Effect of an Herbal-Based Injection on 28-Day Mortality in Patients With Sepsis: The EXIT-SEP Randomized Clinical Trial.

Importance: Previous research has suggested that Xuebijing injection (XBJ), an herbal-based intravenous preparation, may reduce mortality among patients with sepsis. Objective: To determine the effect of XBJ vs placebo on 28-day mortality among patients with sepsis. Design, Setting, and Participants: The Efficacy of Xuebijing Injection in Patients With Sepsis (EXIT-SEP) trial was a multicenter, randomized double-blind, placebo-controlled trial conducted in intensive care units at 45 sites and included 1817 randomized patients with sepsis (sepsis 3.0) present for less than 48 hours. Patients aged 18 to 75 years with a Sequential Organ Failure Assessment score of 2 to 13 were enrolled. The study was conducted from October 2017 to June 2019. The final date of follow-up was July 26, 2019. Data analysis was performed from January 2020 to August 2022. Interventions: The patients were randomized to receive either intravenous infusion of XBJ (100 mL, n = 911) or volume-matched saline placebo (n = 906) every 12 hours for 5 days. Main Outcomes and Measures: The primary outcome was 28-day mortality. Results: Among the 1817 patients who were randomized (mean [SD] age, 56.5 [13.5] years; 1199 [66.0%] men), 1760 (96.9%) completed the trial. In these patients, the 28-day mortality rate was significantly different between the placebo group and the XBJ group (230 of 882 patients [26.1%] vs 165 of 878 patients [18.8%], respectively; P < .001). The absolute risk difference was 7.3 (95% CI, 3.4-11.2) percentage points. The incidence of adverse events was 222 of 878 patients (25.3%) in the placebo group and 200 of 872 patients (22.9%) in the XBJ group. Conclusions and Relevance: In this randomized clinical trial among patients with sepsis, the administration of XBJ reduced 28-day mortality compared with placebo. Trial Registration: ClinicalTrials.gov Identifier: NCT03238742.

Electroacupuncture at Neiguan (PC6) attenuates cardiac dysfunction caused by cecal ligation and puncture via the vagus nerve.

PURPOSE: Previous studies proved the benefits of electroacupuncture (EA) on heart in ischemia reperfusion injury and chronic heart failure. However, the role of EA on sepsis-induced cardiac dysfunction has rarely been elucidated before. In this study, we aimed to investigate the effects of EA on cardiac dysfunction in a rat model of sepsis and to speculate the underlying mechanisms. METHODS: Sepsis was induced by cecum ligation and puncture in anesthetized rats. EA at the acupoint "Neiguan (PC6)" was applied 0.5 h after the induction of sepsis for 20 min. Heart rate variability was obtained immediately after EA to evaluate autonomic balance. Echocardiography was performed at 6 h and 24 h after sepsis induction in vivo. Measurements of hemodynamics, blood gases, cytokines and biochemistry were collected at 24 h. Cardiac tissue underwent immunofluorescence staining to determine the expression of α7 nicotinic acetylcholine receptor (α7nAChR) on macrophages. RESULTS: EA increased vagus nerve activity, prevented the development of hyperlactatemia, attenuated the decline of left ventricle ejection fraction, suppressed systemic and cardiac inflammation and alleviated the histopathological manifestations of heart in sepsis rats. Furthermore, the cardiac tissue from EA treated rats showed increased expressions of α7nAChR on macrophages. The cardio-protective and anti-inflammatory effects of EA were partly or completely prevented in rats with vagotomy. CONCLUSION: EA at PC6 attenuates left ventricle dysfunction and decreases inflammation in sepsis-induced cardiac dysfunction. The cardio-protective effects of EA are mediated through vagus nerve mediated cholinergic pathway.

Research note: effects of different anticoccidial regimens on the growth performance, hematological parameters, immune response, and intestinal coccidial lesion scores of yellow-feathered broilers.

