Single Atom Ru Doped Ni2P/Fe3P Heterostructure for Boosting Hydrogen Evolution for Water Splitting.

Modulating the chemical composition and structure has been considered as one of the most promising strategies for developing high-efficient water splitting catalysts. Here, a single-atom Ru doped Ni2P/Fe3P catalyst is synthesized by introducing the dispersed Ru atoms to adjust Ni2P/Fe3P heterostructure. Single atom Ru provides effective hydrogen evolution reaction (HER) active sites for boosting catalytic activities. The catalyst with only 0.2 wt.% content of Ru exhibits an overpotential of 19.3 mV at 10 mA cm-2, which is obviously lower than 146.1 mV of Ni2P/Fe3P. Notably, an alkaline overall water electrolyzer based on Ru-Ni2P/Fe3P catalysts achieves a cell voltage of 1.47 V and operates over 600 h at 10 mA cm-2, which is superior to that of benchmark RuO2//Pt/C (1.61 V). The theoretical calculations further confirm that Ru single atom doping can effectively optimize the hydrogen/water adsorption free energy of the active site and therefore improve the HER activity of heterostructure. This work provides a valuable reference to design high-activity and durability catalyst for water splitting through the double modulation of interface-effect and atomic doping.

Comparison of neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio for the diagnosis of neonatal sepsis: a systematic review and meta-analysis.

PURPOSE: To compare the performance of Neutrophil-to-Lymphocyte Ratio (NLR) with that of Platelet-to-Lymphocyte Ratio (PLR) in diagnosing neonatal sepsis (NS). METHODS: PubMed and Embase were searched for relevant studies from the inception of the databases to May, 2022. The pooled sensitivity (SEN), specificity (SPE), and area under the receiver operator characteristic curve (AUC) were measured. RESULTS: Thirteen studies involving 2610 participants were included. The SEN, SPE, and AUC of NLR were 0.76 (95%CI: 0.61-0.87), 0.82 (95%CI: 0.68-0.91), and 0.86 (95%CI: 0.83-0.89), respectively, and those of PLR were 0.82 (95%CI: 0.63-0.92), 0.80 (95%CI: 0.24-0.98), and 0.87 (95%CI: 0.83-0.89), respectively. Significant heterogeneity was observed among the studies. Subgroup analysis and meta-regression showed that types of sepsis (p = 0.01 for SEN), gold standard (p = 0.03 for SPE), and pre-set threshold (p<0.05 for SPE) might be the sources of heterogeneity for NLR, whereas the pre-set threshold (p<0.05 for SPE) might be the source of heterogeneity for PLR. CONCLUSIONS: NLR and PLR would be of great accuracy for the diagnosis of NS, and the two indicators have similar diagnostic performance. However, the overall risk of bias was high, and significant heterogeneity was identified among the included studies. The results of this study should be interpreted prudently, and the normal or cut-off values and the type of sepsis should be considered. More prospective studies are needed to further support the clinical application of these findings.

A homologue of yeast acyl-CoA synthetase Faa1 contributes to cytomembrane functionality involved in development and virulence in the insect pathogenic fungus Beauveria bassiana.

Acyl-CoA synthetase (ACS) functions as a hub linking lipid metabolism with in cellular physiologies by producing active intermediate of catalyzes acyl-CoA. However, the biological roles of ACS are largely unknown in filamentous fungi. In this study, an ortholog of yeast Faa1, named BbFaa1, was functionally characterized in the filamentous entomopathogenic fungus Beauveria bassiana. BbFaa1 was associated with vesicular membrane, and its loss resulted in the impaired cytomembrane integrity. Notably, in ΔBbfaa1 mutant strain, the translocation of hydrophobins across cell membrane was significantly hampered, which resulted in the reduced hydrophobicity of aerial mycelia and conidia. In addition, loss of BbFaa1 significantly weakened fungal virulence. Our findings indicate that the metabolism of acyl-CoA synthetase Faa1 contributes to the cytomembrane functionality which cascades hydrophobin translocation and differentiation, thus affecting virulence of B. bassiana.

