ObjectiveTo investigate the mechanism of Si Junzitang in treating liver injury in rats with spleen Qi deficiency syndrome based on transcriptomics and to experimentally verify its effects. MethodsSixty male SD rats were randomly divided into blank group， model group， low-dose Si Junzitang （6 g·kg^-1·d^-1）， medium-dose Si Junzitang group （12 g·kg^-1·d^-1）， high-dose Si Junzitang group （24 g·kg^-1·d^-1）， and natural recovery group， with 10 rats in each group. A composite multifactorial modeling method （forced swimming + intragastric administration of Xiao Chengqitang + irregular diet） was used to establish a spleen Qi deficiency model. After 30 days of continuous intervention， body weight and 3-hour food intake were measured， and macroscopic symptom scores for spleen Qi deficiency syndrome were evaluated. Serum levels of aspartate aminotransferase （AST） and alanine aminotransferase （ALT） in each group were detected， and hematoxylin and eosin （HE） staining was used to observe histopathological changes in liver tissue. Transcriptome sequencing （RNA-Seq） was used to identify differentially expressed genes （DEGs） among the blank， model， and high-dose Si Junzitang groups. Gene ontology（GO） and Kyoto encyclopedia of genes and genome（KEGG） enrichment analyses were performed on the DEGs. Immunofluorescence （IF） and Western blot were used to detect NOD-like receptor protein 3 （NLRP3）， apoptosis-associated speck-like protein （ASC）， Caspase-1， and the N-terminal domain of gasdermin D （GSDMD-N）. Immunohistochemistry （IHC） was used to detect the expression of downstream inflammatory cytokines interleukin-1β （IL-1β）， interleukin-6 （IL-6）， and interleukin-18 （IL-18）. ResultsCompared with the blank group， the model group showed significantly reduced body weight and 3-hour food intake， significantly increased macroscopic symptom scores， and elevated serum AST and ALT levels （P<0.01）， with mild inflammatory liver injury observed histologically. Compared with the model group， Si Junzitang at all doses significantly improved these parameters and alleviated liver injury in a dose-dependent manner （P<0.05，P<0.01）. RNA-Seq analysis revealed 1 254 DEGs between the blank and model groups， and 842 DEGs between the model and high-dose Si Junzitang groups. GO and KEGG enrichment analyses indicated that the NOD-like receptor signaling pathway was activated in liver injury associated with spleen Qi deficiency， suggesting that the NLRP3 inflammasome may be a key target. Results from IF， IHC， and Westernblot showed that compared with the blank group， the expression of NLRP3， ASC， Caspase-1， GSDMD-N， and the downstream inflammatory cytokines IL-1β， IL-6， and IL-18 were significantly increased in the model group （P<0.01）， while these levels were markedly decreased in the high-dose Si Junzitang group （P<0.01）. ConclusionSi Junzitang effectively improves mild inflammatory liver injury in rats with spleen Qi deficiency syndrome in a dose-dependent manner. Its mechanism may be associated with inhibition of the NLRP3/ASC/Caspase-1 signaling pathway， downregulation of the pyroptosis executioner protein GSDMD-N， and reduction of pyroptosis-related inflammatory cytokine release.

OBJECTIVE: To investigate possible associations between physical function assessment scales, such as Short Physical Performance Battery (SPPB) and Berg Balance Scale (BBS), with all-cause mortality in acute decompensated heart failure (ADHF) patients. METHODS: A total of 108 ADHF patients were analyzed from October 2020 to October 2022, and followed up to May 2023. The association between baseline clinical characteristics and all-cause mortality was analyzed by univariate Cox regression analysis, while for SPPB and BBS, univariate Cox regression analysis was followed by receiver operating characteristic curves, in which the area under the curve represented their predictive accuracy for all-cause mortality. Incremental predictive values for both physical function assessments were measured by calculating net reclassification index and integrated discrimination improvement scores. Optimal cut-off value for BBS was then identified using restricted cubic spline plots, and survival differences below and above that cut-off were compared using Kaplan-Meier survival curves and the log-rank test. The clinical utility of BBS was measured using decision curve analysis. RESULTS: For baseline characteristics, age, female, blood urea nitrogen, as well as statins, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, or angiotensin receptor-neprilysin inhibitors, were predictive for all-cause mortality for ADHF patients. With respect to SPPB and BBS, higher scores were associated with lower all-cause mortality rates for both assessments; similar area under the curves were measured for both (0.774 for SPPB and 0.776 for BBS). Furthermore, BBS ≤ 36.5 was associated with significantly higher mortality, which was still applicable even adjusting for confounding factors; BBS was also found to have great clinical utility under decision curve analysis. CONCLUSIONS BBS or SPPB could be used as tools to assess physical function in ageing ADHF patients, as well as prognosticate on all-cause mortality. Moreover, prioritizing the improvement of balance capabilities of ADHF patients in cardiac rehabilitation regimens could aid in lowering mortality risk.