Yellow-feathered broiler chickens generally have a longer growth cycle than white broilers and therefore face different coccidiosis challenges. General single vaccine and drug regimens struggle to prevent coccidiosis for yellow broilers. In this study, a single vaccine, and a combination of coccidiostat regimens was employed to explore the preventative and control effects of different pilot regimens on coccidiosis in yellow-feathered broilers. A total of 2,000 one day old Chinese Huang Youma female broilers were allocated into 4 experimental groups, each with 5 replicates. All birds were fed the same starter feed from Days 1 to 25, and all groups were inoculated with a vaccine on Day 4. After Day 26, the groups were then fed as follows: (1) Negative control group: basal diet + vaccine (NC); (2) NC + maduramycin (NCMD); (3) NC + narasin (NCNR); and (4) NC + salinomycin (NCSL). From Days 26 to 75, the NCNR group had a lower FCR than the other groups. The 75-d BW was higher in the NCNR group than in the NCSL group but was not significantly higher than that in the NC and NCMD groups. The growth performance followed the same trend during the whole experiment (Days 1-75). Compared to the NC group, the NCNR and NCSL groups had higher intestinal mucosa SIgA concentrations at Day 40 and Day 60 (P < 0.001); however the NCMD group had lower IgG levels at Day 40 and Day 60 (P = 0.036, P = 0.006 respectively). The combination groups had significantly reduced AKP levels and urine acid concentrations at Day 60 in comparison to those of the NC group (P = 0.004). The NCNR and NCMD groups had less severe intestinal coccidiosis lesion scores than the NC and NCSL groups in older birds. Thus, a single vaccine and/or combinations with different coccidiostats had different effects on broilers. The NCNR group showed comparatively better growth performance, blood biochemical indices, immune response, and coccidiosis lesion scores.

XueBiJing Injection Versus Placebo for Critically Ill Patients With Severe Community-Acquired Pneumonia: A Randomized Controlled Trial.

OBJECTIVES: To investigate whether XueBiJing injection improves clinical outcomes in critically ill patients with severe community-acquired pneumonia. DESIGN: Prospective, randomized, controlled study. SETTING: Thirty-three hospitals in China. PATIENTS: A total of 710 adults 18-75 years old with severe community-acquired pneumonia. INTERVENTIONS: Participants in the XueBiJing group received XueBiJing, 100 mL, q12 hours, and the control group received a visually indistinguishable placebo. MEASUREMENTS AND MAIN RESULTS: The primary outcome was 8-day improvement in the pneumonia severity index risk rating. Secondary outcomes were 28-day mortality rate, duration of mechanical ventilation and total duration of ICU stay. Improvement in the pneumonia severity index risk rating, from a previously defined endpoint, occurred in 203 (60.78%) participants receiving XueBiJing and in 158 (46.33%) participants receiving placebo (between-group difference [95% CI], 14.4% [6.9-21.8%]; p < 0.001). Fifty-three (15.87%) XueBiJing recipients and 84 (24.63%) placebo recipients (8.8% [2.4-15.2%]; p = 0.006) died within 28 days. XueBiJing administration also decreased the mechanical ventilation time and the total ICU stay duration. The median mechanical ventilation time was 11.0 versus 16.5 days for the XueBiJing and placebo groups, respectively (p = 0.012). The total duration of ICU stay was 12 days for XueBiJing recipients versus 16 days for placebo recipients (p = 0.004). A total of 256 patients experienced adverse events (119 [35.63%] vs 137 [40.18%] in the XueBiJing and placebo groups, respectively [p = 0.235]). CONCLUSIONS: In critically ill patients with severe community-acquired pneumonia, XueBiJing injection led to a statistically significant improvement in the primary endpoint of the pneumonia severity index as well a significant improvement in the secondary clinical outcomes of mortality, duration of mechanical ventilation and duration of ICU stay.

Antitumor effects of ß-elemene via targeting the phosphorylation of insulin receptor.

Ewing sarcoma family tumors (ESFTs) are a group of aggressive and highly metastatic tumors lacking efficient therapies. Insulin-like growth factor 1 receptor (IGF1R) blockade is one of the most efficient targeting therapy for ESFTs. However, the appliance is obstructed by drug resistance and disease recurrence due to the activation of insulin receptor (IR) signaling induced by IGF1R blockade. Herein ß-elemene, a compound derived from natural plants, exhibited a remarkable proliferation repression on ESFT cells, which was weakened by a caspase inhibitor Z-VAD. ß-elemene in combination with IGF1R inhibitors enhanced markedly the repression on cellular proliferation and mTOR activation by IGF1R inhibitors and suppressed the PI3K phosphorylation induced by IGF1R inhibitors. To investigate the mechanisms, we focused on the effects of ß-elemene on IR signaling pathway. ß-elemene significantly suppressed the insulin-driven cell growth and the activation of mTOR and PI3K in tumor cells, while the toxicity to normal hepatocytes was much lower. Further, the phosphorylation of IR was found to be suppressed notably by ß-elemene specifically in tumor cells other than normal hepatocytes. In addition, ß-elemene inhibited the growth of ESFT xenografts in vivo, and the phosphorylation of IR and S6 ribosomal protein was significantly repressed in the ß-elemene-treated xenografts. These data suggest that ß-elemene targets IR phosphorylation to inhibit the proliferation of tumor cells specifically and enhance the effects of IGF1R inhibitors. Thus, this study provides evidence for novel approaches by ß-elemene alone or in combination with IGF1R blockades in ESFTs and IR signaling hyperactivated tumors.