Initial CT-based radiomics nomogram for predicting in-hospital mortality in patients with traumatic brain injury: a multicenter development and validation study.

OBJECTIVE: To develop and validate a radiomic prediction model using initial noncontrast computed tomography (CT) at admission to predict in-hospital mortality in patients with traumatic brain injury (TBI). METHODS: A total of 379 TBI patients from three cohorts were categorized into training, internal validation, and external validation sets. After filtering the unstable features with the minimum redundancy maximum relevance approach, the CT-based radiomics signature was selected by using the least absolute shrinkage and selection operator (LASSO) approach. A personalized predictive nomogram incorporating the radiomic signature and clinical features was developed using a multivariate logistic model to predict in-hospital mortality in patients with TBI. The calibration, discrimination, and clinical usefulness of the radiomics signature and nomogram were evaluated. RESULTS: The radiomic signature consisting of 12 features had areas under the curve (AUCs) of 0.734, 0.716, and 0.706 in the prediction of in-hospital mortality in the internal and two external validation cohorts. The personalized predictive nomogram integrating the radiomic and clinical features demonstrated significant calibration and discrimination with AUCs of 0.843, 0.811, and 0.834 in the internal and two external validation cohorts. Based on decision curve analysis (DCA), both the radiomic features and nomogram were found to be clinically significant and useful. CONCLUSION: This predictive nomogram incorporating the CT-based radiomic signature and clinical features had maximum accuracy and played an optimized role in the early prediction of in-hospital mortality. The results of this study provide vital insights for the early warning of death in TBI patients.

[Determination of sennoside B, sennoside A and physcion in slimming health foods].

OBJECTIVE: To establish a quantitative analysis method for sennoside A, sennoside B and physcion by ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS). METHODS: The sample was extracted by methanol-2 mmol/L ammonium formate(9∶1) at 40 ℃ for 1 h. The separation was performed using Agilent Eclipse Plus C_(18 )(2. 1 mm × 50 mm, 1. 8 µm) column with gradient elution. The mobile phase was consisted of 0. 1% formic acid and methanol. Qualitative and quantitative analysis was conducted with an electrospray ionization source operated in the negative ionization(ESI~-) mode and multiple reaction monitoring(MRM) mode. RESULTS: The linear range of three compounds were from 0. 1 to 10 µg/mL with the correlation coefficients(r) above 0. 995. The spiked recoveries were in the range of 81. 9% to 114. 5% at the concentrations of 0. 02, 0. 15 and 1. 60 mg/g with relative standard devisions(RSDs) ranged from 0. 30% to 3. 43%(n=6). The detection limits of sennoside A and sennoside B were 1. 2 µg/g. The detection limit of physcion was 2. 4 µg/g. Sennoside A, sennoside B or physcion were detected in 19 out of 40 batches of samples. The content of sennoside A ranged from 0. 184 to 6. 33 mg/g and the content of sennoside B ranged from 0. 202 to 7. 23 mg/g. The content of physcion ranged from 0. 042 to 0. 79 mg/g. CONCLUSION: The method is simple, accurate and suitable for the determination of sennoside A, sennoside B and physcion.

Axial Spondyloarthritis: Dual-Energy Virtual Noncalcium CT in the Detection of Bone Marrow Edema in the Sacroiliac Joints.

