Inflammation plays a pivotal role in the etiology and progression of various diseases. In traditional Chinese medicine, the whole plants of Thesium chinense Turcz. and its preparations (e.g. Bairui Granules) have been employed to manage inflammatory conditions. While flavonoids were previously considered the primary anti-inflammatory components, other potentially active constituents have been largely overlooked and not thoroughly investigated. This study presents a novel finding that the total alkaloids of T. chinense (BC-Alk) are potent active substances underlying the traditional and clinical applications of T. chinense and Bairui Granules as anti-inflammatory agents. UPLC-MS/MS analysis identified the composition of BC-Alk as quinolizidine alkaloids. The anti-inflammatory efficacy of BC-Alk was evaluated using a lipopolysaccharide (LPS)-induced lung inflammation model in mice. Results demonstrated that BC-Alk significantly mitigated LPS-induced lung inflammation, attenuated the overproduction of IL-1β and the overproduction of inflammatory factors (TNF-α), and ameliorated lung tissue hyperplasia in mice in vivo. Mechanistic studies in vitro revealed that BC-Alk upregulated the expression of Nrf2 and its downstream proteins NQO1 and glutamate-cystine ligase and modifier subunit (GCLM), inhibited NF-κB phosphorylation, and suppressed NLRP3 activation. Collectively, these findings indicate that BC-Alk exerts potent inhibitory effects against lung inflammation by modulating Nrf2, NF-κB, and NLRP3 pathways. This study provides new insights into the anti-inflammatory constituents of T. chinense and Bairui Granules.
Animals ; Lipopolysaccharides/adverse effects* ; Alkaloids/pharmacology* ; NF-kappa B/metabolism* ; NF-E2-Related Factor 2/metabolism* ; NLR Family, Pyrin Domain-Containing 3 Protein/metabolism* ; Mice ; Signal Transduction/drug effects* ; Anti-Inflammatory Agents/pharmacology* ; Male ; Mice, Inbred C57BL ; Humans ; Drugs, Chinese Herbal/administration & dosage* ; Pneumonia/genetics*

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

The endothelial glycocalyx（EG）is a villous polyglycoprotein complex that covers the apical membrane of endothelial cells，situated between the blood vessel wall and the bloodstream.Due to its unique physiological position，the EG plays a crucial role in vascular permeability，mechanical conduction，coagulation，inflammation，and other processes.EG injury can cause endothelial barrier dysfunction，increase vascular permeability，and promote inflammation and thrombosis.Recent studies have revealed that the involvement of EG in inflammatory responses may contribute significantly to the pathogenesis of certain rheumatic and immune diseases as well as multi-system inflammatory syndrome，Kawasaki disease，rheumatoid arthritis，systemic lupus erythematosus and antiphospholipid syndrome，etc.This review paper aims to provide an overview of the structure and function of EG while highlighting its research progress in diagnosing and treating rheumatic and immune diseases.

Objective To understand the changing composition and antibiotic resistance of bacterial species in the clinical isolates from outpatient and emergency department(hereinafter referred to as outpatients)and inpatient children over time in various hospitals,and to provide laboratory evidence for rational antibiotic use.Methods The data on clinically isolated pathogenic bacteria and antimicrobial susceptibility of isolates from outpatients and inpatient children in the CHINET program from 2015 to 2021 were collected and analyzed.Results A total of 278 471 isolates were isolated from pediatric patients in the CHINET program from 2015 to 2021.About 17.1％of the strains were isolated from outpatients,primarily group A β-hemolytic Streptococcus,Escherichia coli,and Staphylococcus aureus.Most of the strains(82.9％)were isolated from inpatients,mainly SS.aureus,E.coli,and H.influenzae.The prevalence of methicillin-resistant S.aureus(MRSA)in outpatients(24.5％)was lower than that in inpatient children(31.5％).The MRSA isolates from outpatients showed lower resistance rates to the antibiotics tested than the strains isolated from inpatient children.The prevalence of vancomycin-resistant Enterococcus faecalis or E.faecium and penicillin-resistant S.pneumoniae was low in either outpatients or inpatient children.S.pneumoniae,β-hemolytic Streptococcus and S.viridans showed high resistance rates to erythromycin.The prevalence of erythromycin-resistant group A β-hemolytic Streptococcus was higher in outpatients than that in inpatient children.The prevalence of β-lactamase-producing H.influenzae showed an overall upward trend in children,but lower in outpatients(45.1％)than in inpatient children(59.4％).The prevalence of carbapenem-resistant Klebsiella pneumoniae(CRKpn),carbapenem-resistant Pseudomonas aeruginosa(CRPae)and carbapenem-resistant Acinetobacter baumannii(CRAba)was 14％,11.7％,47.8％in outpatients,but 24.2％,20.6％,and 52.8％in inpatient children,respectively.The prevalence of multidrug-resistant E.coli,K.pneumoniae,Proteus mirabilis,P.aeruginosa and A.baumannii strains was lower in outpatients than in inpatient children.The prevalence of fluoroquinolone-resistant E.coli,ESBLs-producing K.pneumoniae,ESBLs-producing P.mirabilis,carbapenem-resistant E.coli(CREco),CRKpn,and CRPae was lower in children in outpatients than in inpatient children,but the prevalence of CRAba in 2021 was higher than in inpatient children.Conclusions The distribution of clinical isolates from children is different between outpatients and inpatients.The prevalence of MRSA,ESBL,and CRO was higher in inpatient children than in outpatients.Antibiotics should be used rationally in clinical practice based on etiological diagnosis and antimicrobial susceptibility test results.Ongoing antimicrobial resistance surveillance and prevention and control of hospital infections are crucial to curbing bacterial resistance.

