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

Background Bacteria are the most diverse and widely sourced microorganisms in the indoor air of subway stations, where pathogenic bacteria can spread through the air, leading to increased health risks. Objective To understand the status and distribution characteristics of indoor air bacterial pollution in subway stations and compartments in a city of Central South China, and to provide a scientific basis for formulating intervention measures to address indoor air bacteria pollution in subways. Methods Three subway stations and the compartments of trains parking there in a city in Central South China were selected according to passenger flow for synchronous air sampling and monitoring. Temperature, humidity, wind speed, carbon dioxide (CO₂), fine particulate matter (PM_2.5), and inhalable particulate matter (PM₁₀) were measured by direct reading method. In accordance with the requirements of Examination methods for public places-Part 3: Airborne microorganisms (GB/T 18204.3-2013), air samples were collected at a flow rate of 28.3 L·min⁻¹, and total bacterial count was estimated. Bacterial microbial species were identified with a mass spectrometer and pathogenic bacteria were distinguished from non-pathogenic bacteria according to the Catalogue of pathogenic microorganisms transmitted to human beings issued by National Health Commission. Kruskal-Wallis H test was used to compare the subway hygiene indicators in different regions and time periods, and Bonferroni test was used for pairwise comparison. Spearman correlation test was used to evaluate the correlation between CO₂ concentration and total bacterial count. Results The pass rates were 100.0% for airborne total bacteria count, PM_2.5, and PM₁₀ in the subway stations and train compartments, 94.4% for temperature and wind speed, 98.6% for CO₂, but 0% for humidity. The overall median (P₂₅, P₇₅) total bacteria count was 177 (138,262) CFU·m⁻³. Specifically, the total bacteria count was higher in station halls than in platforms, and higher during morning peak hours than during evening peak hours (P<0.05). A total of 874 strains and 82 species were identified by automatic microbial mass spectrometry. The results of identification were all over 9 points, and the predominant bacteria in the air were Micrococcus luteus (52.2%) and Staphylococcus hominis (9.8%). Three pathogens, Acinetobacter baumannii (0.3%), Corynebacterium striatum (0.1%), and Staphylococcus epidermidis bacilli (2.2%) were detected in 23 samples (2.6%), and the associated locations were mainly distributed in train compartments during evening rush hours. Conclusion The total bacteria count in indoor air varies by monitoring sites of subway stations and time periods, and there is a risk of opportunistic bacterial infection. Attention should be paid to cleaning and disinfection during peak passenger flow hours in all areas.

OBJECTIVE Optimizing the water extraction technology of Xiangqin jiere granules. METHODS The orthogonal test of 3 factors and 3 levels was designed， and comprehensive scoring was conducted for the above indexes by using G1-entropy weight to obtain the optimized water extraction technology of Xiangqin jiere granules with water addition ratio， extraction time and extraction times as factors， using the contents of forsythoside A， baicalin， phillyrin， oroxylin A-7-O-β-D-glycoside， wogonoside， baicalein and wogonin， and extraction rate as evaluation indexes. BP neural network modeling was used to optimize the network model and water extraction process using the results of 9 groups of orthogonal tests as test and training data， the water addition multiple， decocting time and extraction times as input nodes， and the comprehensive score as output nodes. Then the two analysis methods were compared by verification test to find the best water extraction process parameters. RESULTS The water extraction technology optimized by the orthogonal test was 8-fold water， extracting 3 times， extracting for 1 h each time. Comprehensive score was 96.84 （RSD＝0.90%）. The optimal water extraction technology obtained by BP neural network modeling included 12-fold water， extracting 4 times， extracting for 0.5 h each time. The comprehensive score was 92.72 （RSD＝0.77%）， which was slightly lower than that of the orthogonal test. CONCLUSIONS The water extraction technology of Xiangqin jiere granules is optimized successfully in the study， which includes adding 8-fold water， extracting 3 times， and extracting for 1 hour each time.

