This paper aimed to systematically evaluate the effects of hypoxic training at different fraction of inspired oxygen (FiO₂) on body composition, glucose metabolism, and lipid metabolism in obese individuals, and to determine the optimal oxygen concentration range to provide scientific evidence for personalized and precise hypoxic exercise prescriptions. A systematic search was conducted in the Cochrane Library, PubMed, Web of Science, Embase, and CNKI databases for randomized controlled trials and pre-post intervention studies published up to March 31, 2025, involving hypoxic training interventions in obese populations. Meta-analysis was performed using RevMan 5.4 software to assess the effects of different fraction of inspired oxygen (FiO₂≤14% vs. FiO₂>14%) on BMI, body fat percentage, waist circumference, fasting blood glucose, insulin, HOMA-IR, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C), with subgroup analyses based on oxygen concentration. A total of 22 studies involving 292 participants were included. Meta-analysis showed that hypoxic training significantly reduced BMI (mean difference (MD)=-2.29,95%CI: -3.42 to -1.17, P<0.000 1), body fat percentage (MD=-2.32, 95%CI: -3.16 to -1.47, P<0.001), waist circumference (MD=-3.79, 95%CI: -6.73 to -0.85, P=0.01), fasting blood glucose (MD=-3.58, 95%CI: -6.23 to -0.93, P=0.008), insulin (MD=-1.60, 95%CI: -2.98 to -0.22, P=0.02), TG (MD=-0.18, 95%CI: -0.25 to -0.12, P<0.001), and LDL-C (MD=-0.25, 95%CI: -0.39 to -0.11, P=0.000 3). Greater improvements were observed under moderate hypoxic conditions with FiO₂>14%. Changes in HOMA-IR (MD=-0.74, 95%CI: -1.52 to 0.04,P=0.06) and HDL-C (MD=-0.09, 95%CI: -0.21 to 0.02, P=0.11) were not statistically significant. Hypoxic training can significantly improve body composition, glucose metabolism, and lipid metabolism indicators in obese individuals, with greater benefits observed under moderate hypoxia (FiO>14%). As a key parameter in hypoxic exercise interventions, the precise setting of oxygen concentration is crucial for optimizing intervention outcomes.

Anti-tumor traditional Chinese medicine has a long history of clinic application, in which the star molecules have always been the hotspot of modern drug research, but they are limited by the solubility, stability, targeting, bioactivity or toxicity of the monomer components of traditional Chinese medicine anti-tumor star molecules and other pharmacokinetic problems, which hinders the traditional Chinese medicine anti-tumor star molecules for further clinical translation and application. Currently, the nanosystems prepared by supramolecular technologies such as molecular self-assembly and nanomaterial encapsulation have broader application prospects in improving the anti-tumor effect of active components of traditional Chinese medicine, which has attracted extensive attention from scholars at home and abroad. In this paper, we systematically review the research progress in preparation of supramolecular nano-systems from anti-tumor star molecule of traditional Chinese medicine, and summarize the two major categories and ten small classes of carrier-free and carrier-based supramolecular nanosystems and their research cases, and the future development direction is put forward. The purpose of this paper is to provide reference for the research and clinical transformation of using supramolecular technology to improve the clinical application of anti-tumor star molecule of traditional Chinese medicine.

Three-dimensional graphene hydrogel(3DGH)was successfully prepared through a hydrothermal method,followed by its composition with gold nanoparticles(AuNPs)to construct a highly sensitive Au/3DGH graphene electrochemical transistor(GECT)dopamine(DA)sensor.AuNPs are efficient electrocatalytic materials.However,their tendency to aggregate during electrodeposition hinds the practical application.The porous and interconnected network structure of 3DGH provided abundant attachment sites,effectively preventing AuNPs aggregation.By modifying the sensor's gate with Au/3DGH,the excellent electrocatalytic performance of Au/3DGH towards DA and the high sensitivity of GECT were utilized to achieve highly sensitive detection of DA.The sensor exhibited a low detection limit of 20 nmol/L and a linear range of 20 nmol/L to 2.5 mmol/L.Remarkably,the sensor showed high sensitivity,excellent selectivity and strong stability,and hold great potnetial in highly sensitive portable detection of DA in disease prevention and clinical monitoring.

