Based on ultra-high performance liquid chromatography-quadrupole-Exactive Orbitrap mass spectrometry(UPLC-Q-Exactive Orbitrap-MS) technology and network pharmacology, this study explored the pharmacodynamic substances and potential mechanisms of Huazhuo Sanjie Chubi Decoction in the treatment of gouty arthritis(GA). UPLC-Q-Exactive Orbitrap-MS technology was used to identify the components in Huazhuo Sanjie Chubi Decoction, and the qualitative analysis of its active ingredients was carried out, with a total of 184 active ingredients identified. A total of 897 active ingredient targets were screened through the PharmMapper database, and 491 GA-related disease targets were obtained from the OMIM, GeneCards, CTD databases. After Venn analysis, 60 intersecting targets were obtained. The component target-GA target network was constructed through the Cytoscape platform, and the STRING database was used to construct a protein-protein interaction network, with 16 core targets screened. The core targets were subjected to Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analyses, and the component-target-pathway network was constructed. It was found that the main active ingredients of the formula for the treatment of GA were phenols, flavonoids, alkaloids, and terpenoids, and the key targets were SRC, MMP3, MMP9, REN, ALB, IGF1R, PPARG, MAPK1, HPRT1, and CASP1. Through GO analysis, it was found that the treatment of GA mainly involved biological processes such as lipid response, bacterial response, and biostimulus response. KEGG analysis showed that the pathways related to the treatment of GA included lipids and atherosclerosis, neutrophil extracellular traps(NETs), IL-17, and so on. In summary, phenols, flavonoids, alkaloids, and terpenoids may be the core pharmacodynamic substances of Huazhuo Sanjie Chubi Decoction in the treatment of GA, and the pharmacodynamic mechanism may be related to SRC, MMP3, MMP9, and other targets, as well as lipids and atherosclerosis, NETs, IL-17, and other pathways.
Drugs, Chinese Herbal/therapeutic use* ; Network Pharmacology ; Arthritis, Gouty/metabolism* ; Chromatography, High Pressure Liquid/methods* ; Humans ; Mass Spectrometry/methods* ; Protein Interaction Maps/drug effects*

This study aims to explore the effects and action mechanisms of the active ingredients in Buyang Huanwu Decoction(BYHWD), namely tetramethylpyrazine(TMP) and hydroxy-safflor yellow A(HSYA), on oxygen-glucose deprivation/reglucose-reoxygenation(OGD/R)-induced inflammation and oxidative stress of microglia(MG). Network pharmacology was used to screen the effective monomer ingredients of BYHWD and determine the safe concentration range for each component. Inflammation and oxidative stress models were established to further screen the best ingredient combination and optimal concentration ratio with the most effective anti-inflammatory and antioxidant effects. OGD/R BV2 cell models were constructed, and BV2 cells in the logarithmic growth phase were divided into a normal group, a model group, an HSYA group, a TMP group, and an HSYA + TMP group. Enzyme-linked immunosorbent assay(ELISA) was used to detect the levels of inflammatory cytokines such as interleukin-1β(IL-1β), tumor necrosis factor-α(TNF-α), and interleukin-6(IL-6). Oxidative stress markers, including superoxide dismutase(SOD), nitric oxide(NO), and malondialdehyde(MDA), were also measured. Western blot was used to analyze the protein expression of both inflammation-related pathway [Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB)] and oxidative stress-related pathway [nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)]. Immunofluorescence was used to assess the expression of proteins such as inducible nitric oxide synthase(iNOS) and arginase-1(Arg-1). The most effective ingredients for anti-inflammatory and antioxidant effects in BYHWD were TMP and HSYA. Compared to the normal group, the model group showed significantly increased levels of IL-1β, TNF-α, IL-6, NO, and MDA, along with significantly higher protein expression of NF-κB, TLR4, Nrf2, and HO-1 and significantly lower SOD levels. The differences between the two groups were statistically significant. Compared to the model group, both the HSYA group and the TMP group showed significantly reduced levels of IL-1β, TNF-α, IL-6, NO, and MDA, lower expression of NF-κB and TLR4 proteins, higher levels of SOD, and significantly increased protein expression of Nrf2 and HO-1. Additionally, the expression of the M1-type MG marker iNOS was significantly reduced, while the expression of the M2-type MG marker Arg-1 was significantly increased. The results of the HSYA group and the TMP group had statistically significant differences from those of the model group. Compared to the HSYA group and the TMP group, the HSYA + TMP group showed further significant reductions in IL-1β, TNF-α, IL-6, NO, and MDA levels, along with significant reductions in NF-κB and TLR4 protein expression, an increase in SOD levels, and elevated Nrf2 and HO-1 protein expression. Additionally, the expression of the M1-type MG marker iNOS was reduced, while the M2-type MG marker Arg-1 expression increased significantly in the HSYA + TMP group compared to the TMP or HSYA group. The differences in the results were statistically significant between the HSYA + TMP group and the TMP or HSYA group. The findings indicated that the combined use of HSYA and TMP, the active ingredients of BYHWD, can effectively inhibit OGD/R-induced inflammation and oxidative stress of MG, showing superior effects compared to the individual use of either component.
Oxidative Stress/drug effects* ; Drugs, Chinese Herbal/pharmacology* ; Animals ; Mice ; Glucose/metabolism* ; Cell Line ; Inflammation/genetics* ; Oxygen/metabolism* ; Pyrazines/pharmacology* ; Microglia/metabolism* ; NF-E2-Related Factor 2/immunology* ; NF-kappa B/immunology* ; Toll-Like Receptor 4/immunology* ; Anti-Inflammatory Agents/pharmacology* ; Humans

