Objective To investigate the prevalence of tension-type headache(TTH)in children and adolescents aged 0-19 years globally in 1990-2021,and to provide a basis for the prevention and treatment of TTH.Methods Based on the Global Burden of Disease Study data,the age-standardized prevalence distribution of TTH and its changing trend were analyzed among the children and adolescents aged 0-19 years,with different sexes,age groups,sociodemographic index(SDI)regions and countries/territories.Results The age-standardized prevalence rate(ASPR)of TTH in children and adolescents aged 0-19 globally in 2021 was 17 339.89/100 000,which was increased by 1.73%since 1990.The ASPR in females was slightly higher than that in males(1990:17 707.65/100 000 vs 16 403.78/100 000;2021:17 946.29/100 000 vs 16 763.09/100 000).The ASPR in adolescence was significantly higher than that in school-aged and preschool periods(1990:27 672.04/100 000 vs 10 134.16/100 000;2021:28 239.04/100 000 vs 10 059.39/100 000).Regions with high SDI exhibited a higher ASPR than the other regions,with significant differences in prevalence rates across different countries.From 1990 to 2021,there was a slight increase in global ASPR,with an average annual percentage change(AAPC)of 0.06%.Females experienced a smaller increase than males based on AAPC(0.04%vs 0.07%).There was reduction in ASPR in preschool and school-aged groups,with an AAPC of-0.02%,while there was a significant increase in ASPR in adolescence,with an AAPC of 0.07%.ASPR decreased in regions with low-middle and low levels of SDI,with an AAPC of-0.02%and-0.04%,respectively,while it increased in regions with middle SDI,with an AAPC of 0.24%.Conclusions There is a consistent increase in the ASPR of TTH in children and adolescents aged 0-19 years globally,with significant differences across sexes,age groups,SDI regions and countries/territories.

The clinical tumor therapy was greatly challenged due to the complex characteristics of tumor microenvironment, however, which also provide arena for novel therapeutic strategies. In this study, poly(2-ethyl-2-oxazoline)-poly(lactic acid)-SS-poly(β-amino ester (PEOz-PLA-SS-PBAE) triblock copolymers with pH and GSH double response were synthesized, polymer micelles were prepared by thin film hydration method for loading of silybin to improve its antitumor activity. The critical micelle concentration was determined by pyrene fluorescence method as 1.8 μg·mL^-1. The particle size was 155.30 ± 1.80 nm as determined by dynamic light scattering, with polydispersity index of 0.168 ± 0.004. The drug loading and entrapment efficiency of the micelles were determined by HPLC as (5.48 ± 0.04)% and (68.52 ± 0.48)%, respectively. The in vitro drug release profiles showed that the micelles have low pH sensitivity and high GSH responsiveness, and exhibited sustained release profiles. The good biocompatibility of the material was proved by measuring the hemolysis rate and cytotoxicity of the blank micelle. The cytotoxicity and apoptosis rate of tumor cells showed that the drug loaded PEOz-PLA-SS-PBAE micelles had significant inhibitory effect and apoptosis-inducing effect on MDA-MB-231 cells. The results of wounding healing assay and Transwell invasion test showed that the drug loaded PEOz-PLA-SS-PBAE micelles could significantly inhibit the metastasis of MDA-MB-231 cells. The PEOz-PLA-SS-PBAE drug-loaded micelles prepared in this study have good inhibitory effect on tumor growth and anti-tumor metastasis in vitro, which lays the foundation for the further application of silybin.