Purpose To determine the diagnostic performance of dual-energy virtual noncalcium (VNCa) CT in the detection of bone marrow edema in study participants with sacroiliitis associated with axial spondyloarthritis. Materials and Methods In this prospective study, 47 consecutive participants (mean age, 27 years; age range, 14-41 years [28 male; mean age, 24 years; age range, 14-37 years] [19 female; mean age, 29 years; age range, 17-41 years]) underwent dual-energy CT and 3.0-T MRI between April 2016 and December 2017. Two independent readers visually evaluated all sacroiliac joints for the presence of abnormal marrow attenuation on dual-energy VNCa images using a four-point classification system (0, no edema; 1, mild edema; 2, moderate edema; 3, severe edema). CT numbers on VNCa images were determined with region-of-interest-based quantitative analysis. MRI was the reference standard for presence of bone marrow edema. Results Sensitivity, specificity, and accuracy of readers 1 and 2, respectively, in the identification of bone edema at CT were 87% and 93% (48 and 51 of 55), 94% and 91% (32 and 31 of 34), and 90% and 92% (80 and 82 of 89). Interobserver agreement was excellent (κ = 0.81). CT numbers from VNCa images increased from no edema to severe edema (P < .001). The area under the receiver operating characteristic curve was 0.93 for reader 1 and 0.91 for reader 2 in differentiation of the presence of bone marrow edema from no edema. A cutoff value of -33 HU derived from reader 1 yielded overall sensitivity, specificity, and accuracy of 90% (49 of 55), 83% (28 of 34), and 87% (77 of 89) in the detection of any extent of edema in the sacroiliac joints. Conclusion Dual-energy VNCa CT images had excellent diagnostic performance in evaluation of the extent of bone marrow edema in study participants with sacroiliitis associated with axial spondyloarthritis. © RSNA, 2018 See also the editorial by Guggenberger in this issue.

Activation of EGFR-KLF4 positive feedback loop results in acquired resistance to sorafenib in hepatocellular carcinoma.

Sorafenib is the standard first-line systemic chemotherapeutic drugs for advanced hepatocellular carcinoma (HCC), but acquired resistance to sorafenib is frequently observed in clinical practice. In this study, we first produced three sorafenib resistance (SR) HCC cell lines by using two human HCC cell lines (Hep3B and Huh7) and a human primary HCC cell line. We identified that epidermal growth factor receptor (EGFR) and Kruppel-like factor 4 (KLF4) are dramatically increased in the three SR HCC cell lines. Either inhibition of tyrosine kinase activity of EGFR with Erlotinib/Icotinib or inhibition of KLF4 expression with short hairpin RNA recovered the response of three SR HCC cell lines to sorafenib, suggesting the critical roles of EGFR tyrosine kinase and KLF4 on inducing SR. Luciferase activity and chromatin immunoprecipitation assays further determined that KLF4 promoted EGFR expression through inducing its transcription by directly binding to its promoter. EGFR, conversely, could also promote KLF4 expression through inducing its transcription by binding to its promoter in a tyrosine kinase-dependent manner, suggesting that a positive feedback loop formed by EGFR and KLF4 further amplifies their effects on inducing SR. Up to now, our findings that KLF4 induces the development of SR and it cooperates with EGFR to form a positive feedback loop to amplify their SR-inducing abilities have rarely been reported. Our findings bear possible implications for the improvement of the efficacy of sorafenib in HCC.

[Efficacy and safety of Gantaishu Capsules for viral B hepatitis:a systematic review and Meta-analysis].

To evaluate the efficacy and safety of Gantaishu Capsules in the treatment of viral B hepatitis. The randomized controlled trials( RCT) retrieved from Cochrane Library,PubMed,Sino Med,CNKI,Wan Fang and VIP were enrolled. The methodology quality of the included studies was evaluated,and a Meta-analysis was performed using Rev Man 5. 3 software. A total of six randomized controlled trials were included. Meta-analysis results showed that the similarities in the negative conversion rate of HBe Ag( RR = 2. 09,95%CI[0. 90,4. 85],P = 0. 09,I2= 0%),the HBV-DNA negative rate( RR = 1. 49,95% CI[0. 56,3. 95],P = 0. 43,I2= 0%) and the changes in ALT levels before and after treatment( RR =-6. 28,95%CI[-72. 83,60. 27],P = 0. 85,I2= 99%),with no statistical difference. In terms of quality of life,Gantaishu Capsules can significantly alleviate the symptoms of hepatitis B patients,with less adverse reactions. Gantaishu Capsules and Dongbao Gantai Tablets were similar in antiviral effect. In this term,Gantaishu Capsules was superior to Dangfei Liganning Capsules. It can significantly alleviate the symptoms of chronic hepatitis B patients,with a good clinical safety.Therefore,it can be applied in the case of syndrome differentiation and treatment. In view of the low quality of the included studies,more high-quality clinical trials were required to confirm its efficacy.

