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Introduction. Hyperlipidemia is an underlying process behind cardiovascular disease. Chinese medicine (CM) may be effective in treating hyperlipidemia, but there is a lack of studies with high methodological quality. A major reason for this is heterogeneity in outcome reporting. Therefore, this study explores the degree of outcome reporting variation in CM trials for hyperlipidemia. It then generates a list of potentially important outcomes for developing a core outcome set (COS). Methods. A systematic review of literature focusing on studies of CM for hyperlipidemia was conducted. Outcomes were listed verbatim and grouped into 8 domains. Outcome frequency and definition uniformity were analyzed. Results. 3,702 studies and 452 individual outcomes were identified. These outcomes were reported 27,328 times, of which 1.6% were reported as primary outcomes, and 13.3% were defined. The most frequent outcome was total triglyceride, represented in 86.7% of the studies, followed by total cholesterol (86.0%), total effective rate (75.1%), high-density lipoprotein cholesterol (73.2%), and low-density lipoprotein cholesterol (60.5%). However, 43.6% of outcomes were reported only once. The largest outcome domain was "pathological or pathophysiological outcomes," which included 67.0% of outcomes. Of the "response rate related outcomes" domain, total effective rate was the most frequently reported outcome (n = 2,780), and 95.3% of the studies gave a clear definition. However, these definitions were often contradictory. Only 10 papers reported cardiovascular events, 3 of which referred to them as primary outcomes. Moreover, ten patient-reported outcomes were reported in the retrieved literature 19 times in total. The majority of the outcomes did not report measurement instruments (MIs) (269/453, 59.4%). MIs of the surrogate outcomes were reported more frequently. Conclusion. Outcome reporting in CM trials for hyperlipidemia is inconsistent and ill-defined, creating barriers to data synthesis and comparison. Thus, we propose and are developing a COS for CM trials for hyperlipidemia. [ABSTRACT FROM AUTHOR]

Introduction. Stable angina (SA) in coronary heart disease is a common ischemic heart disease endangering the patient's quality of life and longevity. Clinical trials have demonstrated that the Chinese herbal formula Xuefu Zhuyu (XFZY) has benefits for SA patients. However, there remains a lack of high-quality evidence to support clinical decision-making. Therefore, we designed a randomized controlled trial (RCT) to evaluate the efficacy and safety of XFZY for SA. Methods and Analysis. This multicenter, double-blinded RCT will be conducted in China. 152 eligible participants will be randomly assigned to either an XFZY group or a control group at a 1 : 1 ratio. Participants in the XFZY group will receive XFZY plus routine care, while those in the control group will receive placebo plus routine care. The study period is 26 weeks, including a 2-week run-in period, a 12-week treatment period, and a 12-week follow-up. The primary outcome is the change in visual analogue scale score for angina pain intensity from baseline to 12 weeks. The secondary outcomes are the angina attack frequency and duration, the nitroglycerin dosage consumed, the Canadian Cardiovascular Society grading of effort angina, the Seattle Angina Questionnaire, the EuroQol-5-Dimensions-5-Level, the incidence of major adverse cardiac events, health cost evaluation, and overall assessment for study drugs. Ethics and Dissemination. The study has been approved by the ethics committee of Guangdong Provincial Hospital of Chinese Medicine (approval no. BF2019-175-01). Results will be submitted for publication in peer-reviewed journals and disseminated at scientific conferences. This trial is registered with ChiCTR1900026899, registered on 26 October 2019. [ABSTRACT FROM AUTHOR]

Background: Ethyl chloride spray as a common cooling modality has been widely used in acute sports injuries and joint injection procedures. Several clinical studies reported that use of ethyl chloride has positive effects on swelling, pain reduction and recovery from sports injuries. The main aim of present study was to analyze whether postoperative use of ethyl chloride spray benefits results after primary total knee arthroplasty (TKA).Methods: Between April 1, 2014 and October 21, 2015, 306 subjects undergoing primary TKA used ethyl chloride spray for improving recovery from the damage from surgery. After exclusion of 31 subjects due to adverse events including periprosthetic joint infection (PJI), deep venous thrombosis (DVT), acute myocardial infarction, finally 275 subjects' data regarding pain score, knee range of motion (ROM), knee girth, time of being able to reach 90° knee flexion and analgesic consumption were analyzed.Results: Significant differences in pain score, knee ROM at each time point and knee girth at on 21st and 28th postoperatively were detected without increased incidence of adverse events. Besides, time of being able to reach 90° knee flexion and analgesic consumption in the treatment group were significantly decreased in comparison to the control group.Conclusion: Use of ethyl chloride spray can help patients recovery from the damage from TKA safely. [ABSTRACT FROM AUTHOR]

