Molecular mechanism of Xuebijing in treating pyogenic liver abscess complicated with sepsis

BACKGROUND:Xuebijing(XBJ)can alleviate the inflammatory response,improve organ function,and shorten the intensive care unit(ICU)stay in patients with pyogenic liver abscess(PLA)complicated with sepsis,but the molecular mechanisms have not been elucidated.This study aimed to explore the molecular mechanism of XBJ in treating PLA complicated with sepsis using a network pharmacology approach.METHODS:The active ingredients and targets of XBJ were retrieved from the ETCM database.Potential targets related to PLA and sepsis were retrieved from the GeneCards,PharmGKB,DisGeNet,Online Mendelian Inheritance in Man(OMIM),Therapeutic Targets Database(TTD),and DrugBank databases.The targets of PLA complicated with sepsis were mapped to the targets of XBJ to identify potential treatment targets.Protein-protein interaction networks were analyzed using the STRING database.Potential treatment targets were imported into the Metascape platform for Gene Ontology(GO)functional enrichment and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analyses.Molecular docking was performed to validate the interactions between active ingredients and core targets.RESULTS:XBJ was found to have 54 potential treatment targets for PLA complicated with sepsis.Interleukin-1β(IL-1β),interleukin-6(IL-6),and tumor necrosis factor(TNF)were identifi ed as core targets.KEGG enrichment analysis revealed important pathways,including the interleukin-17(IL-17)signaling pathway,the TNF signaling pathway,the nuclear factor-kappa B(NF-κB)signaling pathway,and the Toll-like receptor(TLR)signaling pathway.Molecular docking experiments indicated stable binding between XBJ active ingredients and core targets.CONCLUSION:XBJ may exert therapeutic eff ects on PLA complicated with sepsis by modulating signaling pathways,such as the IL-17,TNF,NF-κB,and TLR pathways,and targeting IL-1β,IL-6,and TNF.

Xuebijing improves intestinal microcirculation dysfunction in septic rats by regulating the VEGF-A/PI3K/Akt signaling pathway

BACKGROUND:This study aims to explore whether Xuebijing(XBJ) can improve intestinal microcirculation dysfunction in sepsis and its mechanism.METHODS:A rat model of sepsis was established by cecal ligation and puncture(CLP).A total of 30 male SD rats were divided into four groups:sham group,CLP group,XBJ + axitinib group,and XBJ group.XBJ was intraperitoneally injected 2 h before CLP.Hemodynamic data(blood pressure and heart rate) were recorded.The intestinal microcirculation data of the rats were analyzed via microcirculation imaging.Enzyme-linked immunosorbent assay(ELISA) kits were used to detect the serum levels of interleukin-6(IL-6),C-reactive protein(CRP),and tumor necrosis factor-α(TNF-α) in the rats.Histological analysis and transmission electron microscopy were used to analyze the injury of small intestinal microvascular endothelial cells and small intestinal mucosa in rats.The expression of vascular endothelial growth factor A(VEGF-A),phosphoinositide 3-kinase(PI3K),phosphorylated PI3K(p-PI3K),protein kinase B(Akt),and phosphorylated Akt(p-Akt) in the small intestine was analyzed via Western blotting.RESULTS:XBJ improved intestinal microcirculation dysfunction in septic rats,alleviated the injury of small intestinal microvascular endothelial cells and small intestinal mucosa,and reduced the systemic inflammatory response.Moreover,XBJ upregulated the expression of VEGF-A,p-PI3K/total PI3K,and p-Akt/total Akt in the rat small intestine.CONCLUSION:XBJ may improve intestinal microcirculation dysfunction in septic rats possibly through the VEGF-A/PI3K/Akt signaling pathway.