[Experts consensus statement on Xiyanping Injection in clinical practice(children)].

Xiyanping Injection is a commonly used medicine in clinical treatment,which is recommended by many pediatric disease guidelines/consensus. However,the instraction is relatively simple and lack of guidance for clinical application,which affects the efficacy and brings safety risks. Therefore,more detailed clinical guidance is urgently needed. This consensus is formulated by clinical experts of traditional Chinese medicine and Western medicine in pediatrics. This consensus follows Manual for the clinical experts consensus of Chinese patent medicine which published by China Association of Chinese Medicine. The study identified clinical problems using clinical investigation,searched the literature based on PICO clinical problems,using GRADE system to carry out evidences evaluation,classification and recommendation,and adopted the nominal grouping method to reach expert consensus. The consensus combines evidence-based evidence with expert experience,sufficient evidence of clinical problems would lead to " recommendations",and clinical problems with insufficient evidence will lead to " consensus suggestions". This expert consensus recommends the indications,intervention time for treatment,route of drug administration,dose conversion,the indications of being used alone,suitability and taboos of medicine combination,and introduces the safety and clinical application,to provide reference for clinical using.

Role of exosomal proteins in cancer diagnosis.

Exosomes are emerging as a new type of cancer biomarkers. Exosome is a bilayered nano-sized vesicle secreted by various living cells in all body fluids. Based on the expanding albeit incomplete knowledge of their biogenesis, secretion by cells and cancer cell-specific molecular and genetic contents, exosomes are viewed as promising, clinically-relevant surrogates of cancer progression and response to therapy. Preliminary proteomic, genetic and functional profiling of cancer cell-derived or cancer plasma-derived exosomes confirms their unique characteristics. Alterations in protein or nucleic acid profiles of exosomes in plasma correlate with pathological processes of many diseases including cancer. However, previous studies on exosome application in cancer diagnosis and treatment mainly focussed on miRNAs. With the development of rapid large-scale production, purification, extraction and screening of exosomal contents, exosomal protein application can be explored for early stage cancer diagnosis, monitoring and prognosis evaluation. Here, we summarized the recent developments in application of exosomal proteins for cancer diagnosis.

Peroxisome proliferator-activated receptor alpha mediates C/EBP homologous protein to protect mice from acute liver failure.

OBJECTIVE: Peroxisome proliferator-activated receptor α (PPARα) activation has been reported to ameliorate liver injury in cases of acute liver failure (ALF). However, its intrinsic protective molecular mechanisms remain largely undetermined. C/EBP homologous protein (CHOP) is an important mediator of lipopolysaccharide (LPS)-induced inflammation. The aim of the present study was to test the hypothesis that PPARα activation alleviates liver inflammation to protect mice from acute liver failure (ALF) mediated by CHOP. METHODS: In a murine model induced by D-galactosamine (D-GalN, 700 mg/kg) and LPS (10 µg/kg), Wy-14643 (6 mg/kg) was administered to activate PPARα. The mice of different groups were killed 6 h after D-GalN/LPS injection, and the liver and blood were collected for analysis. To find out whether PPARα activation protects the liver from injury due to inflammation by regulating CHOP, we used expression plasmid to increase CHOP expression and demonstrated how PPARα mediated CHOP to regulate inflammation in vivo and in vitro. RESULTS: The expression of PPARα was downregulated and the expression of CHOP was upregulated with the development of D-GalN/LPS-induced liver injury. The protective molecular mechanisms of PPARα activation were dependent on the expression of CHOP. Indeed, (1) PPARα activation decreased the expression of CHOP; on the other hand, PPARα knockdown increased the expression of CHOP in vivo; (2) the depressed liver inflammation by PPARα activation was due to the downregulation of CHOP expression, because overexpression of CHOP by transfect plasmid reversed liver protection and increased liver inflammation again; (3) in vitro, PPARα inhibition by siRNA treatment increased the expression of proinflammatory cytokines, and CHOP siRNA co-transfection reversed the expression of proinflammatory cytokines. CONCLUSIONS: Here, we demonstrated that PPARα activation contributes to liver protection and decreases liver inflammation in ALF, particularly through regulating CHOP. Our findings may provide a rationale for targeting PPARα as a potential therapeutic strategy to ameliorate ALF.

