Vascular damage plays a significant role in the onset and progression of Alzheimer's disease (AD). However, the precise molecular mechanisms underlying the induction of neuronal injury by vascular damage remain unclear. The present study aimed to examine the impact of fibrinogen (Fg) on tau pathology. The results showed that Fg deposits in the brains of tau P301S transgenic mice interact with tau, enhancing the cytotoxicity of pathological tau aggregates and promoting tau phosphorylation and aggregation. Notably, Fg-modified tau fibrils caused enhanced neuronal apoptosis and synaptic damage compared to unmodified fibrils. Furthermore, intrahippocampal injection of Fg-modified tau fibrils worsened the tau pathology, neuroinflammation, synaptic damage, neuronal apoptosis, and cognitive dysfunction in tau P301S mice compared to controls. The present study provides compelling evidence linking Fg and tau, thereby connecting cerebrovascular damage to tau pathology in AD. Consequently, inhibiting Fg-mediated tau pathology could potentially impede the progression of AD.
Animals ; tau Proteins/metabolism* ; Alzheimer Disease/metabolism* ; Fibrinogen/metabolism* ; Mice, Transgenic ; Mice ; Disease Models, Animal ; Memory Disorders/metabolism* ; Male ; Mice, Inbred C57BL ; Brain/metabolism* ; Hippocampus/metabolism* ; Protein Aggregation, Pathological/metabolism* ; Apoptosis ; Phosphorylation

ObjectiveTo investigate the effect of Yunkang oral liquid on postpartum kidney deficiency in mice. MethodPostpartum mice were randomized into model and low-dose （6 mL·kg^-1）， medium-dose （9 mL·kg^-1）， and high-dose （12 mL·kg^-1） Yunkang oral liquid groups. The mouse model of postpartum kidney deficiency was established by sleep deprivation combined with forced swimming. Another 9 female ICR mice were selected as the normal control group. The mice were administrated with Yunkang oral liquid during the period of modeling. The levels of estradiol （E₂）， progesterone （P）， follicle-stimulating hormone （FSH）， and luteinizing hormone （LH） in the serum were measured by the enzyme-linked immunosorbent assay. The morphological changes of ovaries and uterus were observed by hematoxylin-eosin （HE） staining， and the expression of transforming growth factor （TGF）-β and Smad2/3 was determined by immunohistochemistry and Western blotting. ResultThe mice in the model group showed prolonged estrous cycle， reduced voluntary activity， dorsal temperature， grip strength， and bone strength， and whitening tongue coating. Compared with the model group， Yunkang oral liquid shortened the estrous cycle， increased the voluntary activity， dorsal temperature， grip strength， and bone strength， and alleviated the whitening of tongue coating. Moreover， it elevated the E₂ and P levels and lowered the FSH and LH levels in the serum， decreased ovarian follicular atresia rate， promoted uterine repair， and down-regulated the expression of TGF-β and Smad2/3 in the ovarian and uterine tissues. ConclusionYunkang oral liquid can ameliorate postpartum kidney deficiency in mice by regulating the TGF-β/Smads signaling pathway.

Objective:To seek any correlation between cortical activity and the swallowing of dysphagia patients with infratentorial stroke, and to observe any effect of three-needle acupuncture of the tongue on such activity.Methods:Thirty infratentorial stroke survivors with dysphagia were randomly divided into a tongue three-needle group and a sham acupuncture group, each of 15. Functional near-infrared spectroscopy was used to monitor changes in the concentration of oxygenated hemoglobin (ΔHbO 2) at rest, during acupuncture (or sham acupuncture), during real or sham electro-acupuncture, and at rest after the acupuncture or sham acupuncture treatment. The Modified Rankin Scale, a Penetration-Aspiration Scale (PAS), and the Functional Oral Intake Scale were employed to assess overall functional disability and the swallowing of both groups. Results:At rest the average ΔHbO 2 concentrations recorded in the left primary motor cortex, the left dorsolateral prefrontal cortex and the left premotor cortex in both groups were positively correlated with the PAS scores. During the acupuncture ΔHbO 2 concentration in the right inferior frontal gyrus and the left middle temporal gyrus increased significantly in the tongue three-needle group. It decreased significantly in the left somatosensory cortex and the left primary motor cortex. Conclusion:Three-needle acupuncture of the tongue induces changes in cortical activity in infratentorial stroke survivors with dysphagia, suggesting a potential technique for improving disordered swallowing.