OBJECTIVE: This study aimed to explore the association between body mass index (BMI) and mortality based on the 10-year population-based multicenter prospective study. METHODS: A general population-based multicenter prospective study was conducted at four sites in rural China between 2013 and 2023. Multivariate Cox proportional hazards models and restricted cubic spline analyses were used to assess the association between BMI and mortality. Stratified analyses were performed based on the individual characteristics of the participants. RESULTS: Overall, 19,107 participants with a sum of 163,095 person-years were included and 1,910 participants died. The underweight (< 18.5 kg/m ²) presented an increase in all-cause mortality (adjusted hazards ratio [ aHR] = 2.00, 95% confidence interval [ CI]: 1.66-2.41), while overweight (≥ 24.0 to < 28.0 kg/m ²) and obesity (≥ 28.0 kg/m ²) presented a decrease with an aHR of 0.61 (95% CI: 0.52-0.73) and 0.51 (95% CI: 0.37-0.70), respectively. Overweight ( aHR = 0.76, 95% CI: 0.67-0.86) and mild obesity ( aHR = 0.72, 95% CI: 0.59-0.87) had a positive impact on mortality in people older than 60 years. All-cause mortality decreased rapidly until reaching a BMI of 25.7 kg/m ² ( aHR = 0.95, 95% CI: 0.92-0.98) and increased slightly above that value, indicating a U-shaped association. The beneficial impact of being overweight on mortality was robust in most subgroups and sensitivity analyses. CONCLUSION This study provides additional evidence that overweight and mild obesity may be inversely related to the risk of death in individuals older than 60 years. Therefore, it is essential to consider age differences when formulating health and weight management strategies.
Humans ; Body Mass Index ; China/epidemiology* ; Male ; Female ; Middle Aged ; Prospective Studies ; Rural Population/statistics & numerical data* ; Aged ; Follow-Up Studies ; Adult ; Mortality ; Cause of Death ; Obesity/mortality* ; Overweight/mortality*

Objective To study the pharmacokinetics and bioequivalence of two formulations of rasagiline mesylate tablets in healthy subjects under fasting and fed conditions.Methods The two-period,two-sequence,crossover study design was adopted in the fasting study.Thirty-six subjects were enrolled and given either test preparation or reference preparation 1 mg respectively in two periods.After collecting plasma samples,the plasma concentration of rasagiline was determined by liquid chromatography-tandem mass spectrometry(LC-MS/MS)and the bioequivalence was evaluated using the average bioequivalence(ABE)method.The four-period,two-sequence,fully replicate crossover study design was adopted in the fed study.Forty-eight subjects were enrolled and given the test preparation or the reference preparation at a dose of 1 mg twice respectively in four periods.According to the degree of intra-individual variation of Cmax,AUC0-t and AUC0-∞,the equivalence was evaluated using the reference-scaled average bioequivalence and ABE method,respectively.Results In the fasting study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(9.70±3.14)and(9.62±3.85)ng·mL-1,AUC0-t were(6.03±1.47)and(6.02±1.95)ng·h·mL-1,AUC0-∞ were(6.13±1.51)and(6.12±1.97)ng·h·mL-1.The 90％confidence interval(CI)of the geometric mean ratio(GMR)were 94.11％-118.06％,99.22％-107.74％and 99.16％-107.44％for Cmax,AUC0-t and AUC0-∞,respectively,which were within the acceptance criteria of 80.00％-125.00％.In the fed study,the pharmacokinetic parameters of rasagiline of the test and reference preparation were as follow:Cmax were(3.00±1.92)and(3.52±1.77)ng·mL-1,AUC0_t were(5.02±1.20)and(5.06±1.20)ng·h·mL-1,AUC0-∞ were(5.11±1.23)and(5.14±1.22)ng·h·mL-1.The 90％CI of GMR were 96.99％-101.19％and 97.17％-101.41％for AUC0-t and AUC0-∞,which were within the acceptance criteria of 80.00％-125.00％.The 95％upper confidence bound of Cmax for were less than"0",and the point estimate of GMR were within the acceptance criteria of 80.00％-125.00％.The incidence of adverse events in fasting and fed studies was 22.86％and 22.92％,respectively,and all adverse events were moderate to mild.Conclusion The two rasagiline mesylate tablets were bioequivalent,and both the formulations were well tolerated.