Analysis of the Efficacy of Xuebijing Combined with Antimicrobials in the Treatment of Intensive Care Unit Patients with Severe Pneumonia

Objective:To analyze the therapeutic effect of Xuebijing+antimicrobials in intensive care unit(ICU)patients with severe pneumonia.Methods:60 ICU patients with severe pneumonia from June 2021 to June 2023 were selected and divided by the random number table method,with 30 cases in each group.The observation group received Xuebijing+antimicrobial treatment,while the control group received only antimicrobial treatment.The differences in rehabilitation indexes,test indexes,and inflammation indexes were compared between the two groups.Results:Mechanical ventilation time,fever reduction time,cough relief time,and hospitalization time of the observation group were significantly shorter than those of the control group(P<0.05);C-reactive protein,procalcitonin,and white blood cell count of the observation group were significantly lower than those of the control group(P<0.05);interleukin-6 and tumor necrosis factor-aαof the observation group were significantly lower than those of the control group(P<0.05).Conclusion:The treatment of severe pneumonia patients in ICU with Xuebijing+antibacterial drugs can reduce inflammation,enhance immune function,shorten the pneumonia recovery time,and reduce the adverse reactions of severe pneumonia.

Intravenous injection of Xuebijing attenuates acute kidney injury in rats with paraquat intoxication

BACKGROUND: The study aimed to investigate the therapeutic benefits of intravenous Xuebijing on acute kidney injury(AKI) in rats with paraquat intoxication.METHODS: Male Sprague-Dawley rats were randomly divided equally into three groups: sham group(n=8), paraquat group(n=8) and Xuebijing-treated group(n=8) using a random number table. The rats were intraperitoneally injected with 50 mg/kg of paraquat. One hour after paraquat administration, the rats were treated intravenously with Xuebijing(8 mL /kg). At 12 hours after paraquat administration, serum was collected to evaluate kidney function, then the rats were sacrificed and kidney samples were immediately harvested. AKI scores were evaluated by renal histopathology and pro-in? ammatory cytokines mR NA levels in kidney were assayed using real-time RT-PCR.RESULTS: Serum urea nitrogen, creatinine and AKI scores were significantly higher in the paraquat group, compared with the sham group(P<0.05, respectively). Moreover, interleukin(IL)-1β, IL-6 and TNF-α m RNA levels were signi? cantly higher in the paraquat group(P<0.01, respectively). However, intravenous Xuebijing signi? cantly decreased serum urea nitrogen, creatinine, AKI scores and IL-1β, IL-6 and TNF-α m RNA levels, compared with the paraquat group(P<0.05, respectively).CONCLUSION: Intravenous Xuebijing attenuates AKI following paraquat poisoning by suppressing in? ammatory response.

Xuebijing alters tumor necrosis factor-alpha, interleukin-1beta and p38 mitogen activated protein kinase content in a rat model of cardiac arrest following cardiopulmonary resuscitation

We established a rat model of cardiac arrest by clamping the endotracheal tube of adult rats at expiration. Twenty-four hours after cardiopulmonary resuscitation, nerve cell injury and expression of tumor necrosis factor-α, interleukin-1β, and p38 mitogen activated protein kinase content were increased. Rats injected with Xuebijing, a Chinese herb compound preparation, exhibited normal cellular structure and morphology, dense neuronal cytoplasm, and decreased tumor necrosis factor-α, interleukin-1β, and p38 mitogen activated protein kinase expression at 24 hours following cardiopulmonary resuscitation. These data suggest that Xuebijing can attenuate neuronal injury induced by hypoxia and reperfusion during cardiopulmonary resuscitation.

Novel assays for quality evaluation of XueBiJing:Quality variability of a Chinese herbal injection for sepsis management

XueBiJing is an intravenous five-herb injection used to treat sepsis in China.The study aimed to develop a liquid chromatography-tandem mass spectrometry(LC-MS/MS)-or liquid chromatography-ultraviolet(LC-UV)-based assay for quality evaluation of XueBiJing.Assay development involved identifying marker constituents to make the assay therapeutically relevant and building a reliable one-point calibrator for monitoring the various analytes in parallel.Nine marker constituents from the five herbs were selected based on XueBiJing's chemical composition,pharmacokinetics,and pharmacodynamics.A selectivity test(for“similarity of response”)was developed to identify and minimize interference by nontarget constituents.Then,an intercept test was developed to fulfill“linearity through zero”for each analyte(absolute ratio of intercept to C response,<2%).Using the newly developed assays,we analyzed samples from 33 batches of XueBiJing,manufactured over three years,and found small batch-to-batch variability in contents of the marker constituents(4.1%-14.8%),except for senkyunolide I(26.5%).

