The angiogenic response is essential for the repair of ischemic brain tissue. Integrin α6 (Itga6) expression has been shown to increase under hypoxic conditions and is expressed exclusively in vascular structures; however, its role in post-ischemic angiogenesis remains poorly understood. In this study, we demonstrate that mice with endothelial cell-specific knockout of Itga6 exhibit reduced neovascularization, reduced pericyte coverage on microvessels, and accelerated breakdown of microvascular integrity in the peri-infarct area. In vitro, endothelial cells with ITGA6 knockdown display reduced proliferation, migration, and tube-formation. Mechanistically, we demonstrated that ITGA6 regulates post-stroke angiogenesis through the PI3K/Akt-eNOS-VEGFA axis. Importantly, the specific overexpression of Itga6 in endothelial cells significantly enhanced neovascularization and enhanced the integrity of microvessels, leading to improved functional recovery. Our results suggest that endothelial cell Itga6 plays a crucial role in key steps of post-stroke angiogenesis, and may represent a promising therapeutic target for promoting recovery after stroke.
Animals ; Nitric Oxide Synthase Type III/metabolism* ; Mice ; Proto-Oncogene Proteins c-akt/metabolism* ; Integrin alpha6/genetics* ; Endothelial Cells/metabolism* ; Phosphatidylinositol 3-Kinases/metabolism* ; Stroke/pathology* ; Vascular Remodeling/physiology* ; Vascular Endothelial Growth Factor A/metabolism* ; Mice, Knockout ; Signal Transduction/physiology* ; Mice, Inbred C57BL ; Male ; Neovascularization, Physiologic/physiology*

Jiuwei Xifeng Granules have become a Chinese patent medicine in the market. Because the formula contains Os Draconis, a top-level protected fossil of ancient organisms, the formula was to be improved by replacing Os Draconis with Ostreae Concha. To evaluate whether the improved formula has the same effectiveness and safety as the original formula, a randomized, double-blind, parallel-controlled, equivalence clinical trial was conducted. This study enrolled 288 tic disorder(TD) of children and assigned them into two groups in 1∶1. The treatment group and control group took the modified formula and original formula, respectively. The treatment lasted for 6 weeks, and follow-up visits were conducted at weeks 2, 4, and 6. The primary efficacy endpoint was the difference in Yale global tic severity scale(YGTSS)-total tic severity(TTS) score from baseline after 6 weeks of treatment. The results showed that after 6 weeks of treatment, the declines in YGTSS-TSS score showed no statistically significant difference between the two groups. The difference in YGTSS-TSS score(treatment group-control group) and the 95%CI of the full analysis set(FAS) were-0.17[-1.42, 1.08] and those of per-protocol set(PPS) were 0.29[-0.97, 1.56], which were within the equivalence boundary [-3, 3]. The equivalence test was therefore concluded. The two groups showed no significant differences in the secondary efficacy endpoints of effective rate for TD, total score and factor scores of YGTSS, clinical global impressions-severity(CGI-S) score, traditional Chinese medicine(TCM) response rate, or symptom disappearance rate, and thus a complete evidence chain with the primary outcome was formed. A total of 6 adverse reactions were reported, including 4(2.82%) cases in the treatment group and 2(1.41%) cases in the control group, which showed no statistically significant difference between the two groups. No serious suspected unexpected adverse reactions were reported, and no laboratory test results indicated serious clinically significant abnormalities. The results support the replacement of Os Draconis by Ostreae Concha in the original formula, and the efficacy and safety of the modified formula are consistent with those of the original formula.
Adolescent ; Child ; Child, Preschool ; Female ; Humans ; Male ; Double-Blind Method ; Drugs, Chinese Herbal/therapeutic use* ; Tic Disorders/drug therapy* ; Treatment Outcome