[Analysis on quality and differences of Mentha haplocalyx from different regions].

A gas chromatography-mass spectrometry(GC-MS)method was established for the analysis of volatile components in Mentha haplocalyx, and seven principal components were quantified by gas chromatography(GC). Based on these analyses, the differences of volatile components in M. haplocalyx from Jiangsu, Anhui and other regions were compared. The results showed that the volatile oil of M. haplocalyx was divided into four chemical types：menthol-menthone type, pulegone-menthone type, piperitone-menthol type, piperitone epoxide type, and menthol-menthone type was the principal type. Menthol was the highest and pulegone was the lowest. The differences of M. haplocalyx from Anhui and other regions were obvious. The major volatile components and the differences of M. haplocalyx from different regions were confirmed and a quantitative method was established for the determination of volatile components, which provided the basis for improving the quality standard of M. haplocalyx.

The hypoglycemic and antioxidant effects of polysaccharides from the petioles and pedicels of Euryale ferox Salisb. on alloxan-induced hyperglycemic mice.

The present study investigated the potential hypoglycemic and antioxidant effects of polysaccharides extracted from the petioles and pedicels of Euryale ferox Salisb. (EFPP) on alloxan-induced hyperglycemic mice. The EFPP had a total carbohydrate of 65.72 ± 2.81%, uronic acid of 4.56 ± 0.62% and protein of 0.58 ± 0.12%, with an average molecular weight from 1.02 kDa to 11.45 kDa and monosaccharide composition of Man, GlcA, Rha, Glc, Gal and Ara at a molar ratio of 0.12 : 0.01 : 9.57 : 0.41 : 1.00 : 0.24. Administration with EFPP, especially high dose EFPP, was beneficial to reverse body weight loss, reduce blood glucose levels, enhance serum insulin levels, improve oral glucose tolerance, increase hepatic glycogen content and GCK activity, and modulate the mRNA expression of GCK in the liver. Meanwhile, EFPP had protective effects against alloxan-induced oxidative injury in mice, via increasing the activities of SOD, CAT and GSH-Px and decreasing the MDA contents in the liver and kidney of the mice. EFPP ameliorated the damage in pancreas, kidney and liver tissues, which was confirmed by histopathological observation. The results suggested that EFPP possess hypoglycemic and antioxidant activities, and could be a potential source of natural hypoglycemic and antioxidant agents for functional foods or complementary medicines.

New isocoumarin and stilbenoid derivatives from the tubers of Sparganium stoloniferum (Buch.-Ham.).

A new isocoumarin derivative 8,5'-dihydroxy-6'-methoxy-4-phenyl-5,2'-oxidoisocoumarin (1) and a new stilbenoid derivative methyl 5-hydroxy-2-(2-hydroxyphenyl)benzofuran-4-carboxylate (2) together with nine known compounds (3-11) were isolated from the tubers of Sparganium stoloniferum Buch.-Ham.. Another stilbenoid derivative (3) and a xanthone (4) were identified as new natural products and compounds 5-10 were obtained for the first time from the genus Sparganium. All their structures were elucidated by comprehensive spectroscopic analysis and comparison with available literature information.

Digestive evaluation of soy isolate protein as affected by heat treatment and soy oil inclusion in broilers at an early age.

Soy protein isolate (SPI) mixed with soybean oil (SPIO) incubated at 100°C for 8 h was used to evaluate changes of solubility and digestibility of SPI in vitro and digestive function in broilers at an early age. Arbor Acres broilers were allocated to three groups with six replicates of 12 birds, receiving basal diet (CON), 8 h heat-oxidized SPI diet (HSPI) and 8 h heat-oxidized mixture of SPI and 2% soybean oil diet (HSPIO) for 21 days, respectively. Nitrogen solubility index (NSI) declined and soybean oil accelerated the decline of NSI during incubation (P < 0.05). Decreased in vitro digestibility of dry matter (DM) and crude protein (CP) were observed in SPIO (P < 0.05). HSPI and HSPIO decreased body weight gain, relative jejunum weight and pancreatic trypsin activity at day 21 (P < 0.05). HSPIO decreased anterior intestinal trypsin activity at day 14 and amylase and trypsin activity at day 21, pancreatic amylase activity at day 21 and apparent digestibility of DM, organic matter and CP of broilers from days 18 to 20 (P < 0.05). Heat treatment and soybean oil could induce oxidative modification of SPI, and oxidized SPI negatively affected growth and digestion of broilers. © 2016 Japanese Society of Animal Science.

