This study aims to investigate the ameliorating effect of Corni Fructus(CF) on the myocardial ischemic injury and the pharmacokinetic properties of characteristic components of CF. The mouse model of isoproterenol-induced myocardial ischemia was established and administrated with the aqueous extract of CF. The general efficacy of CF in ameliorating the myocardial ischemic injury was evaluated based on the cardiac histopathology and the levels of myocardial injury markers: creatine kinase isoenzyme(CK-MB) and cardiac troponin I(cTn-I). The metabolomics analysis was carried out for the heart and serum samples of mice to screen the biomarkers of CF in ameliorating the myocardial ischemic injury and then the predicted biomarkers were submitted to metabolic pathway enrichment. The pharmacokinetic analysis was performed for morroniside, loganin, and cornuside Ⅰ in mouse heart and serum samples to obtain the pharmacokinetic parameters of these components. The pharmacokinetic parameters were then integrated on the basis of self-defined weighting coefficients to simulate an integrated pharmacokinetic profile of CF iridoid glycosides in the heart and serum of the mouse model of myocardial ischemia. The results indicated that CF reduced the pathological damage to cardiac cells and tissue(hematoxylin-eosin staining) and lowered the levels of CK-MB and cTn-I in the serum of the mouse model of myocardial ischemia(P<0.01). Metabolomics analysis screed out 31 endogenous metabolites in the heart and 35 in the serum as biomarkers of CF in ameliorating the myocardial ischemic injury. These biomarkers were altered by modeling and restored by CF. Six metabolic pathways in the heart and 5 in the serum were enriched based on these metabolic markers. The main integrated pharmacokinetic parameters of CF iridoid glycosides were T_(max)=1 h, t_(1/2)=(1.52±0.05) h in the heart and T_(max)=1 h, t_(1/2)=(1.56±0.50) h in the serum. Both concentration-time curves showed a double-peak phenomenon. In conclusion, CF demonstrated the cardioprotective effect by regulating metabolic pathways such as taurine and hypotaurine metabolism, and pantothenic acid and coenzyme A biosynthesis. The integrated pharmacokinetics reflect the general pharmacokinetic properties of characteristic components in CF.
Animals ; Cornus/chemistry* ; Mice ; Metabolomics ; Drugs, Chinese Herbal/administration & dosage* ; Male ; Myocardial Ischemia/metabolism* ; Humans ; Troponin I/metabolism* ; Myocardium/pathology* ; Disease Models, Animal ; Biomarkers/metabolism* ; Creatine Kinase, MB Form/metabolism*

OBJECTIVE: This study aimed to investigate the prevalence of HIV pretreatment drug resistance (PDR) and the transmission clusters associated with PDR-related mutations in newly diagnosed, treatment-naive patients between 2020 and 2023 in Dehong prefecture, Yunnan province, China. METHODS: Demographic information and plasma samples were collected from study participants. PDR was assessed using the Stanford HIV Drug Resistance Database. The Tamura-Nei 93 model within HIV-TRACE was employed to compute pairwise matches with a genetic distance of 0.015 substitutions per site. RESULTS: Among 948 treatment-naive individuals with eligible sequences, 36 HIV subtypes were identified, with unique recombinant forms (URFs) being the most prevalent (18.8%, 178/948). The overall prevalence of PDR was 12.4% (118/948), and resistance to non-nucleotide reverse transcriptase inhibitors (NNRTIs), nucleotide reverse transcriptase inhibitors (NRTIs), and protease inhibitors (PIs) was 10.7%, 1.3%, and 1.6%, respectively. A total of 91 clusters were identified, among which eight showed evidence of PDR strain transmission. The largest PDR-associated cluster consisted of six CRF01_AE drug-resistant strains carrying K103N and V179T mutations; five of these individuals had initial CD4+ cell counts < 200 cells/μL. CONCLUSION The distribution of HIV subtypes in Dehong is diverse and complex. PDR was moderately prevalent (12.4%) between 2020 and 2023. Evidence of transmission of CRF01_AE strains carrying K103N and V179T mutations was found. Routine surveillance of PDR and the strengthening of control measures are essential to limit the spread of drug-resistance HIV strains.
Humans ; HIV Infections/virology* ; China/epidemiology* ; Drug Resistance, Viral ; Male ; Adult ; Female ; Middle Aged ; HIV-1/genetics* ; Anti-HIV Agents/therapeutic use* ; Myanmar/epidemiology* ; Young Adult ; Prevalence ; Adolescent ; Mutation