Arsenic is a semi-metal,and lipid-soluble arsenic compounds are one of the widespread forms in the environment and food chain,but there is a lack of standards for lipid-soluble arsenic compounds,which is one of the bottlenecks in the current analytical detection and toxicological studies of organic arsenic.In this study,four saturated arsenic-containing hydrocarbons,AsHC 318,AsHC 332,AsHC 346,and AsHC 374(The number is relative molecular mass),were successfully synthesized in three steps by using dimethylarsinic acid,potassium iodide,sodium hydroxide,and four brominated alkanes(1-Bromotetradecane,1-bromopentadecane,1-bromohexadecane,and 1-bromooctadecane)as raw materials.The structures of these four saturated arsenic-containing hydrocarbons were characterized by proton nuclear magnetic resonance(1H NMR)spectroscopy,13C nuclear magnetic resonance(13C NMR)spectroscopy,and high-resolution mass spectrometry(HR-MS).The yields of the method were 8%-10%,and the synthesized compounds could be used in subsequent toxicity evaluation experiments to assess the toxic effects and mechanisms of action of arsenic-containing hydrocarbons.This study provided an effective method for synthesis of arsenic-containing hydrocarbons,enriching the synthesis methods of arsenic-containing hydrocarbons,and provided raw materials for the subsequent toxicological studies of arsenic-containing hydrocarbons.

In view of the few studies on the influence of Armillaria spp. infection on the content of the chemical components in different parts of Polyporus umbellatus sclerotia, this study determined the biomass of P. umbellatus sclerotia and the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in the separated cavity wall of the sclerotia and the uninfected part of the sclerotia in different harvesting years under the conditions of A. gallica and A. mellea infection respectively. According to the difference of content and dynamic changes of the polysaccharide and the steroid substances, the superior Armillaria sp. was screened to obtain the best harvest years of P. umbellatus. Using HPLC and UV-VIS spectrophotometry methods, the contents of ergosterol, polyporusterone A, polyporusterone B and polysaccharide in P. umbellatus sclerotia infected by the two Armillaria spp. in different years were determined. In addition, the differentially expressed genes related to P. umbellatus polysaccharide synthesis were screened according to the transcriptomic data of different parts of P. umbellatus after A. mellea infection. With the increase of years, the biomass of sclerotia infected by different Armillaria spp. had significant differences, and there were significant differences in the four components of sclerotia. The four components of the separated cavity wall of the sclerotia were significantly higher than those of the uninfected part. The best harvest time was the third year after cultivation. Transcriptomic analysis showed that the infection of Armillaria spp. could significantly promote polysaccharide synthesis, which provided a basis for polysaccharide content determination at the molecular level. The study clarified the influence of different Armillaria spp. infection on the accumulation of chemical components of P. umbellatus sclerotia, laying a foundation for exploring the symbiosis mechanism and provided a scientific clue for screening superior Armillaria sp. and guiding the artificial cultivation of P. umbellatus sclerotia.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Objective To investigate the changing antibiotic resistance profiles of E.coli isolated from patients in the 52 hospitals participating in the CHINET program from 2015 to 2021.Methods Antimicrobial susceptibility was tested for clinical isolates of E.coli according to the unified protocol of CHINET program.WHONET 5.6 and SPSS 20.0 software were used for data analysis.Results Atotal of 289 760 nonduplicate clinical strains ofE.coli were isolated from 2015 to 2021,mainly from urine samples(44.7±3.2)％.The proportion of E.coli strains isolated from urine samples was higher in females than in males(59.0％vs 29.5％).The proportion of E.coli strains isolated from respiratory tract and cerebrospinal fluid samples was significantly higher in children than in adults(16.7％vs 7.8％,0.8％vs 0.1％,both P＜0.05).The isolates from internal medicine department accounted for the largest proportion(28.9±2.8)％with an increasing trend over years.Overall,the prevalence of ESBLs-producing E.coli and carbapenem resistant E.coli(CREco)was 55.9％and 1.8％,respectively during the 7-year period.The prevalence of ESBLs-producing E.coli was the highest in tertiary hospitals each year from 2015 to 2021 compared to secondary hospitals.The prevalence of CREco was higher in children's hospitals compared to secondary and tertiary hospitals each year from 2015 to 2021.The prevalence of ESBLs-producing E.coli in tertiary hospitals and children's hospitals and the prevalence of CREco in children's hospitals showed a decreasing trend over the 7-year period.The prevalence of CREco in secondary and tertiary hospitals increased slowly.Antibiotic resistance rates changed slowly from 2015 to 2021.Carbapenem drugs(imipenem,meropenem)were the most active drugs amongβ-lactams against E.coli(resistance rate≤2.1％).The resistance rates of E.coli to β-lactam/β-lactam inhibitor combinations(piperacillin-tazobactam,cefoperazone-sulbactam),aminoglycosides(amikacin),nitrofurantoin and fosfomycin(for urinary isolates only)were all less than 10％.The resistance rate of E.coli strains to antibiotics varied with the level of hospitals and the departments where the strains were isolated,especially for cefazolin and ciprofloxacin,to which the resistance rate of E.coli strains from children in non-ICU departments was significantly lower than that of the strains isolated from other departments(P＜0.05).The E.coli isolates from ICU showed higher resistance rate to most antimicrobial agents tested(excluding tigecycline)than the strains isolated from other departments.The E.coli strains isolated from tertiary hospitals showed higher resistance rates to the antimicrobial agents tested(excluding tigecycline,polymyxin B,cefepime and carbapenems)than the strains from secondary hospitals and children's hospitals.Conclusions E.coli is an important pathogen causing clinical infection.More than half of the clinical isolates produced ESBL.The prevalence of CREco is increasing in secondary and tertiary hospitals over the 7-year period even though the overall prevalence is still low.This is an issue of concern.

