Objective To clarify the expression and distribution of brain⁃derived neurotrophic factor (BDNF) in the cerebrum of plateau yaks and cattle, and to explore the relationship between BDNF function and the adaptability of altitude hypoxia. Methods Five yaks and five cattles were selected.The content and distribution of BDNF in frontal lobe, temporal lobe, parietal lobe, occipital lobe, cerebrum white matter and hippocampus of yak and cattle were analyzed by Real⁃time PCR, Western blotting and Immunohistochemistry. Results Real⁃time PCR result showed that BDNF mRNA expression in the cerebrum of yaks and cattles was highest in temporal cortex, followed by hippocampus, parietal cortex, occipital cortex and frontal cortex, and lowest in white matter. Western blotting results showed that the content of BDNF protein in the cerebrum of yaks was the highest in temporal cortex,followed by hippocampus. The content of BDNF protein in other tissues was parietal cortex, frontal cortex and cerebrum white matter, and the content of BDNF protein was the lowest in occipital cortex. The content of BDNF protein intlecerebrum of cattles was the highest in the temporal cortex, followed by the hippocampus. The content of BDNF protein in other tissues was parietal cortex, occipital cortex and frontal cortex in descending order, and the protein content in cerebrum white matter was the lowest. Immunohistochemical results showed that the positive expression of BDNF protein in the cerebrum of yaks and cattles was basically similar, mainly distributed in the granulosa cells and glial cells in the frontal cortex, temporal cortex, parietal cortex and occipital cortex, glial cells in cerebrum white matter, pyramidal cell layer and polyform cell layer in the hippocampus. There was the small amount of distribution in Martinotti cells and the molecular layer of hippocampus in the cerebral cortex. Conclusion BDNF mRNA and protein are distributed and expressed in different brain regions of yaks and cattles, but the expression level different, which is speculated to be closely related to the specific functions of different cerebrum regions. The expression level of the cerebrum of yak is higher than that of cattle except occipital cortex, suggesting that it is related to the altitude hypoxic environment. BDNF may play an important role in enhancing hypoxic tolerance and protecting internal environmental homeostasis in the process of animal adaptation to hypoxic environment.

Objective To investigate the implementation of surveillance,prevention and control measures for healthcare-associated infection(HAI)in maternal and child healthcare(MCH)institutions,and provide policy evi-dence for optimizing HAI prevention and control in MCH institutions.Methods Stratified sampling was conducted among the MCH institutions at provincial,municipal and county levels in 8 provinces/autonomous regions.A uni-fied questionnaire was designed and the online survey was conducted through"Questionnaire Star".Results The data from 123 MCH institutions were included in the analysis.90.24％of the MCH institutions carried out compre-hensive surveillance on HAI.The ratios of MCH institutions which implemented targeted surveillance on HAI in neonatal intensive care unit(NICU),surgical site infection,multidrug-resistant organisms(MDROs)and HAI in intensive care units(non-NICU excluded)were 89.66％,85.96％,80.77％,and 74.19％,respectively.51.22％MCH institutions adopted information surveillance system on HAI cases.94.31％MCH institutions carried out surveillance on hand hygiene compliance.Over 90％MCH institutions carried out surveillance on environment hy-giene in high-risk departments.71.54％MCH institutions conducted centralized cleaning,disinfection,sterilization and supply for reusable medical instruments in the central sterile supply department(CSSD).Over 90％MCH insti-tutions established three-level pre-examination triage systems.86.18％set up transitional wards.MCH institutions generally adopted a management model with established effective communication,full appointment visits,and sepa-rate visits for special medical groups,such as registered pregnant women,high-risk newborns,healthcare groups,and long-term rehabilitation patients.However,the ratio of institutions conducting on-line follow-up visits was less than 50％.Conclusion MCH institutions have generally carried out comprehensive and targeted surveillance on HAI.Information surveillance need to be facilitated.Hand hygiene and environmental hygiene surveillance has been popularized to a certain extent at all levels of MCH institutions.The cleaning,disinfection,sterilization,and supply processes of reusable medical devices in a few MCH institutions are not standardized.Special medical populations get effective management.On-line healthcare is to be further promoted.