Objective:To analyze the clinical phenotype, sperm morphological characteristics and assisted reproductive therapy efficiency in patients with total globozoospermia.Methods:Four male patients with total globozoospermia were collected during November 2019 to May 2022 from Reproductive Medical and Genetic Center, the People's Hospital of Guangxi Zhuang Autonomous Region. Peripheral blood samples were collected for genetic detection and the whole exome sequencing to explore the pathogenic genes. Semen characteristics, sperm morphology and ultrastructure were analyzed. Four patients were treated with intracytoplasmic sperm injection (ICSI) combined with artificial oocyte activation (AOA). Conventional ICSI cycles ( n=9) were selected as control group, and the development dynamic parameters were monitored by Time-lapse. The fertilization and embryo development parameters, developmental dynamic parameters and clinical outcomes were analyzed between the two groups. Results:Four patients were complicated with low sperm motility and increased sperm DNA fragmentation. Sperm morphology analysis and acrosome fluorescence staining represented that all the spermatozoas were with a small round head lacked of acrosome. By the transmission electron microscope, it was observed that round-headed spermatozoas were lacked of acrosome completely, loose chromatin structure, vacuolation and other abnormal changes in the head, mitochondrial sheath in neck were reduced arranged in disorder, and the structure of "9+2" of the flagellar axial filament was incomplete. Of the 4 patients, 1 was homozygous deletion of DPY19L2 gene and 1 was homozygous frameshift mutation of DPY19L2 gene. There were no significance differences in fertilization rate, two pronuclei fertilization rate, day 3 high-quality embryo rate, day 6 blastocyst formation rate and day 6 high-quality blastocyst formation rate between total globozoospermia group and control group (all P>0.05). The developmental dynamic parameters as the time at which the second polar body is extruded, the time when both (or the last) PN disappear, two to six discrete cells in the total globozoospermia group were significantly earlier than those in control group, and the difference was statistically significant (all P<0.05). There was no significant difference in the embryo cleavage patterns between the two groups ( P>0.05). Among the 4 patients with total globozoospermia, 2 live births with signal healthy male baby were achieved by fresh embryo transfer, and 2 live births with one signal healthy male baby and one healthy female baby were achieved by frozen-thawed embryo transfer respectively. Conclusion:Abnormal morphology characteristics of spermatozoas from patients with total globozoospermia are obvious, patients with total globozoospermia could have favorable clinical outcomes following ICSI combined with AOA.

Objective:To analyze the clinical phenotype, sperm morphological characteristics and assisted reproductive therapy efficiency in patients with total globozoospermia.Methods:Four male patients with total globozoospermia were collected during November 2019 to May 2022 from Reproductive Medical and Genetic Center, the People's Hospital of Guangxi Zhuang Autonomous Region. Peripheral blood samples were collected for genetic detection and the whole exome sequencing to explore the pathogenic genes. Semen characteristics, sperm morphology and ultrastructure were analyzed. Four patients were treated with intracytoplasmic sperm injection (ICSI) combined with artificial oocyte activation (AOA). Conventional ICSI cycles ( n=9) were selected as control group, and the development dynamic parameters were monitored by Time-lapse. The fertilization and embryo development parameters, developmental dynamic parameters and clinical outcomes were analyzed between the two groups. Results:Four patients were complicated with low sperm motility and increased sperm DNA fragmentation. Sperm morphology analysis and acrosome fluorescence staining represented that all the spermatozoas were with a small round head lacked of acrosome. By the transmission electron microscope, it was observed that round-headed spermatozoas were lacked of acrosome completely, loose chromatin structure, vacuolation and other abnormal changes in the head, mitochondrial sheath in neck were reduced arranged in disorder, and the structure of "9+2" of the flagellar axial filament was incomplete. Of the 4 patients, 1 was homozygous deletion of DPY19L2 gene and 1 was homozygous frameshift mutation of DPY19L2 gene. There were no significance differences in fertilization rate, two pronuclei fertilization rate, day 3 high-quality embryo rate, day 6 blastocyst formation rate and day 6 high-quality blastocyst formation rate between total globozoospermia group and control group (all P>0.05). The developmental dynamic parameters as the time at which the second polar body is extruded, the time when both (or the last) PN disappear, two to six discrete cells in the total globozoospermia group were significantly earlier than those in control group, and the difference was statistically significant (all P<0.05). There was no significant difference in the embryo cleavage patterns between the two groups ( P>0.05). Among the 4 patients with total globozoospermia, 2 live births with signal healthy male baby were achieved by fresh embryo transfer, and 2 live births with one signal healthy male baby and one healthy female baby were achieved by frozen-thawed embryo transfer respectively. Conclusion:Abnormal morphology characteristics of spermatozoas from patients with total globozoospermia are obvious, patients with total globozoospermia could have favorable clinical outcomes following ICSI combined with AOA.