OBJECTIVES: To study the clinical characteristics of pediatric Behçet syndrome (BS). METHODS: A retrospective review was conducted on the medical records of children hospitalized in the Department of Pediatrics at the Second Hospital of Hebei Medical University between December 2014 and December 2024 who met diagnostic criteria for BS. RESULTS: Among 45 children with BS, 26 (58%) were male. Oral aphthous ulcers were the most common manifestation (43/45, 96%), followed by genital ulcers (23/45, 51%) and gastrointestinal involvement (18/45, 40%). Genital ulcers were more frequent in girls, whereas ocular involvement was more common in boys (P<0.05). The pathergy test was positive in 10 (22%), and HLA-B51 was positive in 13 (29%). Fecal calprotectin (FC) was elevated in 16 (36%); gastrointestinal involvement was more frequent in children with elevated FC than in those with normal FC (P<0.05). According to the respective criteria, 17 (38%) patients met the International Study Group criteria (1990), 33 (73%) met the International Criteria for Behçet Disease (2014), and 13 (29%) met the Pediatric Behçet Disease criteria (2015). CONCLUSIONS Pediatric BS shows marked clinical heterogeneity. HLA-B51 is associated with disease susceptibility.
Humans ; Behcet Syndrome/genetics* ; Male ; Female ; Child ; Retrospective Studies ; Adolescent ; Child, Preschool ; Leukocyte L1 Antigen Complex/analysis* ; HLA-B51 Antigen

Objective To investigate the mechanism of miR-135a/MYC-mediated resistance to venaclar treatment in myelodysplastic syndromes(MDS)with acute myeloid leukaemia(AML).Methods Eighty-six cases of patients were selected,including 23 healthy donors(control group),47 MDS patients with vinecella resistance(MDS group),and 16 AML patients with vinecella resistance transformed from myelodysplastic syndrome(AML group).The expression levels of miR-135a and MYC in the tissues of the three groups were detected.THP1 cells were divided into miR-NC group(transfected with nonsense sequence)and miR-135a minics group(transfected with miR-135a minics),and the cells were treated with venaclar concentration of 0,0.01,1,and 100 μmol·L-1 for 24 hours,and then detected the cell viability and apoptosis rate in each group.Results The expression of MYC mRNA were 1.00±0.14,0.21±0.04,and 0.25±0.08 in patients of the NC,MDS,and AML groups,respectively;the protein expression of MYC were 1.00±0.15,1.31±0.12 and 1.49±0.16,respectively(P＜0.05).At the cellular level,miR-135a expression were 1.00±0.11,1.31±0.15 and 1.93±0.23 in the BMSCs,MUTZ-1 and THP1 groups;MYC protein expression were 1.00±0.15,1.57±0.22 and 1.97±0.31,the differences were significant(P＜0.05).The methods showed the cell viability of miR-NC group were(100.00±13.26)％,(92.33±10.28)％,(85.41±11.37)％and(28.24±6.02)％at 0,0.01,1,100 μmol·L-1venaclar drug concentration,respectively;cell viability of miR-135a mimics group were(105.12±12.35)％,(82.11±12.07)％,(46.13±8.06)％and(18.20±5.03)％,respectively,there was statistical difference between the two groups only in the 1 μmol·L-1 venaclar drug concentration(P＜0.05).The methods showed that the apoptosis rates in miR-NC group at 0,0.01,1,100 μmol·L-1 venaclar drug concentration were(100.00±11.45)％,(92.48±12.04)％,(108.72±9.63)％and(207.15±21.49)％,the apoptosis rates in miR-135a mimics group were(106.34±16.21)％,(117.26±10.13)％,(269.41±23.59)％and(184.33±19.28)％,respectively;there was statistical difference between the two groups only in 1 μmol·L-1 venaclar drug concentration(P＜0.05).Conclusion The results of this study reveal that miR-135a/MYC mediates the mechanism of resistance to venaclar in the treatment of MDS and AML.

