Background Chronic excessive exposure to fluoride can cause damage to the central nervous system and a certain degree of learning and memory impairment. However, the associated mechanism is not yet clear and further exploration is needed. Objective Using 4D unlabelled quantitative proteomics techniques to explore differentially expressed proteins and their potential mechanisms of action in chronic excessive fluoride exposure induced brain injury. Methods Twenty-four SPF-grade adult SD rats, half male and half male, were selected and divided into a control group and a fluoride group by random number table method, with 12 rats in each group. Among them, the control group drank tap water (fluorine content<1 mg·L⁻¹), the fluoride group drank sodium fluoride solution (fluorine content 10 mg·L⁻¹), and both groups were fed with ordinary mouse feed (fluoride content<0.6 mg·kg⁻¹). After 180 d of feeding, the SD rats were weighed, and then part of the brain tissue was sampled for pathological examination by hematoxylin-eosin (HE) staining and Nissl staining. The rest of the brain tissue was frozen and stored at −80 ℃. Three brain tissue samples from each group were randomly selected for proteomics detection. Differentially expressed proteins were screened and subcellular localization analysis was performed, followed by Gene Ontology (GO) function analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, cluster analysis, and protein-protein interaction analysis. Finally, Western blotting was used to detect the expression levels of key proteins extracted from the brain tissue samples. Results After 180 d of feeding, the average weight of the rats in the fluoride group was significantly lower than that in the control group (P<0.05). The brain tissue stained with HE showed no significant morphological changes in the cerebral cortex of the fluoride treated rats, and neuron loss, irregular arrangement of neurons, eosinophilic changes, and cell body pyknosis were observed in the hippocampus. The Nissl staining results showed that the staining of neurons in the cerebral cortex and hippocampus of rats exposed to fluoride decreased (Nissl bodies decreased). The proteomics results showed that a total of 6927 proteins were identified. After screening, 206 differentially expressed proteins were obtained between the control group and the fluoride group, including 96 up-regulated proteins and 110 down-regulated proteins. The differential proteins were mainly located in cytoplasm (30.6%), nucleus (27.2%), mitochondria (13.6%), plasma membrane (13.6%), and extracellular domain (11.7%). The GO analysis results showed that differentially expressed proteins mainly participated in biological processes such as iron ion transport, regulation of dopamine neuron differentiation, and negative regulation of respiratory burst in inflammatory response, exercised molecular functions such as ferrous binding, iron oxidase activity, and cytokine activity, and were located in the smooth endoplasmic reticulum membrane, fixed components of the membrane, chloride channel complexes, and other cellular components. The KEGG significantly enriched pathways included biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments. The results of differential protein-protein interaction analysis showed that the highest connectivity was found in glucose-6-phosphate isomerase (Gpi). The expression level of Gpi in the brain tissue of the rats in the fluoride group was lower than that in the control group by Western blotting (P<0.05). Conclusion Multiple differentially expressed proteins are present in the brain tissue of rats with chronic fluorosis, and their functions are related to biosynthesis of secondary metabolites, carbon metabolism, and microbial metabolism in diverse environments; Gpi may be involved in cerebral neurological damage caused by chronic overdose fluoride exposure.

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.

Objective We aimed to evaluate the clinical efficacy of promoting blood circulation and eliminating phlegm method in preventing and treating patients with hydrocephalus after acute intracerebral hemorrhage.Methods This study included 139 patients with acute intracerebral hemorrhage who visited Affiliated Hospital of Chengdu University of Traditional Chinese Medicine,Guangyuan Hospital of Traditional Chinese Medicine,Affiliated Hospital of North Sichuan Medical College,Meishan Hospital of Traditional Chinese Medicine,and Xuyong Hospital of Traditional Chinese Medicine from September 2019 to June 2023.Patients who met the exposure factors of"using the method of promoting blood circulation and eliminating phlegm"were classified into the integrated Chinese and Western medicine cohort,while those who did not meet the exposure factors were classified into the Western medicine cohort.Clinical efficacy,incidence of hydrocephalus after intracerebral hemorrhage,sum of maximum distance between the anterior horn of the lateral ventricle and the head of the caudate nucleus(Huckman value),size of the hematoma,incidence of endpoint events,National Institutes of Health Stroke Scale(NIHSS)score,Modified Rankin Scale(mRS)score,and Barthel index score between two cohorts were compared.Results Total clinical effective rates for patients with hydrocephalus in the two cohorts were 60.0%and 75.0%,respectively.The total effective rate of the integrated Chinese and Western medicine cohort was higher than that of the Western medicine cohort(P<0.05).After 28 days of treatment,the incidence of hydrocephalus in patients in the integrated Chinese and Western medicine cohort was lower than that of the Western medicine cohort,and the Huckman value decreased compared with the Western medicine cohort(P<0.05).Compared with 24 hours after onset,both cohorts showed a reduction in hematoma size after 28 days of treatment;compared with the Western medicine cohort,patients in the integrated Chinese and Western medicine cohort had reduced hematoma size(P<0.05).After 6 months of onset,the number of deaths in the integrated Chinese and Western medicine cohort decreased compared with the Western medicine cohort(P<0.05).Compared with 28 days of treatment,the NIHSS and mRS scores of the patients in both cohorts decreased after 6 months,while the Barthel index score increased;compared with the Western medicine cohort,patients in the integrated Chinese and Western medicine cohort showed a decrease in the NIHSS and mRS scores after both 28 days of treatment and 6 months,while the Barthel index score increased(P<0.05).Conclusion Promoting blood circulation and eliminating phlegm can effectively prevent and treat hydrocephalus after intracerebral hemorrhage and does not increase the risk of bleeding within 24 hours.

