Aim To anticipate the mechanism of zuka- mu granules (ZKMG) in the treatment of bronchial asthma, and to confirm the projected outcomes through in vivo tests via using network pharmacology and molecular docking technology. Methods The database was examined for ZKMG targets, active substances, and prospective targets for bronchial asthma. The protein protein interaction network diagram (PPI) and the medication component target network were created using ZKMG and the intersection targets of bronchial asthma. The Kyoto Encyclopedia of Genes and Genomics (KEGG) and gene ontology (GO) were used for enrichment analysis, and network pharmacology findings were used for molecular docking, ovalbumin (OVA) intraperitoneal injection was used to create a bronchial asthma model, and in vivo tests were used to confirm how ZKMG affected bronchial asthma. Results There were 176 key targets for ZKMG's treatment of bronchial asthma, most of which involved biological processes like signal transduction, negative regulation of apoptotic processes, and angiogenesis. ZKMG contained 194 potentially active components, including quercetin, kaempferol, luteolin, and other important components. Via signaling pathways such TNF, vascular endothelial growth factor A (VEGFA), cancer pathway, and MAPK, they had therapeutic effects on bronchial asthma. Conclusion Key components had strong binding activity with appropriate targets, according to molecular docking data. In vivo tests showed that ZKMG could reduce p-p38, p-ERKl/2, and p-I

BACKGROUND:Frog active peptides have rich activities,such as antibacterial and anti-tumor,and are expected to solve the problem of antibiotic resistance. OBJECTIVE:The active peptide QUB2984 was discovered in the skin secretions of Agalychnis callidryas.Its structure and properties were simulated by bioinformatics.The peptide was synthesized,purified,and identified and its biological functions were investigated. METHODS:Agalychnis callidryas skin secretions were collected by electrostimulation.The sequence of QUB2984 was obtained through constructing a cDNA library with isolated mRNA.BLAST was used for peptide sequence alignment.Besides that,Iterative Threading ASSEmbly Refinement(I-TASSER)and HeliQuest tools were used for protein secondary structure simulation.It was synthesized by solid-phase peptide synthesis,purified by reverse-phase high-performance liquid chromatography,and structurally confirmed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.The purified peptide was used to evaluate its biological activity.Its antibacterial effect was evaluated by the minimum inhibitory concentration method.Its cytotoxic effect was detected by MTT assay.Its safety was investigated by a hemolysis test. RESULTS AND CONCLUSION:(1)Peptide QUB2984 had basically α-spiral structure,with a relatively intact hydrophobic surface,and a certain destructive ability to biofilm.The third amino acid position of QUB2984 was composed of W and had a G-X-G structure.(2)The minimum inhibitory concentration of QUB2984 against gram-positive Staphylococcus aureus was 2 μmol/L,the minimum inhibitory concentration against gram-negative Escherichia coli was 2 μmol/L,and the minimum inhibitory concentration against the fungus Candida albicans was 8 μmol/L.(3)The active peptide QUB2984 had obvious inhibitory effect on human non-small cell lung cancer cells NCI-H838 at 10-5 mol/L concentration,and the hemolytic effect on horse red cells at 64 μmol/L concentration was 50%.(4)The results showed that QUB2984 had anti-bacterial and anti-cancer activity,and it had a positive charge of +3,which was conducive to contact with bacteria or cells.

OBJECTIVE: To determine the role of Tripterygium wilfordii multiglycoside (TGW) in the treatment of psoriatic dermatitis from a cellular immunological perspective. METHODS: Mouse models of psoriatic dermatitis were established by imiquimod (IMQ). Twelve male BALB/c mice were assigned to IMQ or IMQ₊TGW groups according to a random number table. Histopathological changes in vivo were assessed by hematoxylin and eosin staining. Ratios of immune cells and cytokines in mice, as well as PAM212 cell proliferation in vitro were assessed by flow cytometry. Pro-inflammatory cytokine expression was determined using reverse transcription quantitative polymerase chain reaction. RESULTS: TGW significantly ameliorated the severity of IMQ-induced psoriasis-like mouse skin lesions and restrained the activation of CD45⁺ cells, neutrophils and T lymphocytes (all P<0.01). Moreover, TGW significantly attenuated keratinocytes (KCs) proliferation and downregulated the mRNA levels of inflammatory cytokines including interleukin (IL)-17A, IL-23, tumor necrosis factor α, and chemokine (C-X-C motif) ligand 1 (P<0.01 or P<0.05). Furthermore, it reduced the number of γ δ T17 cells in skin lesion of mice and draining lymph nodes (P<0.01). CONCLUSIONS TGW improved psoriasis-like inflammation by inhibiting KCs proliferation, as well as the associated immune cells and cytokine expression. It inhibited IL-17 secretion from γ δ T cells, which improved the immune-inflammatory microenvironment of psoriasis.
Male ; Animals ; Mice ; Tripterygium ; Psoriasis/drug therapy* ; Keratinocytes ; Skin Diseases/metabolism* ; Cytokines/metabolism* ; Imiquimod/metabolism* ; Dermatitis/pathology* ; Disease Models, Animal ; Mice, Inbred BALB C ; Skin/metabolism*