Objective: To investigate the characteristics of HIV/AIDS cases among 15-24 year old population reported in Hefei from 2004 to 2022, so as to provide insights into AIDS control among adolescents. Methods: The epidemiological data regarding HIV/AIDS cases between 15 and 24 years old reported in Hefei from 2004 to 2022 were captured from the AIDS comprehensive prevention and control information system of Chinese disease prevention and control information system, and data regarding temporal distribution, population distribution, and routes of infections and detection were descriptively analyzed by descriptive epidemiological methods. Results: From 2004 to 2022, 865 cases of HIV/AIDS were reported in Hefei among 15-24 years old youth, accounting for 21.80% of the total reported cases. Among the HIV/AIDS patients, males accounted for 92.60%(801 cases), the unmarried ones accounted for 93.41% (808 cases)，those with college degree or above accounted for 60.12% (520 cases)，and 25.78%(223 cases) of them were students. The proportion of student cases increased annually( χ 2 trends =47.67, P <0.01). Homosexual transmission accounted for 81.39%, both showed an increasing trend( χ 2 trends =51.23, P <0.01)．Totally 55.49% of cases were found through testing and consultation, and the proportion of cases increased by year( χ 2 trends =112.18, P <0.01). In 2004-2022，the number of newly reported cases among people aged 15-24 showed a rising trend at an average rate of 24.46% by year( Z=4.92, P <0.01), which was higher than the average rate of 21.54% for the entire population( Z=12.75, P <0.01). Conclusion The epidemic of HIV/AIDS among population aged 15-24 years is serious in Hefei. Comprehensive measures for HIV education and prevention intervention are desperately needed to be reinforced among targeted students.

【Objective】 To analyze the RBC products returned by hospitals due to positive direct antiglobulin test (DAT), and explore measures to reduce the discarding rate of blood products and ensure the safety of clinical blood use. 【Methods】 The data of RBC products, which were returned by hospitals due to positive-DAT, in Hebei Blood Center from 2018 to 2020 were retrospectively analyzed. The donation time, hospital, gender of blood donors, donation times and DAT typing results were searched through blood donation code, input into the statistical software SPSS17.0, and analyzed by linear trend χ² and Pearsonχ². 【Results】 1)The discarding rate of RBC products due to positive DAT in 2018, 2019 and 2020 accounted for 0.15‰, 0.32‰ and 0.26‰, respectively, of the overall RBC collection. The total concordance rate was 89.94% by our retest. 2)The concordance rate of returned blood from secondary hospitals and tertiary hospitals was 78.26% and 91.78%, respectively (P<0.05), with the latter higher than the former. 3)No statistical significance was noticed in the DAT-positive blood by months(P>0.05). 4)The DAT-positive rate of female donors was higher than that of male donors, and that of first-time blood donors was higher than that of repeated and regular blood donors with statistical differences (P<0.05). 5)DAT-positive typing results was mainly due to IgG incomplete antibody. 【Conclusion】 In order to reduce the discarding rate of RBC products, it is suggested to strengthen the consultation before blood collection, encourage healthy males to donate blood and increase the proportion of regular blood donors. Meanwhile, the quality management of Transfusion Department in secondary hospitals should be further improved to ensure the safety of clinical blood transfusion.

Objective To explore the application effects of three-dimensional teaching mode for clinical anesthesiology. Methods 43 students were selected into control group, who were from class one, grade 2010 in the Department of Anesthesiology, Ningxia Medical University. 42 students were selected into observation group, who were from class two, grade 2010 in the Department of Anesthesiology, Ningxia Medical University. The traditional teaching mode were used for the students in control group during the teaching of clinical anesthesiology, while three-dimensional teaching mode were used for the students in observation group during the teaching. At the end of teaching, the teaching results were compared between the control group and the observation group, mainly including the usual scores evaluated from an anaesthesia plan plus an anaesthesia case discussion, and the final scores. The teaching satisfaction questionnaire were used to assess the effects of two teaching methods on the students' interest in learning, the capacity of clin-ical practice, the abilities of exploring, analyzing and solving problems, etc. SPSS 17.0 software was used in statistical analysis. The students' teaching results were tested by using two independent samples t-test. The satisfactions of these teaching effects were tested by using the Chi-square test. Results The usual and final scores in the observation group were significantly higher than those in the control group [(88.1±5.1) vs. (75.3±4.2), (82.1±3.3) vs. (75.7±3.9); P<0.05]. Compared with the control group, the satisfactions of teaching effects in the observation group were higher such as to stimulate interest in learning (60.5% vs. 90.5%), to improve the abilities of self-study (30.2% vs. 83.3%) and clinical practice (51.2% vs. 85.7%), to widen the scope of knowledge (46.5% vs. 88.1%) and to cultivate the spirits of innovation (55.8% vs. 83.3%), etc (P<0.05). Conclusion During the teaching of clinical anesthesiology, the three-dimensional teaching mode has more advantages than the traditional one, which is good for improving the students' innovation and practice abilities.

Objective To explore the effect of failure mode and effect analysis (FMEA) method in strengthening the management of critical value of blood specimens in hospital. Methods According to the procedures of FMEA, critical values management team were established, drew flow chart of generating test specimens and crisis value, explored the potential failure mode and failure cause, analyzed the severity, possibility and critical value, and formulate and implement countermeasures according to the research outcome. Results The crisis value of the failure mode fell from 1 320 to 151 after the implementation of FMEA, and rate of decline was 88.56%; number of unqualified blood samples decreased from 510 cases to 78 cases, and the difference is statistically significant (χ2=407.27, P<0.05);critical value processing defects decreased from 85 cases (a total of 236 cases) to 3 cases (a total of 229 cases), and the difference was statistically significant (χ2=91.26, P<0.05). Conclusions FMEA method is helpful to improve the accuracy and precision of critical value management of clinical blood samples, so as to ensure the safety of patients in hospitals.

