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.

Research progress of traditional Chinese medicine in the prevention and treatment of COVID-19 / 中国热带医学

@#Abstract: The coronavirus disease 2019 (COVID-19) has become a global public health problem due to its highly contagious nature. This article aims to discuss the current situation of traditional Chinese medicine in the prevention and treatment of COVID-19, and to provide a basis for traditional Chinese medicine research and scientific and standardized treatment of COVID-19.In this article, the etiology, pathogenesis, treatment plan and research progress were summarized, analyzed and concluded by retrieving and reviewing the literature and clinical reports related to the prevention and treatment of COVID-19 with traditional Chinese medicine. Traditional Chinese medicine has obvious effects in the prevention and treatment of COVID-19, improvement of clinical symptoms, and control of disease progression, which had the unique advantages of mild curative efficacy and safety. It has important practical significance in relieving patients' early symptoms and reducing the incidence of progression from mild to severe, and had great potential for development in the treatment of COVID-19. The traditional Chinese medicine intervention and the formulation of diagnosis and treatment plans for the COVID-19 need to be continuously optimized and improved. Scientific and rational application of traditional Chinese medicine to prevent and treat COVID-19, optimization diagnosis and treatment programs, and in-depth exploration of pharmacological mechanisms, especially the provide reference for early intervention of new coronavirus pneumonia by traditional Chinese medicine, the control of disease progression in the middle stage, and improve prognosis in the late stage with Western medicine.

Integrating Chinese and western medicine for COVID-19: A living evidence-based guideline (version 1).

BACKGROUND: The coronavirus disease 2019 (COVID-19) has turned into a pandemic and resulted in huge death tolls and burdens. Integrating Chinese and western medicine has played an important role in the fight against the COVID-19 pandemic. PURPOSE: We aimed to develop a living evidence-based guideline of integrating Chinese and western medicine for COVID-19. STUDY DESIGN: Living evidence-based guideline. METHODS: This living guideline was developed using internationally recognized and accepted guideline standards, dynamically monitoring the release of new clinical evidence, and quickly updating the linked living systematic review, evidence summary tables, and recommendations. Modified Delphi method was used to reach consensus for all recommendations. The certainty of the evidence, resources, and other factors were fully considered, and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to rate the certainty of evidence and the strength of recommendations. RESULTS: The first version of this living guidance focuses on patients who are mild or moderate COVID-19. A multidisciplinary guideline development panel was established. Ten clinical questions were identified based on the status of evidence and a face-to-face experts' consensus. Finally, nine recommendations were reached consensus, and were formulated from systematic reviews of the benefits and harms, certainty of evidence, public accessibility, policy supports, feedback on proposed recommendations from multidisciplinary experts, and consensus meetings. CONCLUSION: This guideline panel made nine recommendations, which covered five traditional Chinese medicine (TCM) prescription granules/decoction (MXXFJD, QFPD, XFBD, TJQW, and JWDY), three Chinese patent medicines (LHQW granules/capsule, JHQG granules, and LHQK granules), and one Chinese herbal injection (XBJ injection). Of them, two were strongly recommended (LHQW granules/capsule and QFPD decoction), and five were weakly recommended (MXXFJD decoction, XFBD decoction, JHQG granules, TJQW granules, and JWDY decoction) for the treatment of mild and moderate COVID-19; two were weakly recommended against (XBJ injection and LHQK granules) the treatment of mild and moderate COVID-19. The users of this living guideline are most likely to be clinicians, patients, governments, ministries, and health administrators.

The Effect of Xinmailong Infusion on Sepsis-Induced Myocardial Dysfunction: a Pragmatic Randomized Controlled Trial.

ABSTRACT: Sepsis-induced myocardial dysfunction (SIMD) contributes significantly to cardiovascular dysfunction during septic shock. We aimed to evaluate the potential role of Xinmailong injection (XMLI), a polypeptide medicine extracted from Periplaneta americana, in reversing the progression of myocardial damage to SIMD in sepsis patients. This was a multicenter, randomized, double-blind, parallel-group trial. We recruited all patients consecutively admitted to intensive care units (ICUs) who were aged 18 to 85 years old and met the sepsis 3.0 criteria. The primary outcome measure was the incidence of sepsis-induced myocardial dysfunction while in the ICU. Of the 192 patients, 96 were assigned to the treatment group, and 96 to the control group. Subsequently, 41 patients [41/96 (42.7%)] in the XMLI group and 61 patients in the placebo group [61/96 (63.5%)] were confirmed to have diastolic dysfunction on the fifth day (D5). The incidence of diastolic SIMD was significantly different between the two groups (P = 0.004). There were 36 deaths in the two groups during the 28-day follow-up, with a general mortality rate of 18.8% (36/192). The 28-day mortality rates were not significantly different between the groups (P = 0.45). However, the brain natriuretic peptide (BNP) plasma concentration trends on D0, D2, and D5 significantly differed between the two groups (P = 0.049). In septic patients, XMLI decreased the occurrence rate of diastolic SIMD more effectively than the placebo. The improvement in serum BNP concentration was also greater in the XMLI group. XMLI may, therefore, effectively and safely improve cardiac function in patients with sepsis.