Effects of Xuebijing Combined with Ulinastatin on Coagulation Function of Sepsis Patients

[Objectives] To study the effects of Xuebijing combined with ulinastatin on coagulation function of sepsis patients. [Methods]Fifty six patients conforming to the diagnosis criteria for sepsis and receiving the treatment from May 2015 to January 2019 were selected. They were randomly divided into treatment group and control group according to the order of treatment. The two groups were treated according to the International Guidelines for Management of Severe Sepsis and Septic Shock( 2012),in which ulinastatin and Xuebijing were added to the treatment group. Before the treatment and on the seventh day after the treatment,both groups of patients were measured for the activated partial thromboplastin time( APTT),fibrinogen( Fi B),platelet( PLT),and prothrombin time( PT) were measured;the treatment status of the both groups was continuously observed for 7 d,and the mechanical ventilation time,ICU hospitalization time,and 30-day survival rate were recorded. [Results] Both FIB and PLT of the treatment group were significantly increased,and both APTT and PT were significantly shortened.Compared with the control group,the difference was statistically significant( P < 0. 05). The mechanical ventilation time and ICU hospitalization time of the treatment group were significantly shorter than that of the control group,and the 30-day survival rate of the treatment group was significantly higher than that of the control group,and the difference was statistically significant( P < 0. 05). [Conclusions]Xuebijing combined with ulinastatin can improve coagulation disorders of sepsis patients.

Effect of Xuebijing injection on myocardium during cardiopulmonary bypass:A prospective,randomized,double blind trial

BACKGROUND Cardiopulmonary bypass(CPB)is an essential procedure for maintaining the blood supply to vital organs in patients undergoing cardiac surgery.However,perioperative cardiac injury related to CPB remains a severe complication in these patients.Cardiac protection is important for patients undergoing CPB.AIM To evaluate the potential cardioprotective efficacy of the Chinese medicine preparation Xuebijing injection(XBJ)in patients undergoing CPB.METHODS Sixty patients undergoing cardiac surgery with CPB were randomly allocated to the XBJ and control groups(saline).XBJ was administered intravenously three times:12 h prior to surgery,at the beginning of the surgery,and 12 h after the second injection.Cardiac function was evaluated by echocardiography 48 h after surgery.Circulating inflammation-and oxidative-stress-related markers were measured.Clinical outcomes related to intensive care unit(ICU)stay were recorded.RESULTS Compared to control treatment,XBJ was associated with improved PaO2/FiO2 and cardiac systolic function,but reduced troponin I and creatine kinase fraction after surgery(all P<0.05).The circulating concentrations of tumor necrosis factor-α,interleukin(IL)-1βand IL-8 in the XBJ group were significantly lower than those in the control group(all P<0.05),whereas the circulating concentration of IL-10 was significantly higher in the XBJ group(P<0.05).In addition,the lengths of ICU stay and hospitalization after surgery tended to be shorter in the XBJ group than in the control group,although the differences were not significant.CONCLUSION Perioperative administration of XBJ was associated with attenuated cardiac injury during CPB,likely via anti-inflammatory and antioxidative mechanisms.

The protective effects of Xuebijing injection on intestinal injuries of mice exposed to irradiation

Background:Gastrointestinal(GI)injury is one of the most common side effects of radiotherapy.However,there is no ideal therapy method except for symptomatic treatment in the clinic.Xuebijing(XBJ)is a traditional Chinese medicine,used to treat sepsis by injection.In this study,the protective effects of XBJ on radiation-i nduced intestinal injury(RⅢ)and its mechanism were explored.Methods:The effect of XBJ on survival of irradiated C57BL/6 mice was monitored.Histological changes including the number of crypts and the length of villi were evaluated by H&E.The expression of Lgr5^(+)intestinal stem cells(ISCs),Ki67^(+)cells,villin and lysozymes were examined by immunohistochemistry.The expression of cytokines in the intestinal crypt was detected by RT-PCR.DNA damage and apoptosis rates in the small intestine were also evaluated by immunofluorescence.Results:In the present study,XBJ improved the survival rate of the mice after 8.0and 9.0 Gy total body irradiation(TBI).XBJ attenuated structural damage of the small intestine,maintained regenerative ability and promoted proliferation and differentiation of crypt cells,decreased apoptosis rate and reduced DNA damage in the intestine.Elevation of IL-6 and TNF-α was limited,but IL-1,TNF-β and IL-10 levels were increased in XBJ-treated group after irradiation.The expression of Bax and p53 were decreased after XBJ treatment.Conclusions:Taken together,XBJ provides a protective effect on RⅢby inhibiting inflammation and blocking p53-related apoptosis pathway.