Objective To explore the value of serum insulin-like growth factor-1 (IGF-1) levels in diagnosis and treatment of primary hyperthyroidism. Methods 150 patients with primary hyperthyroidism (hyperthyroidism group) and 85 patients with hypothyroidism (hypothyroidism group) were selected as study subjects. During the same period, 60 healthy individuals were selected as control group. The levels of serum IGF-1, thyroid peroxidase antibody (TPOAb), thyroid stimulating hormone (TSH), free triiodothyronine (FT3), free thyroxine (FT4), triiodothyronine (T3) and total thyroxine (T4) were measured in the three groups. The serum visfatin levels in the three groups were detected using an enzyme-linked immunosorbent assay. Multifactor Logistic regression analysis was used to screen for risk factors of primary hyperthyroidism. Results The levels of IGF-1, FT3, FT4, T3 and T4 in the hyperthyroidism group were significantly higher than those in the hypothyroidism and control groups, while TSH levels were significantly lower (P < 0.05). TPOAb and visfatin levels in the hyperthyroidism group were significantly higher than those in the control group, but significantly lower than those in the hypothyroidism group (P < 0.05). The serum IGF-1 levels in patients with primary hyperthyroidism before and after 3 months of treatment were (60.11±7.23) and (30.23± 3.22) μg/L, respectively, showing a statistically significant difference (t=8.436, P < 0.001). Serum FT3, FT4, T3, T4, TPOAb, IGF-1 and visfatin levels increased and serum TSH levels decreased as risk factors for primary hyperthyroidism (P < 0.05). Conclusion The level of serum IGF-1 is closely related to thyroid function and may serve as an important reference indicator for the diagnosis and monitoring of the efficacy of primary hyperthyroidism treatment.

Introduction::The triglyceride to high-density lipoprotein cholesterol (TG/HDL-C) ratio, a novel biomarker for metabolic syndrome (MetS), has been validated in the general population as being significantly correlated with cardiovascular disease (CVD) risk. However, its capabilities to predict CVD in people living with human immunodeficiency virus (HIV; PLWH) remain underexplored.Methods::We conducted a retrospective cohort study of 16,081 PLWH who initiated antiretroviral therapy (ART) at the Third People’s Hospital of Shenzhen (China) from 2005 to 2022. The baseline TG/HDL-C ratio was calculated as TG (mmol/L) divided by HDL-C (mmol/L). We employed a multivariate Cox proportional hazards model to assess the association between the TG/HDL-C ratio and CVD occurrence, using Kaplan-Meier curves and log-rank tests to compare survival distributions. The increase in prediction risk upon the addition of the biomarker to the conventional risk model was examined through the assessment of changes in net reclassification improvement (NRI) and integrated discrimination improvement (IDI). Nonlinear relationships were investigated using a restricted cubic spline plot, complemented by a two-piecewise Cox proportional hazards model to analyze threshold effects.Results::At the median follow-up of 70 months, 213 PLWH developed CVD. Kaplan-Meier curves demonstrated a significant association between the increased risk of CVD and a higher TG/HDL-C ratio (log-rank P <0.001). The multivariate-adjusted Cox proportional hazards regression model indicated that the CVD hazard ratios (HR) (95% confidence intervals [95% CIs]) for Q2, Q3, and Q4 versus Q1 of the TG/HDL-C ratio were 2.07 (1.24, 3.45), 2.17 (1.32, 3.57), and 2.20 (1.35, 3.58), respectively ( P <0.05). The consideration of the TG/HDL-C ratio in the model, which included all significant factors for CVD incidence, improved the predictive risk, as indicated by the reclassification metrics (NRI 16.43%, 95% CI 3.35%-29.52%, P = 0.014). The restriction cubic spline plot demonstrated an upward trend between the TG/HDL-C ratio and the CVD occurrence ( P for nonlinear association = 0.027, P for overall significance = 0.009), with the threshold at 1.013. Significantly positive correlations between the TG/HDL-C ratio and CVD were observed below the TG/HDL-C ratio threshold with HR 5.88 (95% CI 1.58-21.88, P = 0.008), but not above the threshold with HR 1.01 (95% CI 0.88-1.15, P = 0.880). Conclusion::Our study confirms the effectiveness of the TG/HDL-C ratio as a predictor of CVD risk in PLWH, which demonstrates a significant nonlinear association. These findings indicate the potential of the TG/HDL-C ratio in facilitating early prevention and treatment strategies for CVD among PLWH.