The mammalian target of rapamycin (mTOR) is dysregulated in diverse cancers and contributes to tumor progression and drug resistance. The first generation of mTOR inhibitors have failed to show clinical efficiency in treating pancreatic cancers due in part to the feedback relief of the insulin-like growth factor-1 receptor (IGF-1R)-AKT signaling pathway. The second generation of mTOR inhibitors, such as AZD8055, could inhibit AKT activation upon mTOR complex 2 (mTORC2) inhibition. However, whether this generation of mTOR inhibitors can obtain satisfactory activities in pancreatic cancer therapy remains unclear. In this study, we found AZD8055 did not show great improvement compared with everolimus, AZD8055 induced a temporal inhibition of AKT kinase activities and AKT was then rephosphorylated. Additionally, we found that AZD8055-induced transient AKT inhibition increased the expression and activation of epidermal growth factor receptor (EGFR) by releasing its transcriptional factors Fork-head box O 1/3a (FoxO1/3a), which might contribute to cell resistance to AZD8055. The in vitro and in vivo experiments further indicated the combination of AZD8055 and erlotinib synergistically inhibited the mTORC1/C2 signaling pathway, EGFR/AKT feedback activation, and cell growth, as well as suppressed the progression of pancreatic cancer in a xenograft model. This study provides a rationale and strategy for overcoming AZD8055 resistance by a combined treatment with the EGFR inhibitor erlotinib in pancreatic cancer therapy. [ABSTRACT FROM AUTHOR]

In many countries afflicted with dengue fever, traditional medicines are widely used as panaceas for illness, and here we describe the systematic evaluation of a widely known natural product, luteolin, originating from the “heat clearing” class of herbs. We show that luteolin inhibits the replication of all four serotypes of dengue virus, but the selectivity of the inhibition was weak. In addition, ADE-mediated dengue virus infection of human cell lines and primary PBMCs was inhibited. In a time-of-drug-addition study, luteolin was found to reduce infectious virus particle formation, but not viral RNA synthesis, in Huh-7 cells. During the virus life cycle, the host protease furin cleaves the pr moiety from prM protein of immature virus particles in the trans -Golgi network to produce mature virions. Analysis of virus particles from luteolin-treated cells revealed that prM was not cleaved efficiently. Biochemical interrogation of human furin showed that luteolin inhibited the enzyme activity in an uncompetitive manner, with Ki value of 58.6 μM, suggesting that treatment may restrict the virion maturation process. Luteolin also exhibited in vivo antiviral activity in mice infected with DENV, causing reduced viremia. Given the mode of action of luteolin and its widespread source, it is possible that it can be tested in combination with other dengue virus inhibitors. [ABSTRACT FROM AUTHOR]

ContextThe roots ofIlex asprella(Hook. et Arn.) Champ. ex Benth. (Aquifoliaceae) are widely used in Chinese medicine to treat influenza, amygdalitis, pertussis, etc. Their mechanism of action is still unknown, which raises the need to identify new bioactive compounds in this plant. ObjectiveIn this study, we isolated a novel saponin containing sulphonic groups, namely, asprellcoside A (1) and a known phenolic glycoside compound (2) from the roots ofIlex asprellaand evaluated their bioactivities. Materials and methodsMolecular structures were elucidated by analysing their spectral and chemical properties. The viability of A549 cells was tested using a MTT assay. Ability of the compounds to inhibit viruses was determined using the neuraminidase activity assay. Their anti-inflammatory effects were tested using the IP-10 activity assay using various concentrations (compound1: 0.6, 0.2, 0.6, 1.70, 5.00 and 15.00 μM; compound2: 0.4, 1.2, 3.6, 11.0, 33.0 and 100 μM). Their inhibitory effect on platelet aggregation induced by adenosine diphosphate (ADP) in rabbit plasma was determined at 60 and 80 μM. ResultsBoth compounds inhibit influenza virus strain A/PuertoRico/8/1934 (H1N1) strongly with EC50values of 4.1 and 1.7 μM, respectively. Both compounds inhibit the secretion of IP-10 with EC50values of 6.6 and 2.5 μM, respectively. Compound1alone inhibited platelet aggregation significantly, with the rate of suppression being 47 ± 8 and 38 ± 3%, at 60 and 80 μM, respectively. ConclusionsThe results suggest that both compounds may be valid therapeutics against influenza virus infection and that compound1may be a novel agent for treating thrombosis. [ABSTRACT FROM PUBLISHER]