Efficacy of Xuebijing injection for the treatment of coronavirus disease 2019 via network pharmacology

Background:To evaluate the mechanism of Chinese patent drug Xuebijing(XBJ)injection in the treatment of a new coronavirus disease 2019(COVID-19)based on network pharmacology and molecular docking technology.Methods:The TCMSP database was employed to collect and screen the active ingredients of the Chinese herb contained in the XBJ injection.The GeneCards database and STRING database were applied to collect and expand the targets of COVID-19 and compare and screen the related targets of COVID-19 by XBJ injection.Cytoscape was employed to build a network connecting Chinese medicine,compounds,targets,disease,and topology analysis was performed via the Network Analyzer to screen the key ingredients and targets.The software of Schrödinger molecular docking was used to verify the binding activity of the key ingredients of XBJ injection and the key targets of COVID-19.Metascape platform and DAVID database were utilized to conduct Gene Ontology analysis and Kyoto Encyclopedia of Genes and Genomes analysis on the key targets of COVID-19 treated by XBJ injection.Results:Eight key compounds and 15 key targets were screened and verified by molecular docking;these key compounds included luteolin,quercetin,baicalein,and kaempferol.The key targets included DPP4,AR,ESR1,CALM1,and protein kinase 1.Gene Ontology analysis involved an apoptosis and hypoxia reaction and the changes in blood vessel morphology.Kyoto Encyclopedia of Genes and Genomes analysis involved signaling pathways of hypoxia inducible factor-1,VEGF,and PI3K/AKT/NF-κB.Conclusion:The mechanism of XBJ injection when used to treat COVID-19 should be further investigated as the key compounds in XBJ regulated the expression of key targets such as protein kinase 1,VEGF-A,B-cell lymphoma-2,and TNF,which affected the COVID-19 receptors such as angiotensin-converting enzyme 2 and signaling pathways like hypoxia inducible factor-1,PI3K-Akt,and NF-κB,which alleviated the inflammation,respiratory distress,and hypoxia caused by COVID-19 infection.

Effect of traditional Chinese preparation Xuebijing on inflammatory markers in patients with ventilator-associated pneumonia

Objective:To observe the effect of Xuebijing,a complex traditional Chinese preparation,on inflammation and prognosis of patients with pneumonia.Methods:The patients with ventilator-associated pneumonia in the intensive care unit(ICU)were randomly divided into the control group and the treatment group with 35 cases in each group.Both groups were given routine treatment such as anti-inflammatory drugs,rehydration,expectorant,and nutritional support,while the treatment group was additionally given Xuebijing injection.Serum C-reactive protein(CRP),clinical pulmonary infection score(CPIS),acute physiology,and chronic health scoreⅡ(APACHEⅡ)were recorded before treatment,the 3rd and 7th day after treatment.The duration of antibiotic use,mechanical ventilation,ICU stay,and mortality during 28 days was recorded.Results:There was no significant difference in CRP,CPIS,and APACHEⅡbetween the two groups before treatment(P>0.05).The improvement of CRP,CPIS,and APACHEⅡin the treatment group was better than those in the control group on the 3 and 7 days after treatment,and the differences were statistically significant(P<0.05).The duration of antibiotic use,mechanical ventilation,and ICU stay in the treatment group were less than those in the control group(P<0.05).The 28-day mortality of the treatment group was lower than that of the control group,but the difference was not statistically significant(P>0.05).Conclusions:Xuebijing injection can improve the inflammatory indexes of patients with ventilator-associated pneumonia,and can partly improve the prognosis.