Cancer of the Liver Italian Program score helps identify potential candidates for transarterial chemoembolization in patients with Barcelona Clinic Liver Cancer stage C.

BACKGROUND: The Barcelona Clinic Liver Cancer (BCLC) staging system for hepatocellular carcinoma (HCC) recommends transarterial chemoembolization (TACE) as the first line therapy for stage B patients and sorafenib treatment for stage C patients. However, stage C patients exhibit variations in terms of tumor burden, liver function, and extrahepatic metastasis, which could potentially affect disease outcome. Here, we assessed whether the Cancer of the Liver Italian Program (CLIP) scores can help identify stage C patients likely to benefit from TACE. METHODS: Out of 295 BCLC stage C HCC patients enrolled between January 2009 and December 2011, those with platelet counts >30 X 10(9) cells/L, total bilirubin <51 µmoL/L, and an unobstructed main portal vein were scheduled for TACE (n=195). The remaining patients received best supportive care (BSC, n=100). All the patients were followed up for symptoms, performance status, and Child-Pugh classification scores every 4 weeks until death or December 2013. The prognosis of each group was evaluated by using the log-rank test and Cox-Mantel test. RESULTS: The median overall survival (OS) was 6 months [95% confidence interval (CI): 4.64-7.36]. The OS was 9 months for the TACE group and 4 months for the BSC group. The TACE group had a longer OS than the BSC subgroup for CLIP scores 0-2 [13 months (95% CI: 8.55-17.45) vs 4 months (95% CI: 0.00-10.96), P=0.001]. No significant differences were found between the TACE and BSC groups for CLIP scores 3-5. The CLIP score and treatment methods were found to be independent prognostic factors. CONCLUSIONS: BCLC stage C HCC patients exhibit definite disease heterogeneity and can be reclassified by using the CLIP scoring system. Moreover, patients with CLIP scores 0-2 are likely to benefit from TACE. However, additional studies with long-term follow-up will be required to validate these findings.

Clinical Efficacy of Andrographolide Sulfonate in the Treatment of Severe Hand, Foot, and Mouth Disease (HFMD) is Dependent upon Inhibition of Neutrophil Activation.

Andrographolide sulfonate treatment has been shown to improve clinical severe hand, foot, and mouth disease (HFMD) efficacies when combined with conventional therapy. However, the mechanisms for its therapeutic effects remain elusive. In this study, we aimed to investigate whether andrographolide sulfonate exerts its efficacy by acting on neutrophil activation. We obtained serial plasma samples at two time points (before and after 5 days of therapy) from 28 HFMD patients who received conventional therapy and 18 patients who received combination therapy (andrographolide sulfonate plus conventional therapy). Then, we measured plasma myeloperoxidase (MPO), S100A8/A9, histone, and inflammatory cytokine levels. Furthermore, we examined if andrographolide sulfonate had direct effects on neutrophil activation in vitro. We observed that MPO and S100A8/A9 levels were markedly elevated in the HFMD patients before clinical treatment. At 5 days post-medication, the MPO, S100A8/A9, histone, and interleukin-6 levels were markedly lower in the combination therapy group compared with the conventional therapy group. In vitro studies showed that andrographolide sulfonate inhibited lipopolysaccharide-stimulated neutrophil activation, demonstrated by the decreased production of reactive oxygen species and cytokines. These data indicate that neutrophil activation modulation by andrographolide sulfonate may be a critical determinant for its clinical HFMD treatment efficacy. Copyright © 2015 John Wiley & Sons, Ltd.