OBJECTIVE: This study investigated the effects of bis (2-butoxyethyl) phthalate (BBOP) on the onset of male puberty by affecting Leydig cell development in rats. METHODS: Thirty 35-day-old male Sprague-Dawley rats were randomly allocated to five groups mg/kg bw per day that were gavaged for 21 days with BBOP at 0, 10, 100, 250, or 500 mg/kg bw per day. The hormone profiles; Leydig cell morphological metrics; mRNA and protein levels; oxidative stress; and AKT, mTOR, ERK1/2, and GSK3β pathways were assessed. RESULTS: BBOP at 250 and/or 500 mg/kg bw per day decreased serum testosterone, luteinizing hormone, and follicle-stimulating hormone levels mg/kg bw per day (P < 0.05). BBOP at 500 mg/kg bw per day decreased Leydig cell number mg/kg bw per day and downregulated Cyp11a1, Insl3, Hsd11b1, and Dhh in the testes, and Lhb and Fshb mRNAs in the pituitary gland (P < 0.05). The malondialdehyde content in the testis significantly increased, while Sod1 and Sod2 mRNAs were markedly down-regulated, by BBOP treatment at 250-500 mg/kg bw per day (P < 0.05). Furthermore, BBOP at 500 mg/kg bw per day decreased AKT1/AKT2, mTOR, and ERK1/2 phosphorylation, and GSK3β and SIRT1 levels mg/kg bw per day (P < 0.05). Finally, BBOP at 100 or 500 μmol/L induced ROS and apoptosis in Leydig cells after 24 h of treatment in vitro (P < 0.05). CONCLUSION: BBOP delays puberty onset by increasing oxidative stress and apoptosis in Leydig cells in rats. UNLABELLED The graphical abstract is available on the website www.besjournal.com.
Rats ; Male ; Animals ; Leydig Cells/metabolism* ; Testosterone ; Glycogen Synthase Kinase 3 beta/pharmacology* ; Rats, Sprague-Dawley ; Sexual Maturation ; Testis ; Oxidative Stress ; TOR Serine-Threonine Kinases/metabolism* ; Apoptosis

OBJECTIVE: To assess changes of nutritional status by comprehensive nutrition assessment including nutritional risk screening, dietary assessment, blood biochemical index, and body composition in acute leukemia patients who had undergone chemotherapy. METHODS: A total of 169 patients with acute leukemia treated at The First Affiliated Hospital of Soochow University from June 2018 to August 2019 were recruited for this study. Before and after chemotherapy, the NRS-2002 and PG-SGA scales, dietary intake, blood biochemical index and body composition were evaluated to compare the changes of nutritional status. RESULTS: NRS-2002 score and PG-SGA score after chemotherapy were significantly increased than those before chemotherapy (P<0.001). Many patients had insufficient nutritional intake during chemotherapy, and the dietary intake score of patients with induction chemotherapy was significantly lower than that of patients with consolidation chemotherapy (P=0.043). The results of multivariate analysis showed that induction chemotherapy was the independent risk factor for the increase of PG-SGA scores and the decrease of dietary intake (all P<0.05). After chemotherapy, the white blood cell count, hemoglobin, and platelet count were significantly decreased (P<0.001), the prealbumin was significantly increased (P<0.001), and the blood glucose was increased (P=0.04), but albumin was not significantly changed. The weight, body mass index, fat-free mass, skeletal muscle mass and intracellular water were all significantly decreased (P<0.001), and visceral fat area was increased significantly after chemotherapy (P<0.05), especially in newly-diagnosed acute lymphoblastic leukemia patients after the induction of chemotherapy. CONCLUSION The nutritional status of patients with acute leukemia has undergone significant changes after chemotherapy. A single indicator has limited significance for nutritional status assessment. Comprehensive assessment of nutritional status by multiple tools is worthy of clinical application.
Acute Disease ; Humans ; Induction Chemotherapy/methods* ; Leukemia, Myeloid, Acute/drug therapy* ; Nutrition Assessment ; Nutritional Status ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/drug therapy*

Angelicae Sinensis Radix (Danggui) and Ligusticum Chuanxiong Rhizoma (Chuan Xiong) herb-pair (DC) have been frequently used in Traditional Chinese medicine (TCM) prescriptions for hundreds of years to prevent vascular diseases and alleviate pain. However, the mechanism of DC herb-pair in the prevention of liver fibrosis development was still unclear. In the present study, the effects and mechanisms of DC herb-pair on liver fibrosis were examined using network pharmacology and mouse fibrotic model. Based on the network pharmacological analysis of 13 bioactive ingredients found in DC, a total of 46 targets and 71 pathways related to anti-fibrosis effects were obtained, which was associated with mitogen-activated protein kinase (MAPK) signal pathway, hepatic inflammation and fibrotic response. Furthermore, this hypothesis was verified using carbon tetrachloride (CCl

Myocardial ischemia-reperfusion injury (MIRI) is one of the most difficulties in the studies of cardiovascular diseases, and excessive reactive oxygen species (ROS) accumulation in cells is the main cause of it. Reducing ROS level by antioxidant drugs to protect cardiomyocytes is being the spotlight on MIRI treatment. In this review, the research progress of antioxidant drugs in myocardial ischemia-reperfusion injury in recent years was summarized.