ObjectiveTo investigate the effect of 8-week aerobic exercise on the improvement of core behaviors of male and female autistic mice induced by valproic acid (VPA). MethodsExperimental mice were randomly divided into the control group (CTL), VPA-induced autism group (VPA) and VPA+aerobic exercise group (VEX), with 10 mice in each group. The pregnant mice were injected with VPA intraperitoneally at E12.5, and their offspring were used as autistic mice. Pups were weaned 28 d after birth and began an 8-week aerobic exercise intervention. The day after exercise, mice were tested in behavioral experiments to detect exploratory behavior, social skills, repetitive stereotypic behavior, cognitive ability and mood. The mice were tested for social skills, repetitive stereotyped behaviors, cognitive and learning memory abilities, exploratory behaviors, and emotions by behavioral assays on the following day after the exercise. ResultsBoth male and female mice in the CTL group showed a significant decrease in the total distance and percentage of time spent in the interaction zone in the 4th socialization compared to the 1st socialization (P<0.01); the total distance and percentage of time spent in the interaction zone in the 5th socialization was significantly increased compared to the 4th socialization (P<0.01); in VPA group, both male and female mice showed no significant change in the total distance and percentage of time spent in the interaction zone in the 4th and 5th socialization; in the VEX group, the total distance and percentage of time spent in the interaction zone by male mice in the 4th socialization was significantly decreased compared to the 1st socialization (P<0.01, P<0.05); and in the VEX group the total distance and percentage of time spent in the social interaction zone by both male and female mice in the 5th socialization was significantly increased compared to the 4th socialization (P<0.01, P<0.05). The results of the first phase of three-box socialization experiment showed that male and female mice in the CTL group spent more time socializing with their social partners than in contact with the empty cages (P<0.01); there was no difference in the time spent by male and female mice in the VPA group in socializing with their social partners and the empty cages; and male and female mice in the VEX group spent a longer time socializing with their social partners(P<0.01). The results of the second phase of three-box test showed that male and female mice in the CTL group showed a significant tendency to socialize with new social partners (P<0.01), whereas no significant changes were observed in the mice of VPA group; aerobic exercise significantly ameliorated this deficit in male and female mice with autism. Compared with the CTL group, VPA-induced significant decreases were observed in the total distance freely moved in the central area of the open field, the time and percentage of time spent in the open arm of cross maze, and the distance and time spent in the white box in both male and female autistic mice (P<0.01); a significant increase in the number of bead burials and time spent in self-grooming (P<0.01); a significant decrease in the cognitive index (P<0.01); a significantly longer latency to find the platform, and significantly decreased the percentage of time spent in the target quadrant and the number of times they traversed the platform (P<0.01). Compared with the VPA group, after 8 weeks of aerobic intervention, male and female mice in the VEX group showed a significant increase in total distance, open-arm dwell time, and percentage of free movement in the central area of the empty field (P<0. 05), and a trend toward a decrease in the dwell time of females in the white box was not significant, the number of beads burying and the time of self-combing were significantly lower(P<0.01, P<0.05); and a significant increase in cognitive index (P<0.05), a significantly shorter time to find the platform, and significantly increased percentage of time spent in the target quadrant and the number of times they traversed the platform (P<0.01), showing excellent learning memory. ConclusionAutistic mice severely suffer from social and cognitive impairments, repetitive stereotyped behaviors, decreased activity level, and the exhibition of anxiety. 8 weeks of aerobic exercise can improve the social and cognitive abilities, alleviate the stereotyped repetitive behaviors, increase the activity level, and positively regulate the anxiety in autistic mice. It is hypothesized that aerobic exercise has an important role in motor rehabilitation of autism, in order to provide a theoretical basis for clinical research.