Echinacoside ameliorates D-galactosamine plus lipopolysaccharide-induced acute liver injury in mice via inhibition of apoptosis and inflammation.

OBJECTIVE: This study aimed to investigate the protective effects of echinacoside, one of the phenylethanoids isolated from the stems of Cistanche salsa, a Chinese herbal medicine, on D-galactosamine (GalN) and lipopolysaccharide (LPS)-induced acute liver injury in mice. METHODS: We administered GalN (650 mg/kg) together with LPS (30 µg/kg) to mice by intraperitoneal injection to induce acute liver damage. Echinacoside (60 mg/kg) was given intraperitoneally to mice at 1 h prior to GalN/LPS exposure. Mice were sacrificed at different time points following GalN/LPS treatment, and the liver and blood samples were collected for future analysis. RESULTS: It showed that GalN/LPS treatment produced severe hepatic injury, evidenced by significantly elevated plasma alanine aminotransferase (ALT) levels and abnormal histological changes such as hepatocyte necrosis or apoptosis, hemorrhage, fatty degeneration, and neutrophil infiltration. Notably, pretreatment with echinacoside remarkably improved the survival rate of GalN/LPS-treated mice and attenuated acute hepatotoxicity, as demonstrated by decreased ALT levels and improved histological signs. Echinacoside shows both anti-apoptotic and anti-inflammatory properties, characterized by a substantial inhibition of hepatocyte apoptosis and a significant reduction in the inflammatory markers, including myeloperoxidase, extracellular nucleosomes, high-mobility group box 1, and inflammatory cytokines in the plasma of mice, which may be important mechanisms related to its protective effect. CONCLUSION: Our results suggest that echinacoside can provide a pronounced protection against GalN/LPS-induced acute liver injury in mice, which may complement the available strategies for management of acute liver damage in clinical settings.

Elevated levels of circulating histones indicate disease activity in patients with hand, foot, and mouth disease (HFMD).

BACKGROUND: Hand, foot, and mouth disease (HFMD) is a common infectious disease in children, characterized by acute viral infection accompanying acute inflammatory responses. Circulating histones are leading mediators of the inflammatory processes. This study aimed to elucidate whether circulating histones play a contributory role during HFMD. METHODS: We measured plasma levels of histones, myeloperoxidase (MPO), lactate dehydrogenase (LDH), and cytokines in HFMD patients (n = 126) and compared the results with those of a control group (n = 30). RESULTS: Circulating histone levels were significantly increased in HFMD patients (3.794 ± 0.156 µg/ml) compared with healthy controls (0.238 ± 0.023 µg/ml, p < 0.0001). In addition, their levels were remarkably higher in severe HFMD (n = 38) than in mild HFMD patients (n = 88) (5.232 ± 0.246 vs 3.293 ± 0.161 µg/ml, p < 0.0001). As for other inflammatory markers, MPO, LDH, IL-1ß, IL-6, IL-10, MIP-1, and TNF-ɑ were found to be significantly higher in HFMD patients than in healthy subjects. Of these, LDH, IL-6, and TNF-ɑ levels correlated with disease severity (all p < 0.05). In mild HFMD, circulating histones correlated positively with plasma IL-6 and IL-10, whereas in severe HFMD, histones were associated with elevated IL-6 and TNF-ɑ levels. CONCLUSIONS: These data demonstrate that circulating histones are excessively released in patients with HFMD, which may indicate disease severity and contribute to systemic inflammation by promoting cytokine production (e.g. IL-6). We suggest that in mild HFMD, circulating histones may originate largely from neutrophil activation, whereas in severe HFMD, dying tissue cells and neutrophil activation may be synergistically involved in the increased levels of histones.

[Effect of Chinese drugs for Pi strengthening Shen benefiting on the immunity function of HIV patients' specific T cells].