CrkL meditates CCL20/CCR6-induced EMT in gastric cancer.

BACKGROUND: In recent years, Crk-like adapter protein (CrkL) has been identified as a key regulator in the epithelial-to-mesenchymal transition (EMT). However, the molecular mechanisms underlying the CC chemokine receptor 6 (CCR6) and chemokine (C-C motif) ligand 20 (CCL20)-induced EMT in gastric cancer are still unclear. METHODS: We conducted the immunohistochemistry and immunoblotting to detect the expression of CCR6 and CrkL in 90 cases of gastric cancer tissues and five kinds of cell lines. And then, gastric cancer cells were subjected to small interfering RNA (siRNA) treatment and in vitro assay. RESULTS: Both CCR6 and CrkL were aberrantly expressed in gastric cancer specimens and closely correlated with differentiation of cell lines. The expression of CCR6 and CrkL was also significantly associated with metastasis, stage, and poor prognosis of gastric cancer. In addition, we validated CCL20 activated the expression of p-CrkL, p-Erk1/2, p-Akt, vimentin, N-cadherin and MMP2 in MGC803 cells in a dose-dependent manner. However, si-CrkL abrogated the CCL20-induced p-Erk1/2, vimentin, N-cadherin and MMP2 expression. Most importantly, the knockdown of CrkL decreased migration and invasion of MGC803 cells. CONCLUSIONS: CrkL mediates CCL20/CCR6-induced EMT via Akt pathway, instead of Erk1/2 pathway in development of gastric cancer, which indicated CCL20/CCR6-CrkL-Erk1/2-EMT pathway may be targeted to antagonize the progression of gastric cancer.

Content variations of triterpenic acid, nucleoside, nucleobase, and sugar in jujube (Ziziphus jujuba) fruit during ripening.

Jujube (Ziziphus jujuba) fruit is widely consumed as food and traditional Chinese medicine in Asian countries due to its potential effects for human health. To facilitate selection of the maturity stage providing optimum health benefits, jujube fruits were analysed at six stages of growth (S1-6) for triterpenic acids, nucleosides, nucleobases, and sugars by UHPLC-MS/MS or HPLC-ELSD methods. The content levels of most triterpenic acids and sugars increased with ripening, and reached the highest at S5 and S6, respectively. The accumulation of the cyclic nucleotides (cAMP and cGMP) was mainly in the later stage of ripening (S5-6). Therefore, if taking triterpenic acids as the major quality indicator, S5 should be the ideal time to harvest jujube fruit, and the full ripen stage (S6) maybe the best choice when taking sugars and cyclic nucleotides as the most important components.

[Multi-level identification and analysis about infrared spectroscopy of lophatheri herba].

Based on the infrared spectra of Lophatheri Herba and Commelinae Herba, one-dimensional infrared spectra, second derivative spectra and two-dimensional correlated spectra were used to find out the differences between Lophatheri Herba and its imitations, respectively. The common peak ratio and variant peak ratio dual-indexes sequential were calculated and established according to infrared spectra of eleven batches of herbs. Infrared spectral data of Lophatheri Herba cluster analysis was applied to explore the similarity between each sample. The grouping results trend of sequential analysis of dual-indexes and cluster analysis was accordant. The results showed that the differences could be found by multi-level identification, and the source and the quality of the herbs could be effectively distinguished by the two analysis methods. Infrared spectroscopy, used in the present work exhibited some advantages on quick procedures, less sample required, and reliable results, which could provide a new method for the identification of traditional Chinese medicine with the imitations and adulterants, and the control of quality and origin.

Isorhynchophylline protects against pulmonary arterial hypertension and suppresses PASMCs proliferation.