Objective To observe the clinical value of recombinant human erythropoietin injection in the treatment of anemia after chemotherapy in leukemia patients,and to explore the difference of efficacy of different doses.Methods Patients with anemia complicated by leukemia chemotherapy were selected as the study objects and randomly divided into control group,low-dose group and high-dose group.Patients in the control group received conventional treatment(oral ferrous succinate combined with dietary conditioning),and patients in the low-dose group were given 75 U·kg-1 recombinant human erythrophorin treatment on the basis of the control group,subcutaneous injection 3 times a week.High-dose group was treated with 150 U·kg-1 recombinant human erythropoietin on the basis of control group,subcutaneous injection 3 times a week.All three groups were treated for 4 weeks.The clinical efficacy,the anemia-related indexes,the expression of mitogen-activated protein kinase path-related proteins in bone marrow stromal cells,Karnofsky performance status(KPS)score and safety of the three groups were compared.Result Control group,low-dose group and high-dose group were enrolled in 32,33 and 33 cases,respectively,without shedding patients.After treatment,the total effective rate of control group,low-dose group and high-dose group were 62.50％(20 cases/32 cases),78.79％(26 cases/33 cases)and 87.88％(29 cases/33 cases),respectively.There was statistical significance in the total effective rate of control group and high-dose group(P＜0.05).After treatment,the hemoglobin levels of control group,low-dose group and high-dose group were(108.76±6.82),(112.43±7.31)and(116.27±7.72)g·L-1,respectively;red blood cell counts were(3.08±0.42)× 1012,(3.34±0.39)× 1012 and(3.58±0.45)× 1012·L-1,respectively;hematocrit were 0.28±0.05,0.31±0.06 and 0.35±0.07,respectively;the relative expression levels of phosphorylated extracellular regulatory protein kinase 1/2 were 1.12±0.16,1.23±0.17 and 1.35±0.22,respectively;the relative expression levels of phosphorylated stress-activated protein kinase were 0.83±0.13,0.76±0.11 and 0.69±0.09,respectively;the expression levels of p-P38 were 0.92±0.10,0.86±0.09 and 0.80±0.09,respectively;the KPS scores were(69.35±6.43),(72.84±6.62)and(76.35±6.77)points,respectively.The above indexes in the low-dose group and the high-dose group were compared with the control group,respectively,and the above indexes in the high-dose group were compared with the low-dose group,and the differences were statistically significant(all P＜0.05).The adverse drug reactions in the three groups were mainly skin allergy and gastrointestinal reactions.The total incidences of adverse drug reactions in the control group,low-dose group and high-dose group was 12.50％,18.18％and 18.18％,respectively,with no statistical significance(all P＞0.05).Conclusion Recombinant human erythropoietin can significantly correct chemotherapy related anemia in leukemia,and improve health status,and the curative effect of 150 U·kg-1 was better than 75 U·kg-1.

Vasoinhibitory vasovagal syncope（VVS-VI）in children is the most common type of responses in vasovagal syncope（VVS）and has a high incidence. VVS-VI is a recurrent disorder caused by a malfunctioning autonomic nervous system. VVS-VI can be caused by a variety of stimuli such as strong emotions，sudden changes in posture，hot and stuffy environments and prolonged standing. It was found that VVS-VI is a benign disease without organic lesions and is self-limiting and reversible，but VVS-VI children often suffer irreversible consequences due to secondary injuries. VVS-VI seriously affects the life and academic performance of children，endangers their physical and mental health，and causes anxiety among parents，so the number of studies on VVS-VI has increased in recent years. This article summarizes the progress of diagnostic research on VVS-VI in children，and provides a reference for related research.