Effects of Changtuoning and Xuebijing combined with hemoperfusion on serum inflammatory factors and myocardial enzymes in patients with acute severe organophosphorus poisoning

Objective:To investigate the effects of Changtuogning and Xuebijing combined with hemoperfusion on serum inflammatory factors and myocardial enzymes in patients with acute severe organophosphorus pesticide poisoning (AOPP).Methods: A total of 92 patients with acute severe AOPP who were admitted to our hospital from July 2015 to June 2018 were enrolled. All patients were divided into the observation group and the control group by randomized block method (n=46). The control group was treated with Changtuoning and Xuebijing, and the observation group was treated with Changtuoning and Xuebijing combined with blood perfusion. The clinical indexes, serum inflammatory factors, myocardial enzyme indexes, complications and adverse reactions were compared between the two groups.Results:The doses of atropine, recovery waking time, ChE recovery time and hospital stay in the observation group were significantly lower than those in the control group. The cure rate in the observation group was significantly higher than that in the control group (P<0.05). There was no significant difference between the two groups (P>0.05). The levels of TNF-α, IL-8 and IL-18 in the observation group were significantly lower than those in the control group (P<0.05). The levels of CK, CK-MB, LDH and AST in the observation group were significantly lower than those in the control group (P<0.05). The incidence of complications (intermediate syndrome, respiratory failure, pulmonary infection, pulmonary edema) in the observation group was significantly lower than that in the control group (P<0.05). The incidence of adverse reactions (myalgia, fatigue, digestive tract reaction, abnormal liver function) in the observation group was significantly lower than that in the control group (P<0.05).Conclusion:Changtuoning and Xuebijing combined with hemoperfusion have significant effects on patients with acute severe organophosphorus poisoning, which can effectively reduce inflammatory factors and improve myocardial enzyme index.

The effect of Xuebijing on burn patients and its effect on pain and wound healing

Objective:To explore the therapeutic effect of Xuebijing on burn patients and its effect on pain and wound healing.Methods:The burn patients treated in our hospital were selected and divided into two groups according to single and double numbers.The first group,the conventional treatment group(CT group):take conventional treatment to treat this group of burn patients;the second group,Xuebijing group(BWN group):take the CT group+Xuebijing combination treatment of this group of burn patients,37 cases in each group.There was no difference in general data between CT group and BWN group.To explore the differences between prothrombin time(PT),thrombin time(TT),fibrinogen(FIB),pain,secondary effects,and wound healing in CT group and BWN group The therapeutic effect of the patient and its effect on pain and wound healing.Results:Examination showed that the coagulation indexes of patients in CT group were 26.34±4.25,17.69±4.12,2.01±0.78,the coagulation indexes of patients in BWN group were 17.49±3.56,11.07±2.39,3.56±1.14,compared with CT group and BWN group In the CT group,the prothrombin time(PT)and thrombin time(TT)indicators were higher than those in the BWN group,but fibrinogen(FIB)was significantly lower than that in the BWN group(p<0.05).It can be seen from the table that before treatment,the visual analogue scoring(VAS)scores of patients in CT group and BWN group were 6.64±1.12 and 6.98±1.08,respectively,with a small difference(p>0.05).After treatment,CT group and BWN group scores They were 4.56±1.16 and 2.12±0.97 respectively.Compared with CT group and BWN group,the VAS score of CT group was significantly higher than that of BWN group(p<0.05).After treatment,the number of wound healing days in the BWN group(20.68±3.14d)was less than that in the CT group(32.89±4.25d)(P<0.05),but the wound healing rate(96.48±6.89%)was significantly higher than the CT group(81.17±5.74%)(P<0.05).In the CT group,3 patients had blood accumulation,2 infections,and 3 effusions.In the BWN group,there were 0 blood accumulations,1 infection,and 2 effusions.Compared with the CT group and the BWN group,the number and incidence of the BWN group(8.12%)Are less than CT group(21.62%)(p<0.05).The patient's leg suffered third-degree burns.After 5 weeks of treatment,the edge of the allogeneic skin on the CT group began to peel off and the epidermis fell off.Rejection.Conclusion:Conventional treatment+Xuebijing treatment,its curative effect is significant,can significantly accelerate the wound healing rate,and at the same time,reduce the incidence of secondary effects.