OBJECTIVE: To study the distribution and drug resistance of pathogens causing periprosthetic infections after hip and knee arthroplasty, and to formulate prevention and treatment strategies for drug-resistant bacteria. METHODS: The data of 146 cases of periprosthetic infection after primary hip and knee arthroplasty from 2010 to 2015 were collected, including 111 cases of periprosthetic infection after hip arthroplasty and 35 cases of periprosthetic infection after knee arthroplasty. The culture positive rate, pathogenic bacteria composition and drug resistance rate were counted over the years, and the change trend of pathogen distribution and drug resistance was analyzed. RESULTS: One hundredand eight strains of pathogenic bacteria were detected in 146 cases, and the positive rate of culture was 73.97%. Gram positive bacteria accounted for 55.48%, Staphylococcus epidermidis and Staphylococcus aureus accounted for 25.34% and 15.07% respectively. Gram negative bacteria accounted for 13.01%, including Enterobacter cloacae, Pseudomonas aeruginosa and Escherichia coli. There were 4 cases of Mycobacterium tuberculosis infection and mixed infection. The results of culture over the years showed that the constituent ratio of Gram positive bacteria had an increasing trend, fluctuating from 39.13% to 76.47%. The results of drug sensitivity showed that the pathogens were highly resistant to β-lactams, quinolones, clindamycin and gentamicin, and the drug resistance rate was increasing, but it was still sensitive to rifampicin, nitrofurantoin, tigecycline, linezolid and vancomycin. CONCLUSION Gram positive bacteria are the main pathogens of periprosthetic infection, and the proportion is increasing gradually.The pathogens have high resistance to many kinds of antibiotics, and the resistance rate is still increasing. To strengthen the monitoring of the distribution and drug resistance of pathogenic bacteria is helpful to grasp its change trend and formulate targeted prevention and control strategies.
Anti-Bacterial Agents/therapeutic use* ; Arthroplasty, Replacement, Knee/adverse effects* ; Drug Resistance ; Drug Resistance, Bacterial ; Gram-Positive Bacteria ; Microbial Sensitivity Tests ; Retrospective Studies

Docetaxel-loaded nanomicelles were prepared in this study to improve the solubility and tumor targeting effect of docetaxel(DTX),and further evaluate their anticancer effects in vitro. PBAE-DTX nanomicelles were prepared by film-hydration method with amphiphilic block copolymer polyethyleneglycol methoxy-polylactide(PELA) and pH sensitive triblock copolymer polyethyleneglycol methoxy-polylactide-poly-β-aminoester(PBAE) were used respectively to prepare PELA-DTX nanomicelles and PBAE-DTX nanomicelles. The nanomicelles were characterized by physicochemical properties and the activity of mice Lewis lung cancer cells was studied. The results of particle size measurement showed that the blank micelles and drug-loaded micelles had similar particle sizes, ranging from 10 to 100 nm. The particle size of PBAE micelles was changed under weak acidic conditions, with good pH response. The encapsulation efficiency of the above two types of DTX-loaded nanomicelles determined by HPLC was(93.8±1.70)% and(87.2±4.10)%, and the drug loading amount was(5.3±0.10)% and(4.9±0.05)%,respectively. Furthermore,the DTX micelles also showed significant inhibitory effects on Lewis lung cancer cells by MTT assay, and pH-sensitive PBAE-DTX showed better cytotoxicity. The results of flow cytometry indicated that,the apoptosis rate of lung cancer Lewis cells was(20.72±1.47)%,(29.71±2.38)%,and(40.91±1.90)%(P<0.05) at 48 h after treatment in DTX,PELA-DTX,and PBAE-DTX groups. The results showed that different docetaxel preparations could promote the apoptosis of Lewis cells, and PBAE-DTX had stronger apoptotic-promoting effect. The pH-sensitive DTX-loaded micelles are promising candidates in developing stimuli triggered drug delivery systems in acidic tumor micro-environments with improved inhibitory effects of tumor growth on Lewis lung cancer.
Animals ; Antineoplastic Agents ; pharmacology ; Cell Line, Tumor ; Docetaxel ; pharmacology ; Drug Carriers ; Lung Neoplasms ; drug therapy ; pathology ; Mice ; Micelles ; Nanoparticles ; Particle Size ; Taxoids