Aim To anticipate the mechanism of zuka- mu granules (ZKMG) in the treatment of bronchial asthma, and to confirm the projected outcomes through in vivo tests via using network pharmacology and molecular docking technology. Methods The database was examined for ZKMG targets, active substances, and prospective targets for bronchial asthma. The protein protein interaction network diagram (PPI) and the medication component target network were created using ZKMG and the intersection targets of bronchial asthma. The Kyoto Encyclopedia of Genes and Genomics (KEGG) and gene ontology (GO) were used for enrichment analysis, and network pharmacology findings were used for molecular docking, ovalbumin (OVA) intraperitoneal injection was used to create a bronchial asthma model, and in vivo tests were used to confirm how ZKMG affected bronchial asthma. Results There were 176 key targets for ZKMG's treatment of bronchial asthma, most of which involved biological processes like signal transduction, negative regulation of apoptotic processes, and angiogenesis. ZKMG contained 194 potentially active components, including quercetin, kaempferol, luteolin, and other important components. Via signaling pathways such TNF, vascular endothelial growth factor A (VEGFA), cancer pathway, and MAPK, they had therapeutic effects on bronchial asthma. Conclusion Key components had strong binding activity with appropriate targets, according to molecular docking data. In vivo tests showed that ZKMG could reduce p-p38, p-ERKl/2, and p-I

OBJECTIVE To explore the effectiveness, potential mechanism and compatibility characteristics of efficacy groups of Dunhuang medical prescription Daxiefei decoction in preventing and treating pneumonia based on chemical bioinformatics method. METHODS To study the effect of Daxiefei decoction freeze-dried powder solution on the proliferation activity of lung epithelial cells through cell experiments. Daxiefei decoction was divided into three groups: clearing away heat group, resolving phlegm group, and nourishing Yin group according to its efficacy characteristics. The chemical components of Daxiefei decoction were obtained by TCMSP database and literature search, and the targets were predicted in Swiss Target Prediction database. Pneumonia disease targets were obtained by DrugBank, TTD, Genecards and DisGeNET databases. STRING database and Cytoscape were used to construct the intersection target interaction network and "drug-component-target- pathway" network and DAVID database was used for KEGG pathway enrichment analysis. The network was used to analyze the scientific connotation of the compatibility of efficacy groups. Furthermore, molecular docking was used to evaluate the target-compound affinity and molecular dynamics was used to explore the dynamic molecular mechanism. RESULTS Cell experiments showed that Daxiefei decoction can maintain the proliferation of lung epithelial cells, reverse the decrease of mitochondrial activity induced by LPS and reduce apoptosis. Complex network analysis showed that the pathways enriched by the three functional groups contained in Daxiefei decoction were mainly distributed in two modules: inflammation regulation and reducing airway mucus hypersecretion. Each module was connected by a common target gene and had its own focus. The results of molecular docking showed that the components quercetin, baicalein, isorhamnetin etc. might be the effective multi-target components of Daxiefei decoction. SRC, EGFR, PPARA etc. had good affinity with each potential active component, which might be a potential target of Daxiefei decoction for preventing and treating pneumonia. Molecular dynamics simulation showed that the potential active component quercetin formed stable intermolecular interactions with SRC. CONCLUSION This study initially reveal the material basis and molecular mechanism of Daxiefei decoction in the prevention and treatment of pneumonia. It also explores the scientific connotation of Daxiefei decoction in the prevention and treatment of pneumonia with different efficacy groups, and its modern development and clinical application provide chemical bioinformatics basis.

