Based on the strategy of metabolomics combined with bioinformatics, this study analyzed the potential allergens and mechanism of pseudo-allergic reactions (PARs) induced by the combined use of Reduning injection and penicillin G injection. All animal experiments and welfare are in accordance with the requirements of the First Affiliated Experimental Animal Ethics and Animal Welfare Committee of Henan University of Chinese Medicine (approval number: YFYDW2020002). Based on UPLC-Q-TOF/MS technology combined with UNIFI software, a total of 21 compounds were identified in Reduning and penicillin G mixed injection. Based on molecular docking technology, 10 potential allergens with strong binding activity to MrgprX2 agonist sites were further screened. Metabolomics analysis using UPLC-Q-TOF/MS technology revealed that 34 differential metabolites such as arachidonic acid, phosphatidylcholine, phosphatidylserine, prostaglandins, and leukotrienes were endogenous differential metabolites of PARs caused by combined use of Reduning injection and penicillin G injection. Through the analysis of the "potential allergen-target-endogenous differential metabolite" interaction network, the chlorogenic acids (such as chlorogenic acid, neochlorogenic acid, cryptochlorogenic acid, and isochlorogenic acid A) and β-lactam allergens in the combination of the two may be mainly regulated by PLD1, PLA2G12A and CYP1A1. The three upstream signal target proteins mainly activate the arachidonic acid metabolic pathway, promote the degranulation of mast cells, release downstream endogenous inflammatory mediators, and induce PARs.

Based on the interaction between supramolecule of traditional Chinese medicine and enterobacteria, the material basis of Rhei Radix et Rhizoma and Coptidis Rhizoma was explored. Scanning electron microscopy (SEM) and dynamic light scattering (DLS) were used to characterize the morphological differences of Rhubarb single decoction, Coptis single decoction and Rhubarb and Coptis co-decoction. An in vitro antibacterial model (E. coli, E. faecium and B. subtilis) was established to evaluate the damage effect of the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma on enterobacteria. Ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was used to analyze the changes of chemical components of single decoctions and co-decoctions. The co-decoction of Rhei Radix et Rhizoma and Coptidis Rhizoma was turbid after decocting. The spherical particles of 300-400 nm were observed under SEM, and the co-decoction was more uniform and stable than that of single decoction. The interaction between supramolecules formed after the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma and enterobacteria was significantly different from that of single decoction. In the process of interaction between supramolecules and enterobacteria, the spherical state was maintained, and the medicinal ingredients in Coptidis Rhizoma or Rhei Radix et Rhizoma were blocked, which could effectively alleviate the damage to enterobacteria. This study provided a reference for subsequent studies on the regulation of intestinal flora homeostasis by the combination of Rhei Radix et Rhizoma and Coptidis Rhizoma.

Objective To investigate the clinical characteristics,treatment methods,and prognosis of a-cute leukemia patients with extramedullary infiltration.Methods The clinical characteristics and treatment methods of 47 acute leukemia patients with extramedullary infiltration admitted to the Affiliated Hospital of Guizhou Medical University from April 2014 to April 2023 were retrospectively analyzed.Subgroup analysis was performed according to whether there was extramedullary infiltration before transplantation,and whether there was isolated extramedullary recurrence after transplantation.Based on this analysis,the patients were di-vided into the pre-transplantation radiotherapy group and pre-transplantation non-radiotherapy group,the post-transplantation radiotherapy group and post-transplantation non-radiotherapy group.According to the treatment methods of central nervous system leukemia(CNSL),the patients were divided into the intrathecal injection group(n=12)and combination of intrathecal injection and radiotherapy group(n=13).The local remission situation,survival duration,and toxic and side effects of radiotherapy and chemotherapy were com-pared.Results For acute leukemia patients with extramedullary infiltration,the overall survival time(OS)in the radiotherapy group was better than that in the non-radiotherapy group(median OS:706 d vs.151 d,P=0.015).Subgroup analysis showed that the OS of the pre-transplantation radiotherapy group was better than that of the pre-transplantation non-radiotherapy group(median OS:592 d vs.386 d,P=0.035).For CNSL,the combination of intrathecal injection and radiotherapy group had a better OS than the intrathecal injection group(median OS:547 d vs.388 d,P=0.045).The event-free survival time(EFS)of the radiotherapy group was better than that of the non-radiotherapy group(median EFS:175 d vs.50 d,P=0.005).The COX pro-portional-hazards model showed that treatment with or without radiotherapy had a significant impact on the OS of acute leukemia patients with extramedullary infiltration.The risk of death in the pre-transplantation non-radiotherapy group was 2.231 times higher than that in the pre-transplantation radiotherapy group(HR=3.231,95％CI:1.021-10.227,P=0.046).Compared with the non-radiotherapy group,the radiother-apy group had a higher local remission and a lower risk of haematological toxicity,infection,and haemorrhage.Conclusion Radiotherapy can rapidly alleviate the local symptoms of acute leukemia complicated with extr-amedullary infiltration,prolong the survival time of these patients,and reduce the risk of hematologic toxicity,infection,and haemorrhage.