Objective To analyze the stress changes of thoracic vertebra(T)11-sacrum(S)titanium rods in patients with ankylosing spondylitis after vertebral column decancellation(VCD)osteotomy,and provide reference for the selection and improvement of titanium rods before surgery.Methods The original data of the continuous scanning tomographic images of patients with ankylosing spondylitis after VCD osteotomy were imported into Mimics 21.0 in DICOM format,and T11-S vertebrae,screws and titanium rods were respectively reconstructed.They were imported into 3-Matic to establish a preliminary geometric modeling,and then processed with noise removal,paving,smoothing,etc.The improved model was imported into Hypermesh 10 software for grid division,and the material was imported into ANSYS 19.2 to display the finite element model after attribute assignment,Set the boundary and load conditions,and measure the stress value at the connection between the screw and the titanium rod.Results Under neutral position,forward bending,lateral bending,and axial rotation conditions,the titanium rod had the highest stress at the upper vertebrae(T11)and the lowest stress at the top vertebrae(L3);Under the backward extension condition,the titanium rod has the highest stress at the lower end vertebra(L5).Conclusion In the upper and lower vertebrae,it is possible to consider increasing the diameter of the titanium rod,enhancing its hardness,or changing it to a double rod.

Objective To investigate the clinical characteristics and prognosis of pneumococcal meningitis(PM),and drug sensitivity of Streptococcus pneumoniae(SP)isolates in Chinese children.Methods A retrospective analysis was conducted on clinical information,laboratory data,and microbiological data of 160 hospitalized children under 15 years old with PM from January 2019 to December 2020 in 33 tertiary hospitals across the country.Results Among the 160 children with PM,there were 103 males and 57 females.The age ranged from 15 days to 15 years,with 109 cases(68.1% )aged 3 months to under 3 years.SP strains were isolated from 95 cases(59.4% )in cerebrospinal fluid cultures and from 57 cases(35.6% )in blood cultures.The positive rates of SP detection by cerebrospinal fluid metagenomic next-generation sequencing and cerebrospinal fluid SP antigen testing were 40% (35/87)and 27% (21/78),respectively.Fifty-five cases(34.4% )had one or more risk factors for purulent meningitis,113 cases(70.6% )had one or more extra-cranial infectious foci,and 18 cases(11.3% )had underlying diseases.The most common clinical symptoms were fever(147 cases,91.9% ),followed by lethargy(98 cases,61.3% )and vomiting(61 cases,38.1% ).Sixty-nine cases(43.1% )experienced intracranial complications during hospitalization,with subdural effusion and/or empyema being the most common complication[43 cases(26.9% )],followed by hydrocephalus in 24 cases(15.0% ),brain abscess in 23 cases(14.4% ),and cerebral hemorrhage in 8 cases(5.0% ).Subdural effusion and/or empyema and hydrocephalus mainly occurred in children under 1 year old,with rates of 91% (39/43)and 83% (20/24),respectively.SP strains exhibited complete sensitivity to vancomycin(100% ,75/75),linezolid(100% ,56/56),and meropenem(100% ,6/6).High sensitivity rates were also observed for levofloxacin(81% ,22/27),moxifloxacin(82% ,14/17),rifampicin(96% ,25/26),and chloramphenicol(91% ,21/23).However,low sensitivity rates were found for penicillin(16% ,11/68)and clindamycin(6% ,1/17),and SP strains were completely resistant to erythromycin(100% ,31/31).The rates of discharge with cure and improvement were 22.5% (36/160)and 66.2% (106/160),respectively,while 18 cases(11.3% )had adverse outcomes.Conclusions Pediatric PM is more common in children aged 3 months to under 3 years.Intracranial complications are more frequently observed in children under 1 year old.Fever is the most common clinical manifestation of PM,and subdural effusion/emphysema and hydrocephalus are the most frequent complications.Non-culture detection methods for cerebrospinal fluid can improve pathogen detection rates.Adverse outcomes can be noted in more than 10% of PM cases.SP strains are high sensitivity to vancomycin,linezolid,meropenem,levofloxacin,moxifloxacin,rifampicin,and chloramphenicol.[Chinese Journal of Contemporary Pediatrics,2024,26(2):131-138]