Objective To investigate the incidence rate,clinical characteristics,and prognosis of neonatal stroke in Shenzhen,China.Methods Led by Shenzhen Children's Hospital,the Shenzhen Neonatal Data Collaboration Network organized 21 institutions to collect 36 cases of neonatal stroke from January 2020 to December 2022.The incidence,clinical characteristics,treatment,and prognosis of neonatal stroke in Shenzhen were analyzed.Results The incidence rate of neonatal stroke in 21 hospitals from 2020 to 2022 was 1/15 137,1/6 060,and 1/7 704,respectively.Ischemic stroke accounted for 75％(27/36);boys accounted for 64％(23/36).Among the 36 neonates,31(86％)had disease onset within 3 days after birth,and 19(53％)had convulsion as the initial presentation.Cerebral MRI showed that 22 neonates(61％)had left cerebral infarction and 13(36％)had basal ganglia infarction.Magnetic resonance angiography was performed for 12 neonates,among whom 9(75％)had involvement of the middle cerebral artery.Electroencephalography was performed for 29 neonates,with sharp waves in 21 neonates(72％)and seizures in 10 neonates(34％).Symptomatic/supportive treatment varied across different hospitals.Neonatal Behavioral Neurological Assessment was performed for 12 neonates(33％,12/36),with a mean score of(32±4)points.The prognosis of 27 neonates was followed up to around 12 months of age,with 44％(12/27)of the neonates having a good prognosis.Conclusions Ischemic stroke is the main type of neonatal stroke,often with convulsions as the initial presentation,involvement of the middle cerebral artery,sharp waves on electroencephalography,and a relatively low neurodevelopment score.Symptomatic/supportive treatment is the main treatment method,and some neonates tend to have a poor prognosis.

Pharmacokinetics of traditional Chinese medicine(TCM)is a discipline that adopts pharmacokinetic research methods and techniques under the guidance of TCM theories to elucidate the dynamic changes in the absorption,distribution,metabolism and excretion of active ingredients,active sites,single-flavour Chinese medicinal and compounded formulas of TCM in vivo.However,the sources and components of TCM are complex,and the pharmacodynamic substances and mechanisms of action of the majority of TCM are not yet clear,so the pharmacokinetic study of TCM is later than that of chemical medicines,and is far more complex than that of chemical medicines,and its development also confronts with challenges.The pharmacokinetic study of TCM originated in the 1950s and has experienced more than 70 years of development from the initial in vivo study of a single active ingredient,to the pharmacokinetic and pharmacodynamic study of active ingredients,to the pharmacokinetic study of compound and multi-component of Chinese medicine.In recent years,with the help of advanced extraction,separation and analysis technologies,gene-editing animals and cell models,multi-omics technologies,protein purification and structure analysis technologies,and artificial intelligence,etc.,the pharmacokinetics of TCM has been substantially applied in revealing and elucidating the pharmacodynamic substances and mechanisms of action of Chinese medicines,research and development of new drugs of TCM,scientific and technological upgrading of large varieties of Chinese patent medicines,as well as guiding the rational use of medicines in clinics.Pharmacokinetic studies of TCM have made remarkable breakthroughs and significant development in theory,methodology,technology and application.In this paper,the history of the development of pharmacokinetics of TCM and the progress of cutting-edge research was reviewed,with the aim of providing ideas and references for the pharmacokinetics of TCM and related research.