Platycodonis Radix is the dry root of Platycodon grandiflorum of Campanulaceae, which has a variety of pharmacological effects and is a commonly used bulk Chinese medicine. In this study, the chloroplast genome sequences of six P. grandiflorum from different producing areas has been sequenced with Illumina HiSeq X Ten platform. The specific DNA barcodes were screened, and the germplasm resources and genetic diversity were analyzed according to the specific barcodes. The total length of the chloroplast genome of 6 P. grandiflorum samples was 172 260-172 275 bp, and all chloroplast genomes showed a typical circular tetrad structure and encoded 141 genes. The comparative genomics analysis and results of amplification efficiency demonstrated that trnG-UCC and ndhG_ndhF were the potential specific DNA barcodes for identification the germplasm resources of P. grandiflorum. A total of 305 P. grandiflorum samples were collected from 15 production areas in 9 provinces, for which the fragments of trnG-UCC and ndhG_ndhF were amplificated and the sequences were analyzed. The results showed that trnG-UCC and ndhG_ndhF have 5 and 11 mutation sites, respectively, and 5 and 7 haplotypes were identified, respectively. The combined analysis of the two sequences formed 13 haplotypes (named Hap1-Hap13), and Hap4 is the main genotype, followed by Hap1. The unique haplotypes possessed by the three producing areas can be used as DNA molecular tags in this area to distinguish from the germplasm resources of P. grandiflorum from other areas. The haplotype diversity, nucleotide diversity and genetic distance were 0.94, 4.79×10^-3 and 0.000 0-0.020 3, respectively, suggesting that the genetic diversity was abundant and intraspecific kinship was relatively close. This study laid a foundation for the identification of P. grandiflorum, the protection and utilization of germplasm resources, and molecular breeding.

Microorganisms can form biofilms, complex, heterogeneous, multicellular communities that adhere to surfaces. Biofilm formation on the surface of structures in water will accelerate structures’ corrosion, seriously affect their service efficiency and life, and significantly impact the growth of animals, plants, and human life. Hence, clarifying the mechanism of biofilm formation contributes to developing new strategies to control biofilm formation on surface and then reduce infections, biofouling, and contaminations. Biofilm-targeting strategies include the regulation of established biofilms or the modulation of single-cell attachment. In most studies, physicochemical mechanism is frequently applied to explain the initial bacterial adhesion phenomena but rarely to explain other stages of biofilm formation. This review presents a five-step comprehensive description of the physicochemical process from film formation to biofilm maturation: (1) period of film formation; (2) period of bacterial adhesion; (3) period of extracellular-polymeric-substances (EPSs) membrane formation; (4) period of regulating biofilm by quorum sensing (QS); (5) period of biofilm maturation. We first clarify how the film formed by compound molecules affects the surface’s physicochemical properties and initial adhesion, summarizing many factors that affect bacterial adhesion. We then review the types of EPSs and signal molecules secreted by bacteria after irreversible adhesion, as well as their role and QS mechanism in biofilm maturation. Finally, we discuss how bacteria or microcolonies separate from the mature biofilm by physicochemical action and summarize the morphology and adhesion characterization methods after the biofilm matures. This review redefines the role of physicochemical in the whole process of biofilm formation and provides a theoretical basis for the prevention, removal, and utilization of biofilm and other related research fields.