Objective The present study was to investigate the feasibility of use of high resolution magnetic reso?nance vessel wall imaging(HR-VWI)in evaluation of intracranial aneurysms. Methods We prospectively collected data from patients who had intracranial aneurysms and received HR-VWI scan before surgical treatment or conservative treatment. Aneurysms were divided into ruptured group (n=12) and unruptured group (n=88). Aneurysm site, size, neck, aspect ratio(AR), daughter sac and aneurysmal wall enhancement scale were analyzed in both groups. Univariate and multivariate Logistic regression were performed to evaluate the risk factors of aneurysm rupture. Subgroup analysis was also performed to study symptomatic and asymptomatic unruptured aneurysms. Results Aneurysm size(t=2.187,P=0.031),AR(t=3.164,P=0.002),incidence of daughter sac(P=0.012) and aneurysmal wall enhancement scale(P<0.001)were higher in ruptured aneurysm group. Multivariate Logistic regression showed that aneurysmal wall enhance?ment scale was the only independent risk factor of ruptured aneurysms(P=0.002). Subgroup analysis showed aneurysm wall enhancement scale(P<0.001) and AR(t=3.939,P<0.001) were higher in symptomatic unruptured aneurysms. Conclusion Aneurysm wall enhancement on HR-VWI is more frequently seen in ruptured aneurysms and symptomatic unruptured aneurysms. Histological study is needed for better understanding of the mechanism of aneurysm wall enhance?ment.

As the understanding of science creativity becomes more profound,people find out that organizational barriers are greatly deterring and discouraging the advent and development of science creativity.Drawing upon the Situation Theory of Creativity and earlier researches,we identified crucial organizational factors that imposed influence on science creativity and considered those factors as gauge to reflect on the current practice of science research management in China.The findings show that science research funding mode,collaboration and communication opportunities and accesses,science researchers' career development and evaluation system,research group leadership,size and diversity of research teams are all key components of the organizational barriers that failed to nurture and spur Chinese researchers to solve long existed and challenging problems with original approaches and creative thinking.Therefore,innovations of science research management are necessary and urgent.

OBJECTIVETo investigate the effect of protein transduction domain-hepatitis B virus core antigen (CTP-HBcAg18-27)-Tapasin fusion protein-induced specific cytotoxic T lymphocyte (CTL) response on hepatitis B virus (HBV) replication in HBV transgenic mice.

METHODSTwenty HBV-transgenic mice were randomly divided into two groups for a 3-week course of once weekly subcutaneous immunizations with either CTP-HBcAg18-27-Tapasin fusion protein or CTP-HBcAg18-27. Mice administered isotonic saline served as blank controls. Expressions of cytokines in splenocytes were analyzed by flow cytometry. Serum levels of hepatitis B surface antigen (HBsAg) and HBV DNA were determined by microparticle enzyme immunoassay and real-time fluorescent PCR assay, respectively. Expression of HBsAg in hepatic tissues was detected by immunohistochemistry.

RESULTSImmunization with 100 mug of CTP-HBcAg18-27-Tapasin fusion protein led to a significant increase in proportions of CTLs in spleen (2.70%+/-0.20% vs. 50 mug of CTP-HBcAg18-27-Tapasin: 1.66%+/-0.53%, 50 mug of CTP-HBcAg18-27: 1.26%+/-0.56%, and blank controls: 0.75%+/-0.71%; F = 741.45, P = 0.000) and up-regulation of inflammatory cells in hepatic tissue. In addition, both immunizations of CTP-HBcAg18-27-Tapasin led to significant decreases in serum HBsAg and HBV DNA levels compared to those in the CTP-HBcAg18-27 group.

CONCLUSIONHBV-related modification of the expression of the molecular chaperone Tapasin may affect its interaction with intracellular antigen peptides, thereby leading to increases the number of specific CTLs in the spleen, decreases in serum HBsAg and HBV DNA levels, and down-regulation of HBsAg expression in hepatic tissue. These results obtained in HBV-transgenic mice suggest that the CTP-HBcAg18-27-Tapasin fusion protein has anti-HBV activity.

Animals ; DNA, Viral ; blood ; Female ; Hepatitis B ; immunology ; Hepatitis B Core Antigens ; genetics ; Hepatitis B Surface Antigens ; blood ; Hepatitis B virus ; physiology ; Male ; Membrane Transport Proteins ; genetics ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Recombinant Fusion Proteins ; genetics ; immunology ; T-Lymphocytes, Cytotoxic ; immunology ; Transfection ; Virus Replication