The efficacy and safety of Xuebijing injection for corona virus disease 2019: A protocol for a systematic review and meta-analysis.

BACKGROUND: Corona virus disease 2019 (COVID-19) is an epidemic respiratory infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus 2 infection. Now it is popular all over the world on a large scale. COVID-19 has the characteristics of rapid transmission, atypical clinical symptoms, easy missed diagnosis and misdiagnosis, and so on. which has seriously affected social and economic development and people's health. Severe acute respiratory syndrome corona virus type 2 infection may lead to systemic cytokine storm, which leads to a sharp deterioration of the condition of ordinary patients. At present, no specific drug has been found in the clinical treatment of covid-19, while Xuebijing injection has been widely used in severe patients in China as a traditional Chinese medicine. The aim of this study is to assess the effificacy and safety of Xuebijing injection for COVID-19. METHODS: Before the research, we conducted a comprehensive search on relevant websites. Two professional researchers will gradually screen, read the title, abstract and full text if necessary, and independently select qualified documents according to the inclusion and exclusion criteria. We will conduct a meta-analysis of the results related to COVID-19 to assess the risks of bias and data extraction. The heterogeneity of data will be studied by Cochrane X and I tests. The evaluation of publication bias will be carried out by funnel chart analysis and Eger test. RESULTS: This review will be disseminated in print by peer-review. CONCLUSION: Our research is to scientifically analyze the clinical evidence of Xuebijing injection in treating severe COVID-19 patients.

Retracted Article: A high-throughput metabolomics strategy for discovering the influence of differential metabolites and metabolic pathways of huaxian capsules on sepsis-associated Qi deficiency and blood stasis syndrome.

High-throughput metabolomics can be used to investigate the therapeutic targets and metabolic mechanisms of traditional Chinese medicine (TCM) formulae, which have multiple targets in disease therapy, but it is a great challenge to explore their mechanism of action. Huaxian capsule (HXC) is a classical formula in TCM that has therapeutic effects on a sepsis-associated Qi deficiency and blood stasis syndrome (SQBS). However, its targets and metabolic mechanisms need more investigation. To investigate the therapeutic effects of HXC in the treatment of SQBS and elucidate the potential mechanism, we used a high-throughput metabolomics strategy based on the ultraperformance liquid chromatography/mass spectrometry combined with chemometrics to analyze and identify differential metabolites and pathways. The pathological examination of organs and biochemical indices was also performed to verify the successful establishment of the rat model and protective effects of HXC. Pathological symptoms and biochemical indicators of SQBS rats were reversed by the HXC treatment. A total of 24 potential biomarkers were identified to indicate the difference between the control and model groups; they were closely associated with ten metabolic pathways and regulated by the HXC administration. From the pathway analysis, we further understood the protective activity of HXC against SQBS, which affected amino acid metabolism, molecular transport, small molecule biochemistry and cell signaling as well as vitamin and mineral metabolism. In conclusion, HXC protects against SQBS by modulating the metabolic biomarkers and functional pathways.

[Effect of fermented cordyceps powder and prednisone on the Notch2/Hes-1 signaling activation in the kidney tubules of rats with acute aristolochic acid nephropathy].