Objective:To observe the relationship between preoperative controlling nutritional status(CONUT)score and cognitive impairment,as well as short-term prognosis after intravenous thrombolysis(IVT)in patients with acute ischemic stroke(AIS).Methods:187 patients with AIS who were admitted to Shandong Provincial Third Hospital from January 2023 to May 2024 were selected,they were divided into non cognitive impairment group(n=106)and cognitive impairment group(n=81)based on whether cognitive impairment occurred,they were divided into poor prognosis group(n=58 cases)and good prognosis group(n=129 cases)according to the prognosis.Preoperative CONUT scores of patients with AIS for different cognitive impairments and prognoses were compared,correlation was analyzed by Spearman rank correlation,influencing factors were analyzed by multivariate logistic regression model.Results:Preoperative CONUT score in the cognitive impairment group was higher than that in the non cognitive impairment group(P＜0.05).Preoperative CONUT score in the poor prognosis group was higher than that in the good prognosis group(P＜0.05).Spearman rank correlation test results showed that,preoperative CONUT score was positively correlated with cognitive impairment and short-term prognosis after IVT(P＜0.05).Cognitive impairment were associated with age,concomitant hypertension,baseline national institutes of health stroke scale(NIHSS)score,and 25 hydroxyvitamin D3[25-(OH)2D3](P＜0.05).Age increase,concomitant hypertension,baseline NIHSS score increase,25-(OH)2D3 decrease,preoperative CONUT score increase were risk factors for cognitive impairment in patients with AIS(P＜0.05).Conclusion:Preoperative CONUT score increase is positively correlated with cognitive impairment and short-term prognosis after IVT.Meanwhile,age increase,concomitant hypertension,baseline NIHSS score increase,25-(OH)2D3 decrease,preoperative CONUT score increase are risk factors for cognitive impairment in patient with AIS.

Aging is comprehensively influenced by multiple fac-tors such as internal genes,cellular metabolism,external envi-ronment,and lifestyle habits.Among them,epigenetic regula-tion plays a core role.Epigenetic modifications,including DNA methylation,histone modification,heterochromatin remodeling,and non-coding RNA regulation,act in concert with the three-di-mensional genome architecture to precisely regulate gene expres-sion.This review elaborates on the factors influencing epigenetic regulation,as well as the mechanisms of how epigenetics affects the occurrence of organismal aging and the corresponding inter-vention strategies,providing relevant insights for uncovering the mechanisms of aging and preventing/treating aging-related disea-ses.

Disorders of mitochondrial dynamics are closely re-lated to the development of neurodegenerative diseases(NDDs),which are characterized by the loss of neurons in brain and spinal cord cells.Diseases such as Alzheimer's disease,Parkinson's disease,Huntington's disease,and so on are in-volved in NDDs,which are often accompanied by disorders of mi-tochondrial dynamics during the development of these diseases.Recently,the researches on mitochondrial dynamics to study the pathogenesis of neurodegenerative diseases and related medica-tion innovation have garnered significant attention.This review focuses on the fundamental molecular processes of mitochondrial dynamics,such as mitochondrial transport,mitochondrial autoph-agy,and mitochondrial fission-fusion,and their molecular mecha-nisms in the pathogenesis of NDDs.It also outlines the recent research progress on Chinese materia medica and natural prod-ucts in ameliorating NDDs by modulating mitochondrial dynam-ics.The aim is to establish a foundation for researching innova-tive traditional Chinese medicine for NDDs-related diseases by focusing on mitochondrial dynamics.

Aging is comprehensively influenced by multiple fac-tors such as internal genes,cellular metabolism,external envi-ronment,and lifestyle habits.Among them,epigenetic regula-tion plays a core role.Epigenetic modifications,including DNA methylation,histone modification,heterochromatin remodeling,and non-coding RNA regulation,act in concert with the three-di-mensional genome architecture to precisely regulate gene expres-sion.This review elaborates on the factors influencing epigenetic regulation,as well as the mechanisms of how epigenetics affects the occurrence of organismal aging and the corresponding inter-vention strategies,providing relevant insights for uncovering the mechanisms of aging and preventing/treating aging-related disea-ses.

Objective:To observe the relationship between preoperative controlling nutritional status(CONUT)score and cognitive impairment,as well as short-term prognosis after intravenous thrombolysis(IVT)in patients with acute ischemic stroke(AIS).Methods:187 patients with AIS who were admitted to Shandong Provincial Third Hospital from January 2023 to May 2024 were selected,they were divided into non cognitive impairment group(n=106)and cognitive impairment group(n=81)based on whether cognitive impairment occurred,they were divided into poor prognosis group(n=58 cases)and good prognosis group(n=129 cases)according to the prognosis.Preoperative CONUT scores of patients with AIS for different cognitive impairments and prognoses were compared,correlation was analyzed by Spearman rank correlation,influencing factors were analyzed by multivariate logistic regression model.Results:Preoperative CONUT score in the cognitive impairment group was higher than that in the non cognitive impairment group(P＜0.05).Preoperative CONUT score in the poor prognosis group was higher than that in the good prognosis group(P＜0.05).Spearman rank correlation test results showed that,preoperative CONUT score was positively correlated with cognitive impairment and short-term prognosis after IVT(P＜0.05).Cognitive impairment were associated with age,concomitant hypertension,baseline national institutes of health stroke scale(NIHSS)score,and 25 hydroxyvitamin D3[25-(OH)2D3](P＜0.05).Age increase,concomitant hypertension,baseline NIHSS score increase,25-(OH)2D3 decrease,preoperative CONUT score increase were risk factors for cognitive impairment in patients with AIS(P＜0.05).Conclusion:Preoperative CONUT score increase is positively correlated with cognitive impairment and short-term prognosis after IVT.Meanwhile,age increase,concomitant hypertension,baseline NIHSS score increase,25-(OH)2D3 decrease,preoperative CONUT score increase are risk factors for cognitive impairment in patient with AIS.