Objective. Effect of isopropanolic Cimicifuga racemosa extract (iCR) on uterine fibroid size compared with tibolone. Method. The randomized, double-blind, controlled study in China enrolled 244 patients aged 40-60 years with menopausal symptoms (Kupperman Menopause Index ≥ 15). The participants were treated with either iCR of 40mg crude drug/day (N = 122) or tibolone 2.5mg/day (N = 122) orally for 3 months in 2004. Now, we investigated the subset of all women (N = 62) with at least one uterine fibroid at onset of treatment for the effect of iCR (N = 34) on fibroid size compared with tibolone (N = 28) by transvaginal ultrasonography. Results. The median myoma volume decreased upon iCR by as much as -30% (P = 0.016) but increased upon tibolone by +4.7%.The percentage of volume change, mean diameter change and geometricmean diameter change of the iCR group compared to tibolone were statistically significant (P = 0.016, 0.021, 0.016 respectively). Conclusion. Our results suggest that iCR (Remifemin) is a valid herbal medicinal product in patients with uterine myomas as it provides adequate relief from menopausal symptoms and inhibits growth of the myomas in contrast to tibolone. [ABSTRACT FROM AUTHOR]

Signaling of the receptor for advanced glycation end products (RAGE) has been implicated in the development of injury-elicited vascular complications. Soluble RAGE (sRAGE) acts as a decoy of RAGE and has been used to treat pathological vascular conditions in animal models. However, previous studies used a high dose of sRAGE produced in insect Sf9 cells (sRAGE Sf9)and multiple injections to achieve the therapeutic outcome. Here, we explore whether modulation of sRAGE N-glycoform impacts its bioactivity and augments its therapeutic efficacy. We first profiled carbohydrate components of sRAGE produced in Chinese hamster Ovary cells (sRAGE CHO) to show that a majority of its N-glycans belong to sialylated complex types that are not shared by sRAGE Sf9. In cell-based NF-κB activation and vascular smooth muscle cell (VSMC) migration assays, sRAGE CHO exhibited a significantly higher bioactivity relative to sRAGE Sf9 to inhibit RAGE alarmin ligand-induced NF-κB activation and VSMC migration. We next studied whether this N-glycoform-associated bioactivity of sRAGE CHO is translated to higher in vivo therapeutic efficacy in a rat carotid artery balloon injury model. Consistent with the observed higher bioactivity in cell assays, sRAGE CHO significantly reduced injury-induced neointimal growth and the expression of inflammatory markers in injured vasculature. Specifically, a single dose of 3 ng/g of sRAGE CHO reduced neointimal hyperplasia by over 70 %, whereas the same dose of sRAGE Sf9 showed no effect. The administered sRAGE CHO is rapidly and specifically recruited to the injured arterial locus, suggesting that early intervention of arterial injury with sRAGE CHO may offset an inflammatory circuit and reduce the ensuing tissue remodeling. Our findings showed that the N-glycoform of sRAGE is the key determinant underlying its bioactivity and thus is an important glycobioengineering target to develop a highly potent therapeutic sRAGE for future clinical applications. Key message: The specific N-glycoform modification is the key underlying sRAGE bioactivity Markedly reduced sRAGE dose to attenuate neointimal hyperplasia and inflammation Provide a molecular target for glycobioengineering of sRAGE as a therapeutic protein Blocking RAGE alarmin ligands during acute injury phase offsets neointimal growth [ABSTRACT FROM AUTHOR]