ObjectiveAngle-closure glaucoma (ACG) is one of the major eye-blinding diseases. To diagnose ACG, it is crucial to examine the anterior chamber angle. Current diagnostic tools include slit lamp gonioscopy, water gonioscopy, ultrasound biomicroscopy (UBM), and anterior segment optical coherence tomography (AS-OCT). Slit lamp and water gonioscopy allow convenient observation of the anterior chamber angle, but pose risks of invasive operation and eye infections. UBM can accurately measure the structure of the anterior chamber angle. However, it is complex to operate and unsuitable for patients, who have undergone trauma or ocular surgery. Although AS-OCT provides detailed images, it is costly. The aim of this study is to explore a non-invasive, non-destructive optical reflection tomography (ORT) technique. This technique can achieve low-cost three-dimensional imaging and full-field anterior chamber angle measurement of the porcine eye. MethodsThe experiment involved assembling an optical reflection tomography system, which included a complementary metal oxide semiconductor (CMOS) camera, a telecentric system, a stepper motor, and a white light source, achieving a spatial resolution of approximately 8.5 μm. The process required positioning the porcine eye at the center of the field of the imaging system and rotating it around its central axis using a stepper motor. Reflection projection images were captured at each angle with an exposure time of 1.0 ms and an interval of 2°. The collected reflection-projection data were processed using a filtered reflection tomography algorithm, generating a series of two-dimensional slice data. These slices essentially represented cross-sectional views of the three-dimensional structural image, and were reconstructed into a complete three-dimensional structural image. Based on the reconstructed three-dimensional structural image of the porcine eye, the anterior chamber angles at different positions were measured, and a distribution map of these angles was drawn. Simultaneously, the ORT measurements were compared with the standard results obtained from optical coherence tomography (OCT) to assess the accuracy of ORT measurements. ResultsIn this study, we successfully obtained the reflection projection data of a porcine eye using ORT technology, reconstructed its three-dimensional structural image, and measured the anterior chamber angle, generating the corresponding distribution map. To better distinguish the different structural parts of porcine eye, the three-dimensional structural image was marked with blue, green, and yellow dashed lines from the outer to the inner layers. The area between the blue and green dashed lines corresponded to the sclera. The area between the green and yellow dashed lines corresponded to the iris. The area inside the yellow dashed line corresponded to the pupil. The three-dimensional structural image clearly revealed the key anatomical features of the porcine eye. It was able to measure the anterior chamber angle at different positions. Additionally, the anterior chamber angle measurements of the porcine eye using ORT were compared with the measurements obtained using a TEL320C1 type OCT system, showing an average deviation of 0.51° and a mean square error MSE of 0.317. ConclusionORT is a non-invasive, non-destructive, low-cost, and high-resolution imaging technique capable of achieving three-dimensional structural imaging and full-field anterior chamber angle measurement of a porcine eye. This technology offers a new perspective for the diagnosis of angle-closure glaucoma and is significant for the screening, diagnosis, and monitoring of eye diseases, potentially benefiting clinics and small hospitals in remote areas in the future.

WRKY transcription factor is a type of transcription factor unique to plants and plays an important role in various physiological processes of plants. This study is based on the transcriptome data of Atractylodes lancea, the correlation between the FPKM values of the AlWRKY gene and the AlTPS gene of Atractylodes lancea was analyzed. Combined with the analysis results, the candidate gene AlWRKY65 with a significant positive correlation with the expression levels of AlTPS1 and AlTPS6 genes and a relatively high FPKM value was screened. The candidate gene was cloned to obtain the open reading frame ORF of the AlWRKY65 gene, and the related information of its encoded protein was analyzed and the gene expression was studied. The results showed that AlWRKY65 contains a 681 bp open reading frame and encoding 226 amino acids. Through amino acid sequence homology analysis, it was found that AlWRKY65 amino acid sequence had high homology with several plants such as HaWRKY65 and LsWRKY65; AlWRKY65 protein had a typical WRKYGQK domain, belonging to IIe subgroup of WRKY transcription factor family; phylogenetic analysis indicated that AlWRKY65 protein had the higher homology with CcWRKY65 protein; the expression of AlWRKY65 gene in different tissues of two producing areas of Atractylodes lancea were assayed via real-time fluorescence quantitative PCR, and the results showed that all of them were highly expressed in leaves and also has tissue differences. The expression level of AlWRKY65 gene was down-regulated within 48 h of methyl jasmonate (MeJA) induction; subcellular localization and transcriptional activation assay suggested that AlWRKY65 was located in the nucleus and had no transcriptional activation activity. This study provides a reference for further elucidating the biological function of AlWRKY65 in Atractylodes lancea.