Objective: To investigate the pharmacokinetics and the distribution in tumor tissues of docetaxel nanomicelles. Method: The docetaxel nanomicelles was prepared by filming-rehydration method.HPLC was employed to determine the content of docetaxel in biological samples and the corresponding methodological evaluation was carried out.The mouse Lewis lung carcinoma model was established,when dosage of administration in tail vein was 20 mg·kg^-1,and then the effect of free drug(DTX),non-pH-sensitive drug-loaded micelles(PELA-DTX) and pH-sensitive drug-loaded micelles(PBAE-DTX) on the pharmacokinetics and tissue distribution of tumor-bearing mice were investigated. Result: The docetaxel nanomicelles(PELA-DTX and PBAE-DTX) were successfully prepared.The method for the determination of docetaxel in mice was established by HPLC,the linearity,precision of the method and the recovery rate of samples all met the requirements.In the pharmacokinetic study,the plasma concentration of PBAE-DTX was always at a high level within 24 h.Compared with PELA-DTX and DTX,the areas under the curve(AUC_0-∞) of PBAE-DTX were increased by 3.63% and 8.96%,the mean residence times(MRT) were extended by 2.86% and 6.43%,the half-life and the drug blood circulation time were prolonged.In the tissue distribution study,it was found that three docetaxel preparations were distributed in the heart,liver,spleen,lung,kidney and tumor tissue within 1 h after administration,but the distribution of these drugs in the tissues was reduced along with the extension of time,the accumulation of PBAE-DTX in tumor tissue was significantly higher than that in DTX and PELA-DTX at 24 h. Conclusion: PBAE-DTX can prolong the circulation time of docetaxel in the blood,increase its bioavailability,and significantly increase its distribution in tumor tissue.

Background:Mutations in the isocitrate dehydrogenase 1 (IDH1) and IDH2 genes are important for both the integrated diagnosis and the prognosis of diffuse gliomas.The p.R132H mutation of IDH1 is the most frequently observed IDH mutation,while IDH2 mutations were relatively rarely studied.The aim of the study was to determine the pathological and genetic characteristics of lowergrade gliomas that carry IDH2 mutations.Methods:Data from 238 adult patients with lower-grade gliomas were retrospectively analyzed.The status of IDH1/2 gene mutations,telomerase reverse transcriptase (TERT) promoter mutations,O6-methylguanine-DNA-methyltransferase (MGMT) promoter methylation,1p/19q co-deletion and the expressions of IDH1 R132H,alpha-thalassemia X-linked mental retardation,and p53 were evaluated.Progression-free survival (PFS) and overall survival (OS) were calculated via Kaplan-Meier estimation using the log-rank test.Results:Totally,71％ (169/238) of patients were positive for IDH mutations,including 12 patients harboring mutations in IDH2.Among the 12 patients with IDH2 mutations,ten patients harbored the R172K mutation,one patient harbored the R172S mutation and one harbored the R172W mutation.Of these,11 tumors occurred in the frontal lobe and showed morphology typical of oligodendroglioma.The proportion of grade Ⅱ tumors was higher than that of grade Ⅲ tumors in IDH2 mutant-gliomas.IDH2 mutations were frequently associated with TERT promoter mutations,1p/19q co-deletion and MGMT promoter methylation.IDH2 mutations were associated with better outcomes compared with IDH wild-type gliomas (P ＜ 0.05).However,the PFS and OS did not differ from that of IDH1 mutant patients (P =0.95 and P =0.60,respectively).Conclusions:IDH2 mutations are more frequent in oligodendrogliomas and associated with a better prognosis.IDH2 mutations may segregate in distinct clinico-pathological and genetic subtypes of gliomas,and therefore may merit routine investigation.