Efficacy and safety of Xuebijing injection in the treatment of vascular endothelial injury in sepsis patients:A meta-analysis

Objective:To systematically evaluate the efficacy and safety of Xuebijing injection in the treatment of vascular endothelial injury in sepsis,and to provide evidence-based reference for clinical medication.Methods:The randomized controlled trials of Xuebijing injection combined with conventional treatment(experimental group)versus conventional treatment(control group)for sepsis were collected by computer search of Chinese CNKI database,WANFANG database,and VIP database.Literature screening was performed according to the inclusion and exclusion criteria.According to the Cochrane International Collaboration Evaluator Workbook procedure,the quality evaluation and bias analysis were performed for the literatures included in the meta-analysis.Revman 5.3 software was used for systematic meta-analysis.Results:A total of 15 clinical randomized controlled trials with a total of 930 patients were included.Meta-analysis showed that Xuebijing injection combined with conventional therapy could reduce 28-day mortality in sepsis[OR=0.52,95%CI(0.38,0.71),P<0.0001],APACHEⅡintegral[WMD=-2.65,95%CI(-3.23,-2.08),P<0.00001];be effective in decreasing D-dimer[WMD=-0.79,95%CI(-1.17,-0.40),P<0.0001],TNF-α[WMD=-36.71,95%CI(-43.04,-30.39),P<0.00001],vWF[WMD=-15.94,95%CI(-27.60,-4.28),P=0.007],sE-selectin[WMD=-118.30,95%CI(-139.65,-96.95),P<0.00001],ESM-1[WMD=-135.44,95%CI(-186.30,-84.57),P<0.00001],sTM[WMD=-56.46,95%CI(-66.39,-46.53),P<0.00001];can effectively increase platelets[WMD=30.78,95%CI(25.65,35.92),P<0.00001].Conclusion:Xuebijing injection can not only effectively reduce the release of inflammatory factors,thereby improving vascular endothelial injury,reducing coagulation disorders and blocking coagulation-inflammation network;it can also increase the level of platelets,thereby repairing injured vascular endothelial cells,which has a certain value to reduce the condition of sepsis and improve the prognosis.It also provides some basis for the treatment of sepsis secondary to novel coronavirus pneumonia.

Mechanism of Xuebijing injection on hepatic ischemia-reperfusion injury based on network pharmacology

Objective:Using network pharmacology to predict the main active ingredients,targets and signaling pathways of Xuebijing injection in the treatment of hepatic ischemia-reperfusion injury and explore its potential mechanism of action.Methods:Screen the active ingredients and their targets of Danshen,Honghua,Chishao,Chuanxiong,and Danggui in Xuebijing injection through Traditional Chinese Medicine Systems Pharmacology(TCMSP)database and the Hepatic ischemia-reperfusion injury related targets through Online Mendelian Inheritance in Man(OMIM)and GeneCards Suite(The Human Gene Database)database.And acquire drug-disease intersection targets at the same time.The STRING database was used to construct a protein-protein interaction(PPI)network and topologically screen the central targets.Use the R language online search Bioconductor platform to perform GO function enrichment on the target;Database for Annotation,Visualization and Integrated Discovery(DAVID)database was used to perform KEGG channel enrichment analysis on the target.Use Cytoscape 3.7.2 to construct a"ingredient-target-pathway"network diagram and perform a topology analysis.Results:A total of 115 active ingredients were selected from Xuebijing injection,including Quercetin,Luteolin,Kaempferol,Beta-carotene,and Tanshinone IIa,etc.It corresponds to 217 targets.There are 1057 disease-related targets,and 114 drug-disease common targets.PPI topologically screened out 17 target proteins.Topological analysis of the network graph obtained 15 target genes.Thire intersection contains key targets such as JUN,PPARG,PTGS2,AKT1 and MAPK1.A total of 137 related signaling pathways were obtained by GO enrichment analysis.A total of 8 signaling pathways were obtained through KEGG enrichment(P<0.05,FDR<0.05),among which signaling pathways such as Toll-like receptors,T cell receptors,NOD-like receptors,VEGF,and ErbB played an important role in immune regulation,anti-apoptosis,anti-inflammatory,anti-oxidation,and promoting angiogenesis in the treatment.Conclusion:Xuebijing injection can treat hepatic ischemia-reperfusion injury through multiple components,multiple targets and multiple pathways.