Objective:To analyze the differences in whole blood selenium (Se), zinc (Zn), copper (Cu), magnesium (Mg), calcium (Ca), and iron (Fe) levels of rural older adults among areas with different soil selenium levels, and explore the main factors associated with the six nutrient elements status, so as to provide a basis for further evaluating the health risks of people in areas with different soil selenium levels.Methods:Four administrative villages were randomly selected from the Se-deficient (soil Se content < 0.175 mg/kg), Se-sufficient (soil Se content 0.175 - < 0.400 mg/kg), Se-rich (soil Se content 0.400 - < 3.000 mg/kg) and Se-excessive (soil Se content ≥3.000 mg/kg) areas, respectively, in Enshi Tujia and Miao Autonomous Prefecture (Enshi Prefecture) of Hubei Province in 2017 - 2018. And 100 elderly people aged 60 years or older (half male and half female) were randomly selected as the survey subjects in each servey site. The basic information such as general demography and lifestyle was collected through face-to-face questionnaires. Physical examination was performed and fasting venous blood was collected in the morning. The contents of blood Se, Zn, Cu, Mg, Ca, and Fe were determined by inductively coupled plasma mass spectrometry. The main factors associated with the six nutrient elements status were analyzed.Results:A total of 416 subjects were included, including 208 males and 208 females, whose average age was (72.43 ± 5.25) years, and body mass index (BMI) was (22.67 ± 3.49) kg/m 2. There were significant differences of blood Se, Zn, Cu, Mg, Ca and Fe levels between the areas with different Se levels ( Z/F = 288.30, 3.24, 14.81, 29.14, 131.28, 3.37, P < 0.05). Compared with Se-deficient and Se-sufficient areas, blood Se level was higher in Se-rich and Se-excessive areas and blood Zn level was lower in Se-excessive area ( P < 0.05); compared with Se-sufficient area, blood Cu level was lower in Se-deficient, Se-rich and Se-excessive areas, but blood Mg and Ca levels were higher ( P < 0.05), and the blood Fe level was lower in Se-excessive area ( P < 0.05). There were significant differences in the deficiency rates of Se, Zn, Cu, Mg, Ca and Fe among the elderly in different Se level areas (χ 2 = 140.83, 15.39, 31.90, 17.49, 157.60, 30.33, P < 0.01). There were significant differences in blood Zn, Cu, Ca and Fe levels between two gender groups ( P < 0.05); the blood Zn and Fe levels of the smokers were higher than those of the non-smokers, and the blood Cu level was lower than that of the non-smokers ( P < 0.05); the blood Zn and Fe levels of the drinkers were higher than those of the non-drinkers ( P < 0.05). Conclusions:The levels of six nutrient elements in the whole blood of the elderly in areas with different soil Se levels are different. To assess the health risks of the population in areas with different soil Se levels, it is necessary to consider the levels of multiple nutrient elements at the same time.

Objectives To design an objective and structured evaluation system for the clinical competence of orthopedic postgraduates in the diagnosis and treatment of distal radius fractures, and to ana-lyze its reliability and validity. Methods 28 orthopaedic postgraduates representing six levels of surgical training were tested for competence in performing surgical approach for distal radius fracture on cadaver specimens during which four measures were used to assess competency: examination of basic theory based on network item bank, objective structured operation assessment,overall assessment and operation examina-tion results. In addition, the time for completion of the surgery was also recorded. Each assessment tool was correlated with the others as well as with the resident’s level of training. Results There was a significant correlation between the seniority of candidates and the score of theoretical examination (F=6.193, P=0.000), the score of structured operation examination (F=6.374, P=0.002), the score of overall assessment (F=2.321, P=0.030), and the passing rate of final operation examination (F=36.300, P=0.000). No significant differ- ences were found between seniority and time to completion of the surgical approach exposure (F=2.282, P<0.073). Conclusions The results of the present study suggested that both theoretical examination and cadaver testing discriminate between novice and accomplished postgraduates. However, although the theo-retical test scores could predict the operational test results, but the theoretical results can not guarantee excellent operational skills.

Objective: To assess the status of handgrip strength of elderly population from longevity areas in China, and to analyze the correlative factors of handgrip strength of elderly people. Methods: Data from Chinese Longitudinal Healthy Longevity Survey (CLHLS) in 2012 was used, from which1 967 participants aged ≥60 years old with valid data of grip strength value from 8 Chinese longevity areas were included. Information on demographics characteristic, life style and health status was collected using questionnaires. The handgrip strength of both left and right hands were measured by grip dynamometer. The different characteristics of group of participants with different grip strength were compared and then analyzed by adopting the Cumulative odds Logistic regression model to identify main factors associated with hand grip strength. Results: The P₅₀ (P₂₅-P₅₀) of hand grip strength of elderly people from the eight longevity areas was 20 (11-28) kg; The hand grip strength of males was 26 (18-34) kg, which was higher than that of females(14 (9-20) kg) (P<0.001). Cumulative odds Logistic regression model showed that the hand grip strength of females was lower than males, whose β value (95%CI) was-1.22 (-1.43--1.00). The elderly who was at a higher age, smoking, drinking or with anemia, had a comparatively lower handgrip strength, whose β (95%CI) value were separately-0.08(-0.09~-0.07),-0.29(-0.56~-0.02),-0.54(-0.80~-0.28), and-0.41(-0.62~-0.20). And the elderly who had a higher boby mass index, drinking tea and outdoor activities, had a comparatively higher handgrip strength, whose β(95%CI) value were separately 0.28 (0.15-0.40), 0.25(0.03-0.47) and 0.51(0.30-0.71). Conclusion Age and gender were the main correlative factors, lifestyles and physical conditions might also be correlative factors of hand grip strength of the elderly from longevity areas in China.