Constipation is a prevalent ailment which might significantly impact the quality of people's life and rise some associated deseases risks. In this study, a chronic constipation mouse model was established using loperamide hydrochloride. Mice were gavaged an Angelica sinensis Cistanche Fiber Compound, comprised of Dang Gui [Angelica sinensis (Oliv.) Diels], Rou Cong Rong (Cistanche deserticola Y.C.Ma), wheat fiber, and low-molecular-weight xylan at high dosage (3.6 g·kg^-1, 30 times the recommended human dose) and low dosage (0.6 g·kg^-1, 5 times the recommended human dose) for 14 days. The study assessed the therapeutic efficacy of the compound by observing fecal morphology, measuring water content, and conducting small intestine motility experiments. Furthermore, enzyme-linked immunosorbent assays (ELISA) were conducted to evaluate the serum levels of gastrointestinal hormones including motilin (MTL), gastrin (GAS), the inflammatory factors interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Histopathological examination with H&E staining was employed to evaluate colonic tissue damage. Additionally, Western blot and immunohistochemistry experiments were conducted to examine the expression levels of aquaporin-3 (AQP3) and c-Kit in the colon. The results indicated that the Angelica sinensis Cistanche Fiber Compound could improve fecal morphology, increase fecal water content, enhance small intestinal transit rates in mice. Additionally, there was a significant elevation in the serum levels of gastrointestinal hormones and a notable reduction in the levels of inflammatory factors. The improvement in colonic histopathological damage was accompanied by a marked decrease in the expression of the colonic water channel protein AQP3 and a significant increase in c-Kit expression. These results collectively suggested the presence of a dose-response relationship. These findings indicate that the Angelica sinensis Cistanche Fiber Compound effectively alleviates constipation in mice. Its action is associated with the regulation of colonic water channel protein AQP3 and c-Kit expression, along with the modulation of serum inflammatory factors and gastrointestinal hormones. This experiment was approved by the Animal Experiment Ethics Committee of Jinan University.

Background: Genetic defects in the human thyroid-stimulating hormone (TSH) receptor (TSHR) gene can cause congenital hypothyroidism (CH). However, the biological functions and comprehensive genotype–phenotype relationships for most TSHR variants associated with CH remain unexplored. We aimed to identify TSHR variants in Chinese patients with CH, analyze the functions of the variants, and explore the relationships between TSHR genotypes and clinical phenotypes. Methods: In total, 367 patients with CH were recruited for TSHR variant screening using whole-exome sequencing. The effects of the variants were evaluated by in-silico programs such as SIFT and polyphen2. Furthermore, these variants were transfected into 293T cells to detect their Gs/cyclic AMP and Gq/11 signaling activity. Results: Among the 367 patients with CH, 17 TSHR variants, including three novel variants, were identified in 45 patients, and 18 patients carried biallelic TSHR variants. In vitro experiments showed that 10 variants were associated with Gs/cyclic AMP and Gq/11 signaling pathway impairment to varying degrees. Patients with TSHR biallelic variants had lower serum TSH levels and higher free triiodothyronine and thyroxine levels at diagnosis than those with DUOX2 biallelic variants. Conclusions We found a high frequency of TSHR variants in Chinese patients with CH (12.3%), and 4.9% of cases were caused by TSHR biallelic variants. Ten variants were identified as loss-of-function variants. The data suggest that the clinical phenotype of CH patients caused by TSHR biallelic variants is relatively mild. Our study expands the TSHR variant spectrum and provides further evidence for the elucidation of the genetic etiology of CH.

Objective To evaluate the pharmacokinetic characteristics and safety of single and multiple oral azvudine tablets in healthy young and elderly Chinese subjects.Methods This was a open-label and parallel-group study.The trial consisted of two groups:healthy young subjects group and healthy elderly subjects group,with 12 subjects in each group.Enrolled subjects were first given a single dose,fasting oral azvudine tablet 5 mg,after a 3-day cleansing period entered the multiple dose phase,fasting oral azvudine tablet 5 mg·d-1 for 7 days.Results After a single dose of azvudine 5 mg,Cmax and AUC0-∞ were(4.76±2.12)ng·mL-1,(6.53±2.20)ng·mL-1·h,and Tmax,t1/2 were 0.75,1.87 h in young subjects;Cmax and AUC0-∞ were(6.40±3.25)ng·mL-1,(9.50±3.70)ng·mL-1·h,and Tmax,t1/2 were 0.63,2.66 h in elderly subjects.After a multiple dose of azvudine 5 mg·d-1 for 7 d,Cmax and AUC0-∞ were(3.26±1.61)ng·mL-1,(5.38±2.19)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.88,2.13 h in young subjects;Cmax,ss and AUC0-∞,ss were(3.97±2.09)ng·mL-1,(6.71±3.26)ng·mL-1·h,and Tmax,ss,t1/2,ss were 0.75,2.56 h in elderly subjects.Elderly/young geometric mean ratios and 90％CIs were 128.37％(88.23％-186.76％),139.93％(105.42％-185.72％),140.03％(106.33％-184.41％)for azvudine Cmax,AUC0-t,AUC0-∞ after a single dose,and were 118.66％(80.83％-174.20％),118.41％(83.60％-167.69％),118.95％(84.78％-166.89％)for azvudine Cmax,AUC0-t,AUC0_∞ after a multiple dose of azvudine 5 mg·d-1 for 7 d.Conclusion After single and multiple oral administration of azvudine tablets,systemic exposure to azvudine was higher in healthy elderly subjects compared with healthy young subjects.After taking azvudine tablets,the types,severity and incidence of adverse events and adverse drug reactions in healthy elderly people were not significantly different from those in healthy young subjects.Azvudine was found to be safe and well tolerated in healthy elderly subjects.