Uncovering the multi-target pharmacological mechanism of Xuebijing injection against sepsis by a systems pharmacology approach

Sepsis is a life-threatening organ dysfunction that is associated with a high risk of death.Xuebijing(XBJ)injection,a Chinese herbal compound preparation,has been widely used for the treatment of sepsis in China.The purpose of this research is to decipher the underlying multi-target pharmacological mechanism of XBJ in the treatment of sepsis using a systems pharmacology approach.Compounds in XBJ were collected by literature retrieval.The corresponding putative targets of XBJ were screened from the Traditional Chinese Medicine Systems Pharmacology(TCMSP),Swiss Target Prediction(STP),and Search Tool for Interacting Chemicals(STITCH)databases.Sepsis-related targets were summarized using the Genecards,DrugBank,and Online Mendelian Inheritance in Man(OMIM)databases.The intersection targets were obtained with Venny 2.1.Subsequently,protein-protein interaction(PPI)networks were constructed with the STRING database and Cytoscape 3.7.1.Then,degree,betweenness,and closeness were calculated to recognize the core targets in the PPI network.Moreover,the pharmacological mechanism of XBJ against sepsis was predicted via gene ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment.After the literature review,the 33 most commonly cited chemical ingredients,were screened out as major compounds.Bioinformatics analysis revealed that the major compounds of XBJ modulated 218 common targets associated with sepsis.Through PPI network analysis,41 genes,including IL-6,AKT1,STAT3,TP53,and MAPK1,were identified as core targets.The results of GO and KEGG enrichment revealed that the potential biological functions of XBJ against sepsis were mainly involved in cytokine receptor binding,cytokine activity,growth factor receptor binding,growth factor activity,and chemokine activity.The crucial pathways were closely associated with initial immune activation(CLR/TLR4-NF-κB/MAPK pathway),the acute inflammatory response(TNFMAPK/caspase and IL-MAPK/STAT pathways),and the late inflammation and coagulation process(HMGB1-RAGE and HIF-1 signaling pathways).This study revealed that the multiple components of XBJ exert multitarget effects against sepsis by regulating initial immune activation,the acute inflammatory response,and the late inflammation and coagulation process.

Effects of blood purification combined with Xuebijing on coagulation, immunity, inflammation and vascular factors in sepsis patients

Objective:To investigate the effects of blood purification combined with Xuebijing on coagulation, immunity, inflammation and vascular factors in sepsis patients.Methods: 82 sepsis patients admitted to the Xuzhou Municipal Hospital Affiliated to Xuzhou Medical University from January 2017 to January 2019 were selected as the research objects. According to the random drawing method, 41 cases in the control group and 41 cases in the observation group were divided into two groups. The control group was treated with routine western medicine, including antibiotic therapy, blood sugar control, respiratory support and nutritional support. The observation group was treated with continuous blood purification combined with Xuebijing on the basis of the control group. The changes of coagulation index, immune factor, inflammatory reaction and vascular factor levels were observed before and after treatment in two groups.Results:After treatment, the levels of activated partial thromboplastin time (APTT), prothrombin time (PT), D-Dimer (DD), CD8+, procalcitonin (PCT), Tumor Necrosis Factor-α (TNF-α), high mobility group box-B1 (HMGB1) and soluble fms-like tyrosine kinase,(sFLT)in the two groups were significantly lower than those before treatment, while the levels of CD4+, CD4+/CD8+, and vascular endothelial growth factor (VEGF) were significantly higher than those before treatment;and the levels of APTT, PT, DD, CD8+, PCT, TNF-a, HMGB1 and sFLT in the observation group after treatment were significantly lower than those in the control group, the levels of CD4+, CD4+/CD8+, and VEGF in the observation group after treatment were significantly higher than those in the control group, there was a significant difference in each indexes between the different groups after treatment. Conclusions:Continuous blood purification combined with Xuebijing therapy can effectively improve the coagulation function of sepsis patients, enhance the immune mechanism of patients, reduce inflammation and protect vascular endothelial function. It has clinical popularization significance.