Objective: To explore the relationship between the ratio of dietary vitamin A (VitA) to body weight and hypertension among children, so as to provide a reference for blood pressure control through dietary nutritional interventions and childhood hypertension prevention. Methods: Utilizing the baseline survey and followup sample data from the Healthy Children Cohort established in urban and rural areas of Chongqing from 2014 to 2019, structured quantitative dietary questionnaire and selfdesigned questionnaire were used to investigate the information of dietary intake and socioeconomic characteristics of 15 279 children, as well as blood pressure, height, weight measurement. The ratio of dietary VitA to body weight was divided into four groups based on quartiles [≤P25(Q1), >P25~P50(Q2), >P50~P75(Q3), >P75(Q4)]. Generalized linear regression models and Logistic regression models were used to analyze the correlation between ratio of dietary VitA to body weight with blood pressure levels and prevalence of hypertension. Results: The results of the 2014 baseline survey indicated that, after adjusting for confounding factors such as demographic indicators and nutritional intake, significant differences were observed in systolic blood pressure (SBP), diastolic blood pressure (DBP), and mean arterial pressure (MAP) among different groups categorized by the ratio of dietary VitA to body weight (F=157.57, 44.71, 95.92, P<0.01). The baseline ratio of dietary VitA to body weight in children exhibited a negative correlation with DBP, SBP and MAP at baseline and in 2019[baseline: β(95%CI)=-0.65(-0.89--0.42), -0.22(-0.42--0.01), -0.36(-0.56--0.16); 2019: β(95%CI)=-0.77(-1.34--0.19), -0.62(-1.21--0.02), -0.77(-1.34--0.19), P＜0.05]. Compared to Q1 group, the risk of hypertension decreased among children in Q4 at baseline and followup in 2019 [OR(95%CI)=0.63(0.49-0.81), 0.18(0.08-0.42), P<0.01]. Conclusions The ratio of dietary VitA to body weight is significantly negatively correlated with blood pressure levels among children, and dietary VitA deficiency is an independent risk factor for hypertension among children. Measures should be taken to actively adjust childrens dietary nutrition and reduce the risk of childhood hypertension.

Protein phosphorylation modification is one of the key regulatory mechanisms in cellular signaling transduction and metabolic processes. The phosphorylation state of target proteins is regulated by specific protein kinases and phosphatases, which add or remove phosphate groups. Histidine phosphorylation (pHis) plays a crucial role in both prokaryotes and eukaryotes life activities and is linked to various pathological processes. Unlike the stable phosphorylation of proteins via phosphate ester bonds, histidine phosphorylation is linked through phosphoramide bonds, making it highly sensitive to high temperatures and low pH. This sensitivity has historically impeded progress in identifying and studying histidine phosphorylation. In recent years, the development of new techniques in phosphoproteomics and the emergence of pHis-specific antibodies have promoted the identification and functional research of pHis-modified substrates. For the first time, more than 700 pHis-modified proteins have been identified in mammalian cells, and pHis-modified substrates such as focal adhesion kinase (FAK) and phosphoglycerate mutase 1 (PGAM1) have been found to promote tumor development. This article mainly reviewed the key mechanisms and functions of histidine kinases and histidine phosphatases in regulating the histidine phosphorylation of specific substrates, and highlights their significant roles in human physiological and pathological processes, aiming to provide guidance for further research into the biological functions of histidine phosphorylation.