OBJECTIVE: To explore the effect of Chinese drugs for Pi strengthening Shen benefiting (CDPSSB) on the immunity function of HIV/AIDS patients' specific T cells. METHODS: Totally 20 patients were randomly recruited from the treated group [treated by CDPSSB combined highly active anti-retroviral therapy (HAART)] and 23 patients were randomly recruited from the control group (treated by HAART alone). All patients were follow-up infected persons form You'an Hospital between from June 2010 to June 2012. CD4+ T absolute counts and HIV viral load were detected. Meanwhile, HIV whole gene overlapping peptides were used as stimulating antigen. The response intensity of HIV specific T cells was detected in the two groups. RESULTS: There was no statistical difference in CD4 T absolute counts or HIV viral load between the two groups (P > 0.05). The response intensity of HIV specific T cells was significantly enhanced in the treated group, when compared with the control group (P < 0.05). Along with elongation of treatment time (6, 12, 18, and 24 months) in the treated group, the response intensity of HIV specific T cells showed enhancing tendency, but there was no statistical difference among these time points (P > 0.05). CONCLUSION: CDPSSB could enhance improve the immunity function of HIV specific T cells, which might be one of its mechanisms.

Circulating histones exacerbate inflammation in mice with acute liver failure.

Circulating histones are a newly recognized mediator implicated in various inflammatory diseases. It is likely that the release of histones, from dying hepatocytes or inflammatory leukocytes, into the circulation initiates and amplifies inflammation during the course of acute liver failure (ALF). In this study, we investigated a putative pathogenic role of circulating histones in a murine model of ALF induced by D-galactosamine (GalN) plus lipopolysaccharide (LPS). Hepatic function and histological indexes, myeloperoxidase (MPO) activity, hepatocyte apoptosis and the levels of circulating histone were measured in GalN/LPS-treated mice. GalN/LPS caused severe liver damage and a notable increase in plasma concentration of circulating histones. To further assess the role of circulating histones in our model, we administered exogenous histones and anti-histone H4 antibody. Notably, exogenous histones aggravated GalN/LPS-induced hepatotoxicity, whereas anti-histone antibody significantly protected mice. Circulating histones may serve as both a functional marker of ALF activity and as an inflammatory mediator contributing to the progression of ALF. Blockade of circulating histones shows potent protective effects, suggesting a potential therapeutic strategy for ALF.

Reduning injection for fever, rash, and ulcers in children with mild hand, foot, and mouth disease: a randomized controlled clinical study.

OBJECTIVE: To assess the efficacy and safety of Reduning injection for fever, rash, and ulcers in children with mild hand, foot, and mouth disease (HFMD). METHODS: A stratified-block randomized, double-blind, parallel-controlled, and multicenter clinical trial was conducted with 360 patients in five hospitals across China: Quanzhou Children's Hospital, Shijiazhuang No. 5 Hospital, Shanghai Public Health Centre, Hunan Provincial Children's Hospital, and Kaifeng Children's Hospital. Patients were randomized into three groups with 120 in each. Group A was treated with Western Medicine, group B with Reduning injection, a Chinese herbal medicine, and group C with both Reduning injection and Western Medicine. Results were compared for treatment efficacy and safety on HFMD. The clinical outcomes were observed as follows: fever and onset time of antifebrile effect (time to bring the body temperature down > or = 0.5 degrees C after medication); cumulative time for fever recovery (body temperature recovering to normal and lasting more than 24 h without medication); cumulative time for rash disappearance (without new rashes or ulcers appearing and the original ones fading away); and cumulative time for mouth ulcer disappearance. RESULTS: For the onset time of the antifebrile effect, there was no statistical difference between groups A and B (P > 0.05) and groups B and C (P > 0.05). However, there was a statistical difference between groups A and C (P < 0.05), and the effect in group C was the best. For the cumulative time for rash disappearance, there was no statistical difference between groups A and B (P > 0.05). There were statistical differences between groups A and C, and groups B and C (P < 0.05), and the effect in group C was the best. For the cumulative time for mouth ulcers disappearance, there were no statistical differences among the three groups (P > 0.05). CONCLUSION: Reduning injection with Western Medicine for symptomatic treatment is most effective for mild HFMD. No adverse reactions were observed.