Increased pulmonary arterial smooth muscle cells (PASMCs) proliferation is a key pathophysiological component of pulmonary vascular remodeling in pulmonary arterial hypertension (PAH). Isorhynchophylline (IRN) is a tetracyclic oxindole alkaloid isolated from the Chinese herbal medicine Uncaria rhynchophylla. It has long been used clinically for treatment of cardiovascular and cerebrovascular diseases. However, very little is known about whether IRN can influence the development of PAH. Here we examined the effect of IRN on monocrotaline (MCT) induced PAH in rats. Our data demonstrated that IRN prevented MCT induced PAH in rats, as assessed by right ventricular (RV) pressure, the weight ratio of RV to (left ventricular+septum) and RV hypertrophy. IRN significantly attenuated the percentage of fully muscularized small arterioles, the medial wall thickness, and the expression of smooth muscle α-actin (α-SMA) and proliferating cell nuclear antigen (PCNA). In vitro studies, IRN concentration-dependently inhibited the platelet-derived growth factor (PDGF)-BB-induced proliferation of PASMCs. Fluorescence-activated cell-sorting analysis showed that IRN caused G0/G1 phase cell cycle arrest. IRN-induced growth inhibition was associated with downregulation of Cyclin D1 and CDK6 as well as an increase in p27Kip1 levels in PDGF-BB-stimulated PASMCs. Moreover, IRN negatively modulated PDGF-BB-induced phosphorylation of PDGF-Rß, ERK1/2, Akt/GSK3ß, and signal transducers and activators of transcription 3 (STAT3). These results demonstrate that IRN could inhibit PASMCs proliferation and attenuate pulmonary vascular remodeling after MCT induction. These beneficial effects were at least through the inhibition of PDGF-Rß phosphorylation and its downstream signaling pathways. Therefore, IRN might be a potential candidate for the treatment of PAH.

Hydrophilic interaction ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry for determination of nucleotides, nucleosides and nucleobases in Ziziphus plants.

In this study, a rapid and sensitive analytical method was developed for the determination of 20 nucleobases, nucleosides and nucleotides in Ziziphus plants at trace levels by using hydrophilic interaction ultra-high performance liquid chromatography coupled with triple-quadrupole tandem mass spectrometry (HILIC-UHPLC-TQ-MS/MS) in multiple-reaction monitoring (MRM) mode. Under the optimized chromatographic conditions, good separation for 20 target compounds were obtained on a UHPLC Amide column with sub-2µm particles within 10min. The overall LODs and LOQs were between 0.11-3.12ngmL(-1) and 0.29-12.48ngmL(-1) for the 20 analytes, respectively. It is the first report about simultaneous analysis of nucleobases, nucleosides and nucleotides in medicinal plants using HILIC-UHPLC-TQ-MS/MS method, which affords good linearity, precision, repeatability and accuracy. The developed method was successfully applied to Ziziphus plant (Z. jujuba, Z. jujuba var. spinosa and Z. mauritiana) samples. The analysis showed that the fruits and leaves of Ziziphus plants are rich in nucleosides and nucleobases as well as nucleotides, and could be selected as the healthy food resources. Our results in present study suggest that HILIC-UHPLC-TQ-MS/MS method could be employed as a useful tool for quality assessment of the samples from the Ziziphus plants as well as other medicinal plants or food samples using nucleotides, nucleosides and nucleobases as markers.

Croton megalocarpus oil-fired micro-trigeneration prototype for remote and self-contained applications: experimental assessment of its performance and gaseous and particulate emissions.

According to the International Energy Agency's World Energy Outlook 2011, 60 per cent of the population in Africa, some 587 million people, mostly in sub-Saharan Africa, lacked access to electricity in 2009. We developed a 6.5 kWe micro-trigeneration prototype, on the basis of internal combustion engine with pure Croton megalocarpus oil (CMO) fuelling, which configures a distributed energy system to generate power, heating and cooling from a single sustainable fuel source for remote users. Croton megalocarpus is an indigenous tree in East and South Africa which has recently attracted lots of interests as a biofuel source because of its high oil-yield rate. The direct and local use of CMO, instead of CMO biodiesel converted by the transesterification process, minimizes the carbon footprints left behind because of the simple fuel production of CMO. The experimental assessment proves that the prototype fuelled with CMO achieves similar efficiency as with diesel. Also, with the elevation of the oil injection temperature, the gaseous and particulate emissions of CMO could be ameliorated to some extent as improvement of the atomization in the spray and the combustion in the engine cylinder.

[Changes of endogenous ouabain in rat serum and certain tissues after exposure to simulated weightlessness].

OBJECTIVE: To investigate the changes of endogenous ouabain (EO) in rat serum and some tissues after exposure to simulated weightlessness and to investigate its possible pathophysiology. METHOD: Male Wistar rats were randomly divided into control group (Con) and 1 week tail-suspension group (TS). Enzyme-linked immunosorbent assay (ELISA) was used to detect the content of EO in serum, hypothalamus, pituitary, adrenal gland, kidney, heart and liver. RESULT: Compared with Con, EO increased significantly in serum, hypothalamus, adrenal gland and kidney after tail suspension (P<0.05). CONCLUSION: Simulated weightlessness induced changes of EO in serum and some tissues, which may have some effects on the regulation of hydro-electrolyte metabolism and cardiovascular functions.