Rehabilitation of Sepsis Patients with Acute Kidney Injury Based on Intelligent Medical Big Data

The objective of this study was to explore rehabilitation of patients with acute kidney injury (AKI) treated with Xuebijing injection by using intelligent medical big data analysis system. Based on Hadoop distributed processing technology, this study designed a medical big data analysis system and tested its performance. Then, this analysis system was used to systematically analyze rehabilitation of sepsis patients with AKI treated with Xuebijing injection. It is found that the computing time of this system does not increase obviously with the increase of cases. The results of systematic analysis showed that the glomerular filtration rate (59.31 ± 3.87% vs 44.53 ± 3.53%) in the experimental group was obviously superior than that in the controls after one week of treatment. The levels of urea nitrogen (9.32 ± 2.21 mmol/L vs. 14.32 ± 0.98 mmol/L), cystatin C (1.65 ± 0.22 mg/L vs. 2.02 ± 0.13 mg/L), renal function recovery time (6.12 ± 1.66 days vs. 8.66 ± 1.17 days), acute physiology and chronic health evaluation system score (8.98 ± 2.12 points vs. 12.45 ± 2.56 points), sequential organ failure score (7.22 ± 0.86 points vs. 8.61 ± 0.97 points), traditional Chinese medicine (TCM) syndrome score (6.89 ± 1.11 points vs. 11.33 ± 1.23 points), and ICU time (16.43 ± 2.37 days vs. 12.15 ± 2.56 days) in the experimental group were obviously lower than those in the controls, and the distinctions had statistical significance ( P < 0.05 ). The significant efficiency (37.19% vs. 25.31%) and total effective rate (89.06% vs. 79.06%) in the experimental group were obviously superior than those in the controls, and distinction had statistical significance ( P < 0.05 ). In summary, the medical big data analysis system constructed in this study has high efficiency. Xuebijing injection can improve the renal function of sepsis patients with kidney injury, and its therapeutic effect is obviously better than that of Western medicine, and it has clinical application and promotion value.

Detecting Critical Functional Ingredients Group and Mechanism of Xuebijing Injection in Treating Sepsis

Sepsis is a systemic inflammatory reaction caused by various infectious or noninfectious factors, which can lead to shock, multiple organ dysfunction syndrome, and death. It is one of the common complications and a main cause of death in critically ill patients. At present, the treatments of sepsis are mainly focused on the controlling of inflammatory response and reduction of various organ function damage, including anti-infection, hormones, mechanical ventilation, nutritional support, and traditional Chinese medicine (TCM). Among them, Xuebijing injection (XBJI) is an important derivative of TCM, which is widely used in clinical research. However, the molecular mechanism of XBJI on sepsis is still not clear. The mechanism of treatment of “bacteria, poison and inflammation” and the effects of multi-ingredient, multi-target, and multi-pathway have still not been clarified. For solving this issue, we designed a new systems pharmacology strategy which combines target genes of XBJI and the pathogenetic genes of sepsis to construct functional response space (FRS). The key response proteins in the FRS were determined by using a novel node importance calculation method and were condensed by a dynamic programming strategy to conduct the critical functional ingredients group (CFIG). The results showed that enriched pathways of key response proteins selected from FRS could cover 95.83% of the enriched pathways of reference targets, which were defined as the intersections of ingredient targets and pathogenetic genes. The targets of the optimized CFIG with 60 ingredients could be enriched into 182 pathways which covered 81.58% of 152 pathways of 1,606 pathogenetic genes. The prediction of CFIG targets showed that the CFIG of XBJI could affect sepsis synergistically through genes such as TAK1, TNF-α, IL-1β, and MEK1 in the pathways of MAPK, NF-κB, PI3K-AKT, Toll-like receptor, and tumor necrosis factor signaling. Finally, the effects of apigenin, baicalein, and luteolin were evaluated by in vitro experiments and were proved to be effective in reducing the production of intracellular reactive oxygen species in lipopolysaccharide-stimulated RAW264.7 cells, significantly. These results indicate that the novel integrative model can promote reliability and accuracy on depicting the CFIGs in XBJI and figure out a methodological coordinate for simplicity, mechanism analysis, and secondary development of formulas in TCM.

Scientific Evidence of Xuebijing Injection in the Treatment of Sepsis

Objectives. To systematically collate, appraise, and synthesize the current evidence on the Xuebijing injection (XBJI) for sepsis. Methods. Eight databases were searched for systematic reviews (SRs) or meta-analyses (MAs) on XBJI for sepsis. Assessing the Methodological Quality of Systematic Reviews-2 (AMSTAR-2), Preferred Reporting Item for Systematic Reviews and Meta-Analyses (PRISMA), and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methods were used to assess the methodological quality, reporting quality, and evidence quality of the enrolled studies, respectively. Results. Out of the 13 studies that were included, all studies were rated critically low quality based on AMSTAR-2 results. Based on the results obtained from PRISMA, all studies were reported to be over 80%, while the GRADE system yielded three outcome measures rated high-quality, 16 were of moderate quality, and the rest were of low or critically low quality. Conclusions. The combination of XBJI and Western medicine (WM) showed significant synergy for the treatment of sepsis compared to WM alone. However, this conclusion should be treated with caution since the quality of the SRs/MAs providing the evidence was relatively low.