Objective To explore the effects of dydrogesterone combined with granulocyte colony-stimulating factor(G-CSF)on blood flow parameters and sex hormone levels in patients with thin endometrial(TE)infertility.Methods TE infertility patients were randomly divided into control group and treatment group.All patients were treated with freezing-thawing embryo transfer.The control group was treated with desdrogesterone after ovulation monitoring by vaginal ultrasound,10 mg each time,bid,and stopped until the 14th day after ovulation.In treatment group,G-CSF was given on the basis of control group,and the endometrial thickness and hemodynamic parameters were monitored by vaginal ultrasound 3 days later,and then embryo transfer was performed.Blood flow parameters,ultrasound parameters,endometrial morphology,sex hormone levels[follicle stimulating hormone(FSH),luteinizing hormone(LH),estradiol(E2),progesterone(P)]and pregnancy status were compared between the two groups.Results There were 49 cases in treatment group and 49 cases in control group.After treatment,endometrial thickness in treatment group and control group were(9.59±1.35)and(7.89±1.14)mm;follicle diameter were(19.35±1.58)and(17.75±1.42)mm;uterine volume were(92.68±7.85)and(85.69±6.74)cm3;PI were 1.29±0.27 and 1.74±0.32;RI were 0.32±0.09 and 0.50±0.11;peak systolic/end-diastolic velocity(S/D)were 2.03±0.28 and 2.21±0.25;P were(45.98±5.75)and(39.15±5.78)nmol·L-1;E2 were(462.58±58.42)and(339.45±45.97)pg·mL-1;FSH were(12.18±2.58)and(9.42±1.42)U·L-1;LH were(29.42±4.18)and(22.25±3.40)U·L-1;there were statistically significant differences between the two groups(all P＜0.05).The clinical pregnancy rate(51.02％)and implantation rate(57.14％)in treatment group were higher than those in control group(30.61％and 36.73％),and the differences were statistically significant(all P＜0.05).Conclusion Dydrogesterone combined with G-CSF can improve blood flow parameters,endometrial thickness and sex hormone levels in TE infertility patients,and help to increase the embryo implantation rate.

Objective To explore the potential mechanism of action of paeoniflorin in diabetes mellitus,the related targets and pathways were preliminarily discussed,based on the network pharmacology and molecular docking technology.Methods Analyze the potential targets of paeoniflorin using the Swiss Target Prediction database.Genecards and OMIM databases yielded the genes of diabetes-related illnesses.After taking the intersection of the two,protein-protein interaction network(PPI)was established using STRING and Cytoscape programs to search for key genes with strong correlation and complete gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis.Use AutoDockTools and Pymol programs to complete protein molecule docking validation.Results The pharmacologically-related study revealed 63 targets associated with paeoniflorin,4 758 genes related to diabetes,and 50 intersection targets.15 key genes including vascular endothelial growth factor A(VEGFA),epidermal growth factor receptor(EGFR),V-Ha-ras harvey(HRAS),V-src sarcoma(SRC)and heat shock protein hs 90-alpha(HSP90AA1)were screened.RAs-associated protein 1,Ras,calcium and other signaling pathways were obtained by KEGG pathway analysis.Molecular docking results showed that paeoniflorin had good binding ability with key genes.Conclusion Paeoniflorin can treat diabetes through multiple targets and pathways,and this mechanism can provide a basis for the application of paeoniflorin in anti diabetes and drug research and development.

Objective To observe the intervention effect of hypericin(HYP)on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced Parkinson's disease(PD)mice model and its mechanism.Methods Thirty C57BL/6 mice were randomly divided into normal,model and experimental groups with 10 mice per group.PD mouse model was established after 7 days of intraperitoneal injection of MPTP,and drug intervention was carried out from the first day of modeling.Normal group and model group were intraperitoneally injected with 500 μL·kg·d-1 0.9％NaCl.The experimental group was intraperitoneally injected with 25 mg·kg·d-1 HYP.The three groups of rats were given the drug once each time for 14 days.The expression levels of tyrosine hydroxylase(TH),Nod-like receptor thermal protein domain protein 3(NLRP3)and ionized calcium binding adapter molecule 1(Iba1)in the striatum of nigra were detected by Western blot.Results The climbing time of normal,model and experimental groups was(5.35±0.43),(9.71±1.19)and(8.07±0.34)s;suspension scores were(2.92±0.15),(1.38±0.28)and(1.96±0.28)points;the relative expression levels of TH protein were 1.04±0.06,0.51±0.09 and 0.75±0.07;the relative expression levels of NLRP3 protein were 0.51±0.03,1.00±0.04 and 0.77±0.06;the relative expression levels of Iba1 protein were 0.68±0.10,1.30±0.28 and 0.89±0.05,respectively.The above indexes in the model group were statistically significant compared with the experimental group and the normal group(all P＜0.01).Conclusion HYP plays a therapeutic role in PD by inhibiting the expression of NLRP3 inflammasome in PD mice.