Objective To monitor the susceptibility of clinical isolates to antimicrobial agents in tertiary hospitals in major regions of China in 2022.Methods Clinical isolates from 58 hospitals in China were tested for antimicrobial susceptibility using a unified protocol based on disc diffusion method or automated testing systems.Results were interpreted using the 2022 Clinical &Laboratory Standards Institute(CLSI)breakpoints.Results A total of 318 013 clinical isolates were collected from January 1,2022 to December 31,2022,of which 29.5％were gram-positive and 70.5％were gram-negative.The prevalence of methicillin-resistant strains in Staphylococcus aureus,Staphylococcus epidermidis and other coagulase-negative Staphylococcus species(excluding Staphylococcus pseudintermedius and Staphylococcus schleiferi)was 28.3％,76.7％and 77.9％,respectively.Overall,94.0％of MRSA strains were susceptible to trimethoprim-sulfamethoxazole and 90.8％of MRSE strains were susceptible to rifampicin.No vancomycin-resistant strains were found.Enterococcus faecalis showed significantly lower resistance rates to most antimicrobial agents tested than Enterococcus faecium.A few vancomycin-resistant strains were identified in both E.faecalis and E.faecium.The prevalence of penicillin-susceptible Streptococcus pneumoniae was 94.2％in the isolates from children and 95.7％in the isolates from adults.The resistance rate to carbapenems was lower than 13.1％in most Enterobacterales species except for Klebsiella,21.7％-23.1％of which were resistant to carbapenems.Most Enterobacterales isolates were highly susceptible to tigecycline,colistin and polymyxin B,with resistance rates ranging from 0.1％to 13.3％.The prevalence of meropenem-resistant strains decreased from 23.5％in 2019 to 18.0％in 2022 in Pseudomonas aeruginosa,and decreased from 79.0％in 2019 to 72.5％in 2022 in Acinetobacter baumannii.Conclusions The resistance of clinical isolates to the commonly used antimicrobial agents is still increasing in tertiary hospitals.However,the prevalence of important carbapenem-resistant organisms such as carbapenem-resistant K.pneumoniae,P.aeruginosa,and A.baumannii showed a downward trend in recent years.This finding suggests that the strategy of combining antimicrobial resistance surveillance with multidisciplinary concerted action works well in curbing the spread of resistant bacteria.

Objective To investigate the distribution and antimicrobial resistance profiles of the common pathogens isolated from urine from 2015 to 2021 in the CHINET Antimicrobial Resistance Surveillance Program.Methods The bacterial strains were isolated from urine and identified routinely in 51 hospitals across China in the CHINET Antimicrobial Resistance Surveillance Program from 2015 to 2021.Antimicrobial susceptibility was determined by Kirby-Bauer method,automatic microbiological analysis system and E-test according to the unified protocol.Results A total of 261 893 nonduplicate strains were isolated from urine specimen from 2015 to 2021,of which gram-positive bacteria accounted for 23.8％(62 219/261 893),and gram-negative bacteria 76.2％(199 674/261 893).The most common species were E.coli(46.7％),E.faecium(10.4％),K.pneumoniae(9.8％),E.faecalis(8.7％),P.mirabilis(3.5％),P.aeruginosa(3.4％),SS.agalactiae(2.6％),and E.cloacae(2.1％).The strains were more frequently isolated from inpatients versus outpatients and emergency patients,from females versus males,and from adults versus children.The prevalence of ESBLs-producing strains in E.coli,K.pneumoniae and P.mirabilis was 53.2％,52.8％and 37.0％,respectively.The prevalence of carbapenem-resistant strains in E.coli,K.pneumoniae,P.aeruginosa and A.baumannii was 1.7％,18.5％,16.4％,and 40.3％,respectively.Lower than 10％of the E.faecalis isolates were resistant to ampicillin,nitrofurantoin,linezolid,vancomycin,teicoplanin and fosfomycin.More than 90％of the E.faecium isolates were ressitant to ampicillin,levofloxacin and erythromycin.The percentage of strains resistant to vancomycin,linezolid or teicoplanin was＜2％.The E.coli,K.pneumoniae,P.aeruginosa and A.baumannii strains isolated from ICU inpatients showed significantly higher resistance rates than the corresponding strains isolated from outpatients and non-ICU inpatients.Conclusions E.coli,Enterococcus and K.pneumoniae are the most common pathogens in urinary tract infection.The bacterial species and antimicrobial resistance of urinary isolates vary with different populations.More attention should be paid to antimicrobial resistance surveillance and reduce the irrational use of antimicrobial agents.