been reported. A total of 42 cases with ACTL6B gene variation were reported in the literature and in this study. There were 11 de novo heterozygous variations and 31 bi-allelic variations inherited from the parents (24 homozygous and 7 compound heterozygous). Individuals with variations tended to have epilepsy, development delay, ambulation disability, speech disability and dystonia. Minor facial dysmorphisms and autism spectrum disorder also can be seen. Conclusion:This paper summarizes the clinical and genetic features of patients with ACTL6B gene variations, reports 2 novel variations and a novel combination of this gene with cherry erythema in the fundus.

Objective : To study the damage effect of sunlight ultraviolet exposure on skin. Methods : No exposure group, low exposure group and high exposure group were set up with 10 mice in each. The exposure doses of sunlight ultraviolet were 0, 10 J/cm2 and 20 J/cm2, respectively. The skin of mice was irradiated by a sunlight ultraviolet simulator for 5 days a week, 13 weeks. At the end of the experiment, the skin appearance of mice was examined; the skin moisture, oil content, texture density, hydroxyproline ( HYP ), hyaluronic acid (HA), malondialdehyde ( MDA ), glutathione ( GSH ) and superoxide dismutase ( SOD ) activities were detected; and the skin tissue morphology, collagen fiber morphology and elastic fiber morphology were observed. Results : The skin appearance of mice in the no exposure group was normal; in the low exposure group, only one mouse had mild skin desquamation; in the high exposure group, the skin was loose and wrinkled, dry and desquamated, local thickening and erythema formation. Compared with the no exposure group, the contents of skin moisture, HYP, HA and SOD activity were lower, texture density, MDA content, morphological scores of skin tissue, collagen fiber tissue and elastic fiber tissue were higher in the high exposure group ( all P<0.05 ). Compared with the low exposure group, the HA content and SOD activity were lower, the skin texture density, MDA content, and histomorphological scores of skin tissue and collagen fibers were higher in the high exposure group ( all P<0.05 ). Conclusion Exposure to 20 J/cm2 sunlight ultraviolet can significantly lead to abnormal skin appearance and function in mice.

Objective: To study the effects of Lycium barbarum polysaccharides ( LBP ) on blood indexes and liver tissue morphology in rats with intrahepatic cholestasis. Methods: Sprague-Dawley rats were randomly divided into the control group, the model group, and LBP low, medium and high dose group. The rats in the model group and LBP dose groups were given 60 mg/kg alpha-naphthylisothiocyanate ( ANIT ) by gavage every three days of the experiment, and the rats in the control group were given salad oil instead of ANIT. From the third day, the rats in each dose group were given 40, 150 and 600 mg/kg LBP, and the rats in the model group were given distilled water. After four weeks, the blood and urine indexes were measured, and the morphological changes of liver tissue were observed. Results: From the third day of the experiment, the activity of rats in the model group and LBP dose groups decreased, and the color of urine changed to dark yellow. There was no abnormality in the group. In the model group, the levels of serum total bilirubin, direct bilirubin, total bile acid ( TBA ), alkaline phosphatase ( ALP ), γ-glutamyltransferase(γ-GGT), cholesterol, alanine aminotransferase ( ALT ), aspartate aminotransferase ( AST ), white blood cell ( WBC ), percentage of granulocyte, urinary bilirubin, urinary bile acid, liver mass and liver to body ratio were higher than those in the control group, while red blood cell and percentage of lymphocyte were lower than those in the control group ( all P<0.05 ). Pathological changes of liver tissue were observed. The levels of serum TBA, ALP, γ-GGT, ALT, AST, WBC and liver to body ratio in LBP high dose group were lower than those in the model group ( all P<0.05 ). The infiltration of inflammatory cells, proliferation and expansion of bile duct, degeneration and necrosis of liver cells were alleviated. Conclusions LBP can improve the blood indexes and pathological changes of liver tissue in rats with intrahepatic cholestasis at the dosage of 600 mg/kg. Inhibition of inflammatory response and reduction of oxidative stress injury may be the mechanism for alleviating cholestatic liver injury.

Objective To explore the application effect of the multidisciplinary collaborations in control of peritoneal dialysis patients with hypertension. Methods A total of 220 cases of peritoneal dialysis patients divided into experimental group and control group (each group had 110 cases) according to the random number table. In which, the control group received routine capacity control and health education with a total of 105 patients finished the study. The experimental group received of multidisciplinary collaborations on the basis of routine capacity control and health education with a total of 107 patients finished the study. Observe changes with knowledge of drugs, medication compliance, self-management behavior and blood pressure of patients before and after the intervention respectively. Results In experimental group,the scores of drug knowledge, medication compliance and self-management behaviors were (0.93 ± 0.49), 0.00 (0.00, 0.25), (2.69 ± 0.25) points before the intervention, 6 months after the intervention were (1.17 ± 0.54), 0.25 (0.00, 0.50), (2.86 ± 0.15) points, the difference between the groups was statistically significant (t=38.60, Z=4.34, t= 2.45, P < 0.01 or 0.05). In control group,the scores of drug knowledge, medication compliance and self-management behaviors were (0.87 ± 0.45), 0.00 (0.00, 0.25), (2.64 ± 0.27) points before the intervention, 6 months after the intervention were (0.89 ± 0.43), 0.00 (0.00, 0.38), (2.73 ± 0.27) points, there was no significant difference between drug knowledge and medication compliance (t=0.44, Z=1.83, P > 0.05), there were statistically significant differences in self-management behavior (t=6.23, P<0.01);there was no difference between the statistical significance between the 2 groups before intervention (t=1.02, Z=1.46, t=1.32, P > 0.05); there was significant difference between the 2 groups after intervention (t=4.11, Z=4.03, t=4.34, P<0.01). Patients in the experimental group with the systolic and diastolic blood pressure were (147.11 ± 14.31), (90.16 ± 13.02) mmHg (1 mmHg=0.133 kPa) respectively, before the intervention; 6 months after the intervention were (139.39 ± 17.05), (83.76 ± 12.52) mmHg respectively, the difference was statistically significant (t=3.59, 2.92, P<0.01). The control group before intervention were (149.56 ± 18.11), (93.56 ± 15.09) mmHg respectively, 6 months after the intervention were (145.14±20.50), (88.14±10.88) mmHg respectively, the difference was statistically significant (t=2.02, 2.72, P<0.05 or 0.01);there was no significant difference between the two groups before intervention (t=1.09, 1.82, P>0.05);6 months after the intervention there was significant difference between the 2 groups (t=2.22, 2.72, P < 0.05 or 0.01). Conclusions Multidisciplinary collaborations have a significant role in patients with peritoneal dialysis, especially in blood pressure control, medication compliance and self-management behavior.