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To understand the current situation of human brain donation in Hebei Province by analyzing the basic information of Human Brain Bank samples of Hebei Medical University in order to provide basic data support for subsequent scientific research.Methods The samples collected from the Human Brain Bank of Hebei Medical University were analyzed(from December 2019 to February 2024),including gender,age,cause of death,as well as quality control data such as postmortem delay time,pH value of cerebrospinal fluid and and RNA integrity number and result of neuropathological diagnosis.Results Until February 2024,30 human brain samples were collected and stored in the Human Brain Bank of Hebei Medical University,with a male to female ratio of 9∶1.Donors over 70 years old accounted for 53％.Cardiovascular and cerebrovascular diseases(36.67％)and nervous system diseases(23.33％)accounted for a high proportion of the death causes.The location of brain tissue donors in Shijiazhuang accounted for 90％donations,and the others were from outside the city.The postmortem delay time was relatively short,90％within 12 hours and 10％more than 12 hours.69.23％of the brain samples had RNA integrity values greater than 6.Cerebrospinal fluid pH values ranged from 5.8 to 7.5,with an average value of 6.60±0.45.Brain weights ranged from 906-1496 g,with an average value of(1210.78±197.84)g.Three apolipoprotein E(APOE)alleles were detected including five genotypes(ε2/ε3,ε2/ε4,ε3/ε3,ε3/ε4,ε4/ε4).Eleven staining methods related to neuropathological diagnosis had been established and used.A total of 12 cases were diagnosed as neurodegenerative diseases(including Alzheimer's disease,Parkinson's disease,multiple system atrophy,corticobasal degeneration and progressive supranuclear palsy,etc.),accounting for 40％donated brains.The comorbidity rate of samples over 80 years old was 100％.Conclusion The summary and analyses of the data of brain donors in the Human Brain Bank of Hebei Medical University can reflect the current situation of the construction and operation of the brain bank in Hebei Province,and it can also be more targeted to understand and identify potential donors.Our information can provide reference for the construction of brain bank and provides more reliable materials and data support for scientific research.

Objective To investigate the activated phenotype and the expression of the receptor of advanced glycation endproducts(RAGE)of astrocytes after hypoxic-ischemic brain damage(HIBD)in neonatal rats and the effects of gastrodin(GAS)intervention on them.Methods Totally 48 neonatal 3 days SD rats were used to construct HIBD model and randomly divided into sham group,HIBD group and HIBD+GAS group(100 mg/kg),and the expressions of Al type astrocyte marker C3,A2 type astrocyte marker S100A10,RAGE,tumor necrosis factor-α(TNF-α),brain-derived neurotrophic factor(BDNF),and insulin-like growth factor(IGF-1)in the corpus callosum of the ischemic side were detected by Western blotting and immunohistochemical staining on day 1 and day 3 after HIBD.TNC-1 cells were divided into control group,oxygen glucose deprivation(OGD)group,OGD+GAS(0.34 mmol/L)group and GAS group,and then the protein expressions of RAGE,TNF-α,BDNF and IGF-1 were detected by Western blotting and immunofluorescence.Results In vivo,Western blotting showed that compared with the sham group,the protein expression levels of C3,S100A10,RAGE,TNF-α and IGF-1 in the 1 day and 3 days groups after HIBD group in 1 day group were significantly higher than those in the sham group(P＜0.05),but the protein expression level of BDNF decreased in 1 day group and increased in 3 days group(P＜0.05).Compared with the HIBD group,the C3,RAGE and TNF-α protein expression levels were significantly attenuated in the HIBD+GAS group(P＜0.05),and the protein expression levels of BDNF and IGF-1 further increased(P＜0.05).The protein expression of S100A10 in the 3 days group was higher than that in the HIBD group after GAS treatment(P＜0.05).The immunohistochemical staining results of C3,S100A10,and RAGE in the 1 day and 3 days groups after HIBD were consistent with Western blotting results.Furthermore,the protein expressions of RAGE and TNF-α were significantly enhanced in OGD-stimulated astrocytes(P＜0.05).After GAS intervention,while the expressions of both RAGE and TNF-α decreased significantly(P＜0.05),the expressions of BDNF and IGF-1 increased significantly(P＜0.05).Conclusion With inhibiting the up-regulation of RAGE signal in astrocyte after HIBD and expressions of A1 astrocyte and neuroinflammatory factors,gastrodin can promot the expressions of A2 astrocyte and nutritional factors,which play an important role in neuro-protective effect.