Xuebijing Injection Affects the Dynamic Change of Metabolism in CLP-Induced Septic Rats

Xuebijing injection has been widely applied to treat sepsis. However, its roles in the dynamic change of metabolism in sepsis are still unknown. In our study, Gas chromatography-mass spectrometer (GC-MS) combined with multivariate statistical techniques was used to detect the metabolic change in septic rats with or without XBJ injection treatment. The KEGG pathway analysis was used to further analyze the related metabolic pathways in which the identified metabolites were involved. Based on the fold change, variable important in projection, and P value, we found 11, 33 and 26 differential metabolites in the sepsis group at 2, 6 and 12 hours post CLP, compared with the control group. Besides, we also found 32, 23 and 28 differential metabolites in the XBJ group at 2, 6 and 12 hours post CLP. The related pathways of differential metabolites were glycometabolism at 2h, glycometabolism and amino acid metabolism at 6h and amino acid metabolism at 12h post CLP in the sepsis group compared with the control group. Besides, glycometabolism, amino acid metabolism and lipid metabolism changed markedly after XBJ injection for 2 hours; while only amino acid metabolism changed significantly with the treatment of XBJ injection for 6 and 12 hours, compared with the sepsis group. Further analysis showed 3, 6 and 6 differential metabolites were overlapped in the sepsis group and XBJ group at 2, 6 and 12 hours post CLP. These identified differential metabolites were majorly involved in arginine and proline metabolism, suggesting that XBJ injection is capable of improving metabolic disorders in CLP-induced septic rat to a certain extent.

Efficacy of Xuebijing Injection for Acute Pancreatitis: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background and Aim. Xuebijing injection is a traditional Chinese medicine compound for the improvement of systemic inflammation response. This meta-analysis of randomized controlled trials (RCTs) aimed to explore the clinical efficacy and safety of Xuebijing injection for the treatment of acute pancreatitis (AP). Methods. PubMed Medline, Embase, Cochrane Library, China National Knowledge Infrastructure, China Biology Medicine disc, VIP, and Wanfang databases were searched. The primary outcome was treatment response. The secondary outcomes included changes in clinical and laboratory indicators and incidence of AP-related complications. Meta-analyses were performed by using a random-effect model. Risk ratios (RRs) with 95% confidence intervals (CIs) or weighted mean differences (WMDs) with 95% CIs were calculated. Results. Overall, 23 RCTs were included. The rates of overall (RR = 1.16; 95% CI = 1.12 to 1.20; P < 0.00001 ) and complete (RR = 1.40; 95% CI = 1.30 to 1.50; P < 0.00001 ) responses were significantly higher in the Xuebijing injection group. After treatment, the levels of interleukin-6 (WMD = −18.22; 95% CI = −23.36 to −13.08; P < 0.00001 ), tumor necrosis factor-α (WMD = −16.44; 95% CI = −20.49 to −12.40; P < 0.00001 ), serum amylase (WMD = −105.61; 95% CI = −173.77 to −37.46; P = 0.002 ), white blood cell (WMD = −1.51; 95% CI = −1.66 to −1.36; P < 0.00001 ), and C-reactive protein (WMD = −11.05; 95% CI = −14.32 to −7.78; P < 0.00001 ) were significantly lower in the Xuebijing injection group. Abdominal pain (WMD = −1.74; 95% CI = −1.96 to −1.52; P < 0.00001 ), abdominal distension (WMD = −1.56; 95% CI = −2.07 to −1.04; P < 0.00001 ), gastrointestinal function (WMD = −2.60; 95% CI = −3.07 to −2.13; P < 0.00001 ), body temperature (WMD = −2.16; 95% CI = −2.83 to −1.49; P < 0.00001 ), serum amylase level (WMD = −1.81; 95% CI = −2.66 to −0.96; P < 0.0001 ), and white blood cell (WMD = −2.16; 95% CI = −2.99 to −1.32; P < 0.00001 ) recovered more rapidly in the Xuebijing injection group. The incidence of multiple organ dysfunction syndrome (RR = 0.18; 95% CI = 0.05 to 0.62; P = 0.006 ), pancreatic pseudocyst (RR = 0.17; 95% CI = 0.04 to 0.77; P = 0.02 ), and renal failure (RR = 0.16; 95% CI = 0.05 to 0.60; P = 0.006 ) was significantly lower in the Xuebijing injection group. Conclusions. Xuebijing injection added on the basis of conventional treatment has a potential benefit for improving the outcomes of AP.

Paeoniflorin and Hydroxysafflor Yellow A in Xuebijing Injection Attenuate Sepsis-Induced Cardiac Dysfunction and Inhibit Proinflammatory Cytokine Production

Sepsis-induced myocardial dysfunction is a major contributor to the poor outcomes of septic shock. As an add-on with conventional sepsis management for over 15 years, the effect of Xuebijing injection (XBJ) on the sepsis-induced myocardial dysfunction was not well understood. The material basis of Xuebijing injection (XBJ) in managing infections and infection-related complications remains to be defined. A murine cecal ligation and puncture (CLP) model and cardiomyocytes in vitro culture were adopted to study the influence of XBJ on infection-induced cardiac dysfunction. XBJ significantly improved the survival of septic-mice and rescued cardiac dysfunction in vivo. RNA-seq revealed XBJ attenuated the expression of proinflammatory cytokines and related signalings in the heart which was further confirmed on the mRNA and protein levels. Xuebijing also protected cardiomyocytes from LPS-induced mitochondrial calcium ion overload and reduced the LPS-induced ROS production in cardiomyocytes. The therapeutic effect of XBJ was mediated by the combination of paeoniflorin and hydroxysafflor yellow A (HSYA) (C0127-2). C0127-2 improved the survival of septic mice, protected their cardiac function and cardiomyocytes while balancing gene expression in cytokine-storm-related signalings, such as TNF-α and NF-κB. In summary, Paeoniflorin and HSYA are key active compounds in XBJ for managing sepsis, protecting cardiac function, and controlling inflammation in the cardiac tissue partially by limiting the production of IL-6, IL-1β, and CXCL2.