italic>Schisandra chinensis is a traditional Chinese medicine with the functions of reinforcing deficiency, strengthening, and inducing astringency, appliable to treat the chronic cough and deficiency in breath, palpitation, and insomnia, etc. A hybrid mass spectrometry scanning strategy (high-definition data-independent/data-dependent acquisition, HDDIDDA), enabling the ion mobility separation and alternating data-independent acquisition/data-dependent acquisition, was established, which, in combination with in-house library-driven automatic peak annotation workflows facilitated by the UNIFI software, was utilized to systematically characterize the multi-classes of chemical components from S. chinensis. The use of an HSS T3 column (100 mm × 2.1 mm, 1.8 μm), 0.1% formic acid in H₂O-acetonitrile as the mobile phase running at the flow rate of 0.3 mL·min^-1, and column temperature at 35 ℃, could enable good separation of the S. chinensis components within 42 min. HDDIDDA scan in both the positive and negative ion modes was employed for data acquisition. Based on the automatic peak annotation, reference standards comparison, MS² data interpretation, and literature analysis, we were able to identify or tentatively characterize 105 compounds in the S. chinensis decoction, involving 56 terpenoids, 42 lignans, five glycosides, one organic acid, and one flavonoid. HDDIDDA scanning can improve the coverage of data acquisition and improve the accuracy of identification, while CCS prediction analysis provides the possibility to distinguish isomers by the ion mobility technology. The results provide reference for the intelligent material basis research of TCM.

Objective To assess the nutritional status of vitamin D and associated factors among adults of six ethnic minority groups native to Yunnan Province,and provide evidence for policy making.Methods Between May 2019 and August 2020,a total of 690 adults were selected from Jinuo,Bulang,Jingpo,Deang,Achang and Pumi ethnic groups according to the sex and age composition in the 6th national census.A questionnaire survey and an anthropometric examination were conducted by trained health workers,and serum 25(OH)D levels were determined with high-performance liquid chromatography-tandem mass spectrometry.Results The median of serum 25(OH)D was 28.7(P25～P75∶24.3～33.8)ng/mL,and the prevalence of vitamin D sufficiency,insufficiency and deficiency were 44.2%、47.5%and 8.3%,respectively.There were significant differences in serum 25(OH)D levels among the six ethnic groups(χ2=139.29,P<0.01).Multivariate logistic regression showed that ethnic groups living in higher latitude areas(Pumi,Jingpo,Deang,and Achang),women,and those whose BMI≥24.0 were more likely to be vitamin D insufficient or deficient.Conclusion More than half of the ethnic adults suffer from vitamin D malnutrition which also varies across ethnicities.Further surveillance and interventions among key areas and populations are needed.

Objective To investigate the anti-inflammatory effects of Bupi Yichang Pills on mice with experimental colitis and its potential mechanism of action.Methods Dextran sulfate sodium(DSS)was used to model the experimental colitis,and low-,medium-and high-doses of Bupi Yichang Pills(1.5,3.0,6.0 g·kg-1·d-1)and Mesalazine(300 mg·kg-1·d-1)were fed at the same time.Mice were observed for general behavior and weighed.Hematoxylin-eosin staining was used to observe the pathological injury of colonic tissues.qPCR and ELISA were used to detect the levels of inflammatory cytokines(TNF-α,IL-1β,IL-6,IL-10,IL-35 and TGF-β1),qPCR and Western Blot were used to detect the mRNA and protein levels of glucose transporters and glycolytic kinases.Results Low-,medium-and high-doses of Bupi Yichang Pills significantly down-regulated disease activity index in colitis mice(P＜0.05,P＜0.01).The body mass and colon length were significantly increased,while colon mass,colon mass index and unit colon mass index were significantly reduced(P＜0.05,P＜0.01),and ulcer formation and inflammatory cell infiltration in colonic tissue were significantly improved.In addition,medium-and high-doses of Bupi Yichang Pills significantly down-regulated the mRNA levels and concentrations of pro-inflammatory cytokines including TNF-α,IL-1β and IL-6(P＜0.01),while significantly up-regulated the mRNA levels and concentrations of anti-inflammatory cytokines such as IL-10,IL-35 and TGF-β1(P＜0.01).We further found that high-dose of Bupi Yichang Pills significantly down-regulated the mRNA and protein expressions of glucose transporters(Glut1,Glut2,Glut4)and glycolytic kinases(HK2,Aldolase A,PKM2)in colonic tissue(P＜0.01).Conclusions Bupi Yichang Pills effectively alleviates DSS-induced experimental colitis,and its specific mechanism of action is related to the improvement of glycolytic metabolic pathways and the regulation of inflammatory cytokine expression.