Objective To develop a matrix metalloproteinase(MMP)-responsive hyaluronic acid(HA)-based controlled-release material for brain-derived neurotrophic factor(BDNF)to provide a novel therapeutic strategy for intervention and repair of traumatic brain injury(TBI).Methods HA was modified with amination,followed by condensation with Suflo-SMCC carboxyl group to form amide,and then linked with glutathione(GSH)to synthesize HA-GSH.The recombinant glutathione S-transferase(GST)-tissue inhibitor of metalloproteinase(TIMP)-BDNF(GST-TIMP-BDNF)expression plasmid was constructed using molecular cloning technique with double enzyme digestion by Bam H Ⅰ and Eco R Ⅰ.The recombinant GST-TIMP-BDNF protein was expressed in the Escherichia coli prokaryotic expression system,and purified by ion exchange chromatography,confirmed by Western blotting.MMP diluents were supplemented with PBS,MMP inhibitor marimastat,and varing concentrations(0.4,0.6,0.8 mg/ml)of GST-TIMP-BDNF or GST-BDNF.MMP-2 activity was analyzed using an MMP activity detection kit to evaluate the inhibitory effect of the recombinant protein on MMP.Primary rat neurons were extracted and cultured to establish an iron death model induced by RSL3.The effect of recombinant protein GST-TIMP-BDNF on neuronal injury was detected by immunofluorescence staining.Results MRI hydrogen spectrum identification confirmed the successful synthesis of HA-GSH.Western blotting results showed the successful expression of the recombinant protein GST-TIMP-BDNF containing the GST tag using the E.coli prokaryotic expression system.MMP activity detection results indicated that the recombinant protein GST-TIMP-BDNF had a superior inhibitory effect on MMP-2 activity compared to GST-BDNF(P<0.05).Immunofluorescence staining results showed a significant increase in fluorescence intensity in rat neurons treated with GST-TIMP-BDNF after RSL3 induction(P<0.05).Conclusion A MMP-responsive HA-based BDNF controlled-release material has been successfully developed,exhibiting a protective effect on neuron damage.

This study was aimed at exploring the epidemiological characteristics of plague,and the evolutionary relation-ships among the isolated plague strains in the Yunnan border area,to provide clues for further studying epidemic causes and ep-idemiological patterns.Plague epidemic data in the border area during the second epidemic period(1982-2007)were collected and analyzed with descriptive epidemiological methods.Whole genome sequences of 262 strains of Yersinia pestis in the border area were obtained for phylogenetic analysis.Plague outbreaks occurred in 17 counties(cities)among 25 border counties(cit-ies);a total of 552 epidemic foci and 123 human cases were identified.The 1.ORI2,1.ORI3,1.IN3,2.ANT and 2.MED geno-types were identified among Yersinia pestis isolated from the Yunnan border area,among which the 1.ORI2 population was dominant.A total of 258 strains of Yersinia pestis from the 1.OR12 population belonged to four subclusters.The Myanmar and Vietnam clade was embedded within the Yunnan clade in the overall phylogeny.The above results indicated that during the sec-ond period of the epidemic,the intensity of plague epidemics in Yunnan's border areas was high,showing a trend of devel-opment from west to south and east.Our findings indicated a risk of cross-border transmission of plague between Yunnan and neighboring countries;therefore,the surveillance,pre-vention,and control of plague in border areas should be strengthened.

This study aimed to determine the drug resistance phenotype and genetic characteristics of Listeria monocytogenes ST5 LK100 isolated from a neonate,which provided a basis for the diagnosis and treatment of L.monocyto-genes infection and to enhance the understanding of the genomic characteristics of this strain.A suspected L.monocytogenes strain was isolated from the gastric juice sample of an infected neonate,and identified with a VITEK2 Compact automatic mi-crobial identification instrument and 16S RNA sequencing.Five drug sensitivity tests were conducted on the identified strain with the E-test method.Additionally,the whole genome of the strain was sequenced using a third-generation sequencing plat-form.The antibiotic resistance elements of the strain were identified by BlastN with the CARD antibiotic resistance gene data-base.The multilocus sequence typing(MLST),serotyping,and virulence genes of the strain was determined by Pasteur da-tabase,the virulence gene distribution was analyzed using the virulence analysis website.The prophages of the strain were predicted and annotate by PHASTER online website.The strain(LK100)isolated from the neonate was identified as L.monocytogenes.This strain was sensitive to penicillin,ampicil-lin,meropenem,erythromycin,and trimethoprim-sulfame-thoxazole antibiotics.The MLST type and serotype was ST5 and 1/2b-3b,respectively.The total length of the chromoso-mal genome of LK100 was 3 032 582 bp with a GC content of 37.91％,and it contained a complete circular plasmid with a se-quence length of 52 822 bp.The strain LK100 carried complete InlA protein,LIPI-1 pathogenicity island,SSI-1 stress survival island,and an LGI2 genomic island.The intrinsic antibiotic resistance genes were mainly located on the chromosome.Five prophage sequences were predicted in the LK100 genome.This study identified a strain of ST5 L.monocytogenes LK100 from an infected neonate and characterized its genome and antibiotic sensitivity,laying the foundation for further research on ST5 L.monocytogenes.