Disorders of mitochondrial dynamics are closely re-lated to the development of neurodegenerative diseases(NDDs),which are characterized by the loss of neurons in brain and spinal cord cells.Diseases such as Alzheimer's disease,Parkinson's disease,Huntington's disease,and so on are in-volved in NDDs,which are often accompanied by disorders of mi-tochondrial dynamics during the development of these diseases.Recently,the researches on mitochondrial dynamics to study the pathogenesis of neurodegenerative diseases and related medica-tion innovation have garnered significant attention.This review focuses on the fundamental molecular processes of mitochondrial dynamics,such as mitochondrial transport,mitochondrial autoph-agy,and mitochondrial fission-fusion,and their molecular mecha-nisms in the pathogenesis of NDDs.It also outlines the recent research progress on Chinese materia medica and natural prod-ucts in ameliorating NDDs by modulating mitochondrial dynam-ics.The aim is to establish a foundation for researching innova-tive traditional Chinese medicine for NDDs-related diseases by focusing on mitochondrial dynamics.

Objective To establish the pharmacokinetic model of linezolid in neonates,and to optimize the administration regimen. Methods A prospective study was conducted among 64 neonates with sepsis who received linezolid as anti-infective therapy,and liquid chromatography-tandem mass spectrometry was used to measure the plasma concentration of the drug. Clinical data were collected,and nonlinear mixed effects modeling was used to establish a population pharmacokinetic (PPK) model. Monte Carlo simulation and evaluation was performed for the optimal administration regimen of children with different features. Results The pharmacokinetic properties of linezolid in neonates could be described by a single-compartment model with primary elimination,and the population typical values for apparent volume of distribution and clearance rate were 0.79 L and 0.34 L/h,respectively. The results of goodness of fit,visualization verification,and the Bootstrap method showed that the model was robust with reliable results of parameter estimation and prediction. Monte Carlo simulation results showed that the optimal administration regimen for linezolid in neonates was as follows:6 mg/kg,q8h,at 28 weeks of gestational age (GA);8 mg/kg,q8h,at 32 weeks of GA;9 mg/kg,q8h,at 34-37 weeks of GA;11 mg/kg,q8h,at 40 weeks of GA. Conclusions The PPK model established in this study can provide a reference for individual administration of linezolid in neonates. GA and body weight at the time of administration are significant influencing factors for the clearance rate of linezolid in neonates.

Objective To monitor the antifungal resistance of clinical isolates of Candida spp.in the East China region.Methods MALDI-TOF MS or molecular methods were used to re-identify the strains collected from January 2018 to December 2022.Antifungal susceptibility testing was performed using the broth microdilution method.The susceptibility test results were interpreted according to the breakpoints of 2022 Clinical and Laboratory Standards Institute(CLSI)documents M27 M44s-Ed3 and M57s-Ed4.Results A total of 3 026 strains of Candida were collected,65.33％of which were isolated from sterile body sites,mainly from blood(38.86％)and pleural effusion/ascites(10.21％).The predominant species of Candida were Candida albicans(44.51％),followed by Candida parapsilosis complex(19.46％),Candida tropicalis(13.98％),Candida glabrata(10.34％),and other Candida species(0.79％).Candida albicans showed overall high susceptibility rates to the 10 antifungal drugs tested(the lowest rate being 93.62％).Only 2.97％of the strains showed dose-dependent susceptibility(SDD)to fluconazole.Candida parapsilosis complex had a SDD rate of 2.61％and a resistance rate of 9.42％to fluconazole,and susceptibility rates above 90％to other drugs.Candida glabrata had a SDD rate of 92.01％and a resistance rate of 7.99％to fluconazole,resistance rates of 32.27％and 48.24％to posaconazole and voriconazole non-wild-type strains(NWT),respectively,and susceptibility rates above 90％to other drugs.Candida tropicalis had resistance rates of 29.55％and 26.24％to fluconazole and voriconazole,respectively,resistance rates of 76.60％and 21.99％to posaconazole and echinocandins non-wild-type strains(NWT),and a resistance rate of 2.36％to echinocandins.Conclusions The prevalence and species distribution of Candida spp.in the East China region are consistent with previous domestic and international reports.Candida glabrata exhibits certain degree of resistance to fluconazole,while Candida tropicalis demonstrates higher resistance to triazole drugs.Additionally,echinocandins resistance has emerged in Candida albicans,Candida glabrata,Candida tropicalis,and Candida parapsilosis.