Objective To compare the complications and outcomes of urgent?start peritoneal dialysis (PD) and hemodialysis (HD) in end?stage renal disease (ESRD) patients, and explore the safety and effectiveness of PD which was as an urgent?start dialysis modality in ESRD patients. Methods All patients for urgent?start dialysis, who initiated dialysis without a long?term dialysis access or had the long?term dialysis access under 30 days in Renji Hospital from January 1st 2013 to December 31st 2014, were enrolled. According to the dialysis modalities, patients were divided into PD group and HD group. Participants were followed up until death, transferred to other centers, lost of follow up or January 1st 2016. Dialysis?related complications within 30 days of implantation, complications of reimplantation and the occurrence of bacteremia between two groups were compared, and their survival rates were tested by Kaplan?Meier curves. Results Among 178 patients in this study, there were 96 (53.9%) patients in PD group and 82 (46.1%) patients in HD group. Compared with those of HD group, patients of PD group presented more cardiovascular disease [21(21.9%) vs 8(9.8%), P=0.029], higher serum potassium [(4.5±0.8) mmol/L vs (4.3±0.8) mmol/L, P=0.038], but less heart failure (NYHA Ⅲ?Ⅳ) [26(30.2%) vs 40 (48.8%), P=0.014], lower brain natriuretic peptide (BNP) [328.5 (129.5, 776.8) ng/L vs 503.5(206.0, 1430.0) ng/L, P=0.008], higher hemoglobin [(81.5 ± 17.7) g/L vs (75.3 ± 22.5) g/L, P=0.039], higher serum albumin (33.5±5.7) g/L vs (31.3±6.7) g/L, P=0.022] and higher serum pre?albumin (304.5±78.0) mg/L vs (257.0 ± 86.1) mg/L, P<0.001]. PD group presented less dialysis?related complications [5 (5.2%) vs 20(24.4%), P<0.001], less dialysis?related complications requiring reimplantation [1(1.0%) vs 20(24.4%), P<0.001] and less bacteraemia [3(3.1%) vs 11(13.4%), P=0.011]. The 3?, 6?and 12?month patient survival rates of PD and HD group were 97.9% vs 98.4%, 97.9% vs 98.4%, and 92.1%vs 93.0% respectively, and no significant difference was found (Log ? rank=0.004, P=0.947). Conclusions Patients with urgent?start PD have less complications within 30 days of implantation and occurrence of bacteremia than patients with urgent?start HD, and the same survival rates. PD may be a feasible and safe urgent?start dialysis modality for ESRD patients.

This paper reports investigations into the preparation and characterization of surface molecularly imprinted nanoparticles (SMINs) designed to adhere to Helicobacter pylori (H. pylori). Imprinted nanoparticles were prepared by the inverse microemulsion polymerization method. A fraction of Lpp20, an outer membrane protein of H. pylori known as NQA, was chosen as template and modified with myristic acid to facilitate its localization on the surface of the nanoparticles. The interaction between these SMINs with the template NQA were evaluated using surface plasmon resonance (SPR), change in zeta potential and fluorescence polarization (FP). The results were highly consistent in demonstrating a preferential recognition of the template NQA for SMINs compared with the control nanoparticles. In vitro experiments also indicate that such SMINs are able to adhere to H. pylori and may be useful for H. pylori eradication.

We established an ELISPOT for bovine interferon-gamma (BoIFN-γ), and applied it in the diagnosis of bovine tuberculosis (bTB). Monoclonal antibodies that can bind with native BoIFN-γ were screened as the coating antibody and detecting antibody. After optimization of detecting conditions including coating antibody concentration, cell number, and detecting antibody concentration, the ELISPOT assay was established. Peripheral mononuclear cells (PBMCs) isolated from 30 cows were co-cultured with PPD, and detected with the ELISPOT assay. The optimal conditions of ELISPOT assay were 2.5 μg/mL coating antibody 2G5, 2.5 x 10(5) cells/well, and 1 μg/mL detecting antibody Bio-5E11. In these 30 cows tested both with the ELISPOT assay and the BOVIGAM kit, 11 cows were proved to be positive in ELISOPT assay with the sensitivity of 78.6%, and 12 cows were proved to be negative in ELISOPT assay with the specificity of 75%. The ELISPOT assay for BoIFN-γ could be used to detect bTB efficiently and it might be an alternative method for the diagnosis of bTB.
Animals ; Antibodies, Monoclonal ; Cattle ; Enzyme-Linked Immunospot Assay ; veterinary ; Female ; Interferon-gamma ; isolation & purification ; Sensitivity and Specificity ; Tuberculosis, Bovine ; diagnosis