Objective:To detect the pharmacokinetic(PK)parameters of coagulation factor Ⅷ(FⅧ)in adult patients with severe hemophilia A,identify the potential factors influencing FⅧ PK,and optimize the use of FⅧ in individual prophylaxis regimens.Methods:PK characteristics of FⅧ were studied in a total of 23 severe hemophilia A adults.The correlation of patients'characteristics including age,von Willebrand factor antigen(vWF:Ag),blood group,weight,body mass index(BMI)and FⅧ genotype,with FⅧ PK were evaluated.Individual prophylaxis regimens were given based on FⅧ PK parameters.Results:The mean terminal half-life(t1/2)of FⅧ was 20.6±9.3 h,ranged from 11.47 h to 30.12 h.The age(r=0.580)and vWF:Ag(r=0.814)were significantly positively correlated with t1/2 of FⅧ.The mean area under the plasma concentration curve(AUC)of FⅧ was 913±399(328-1 878)IU h/dl,and the AUC of FⅧ was positively correlated with age(r=0.557)and vWF:Ag(r=0.784).The mean residence time(MRT)of FⅧ was 24.7±12.4(13.2-62.2)h,and the MRT of FⅧ was positively correlated with age(r=0.664)and vWF:Ag(r=0.868).The mean in vivo recovery(IVR)of FⅧ was 2.59±0.888(1.5-4.29)IU/dl per IU/kg,the mean clearance(CL)of FⅧ was 3±1.58(0.97-7.18)ml/(kg·h),and there was no significant correlation of IVR and CL with age and vWF:Ag.According to the individual PK parameters,ultra low-dose,low-dose and moderate-dose FⅧ were applied to 15,6,2 adults patients with severe hemophilia A for prophylaxis,respectively.Conclusion:There are significant individual differences in the FⅧ half-life of adult patients with severe hemophilia A.The older the patient,the higher the vWF:Ag level,and the longer the FⅧ half-life.Individual administration is required based on the FⅧ PK parameters to optimize prophylaxis treatment.

Background: Diabetes-induced cardiac fibrosis is one of the main mechanisms of diabetic cardiomyopathy. As a common histone methyltransferase, enhancer of zeste homolog 2 (EZH2) has been implicated in fibrosis progression in multiple organs. However, the mechanism of EZH2 in diabetic myocardial fibrosis has not been clarified. Methods: In the current study, rat and mouse diabetic model were established, the left ventricular function of rat and mouse were evaluated by echocardiography and the fibrosis of rat ventricle was evaluated by Masson staining. Primary rat ventricular fibroblasts were cultured and stimulated with high glucose (HG) in vitro. The expression of histone H3 lysine 27 (H3K27) trimethylation, EZH2, and myocardial fibrosis proteins were assayed. Results: In STZ-induced diabetic ventricular tissues and HG-induced primary ventricular fibroblasts in vitro, H3K27 trimethylation was increased and the phosphorylation of EZH2 was reduced. Inhibition of EZH2 with GSK126 suppressed the activation, differentiation, and migration of cardiac fibroblasts as well as the overexpression of the fibrotic proteins induced by HG. Mechanical study demonstrated that HG reduced phosphorylation of EZH2 on Thr311 by inactivating AMP-activated protein kinase (AMPK), which transcriptionally inhibited peroxisome proliferator-activated receptor γ (PPAR-γ) expression to promote the fibroblasts activation and differentiation. Conclusion Our data revealed an AMPK/EZH2/PPAR-γ signal pathway is involved in HG-induced cardiac fibrosis.