Post-endoscopic retrograde cholangiopancreatography pancreatitis(PEP)is one of the most common complications after endoscopic retrograde cholangiopancreatography(ERCP).Numerous PEP prediction models have been established based on different statistical methods at home and abroad.The PEP prediction model,as a tool for evaluating and screening high-risk populations,can provide a basis for medical staff to find high-risk PEP patients early and take effective preventive measures.In recent years,new PEP prediction models have appeared one after another,but there is still a lack of recognized reliable prediction models in clinic.This article reviews the research status of PEP risk prediction models,aim to provide a direction for establishing a more reliable,accurate,and practical PEP risk prediction model in the later period.

Aim To investigate the protective effect of fisetin on testis and sperm of rats with oligoasthenosper-mia and to explore its mechanism.Methods The rat model of oligoasthenospermia was established.The rats were randomly divided into the blank group,model group,low-,medium-,and high-dose fisetin treat-ment groups,and LKB1 agonist group,with 10 rats in each group.ELISA was used to detect the levels of FSH,LH,T,E2 and PRL.Flow cytometry was used to detect sperm cell apoptosis.HE staining was used to detect testicular tissue damage.Transmission electron microscopy was used to detect the ultrastructure of sperm cells.qRT-PCR and Western blot were used to detect the mRNA and protein expression of LKB1,AMPK,mTOR,and p70S6K.Results Compared with the blank group,the levels of FSH,LH,PRL,T and other hormones in the model group and LKB1 ago-nist group were significantly reduced,and sperm cell apoptosis and testicular injury were severe.The ex-pressions of LKB1 and p-AMPK/AMPK were signifi-cantly up-regulated,while the expressions of mTOR and p-p70S6K/p70S6K were significantly down-regula-ted(P＜0.05).Compared with the model group,af-ter different doses of fisetin treatment,the number of apoptotic sperm cells was significantly reduced,the levels of FSH,LH,PRL,T and other hormones markedly increased,the expression of LKB1 and p-AMPK/AMPK was significantly down-regulated,and the expression of mTOR and p-p70S6K/p70S6K was evidently up-regulated(P＜0.05).Conclusion Fi-setin is effective in the treatment of oligoasthenospermia rats,which may be related to LKB1-AMPK-mTOR-p70S6K signaling pathway.