Objective To explore the clinical significance and antimicrobial resistance of group B Streptococcus(GBS)isolated from midstream urine culture,aiming to provide a basis for the diagnosis and treatment of clinical urinary tract infection(UTI).Methods Information about GBS strains isolated from midstream urine culture of in-patients and outpatient in a hospital in Nanjing from February 2020 to December 2022 were retrieved through labora-tory information system,strains with complete data were screened out.Case data,urine routine,and antimicrobial susceptibility testing results were reviewed.Results A total of 9 081 non-repetitive bacterial strains were detected from midstream urine culture,including 425 GBS strains,accounting for 4.7％,ranking sixth.Strains with incom-plete data were excluded,a total of 365 patients were included in the study.169(46.3％)were males and 196(53.7％)were females,with an average age of(55.4±15.2)years.365 patients who were detected GBS were from 17 de-partments,with the highest proportion being department of urology(n=237,64.9％).The underlying diseases of patients mainly included hypertension(n=136),diabetes(n=95),urolithiasis(n=120)and urinary tumors(n=98).211 patients underwent urological surgery,all were treated with antimicrobial agents before surgery,and 205 patients underwent indwelling urinary catheters after surgery;9 patients were detected GBS from urine during the middle and advanced stage of pregnancy.36.4％(n=133),38.9％(n=142)and 24.7％(n=90)patients had GBS colony count ≤104 CFU/mL,104-105 CFU/mL,and ≥105 CFU/mL,respectively.Patients with symptoms of UTI accounted for 24.9％(n=91),and asymptomatic bacteriuria accounted for 75.1％(n=274).The incidence of UTI symptoms in males was lower than that in females(19.5％vs 29.6％,P＜0.05).As the GBS colony count in urine culture increased,the proportion of patients with symptoms of UTI showed an upward trend(P＜0.05).On the day of urine culture,the positive rates of urine routine white blood cells,leukocyte esterase,and nitrite were 53.2％,50.1％,and 3.8％,respectively.The positive rates of urine occult blood,leukocyte esterase,white blood cells,and urine protein in patients with symptomatic UTI were all higher than those with asymptomatic bacteriuria patients(all P＜0.05).No GBS were found to be resistant to penicillin,ampicillin,vancomycin,linezolid,and tigecycline.The resistance rate to levofloxacin and moxifloxacin was about 40％,and resistance rate to tetracycline and clindamycin was over 60％.Conclusion GBS isolated from urine is more common in non-pregnant adults,and only a small percentage have symptoms of UTI.The results of urine culture and urine routine should be comprehen-sively judged based on patient's clinical symptoms and signs.GBS in urine is susceptible to multiple antimicrobial agents,and clinical medication should be adopted rationally based on antimicrobial susceptibility testing result.

AIM To study the neoflavonoids from Dalbergia cochinchinensis Pierre ex Laness and their anti-hypoxia/reoxygenation injury activities on H9c2 myocardial cells.METHODS The 70%ethanol extract from D.cochinchinensis was isolated and purified by silica gel,Sephadex LH-20 and reverse-preparative HPLC,then the structures of obtained compounds were identified by physicochemical properties and spectral data.The CCK-8 method was used to detect their activities on H9c2 cells and protective effects on hypoxia-reoxygenation injury of H9c2 cells,and their structure-activity relationship was analyzed.RESULTS Twelve compounds were isolated and identified as latifolin(1),5-O-methyllatifolin(2),mimosifoliol(3),5-O-methydalbergiphenol(4),dalbergiphenol(5),cearoin(6),2,4-dihydroxy-5-methoxy-benzophenone(7),2-hydroxy-4,5-dimethoxybenzophenone(8),melannoin(9),2,2′,5-trihydroxy-4-methoxybenzophenone(10),dalbergin(11),4-methoxydalbergione(12).The dalbergiphenols and dalbergins had little toxicity to H9c2 cells,and dalbergiphenols had strong activity against hypoxia-reoxygenation injury of H9c2 cells.CONCLUSION Compound 8 is a new natural product.Compounds 4,9 are isolated from this plant for the first time.Dalbergiphenols may be the main neoflavonoids against hypoxia-reoxygenation injury of H9c2 cells.