OBJECTIVE: To investigate the effect of both fermented Cordyceps powder (CS) and prednisone on the Notch2/hes-1 signaling activation in the kidney tubules of rats with acute aristolochic acid nephropathy (AAAN). METHODS: Totally 50 SD rats were randomly divided into 4 groups, i.e., the normal group, the model group, the CS group, the prednisone group, and the CS plus prednisone group, 10 in each group. The AAAN rat model was induced by intragastric administration of pure aristolochic acid A at the daily dose of 100 mg/kg for 3 days. Rats in the CS group were administered with CS at the daily dose of 5.0 g/kg by gastrogavage, while those in the prednisone group were administered with prednisone at the daily dose of 0.5 mg/kg. Rats in the CS plus prednisone group were treated by CS and prednisone. All treatment lasted for 3 successive weeks. Kidney functions [urea nitrogen (BUN) and serum creatinine (SCr)] were detected. The pathological changes of kidneys were observed by Hematoxylin-Eosin staining. The apoptosis of the renal tubular epithelial cells was detected by TUNEL. The protein expressions of Notch2 and Hes-1 in the renal tissue were detected by immunohistochemical assay and Western blot. RESULTS: Results of HE staining showed the structure in the nephridial tissue was regular in rats of the normal group. The renal tubular necrosis occurred in the rats of the model group. The pathological changes of kidneys were obviously improved in the CS group, the prednisone group, and the CS plus prednisone group. Compared with the normal group, levels of BUN and SCr, semi-quantitative score of the tubular interstitial tissue, ratio of apoptotic cells, and expressions of Notch2 and Hes-1 proteins significantly increased in the model group (P < 0.01). Compared with the model group, the aforesaid indices significantly decreased in the 3 treatment groups (P < 0.01). All indices decreased most obviously in the CS plus prednisone group (P < 0.05, P < 0. 01). CONCLUSIONS: Notch2/hes-1 signaling activation might be associated with apoptosis of renal tubular epithelial cells. Both CS and prednisone could play a nephroprotective role for AAAN. But CS plus prednisone could achieve the best effect. Inhabiting the Notch2/hes-1 signaling activation could be its nephroprotective mechanism.

[Translational frameshift may be occur in p11, an interaction protein of Cx31, in yeast].

Connexin 31 is a member of connexin family. The carboxy-terminal cytosolic domain of connexin 31 contains several potential phosphorylation sites. In this work, a yeast two-hybrid protein interaction screen have been used to identify proteins that bind to the carboxy-terminus of connexin 31, and the p11 protein, an unique member of S100 protein family, and one of the two subunits of the annexin II tetramer was isolated. Interestingly, from yeast two-hybrid AD's coding sequence, three different reading frames of p11 DNA sequence were found,which come from different AD plasmids. By constructing AD plasmids using p11 ORF or 5' UTR, the protein coding by p11 ORF bind to connexin 31, while polypeptides coding by three kinds of 5 UTR did not bind to connexin 31, suggesting a translational frameshift of p11 fusion protein. To construct baits by dividing connexin 31 C-terminus into two domain, the p11 binding domain of connexin 31 was found located between 206-237 codons. The plasmid Cx31CT-pGEX-4T-2 was constructed for expression and purification of GST-Cx31CT; and p11-pQE30 for expression and purification of 6xHis-p11. In vitro binding assay showed that recombinant Cx31 interacted with recombinant p11.

[Expression and purification of p11 fusion protein in E. coli and preparation of antiserum against GST-p11].

OBJECTIVE: To obtain p11 fusion protein and prepare specific polyclonal antibody against p11. METHODS: A full-length human p11 gene was cloned into expression vectors, pGEX-4T-2 and pQE30, and transformed into E. coli. The expressed proteins were purified from lysates with Glutathione Sepharose 4B and the Ni-NTA agarose column, respectively. The purified GST-p11 was mixed with Freund's complete or incomplete adjuvant and immunized rabbits. RESULTS: A high level of expression of target proteins was detected after IPTG induction and purified proteins were obtained by affinity chromatography with Glutathione Sepharose 4B and the Ni-NTA agarose column, respectively. Western blotting analysis suggested that the polyclonal antibody can recognize 6xHis-p11 and GST protein. CONCLUSION: The antiserum against p11 prepared by prokaryotic expression of GST-p11 fusion protein has good specificity.

Effect of serum obtained from rat treated orally with Traditional Chinese Medicine Nao Yi-An on MAPK signal transduction in injured cultured neurons / 中国康复理论与实践

@#ObjectiveTo explore the effects of the serum of traditional Chinese medicine Nao Yi An on glutamate induced cell death in cultured hippocampal neurons of rat and the underlying mechanisms. MethodsHippocampal neurons were cultured. The excitatory amino acid induced toxicity on cultured neurons was investigated. The viability of injured neurons was determined with the measurement of Lactate dehydrogenase (LDH) activity. Mitogen activated protein kinase (MAPK) were determined by immunoprecipitation /kinase assays /western blot detection.ResultsThe serum of Nao Yi-An raised cell viability. The serum of Nao Yi-An upregulated the expression of extracellular regulated protein kinases(ERK) and downregulated the expression of c-Jun N terminal kinase/stress activited protein kinase(JNK) in cultured neurons. The serum of Nao Yi-An induced upregulation of ERK and its anti death action were prevented with the specific ERKs inhibitor PD98059. Conclusions Activation of ERK signaling together with inhibition of JNK signaling by Chinese medicine Nao Yi-An appears to be an important mechanism for its survival effects on cultured hippocampal neurons.