Objective To compare the efficacy and safety of Saccharomyces boulardii and other probiotics in the treatment of pediatric diarrhea.Methods Retrieved from PubMed,Embase,CBM,Wanfang data,CNKI and VIP,randomized controlled trial(RCTs)about Saccharomyces boulardii(treatment group)vs other probiotics(control group)were collected.After screening the literature,extracting data and evaluating the quality,Meta-analysis was performed by using RevMan 5.3 and Stata 17.0 software.Results A total of 30 RCTs were included,involving 3 082 children.Results of Meta-analysis showed there was no statistical significance in the duration of diarrhea[mean difference(MD)=-0.65,95％confidence interval(CI)=-1.44-0.14,P＞0.05]or the total incidence of adverse reactions[odds ratio(OR)=0.85,95％CI=0.44-1.62,P＞0.05].The total effective rate(OR=1.60,95％CI=1.08-2.36,P＜0.05)and the number of stools(MD=-0.66,95％CI=-1.00--0.32,P＜0.01)in the treatment group were significantly better than control group.There was statistically significant difference in the duration of diarrhea between the two groups treated with diarrhea with fever(MD=1.81,95％CI=1.12-2.49,P＜0.01)and rotavirus gastroenteritis(MD=-0.92,95％CI=-1.20--0.64,P＜0.01).In the treatment of diarrhea with fever,the duration of diarrhea in the control group was significantly shorter than that in the treatment group.The duration of diarrhea in the treatment group was significantly shorter than that control group.At the same time,the duration of diarrhea in children with diarrhea treated with treatment group was significantly shorter than that of control group Bifidobacterium tetragenous viable(MD=-0.84,95％CI=-1.09--0.58,P＜0.01)and control group combined Bacillus subtilis and Enterococcus faecium enteric-coated(MD=-1.35,95％CI=-2.30-0.39,P＜0.01).Conclusion The safety of Saccharomyces boulardii are similar to other probiotics.The efficacy and the number of stools with Saccharomyces boulardii are significantly better than other probiotics in the treatment of diarrhea.The duration of diarrhea in Saccharomyces boulardii group was significantly shorter than other probiotics,while in the treatment of antibiotic-associated diarrhea,the duration of diarrhea of Saccharomyces boulardii was the same as that of other probiotics.However,the duration of diarrhea in children with diarrhea treated with Saccharomyces boulardii was significantly longer than other probiotics.

Objective To explore characteristics of clinical parameters and cytokines in patients with drug-induced liver injury(DILI)caused by different drugs and their correlation with clinical indicators. Method The study was conducted on patients who were up to Review of Uncertainties in Confidence Assessment for Medical Tests(RUCAM)scoring criteria and clinically diagnosed with DILI.Based on Chinese herbal medicine,cardiovascular drugs,non-steroidal anti-inflammatory drugs(NSAIDs),anti-infective drugs,and other drugs,patients were divided into five groups.Cytokines were measured by Luminex technology.Baseline characteristics of clinical biochemical indicators and cytokines in DILI patients and their correlation were analyzed. Results 73 patients were enrolled.Age among five groups was statistically different(P=0.032).Alanine aminotransferase(ALT)(P=0.033)and aspartate aminotransferase(AST)(P=0.007)in NSAIDs group were higher than those in chinese herbal medicine group.Interleukin-6(IL-6)and tumor necrosis factor alpha(TNF-α)in patients with Chinese herbal medicine(IL-6:P<0.001;TNF-α:P<0.001)and cardiovascular medicine(IL-6:P=0.020;TNF-α:P=0.001)were lower than those in NSAIDs group.There was a positive correlation between ALT(r=0.697,P=0.025),AST(r=0.721,P=0.019),and IL-6 in NSAIDs group. Conclusion Older age may be more prone to DILI.Patients with NSAIDs have more severe liver damage in early stages of DILI,TNF-α and IL-6 may partake the inflammatory process of DILI.