Objective This study aimed to clarify the intervention effect of salidroside(SAL)on lung injury caused by PM2.5 in mice and illuminate the function of SIRT1-PGC-1ɑ axis. Methods Specific pathogen-free(SPF)grade male C57BL/6 mice were randomly assigned to the following groups:control group,SAL group,PM2.5 group,SAL+PM2.5 group.On the first day,SAL was given by gavage,and on the second day,PM2.5 suspension was given by intratracheal instillation.The whole experiment consist of a total of 10 cycles,lasting 20 days.At the end of treatment,blood samples and lung tissues were collected and analyzed.Observation of pathological changes in lung tissue using inverted microscopy and transmission electron microscopy.The expression of inflammatory,antioxidants,apoptosis,and SIRT1-PGC-1ɑ proteins were detected by Western blotting. Results Exposure to PM2.5 leads to obvious morphological and pathologica changes in the lung of mice.PM2.5 caused a decline in levels of antioxidant-related enzymes and protein expressions of HO-1,Nrf2,SOD2,SIRT1 and PGC-1ɑ,and an increase in the protein expressions of IL-6,IL-1β,Bax,caspase-9 and cleaved caspase-3.However,SAL reversed the aforementioned changes caused by PM2.5 by activating the SIRT1-PGC-1α pathway. Conclusion SAL can activate SIRT1-PGC-1ɑ to ameliorate PM2.5-induced lung injury.

AIM To explore the effects of Buyang Huanwu Decoction on mitochondrial oxidative damage and PKCε-Nampt pathway in rats following cerebral ischemia reperfusion(I/R).METHODS The rats were randomly divided into the sham operation group,the model group,Buyang Huanwu Decoction group(14.3 g/kg)and edaravone group(3 mg/kg).Except those of the sham operation group,SD rats of other groups were induced into models of brain I/R injury by MCAO method,followed by corresponding drug administration 24 hours after operation.After 7 days of administration,the rats had their neurological deficit evaluated by neurological function scoring;thier expression of neuron marker MAP-2 detected by immunofluorescence staining;their neuron damage observed and the oxidative damage evaluated through assessment of their ROS levels and MDA and SOD activities;their changes of mitochondrial membrane potential detected by fluorescent probe JC-1;their ratio of NAD+/NADH detected using modified enzyme circulation method;their expressions of PKCε,p-PKCε and Nampt proteins detected with Western blot;and their positive expressions of p-PKCε and Nampt proteins detected with immunohistochemistry method.RESULTS Compared with the model group,Buyang Huanwu Decoction group shared decreased cerebral infarction volume and neurological function score(P<0.05);increased cerebral fluorescence intensity of MAP-2(P<0.05);reduced neuronal damage,decreased cerebral levels of ROS and MDA(P<0.05);increased SOD activity,mitochondrial membrane potential and NAD+/NADH ratio(P<0.05);and increased protein expressions of p-PKCε and Nampt(P<0.05).CONCLUSION Buyang Huanwu Decoction can improve mitochondrial function and reduce brain I/R injury in rats by activating their PKCε-Nampt signaling pathway.

Objective:To evaluate the efficacy and safety of hypomethylating agents (HMA) in patients with myelodysplastic syndromes (MDS) .Methods:A total of 409 MDS patients from 45 hospitals in Zhejiang province who received at least four consecutive cycles of HMA monotherapy as initial therapy were enrolled to evaluate the efficacy and safety of HMA. Mann-Whitney U or Chi-square tests were used to compare the differences in the clinical data. Logistic regression and Cox regression were used to analyze the factors affecting efficacy and survival. Kaplan-Meier was used for survival analysis. Results:Patients received HMA treatment for a median of 6 cycles (range, 4-25 cycles) . The complete remission (CR) rate was 33.98% and the overall response rate (ORR) was 77.02%. Multivariate analysis revealed that complex karyotype ( P=0.02, OR=0.39, 95% CI 0.18-0.84) was an independent favorable factor for CR rate. TP53 mutation ( P=0.02, OR=0.22, 95% CI 0.06-0.77) was a predictive factor for a higher ORR. The median OS for the HMA-treated patients was 25.67 (95% CI 21.14-30.19) months. HMA response ( P=0.036, HR=0.47, 95% CI 0.23-0.95) was an independent favorable prognostic factor, whereas complex karyotype ( P=0.024, HR=2.14, 95% CI 1.10-4.15) , leukemia transformation ( P<0.001, HR=2.839, 95% CI 1.64-4.92) , and TP53 mutation ( P=0.012, HR=2.19, 95% CI 1.19-4.07) were independent adverse prognostic factors. There was no significant difference in efficacy and survival between the reduced and standard doses of HMA. The CR rate and ORR of MDS patients treated with decitabine and azacitidine were not significantly different. The median OS of patients treated with decitabine was longer compared with that of patients treated with azacitidine (29.53 months vs 20.17 months, P=0.007) . The incidence of bone marrow suppression and pneumonia in the decitabine group was higher compared with that in the azacitidine group. Conclusion:Continuous and regular use of appropriate doses of hypomethylating agents may benefit MDS patients to the greatest extent if it is tolerated.