Objective: To explore the association between biomarkers and activities of daily living (ADL) in the elderly over 65 years old from longevity areas in China. Methods: A total of 2 439 people from 8 longevity areas were included in our baseline survey in 2012. Using questionnaires, body measurements, and blood biochemical examinations, information on demographics characteristic, life style, ADL, blood pressure and biomarkers were collected. Based on these six items of ADL (bathing, dressing, indoor activities, toileting, eating, bowel and bladder control), we constructed a dichotomous indicator for ADL. A respondent was defined as ADL disabled if any difficulty in one or more of the above six activities was reported. Information were collected in the follow-up in 2014 using the same questionnaires and examinations. We excluded information on the elderly who lacked ADL or biomarkers test results or with ADL disability at baseline study. Finally 938 elderly people over 65 years old were included in this analysis. Multivariate logistic regression model was used to analyze the influence factors of ADL disability. Results: During the 2-year follow-up, 100 (10.7%) participants developed into ADL disability, with a rate at 10.7%. Multivariate logistic regression analysis indicated that each year increase in age or each 1 mmHg (1 mmHg=0.133 kPa) increase in systolic blood pressure (SBP) would cause the risk of ADL disability to increase 9% or 1%, whose OR (95%CI) were separately 1.09 (1.06-1.12), 1.01 (1.00-1.02). Han nationality or cognitive impairment increased the risk of ADL disability, whose OR (95%CI) values were separately 4.90 (1.13-21.24), 2.47 (1.44-4.25), while increased lymphocyte count (>1.60×10⁹/L), being married, or participating in recreational activities decreased the risk of ADL disability, whose OR (95%CI) values were separately 0.51 (0.31-0.82), 0.52 (0.28-0.96), 0.43 (0.23-0.80). Conclusion In the elderly elevated lymphocyte count was associated with lower risk of ADL disability. In addition, incresed age, increased SBP, unmarried, Han nationality or cognitive impairment were associated with the increasing risk of ADL disability in older people, while participating in recreational activities would reduce the risk.

Objective: To investigate the influence factors of survival outcome among elderly aged ≥80 years old. Methods: In baseline survey in 2009, 930 participants aged ≥80 years old were enrolled from 7 longevity areas, to collect the information of socioeconomic factors, life style, cognitive function, activities of daily living and diseases, as well as physical examination to test biomarkers of blood and urine. The survival status was followed up at 2012 and 2014 survey. Stepwise Cox proportional hazards models were used to screen influence factors of 5-year survival. Results: During 5 years of follow-up, 571 participants died, 133 participants were lost to follow up, and the all-cause mortality was 63.4%. In stepwise Cox proportional hazards models, male, unmarried, self-reported poor life quality, disability in daily life, cognitive impairment, cardiovascular and cerebrovascular diseases, chronic kidney diseases were risk factors for elderly survival outcome, with the HR (95%CI) at 1.75 (1.40-2.12), 1.49 (1.10-2.03), 1.40 (1.16-1.69), 1.37 (1.11-1.70), 1.51 (1.22-1.88), 1.62 (1.18-2.23) and 1.48 (1.23-1.77) respectively. Each 1 year increase in age corresponded to 4% increase in mortality risk (HR (95%CI)=1.04 (1.02-1.05)); each 1 kg/m² increase in BMI corresponded to 5% increase in mortality risk (HR (95%CI)=0.95 (0.93-0.98)); each 1.0×10⁹/L increase in total lymphocyte count (TLC) corresponded to 13% increase in mortality risk (HR (95%CI)=0.87 (0.76-0.99)). Additionally, the mortality risk decreased 19% (HR (95%CI)=0.81 (0.66-0.98)) in participants with regularly physical exercise compared to those without; and the mortality risk decreased 41% (HR (95% CI)=0.59 (0.40-0.88)) in participants with elevated triglycerides (TG, ≥2.26 mmol/L) compared to those without. Conclusion In Chinese longevity areas, some nutritional and immune indices such as relatively higher level of BMI, TLC and TG were independent protective factors for 5-year survival outcome, which was different from general adults and younger elderly.