Objective: The aim of this study was to investigate the efficacy of endoscopically visualized radiofrequency for treating sacroiliac joint pain. Methods: The study protocol was preregistered on INPLASY (INPLASY202450011). A systematic search was carried out across multiple databases, including PubMed, Embase, Cochrane CENTRAL, and Web of Science, from their inception until May 6, 2024. Peer-reviewed studies on human participants with low back pain diagnosed with sacroiliac joint pain and treated with endoscopically visualized radiofrequency ablation (RFA) were included. The study focused on evaluating changes in the visual analogue scale (VAS) and Oswestry Disability Index (ODI) from before the commencement of endoscopically visualized radiofrequency to postoperation. The quantitative syntheses employed a random-effects model, with effect sizes reported using the mean difference. Subgroup analyses were conducted based on 6-month and 12-month postoperative time points. Results: Four studies were ultimately included in this meta-analysis. Three of the studies were case series, while one was a retrospective cohort study. The mean difference of VAS scores between the preoperative and 6-month and 12-month postoperative assessments was -5.60 and -5.96, respectively. The mean difference of the ODI between preoperative and 6-month and 12-month postoperative assessments was -21.03 and -23.67, respectively. A subgroup analysis of both outcome measurement indices at the 2 follow-up time points did not reveal any statistically significant differences. Conclusion Endoscopically visualized RFA demonstrates potential as a treatment modality for sacroiliac joint pain; however, there is currently insufficient evidence to substantiate its long-term efficacy.

Objective: To investigate the outcomes including major complications and prognosis of extremely preterm infants with gestational age ≤25⁺⁶ weeks. Methods: The cross-sectional study enrolled 233 extremely preterm infants with gestational age ≤25⁺⁶ weeks who were admitted to the Department of Neonatology of Shenzhen Maternity and Child Healthcare Hospital from January 2015 to December 2021. The clinical data including perinatal factors, treatments, complications, and prognosis were extracted and analyzed. These extremely preterm infants were also grouped according to gestational age and year of admission to further analyze their survival rate, major complications, causes of death, and long-term outcomes. The comparisons between the groups were performed with Chi-square test and Kruskal-Wallis. Results: Among these 233 extremely preterm infants, 134 (57.5%) were males and 99 (42.5%) females. The gestational age was (24.6±0.9) weeks, the birth weight was 710.0 (605.0,784.5) g, and the overall survival rate was 61.8% (144/233). Among the surviving extremely preterm infants, the earliest gestational age was 22⁺² weeks and the lowest birth weight was 390 g. There were 17.6% (41/233) of extremely preterm infants had treatment withdrawn and were discharged in line with the will of guardians. Among the rest 192 extremely preterm infants managed with aggressive treatments, 14 (7.3%) died in hospital and 34 (17.7%) had treatment withdrawn later due to severe complications. Of the 192 extremely preterm infants, 144 (75.0%) survived, and the survival rate increased year by year (χ²=26.28, P<0.001) while the mortality decreased year by year (χ²=14.09, P=0.027). Among the survivors, 20.8%(30/144) had no major complications, and the incidence of complications was also negatively related with the gestational age (χ²=7.24, P=0.044), and the length of invasive ventilation was negatively related to the gestational age (χ²=29.14, P<0.001). In the group of less than 23⁺⁶ weeks, all extremely preterm infants had one or more major complications. The follow-up were completed in 122 infants and revealed that delayed motor development, language retardation, and hearing and vision impairment accounted for 17.2% (21/122), 8.2% (10/122) and 17.2% (21/122), respectively. Conclusions: Extremely preterm infants with gestational age ≤25⁺⁶ weeks are difficult to treat, but the survival rate of infants undergoing aggressive treatments increases year by year. Although the prevalence of major complications is still high, most extremely preterm infants have acceptable prognosis during follow-up.
Female ; Humans ; Infant ; Infant, Newborn ; Male ; Pregnancy ; Birth Weight ; Cross-Sectional Studies ; Gestational Age ; Infant, Extremely Premature ; Prognosis ; Retrospective Studies