In cardiovascular disorders, neurological diseases, and chronic metabolic diseases, the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway is essential for maintaining cell homeostasis. According to studies, boosting Nrf2 expression can be used to cure or prevent chronic diseases that are characterized by oxidative stress, inflammation, and mitochondrial dysfunction. Nonalcoholic fatty liver disease (NAFLD) is a chronic metabolic liver disease characterized by hepatic steatosis brought on by a number of causes other than alcohol. In recent years, its incidence has gradually risen across the globe. According to relevant studies, NAFLD and the Nrf2 signaling pathway are tightly connected. Inhibiting lipid production and metabolism-related enzymes, repairing impaired liver metabolism, and lowering hepatic lipid storage are all possible with Nrf2 activation. Exercise is a powerful tool for treating and preventing NAFLD. However, exercise type, exercise intensity, environment, and exhaustion all have an impact on the Nrf2 signaling pathway. By activating Nrf2, exercise can lessen liver inflammation, oxidative stress, endoplasmic reticulum stress, and insulin resistance, and ameliorate liver damage to improve NAFLD. The activation of Nrf2 signaling pathway, its associated mechanism of controlling antioxidation, and the impact of exercise on the Nrf2 signaling pathway are all explained in this work. Based on the pathogenesis of NAFLD, this article examines the connection between exercise, Nrf2, and NAFLD, and the current state of knowledge regarding Nrf2’s role in the amelioration of NAFLD through exercise. It offers a theoretical frame of reference for future research into how Nrf2 might be used to improve NAFLD.

ObjectiveGastric cancer (GC) seriously affects human health and life, and research has shown that it is closely related to the serine/glycine metabolism. The proliferation ability of tumor cells is greatly influenced by the metabolism of serine and glycine. The aim of this study was to investigate the molecular mechanism of serine/glycine metabolism can affect the proliferation of gastric cancer cells. MethodsIn this work, a stable metabolic dynamic model of gastric cancer cells was established via a large-scale metabolic network dynamic modeling method in terms of a potential landscape description of stochastic and non-gradient systems. Based on the regulation of the model, a quantitative analysis was conducted to investigate the dynamic mechanism of serine/glycine metabolism affecting the proliferation of gastric cancer cells. We introduced random noise to the kinetic equations of the general metabolic network, and applied stochastic kinetic decomposition to obtain the Lyapunov function of the metabolic network parameter space. A stable metabolic network was achieved by further reducing the change in the Lyapunov function tied to the stochastic fluctuations. ResultsDespite the unavailability of a large number of dynamic parameters, we were able to successfully construct a dynamic model for the metabolic network in gastric cancer cells. When extracellular serine is available, the model preferentially consumes serine. In addition, when the conversion rate of glycine to serine increases, the model significantly upregulates the steady-state fluxes of S-adenosylmethionine (SAM) and S-adenosyl homocysteine (SAH). ConclusionIn this paper, we provide evidence supporting the preferential uptake of serine by gastric cancer cells and the important role of serine/glycine conversion rate in SAM generation, which may affect the proliferation ability of gastric cancer cells by regulating the cellular methylation process. This provides a new idea and direction for targeted cancer therapy based on serine/glycine metabolism.