Objective:To study the changes in skeletal muscle and serum nutritional indicators during concurrent chemoradiotherapy in cervical cancer patients,and to evaluate their correlation with short-term efficacy and long-term prognosis. Methods:A retrospective analysis was conducted on 114 patients with cervical cancer who underwent radical concurrent chemoradiotherapy in the Department of Oncology,Nanjing Drum Tower Hospital from February 2019 to February 2023. All patients underwent a treatment regimen comprising external beam radiation (EBRT),internal radiation,and concurrent chemotherapy. Serum nutritional data of the patients were collected before radiotherapy,one week,two weeks and five weeks after the onset of radiotherapy. CT images of the patients at the time of simulation and about five weeks after the onset of radiotherapy were imported into the Pinnacle 39.10 planning system,and the skeletal muscle index (SMI) of the third lumbar vertebra (L3) were calculated for each patients. The changes of the serum nutritional indicators of the patients prior to and post EBRT were analyzed statistically. The patients are categorized into two groups according to the baseline SMI:a sarcopenic group consisting of 35 cases and a non-sarcopenic group comprising 79 cases. The therapeutic outcomes between the two groups were compared,and logistic analysis of the relevant factors affecting the occurrence of sarcopenia during radiotherapy was conducted. The survival curves were drawn using Kaplan-Meier method and disease-free survival (DFS) between the two groups was compared using Log Rank test. We used Cox univariate and multivariate regression analysis to identify prognostic factors related to DFS. Results:The serum nutritional indicators of the patient at one week,two weeks,and five weeks after the beginning of EBRT were significantly lower than those before radiotherapy (P<0.05). The SMI from the CT images of simulation at five weeks after the onset of radiotherapy was significantly lower than that before radiotherapy (P<0.001). There was a significant correlation between hemoglobin levels prior to radiotherapy and incidence of sarcopenia during radiotherapy (P=0.046). There was no significant difference in efficacy between the two groups at the end of EBRT (P>0.05). At the end of radiotherapy,the complete response (CR) rate of the non-sarcopenia group was significantly higher than that of the sarcopenia group (P=0.040). However,the objective response rate (ORR) and disease control rate (DCR) of both groups at the end of radiotherapy were 100％. The 2-year DFS of the sarcopenia group and the non-sarcopenia group were 66.7％ and 85.5％,respectively,and the difference was statistically significant (P=0.016). Only four patients died during the 2-year follow-up,so OS was not reached. Baseline SMI,serum squamous cell antigen levels prior to radiotherapy,and degree of bone marrow suppression were three independent prognostic factors affecting DFS in the patients. Conclusion:Cervical cancer patients experience significant nutritional loss during chemoradiotherapy,and baseline SMI is significantly correlated with short-term efficacy and long-term prognosis and can serve as a predictive marker for patients with cervical cancer receiving chemoradiotherapy.

Further evidence is needed to explore the impact of high-altitude environments on the neurologic function of neonates.Non-invasive techniques such as cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography can provide data on cerebral oxygenation and brain electrical activity.This study will conduct multiple cerebral near-infrared spectroscopy and amplitude-integrated electroencephalography monitoring sessions at various time points within the first 3 days postpartum for healthy full-term neonates at different altitudes.The obtained data on cerebral oxygenation and brain electrical activity will be compared between different altitudes,and corresponding reference ranges will be established.The study involves 6 participating centers in the Chinese High Altitude Neonatal Medicine Alliance,with altitude gradients divided into 4 categories:800 m,1 900 m,2 400 m,and 3 500 m,with an anticipated sample size of 170 neonates per altitude gradient.This multicenter prospective cohort study aims to provide evidence supporting the impact of high-altitude environments on early brain function and metabolism in neonates.[Chinese Journal of Contemporary Pediatrics,2024,26(4):403-409]

Butyric acid is a type of short chain fatty acid and an important nutrient in intestinal epithelial cells.In addition to its important role in intestinal health,it has application value in anti-tumor,treatment of neuritis and di-abetes.At the same time,based on the demand for green development in the livestock industry,its anti-inflammato-ry effect can avoid the abuse of antimicrobial agents.As a green,pollution-free,and residue-free new feed,butyric acid ensures the sustainable and healthy development of the livestock industry.This article mainly summarizes the production of butyric acid in the intestine,its effects on the balance of gut microbiota,digestion ability,and inflam-mation in humans and animals,elaborates its application in human health and animal production.

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.