The research idea of Xuebijing injection in influencing severe pneumonia-pulmonary fibrosis with blood stasis syndrome evolution by inhibiting inflammation, endotoxin and dispersing blood stasis

Severe pneumonia is one of the most serious infectious diseases.Delayed intervention may lead to pulmonary fibrosis,which greatly threatens people’s life and health.Blood stasis syndrome is an important underlying syndrome throughout the evolution of severe pneumonia-pulmonary fibrosis.Xuebijing injection(XBJ)was developed under the theoretical system of“Three syndromes and three methods”,demonstrating a good efficacy in treating severe pneumonia and pulmonary fibrosis due to its effect of removing blood stasis and dispersing toxins.Previous studies have shown that XBJ can protect vascular endothelial function,improve coagulation function and regulate immunity by inhibiting inflammatory.Hence,the research hypothesis is put forward that XBJ treats blood stasis syndrome by removing blood stasis and dredging blood vessels,to inhibit the disease progress of severe pneumonia to pulmonary fibrosis.Further researches are need to confirm the function and explore the mechanism of XBJ.

Effect of Xuebijing injection on hematopoietic homeostasis of LPS induced sepsis in mice

Objective:To explore the effect and mechanism of Xuebijing injection (XBJ) on the hematopoietic homeostasis of bone marrow (BM) in septic mice. Methods:BM cells stimulated with XBJ were analyzed by inverted optical microscope and qPCR, to evaluate the effect of XBJ on differentiation function of BM cells in vitro. Lipopolysaccharide (LPS) 055:B5 at the dose of 20mg/kg was used to establish the sepsis model. To determine the hematopoietic stem cells homeostasis affected by LPS in mice, BM cells were isolated and analyzed by flow cytometry based on the immunophenotypic surface markers. 20ml/kg of XBJ was administered by tail vein once/day after peritoneal injection of LPS. All animals were sacrificed on the fifth day. The frequency of hematopoietic stem cells (HSC) and immune cells in mice were quantified by flow cytometry. The gene expression of transcription factors were detected by qPCR. Results:XBJ promoted myeloid differentiation of BM cells in vitro, which may be related to the mRNA expression of the transcription factors. The results in vivo showed the percentage of BM Lin-SCA-1+c-KIT+(LSK) cells, and Long-term HSCs (LT-HSC) were significantly increased in LPS group. But the percentage of multipotential progenitors (MPPs), granulocyte-monocyte progenitor (GMP) and megakaryocytic-erythroid precursor (MEP) were significantly decreased in LPS group. Whereas, XBJ improved the immune function in sepsis mice by suppression the LSK expansion in vivo. The result of qPCR showed that LSD1 and PU.1 mRNA expression in XBJ group were significantly higher than LPS group and control group respectively. Conclusion:Xuebijing injection can improve immune function in sepsis mice by regulating hematopoietic homeostasis. Its mechanism may be related to the up-regulation of LSD1 and PU.1 gene expressions.

Effect of Xuebijing combined with ulinastatin on the homeostasis of sepsis patients

Objective:To investigate the effect of Xuebijing combined with ulinastatin on the homeostasis of sepsis patients.Methods: 78 patients with post-burn sepsis who received treatment in our hospital between January 2016 and January 2019 were included in the study. The treatment regimen was retrospectively analyzed and used to divide the patients into the group A (n=40) receiving ulinastatin treatment and the group B (n=38) receiving Xuebijing combined with ulinastatin treatment. The efficacy was evaluated after 7 d of continuous treatment.Results:Before treatment, there were no significant differences in levels of inflammatory factors, oxidative stress indicators, myocardial injury markers or coagulation function indicators between the two groups. After treatment, serum high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-α (TNF-α) contents in group B were lower than those in group A;serum total antioxidant capacity (T-AOC) and glutathione peroxidase (GSH-Px) contents were higher than those in group A, while lipid hydroperoxide (LHP) and advanced protein oxidation product (AOPP) contents were lower than those in group A;serum lactate dehydrogenase (LDH), troponin I (cTn I) and B-type brain natriuretic peptide (BNP) contents were lower than those in group A;peripheral blood prothrombin time (PT), thrombin time (TT) and partial thromboplastin time (APTT) levels were higher than those in group A, while fibrinogen (FIB) level was lower than that in group A.Conclusion: Xuebijing combined with ulinastatin can effectively reduce the inflammatory stress response, actively protect the myocardial function and reduce the hypercoagulable state in patients with post-burn sepsis.