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The quality evaluation of compound Chinese medicines is an important but challenging issue in this research field, which has been paid much controversial due to the constrained association with clinical efficacy. Developing a methodology for quality evaluation of compound Chinese medicines related to clinical efficacy is an important measure in research on Chinese material medica quality to ensure clinical effectiveness and safety. Therefore, based on the research concept that "originating from clinic-testing in experiment-returning to clinic", and taking Xiaoke prescription as an example, the characteristic information of metabolome, proteome and microbiome are discussed from the clinical aspect, and the integrated markers associated with clinical efficacy constructed with artificial intelligence technology. Taking the integrated markers as the link and indication are connecting the clinical and basic, the main pharmacodynamic substances and key targets of Xiaoke prescription that are related to clinical efficacy are explained. Clinical samples are used for validation. Based on the main pharmacodynamic substances and key targets, methods and key technologies for chemical and biological evaluation of the quality of Xiaoke prescription are established, providing a methodology for quality evaluation of compound Chinese medicines, including clinical efficacy response indicators (related to clinic), main pharmacodynamic substances (chemical evaluation), and key targets (biological evaluation), to provide new ideas and methods for improving the quality evaluation of compound Chinese medicines.
ABSTRACT
<p><b>OBJECTIVE</b>To investigate the possible mechanism of San-Cao Granule (SCG, ) mediating antiliver fibrosis.</p><p><b>METHODS</b>A total of 60 male Sprague-Dawley rats were randomly divided into the normal control group, porcine serum-treated group, ursodesoxycholic acid (UDCA, 60 mg/kg), SCG (3.6 g/kg) group, SCG (1.8 g/kg) group and SCG (0.9 g/kg) group, with 10 rats in each group. Liver fibrosis was induced with porcine serum by intraperitoneal injection for 8 weeks, except for the normal control group. Then, the rats in the three SCG-treated groups and UDCA group were administered SCG and UDCA respectively for 4 weeks. The serum levels of alanine transaminase (ALT), aspartate transaminase (AST), albumin (ALB), total bilirubin (TBIL), hyaluronic acid (HA), laminin (LN), and type IV collagen (IVC) were examined using commercial kits and hepatic histopathology was examined with hematoxylin and eosin and Masson staining. Moreover, the protein expression levels of high mobility group box-1 protein (HMGB1), transforming growth factor β1 (TGF-β1), phosphorylated mothers against decapentaplegic homolog 3 (p-Smad3), Smad7, toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88), nuclear factor-kappa B (NF-κB) and α-smooth muscle actin (α-SMA) were determined by western blot, immunohistochemistry and real time quantitative-reverse transcription polymerase.</p><p><b>RESULTS</b>Both SCG (3.6 and 1.8 g/kg) and UDCA significantly ameliorated the liver fibrosis induced by porcine serum as indicated by retarding the serum levels increasing of ALT, AST, TBIL, HA, LN and IVC and preventing the serum level reducing of ALB compared with the model group (all P<0.01). Meanwhile, the collagen deposition was attenuated by SCG and UDCA treatment. Furthermore, SCG markedly reduced the expressions of HMGB1, TGF-β1, p-Smad3, TLR4, MyD88, NF-κB and α-SMA, and enhanced the expression of the Smad7 compared with the model group (all P<0.01).</p><p><b>CONCLUSION</b>SCG ameliorates hepatic fibrosis possibly through inhibiting HMGB1, TLR4/NF-κB and TGF-β1/Smad signaling pathway.</p>
Subject(s)
Animals , Male , Rats , Disease Models, Animal , Drugs, Chinese Herbal , Therapeutic Uses , HMGB1 Protein , Metabolism , Liver , Metabolism , Pathology , Liver Cirrhosis , Drug Therapy , Metabolism , Pathology , Rats, Sprague-Dawley , Signal Transduction , Smad Proteins , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To evaluate the efficacy and safety of ruxolitinib in treatment of myeloproliferative neoplasm.</p><p><b>METHODS</b>Random clinical trials (~September 30, 2017) were identified from PubMed, Embase, Cochrane Library, Clinical Trials, CBM and Chinese Journal Full-text Database. The quality of RCT was assessed by Cochrane risk bias. Meta analysis was performed with Revman 5.3.</p><p><b>RESULTS</b>Ruxolitinib was efficacious in relieving splenomegaly (RR 49.12, 95% CI [15.81-152.59], P<0.001). The incidence of anemia significantly increased after ruxolitinib treatment (RR 1.71, 95% CI [1.05-2.77], P=0.16), while the thrombocytopenia (RR 1.04, 95% CI [0.50-2.16], P=0.92) and neutropenia (RR 2.46, 95% CI [0.91-6.61], P=0.07) had no statistical difference as compared with that in control group. Ischemia events had no significant difference as compared with control (RR 0.57, 95% CI [0.33-1.00], P=0.05). Infection events had no significant difference as compared with the control group (RR 1.18, 95% CI [0.79-1.78], P=0.24).</p><p><b>CONCLUSION</b>Ruxolitinib is an efficacious therapeutic strategy on MPD with controlling splenomegaly. However,anemia events and bleeding events may threat its clinical safety, so more high quality RCT are needed.</p>
Subject(s)
Humans , Myeloproliferative Disorders , Neoplasms , Pyrazoles , ThrombocytopeniaABSTRACT
The prescription of clinical curative effect has promoted the formation and development of the dominant diseases in traditional Chinese medicine, but it has been controversial for a long time because its mechanism has not been effectively explained. Breaking the gap between animal/cell research and clinical research, and understanding the mechanism of dominant diseases in traditional Chinese medicine based on evidence-based medicine has become an important breakthrough in this scientific issue. Therefore, based on evidence-based medicine, we established the research concept that "originating from clinic, testing in experiment, returning to clinic". Taking the classic formula (Jinqi Jiangtang formula) treating diabetes as an example to find characteristic markers of diabetes supported by evidence-based medicine from clinic. We used the reverse analysis strategy of the response of characteristic markers to explore the intervention mechanism of Jinqi Jiangtang formula on characteristic markers. Then, we verified the key signaling molecules of the metabolic regulation of the Jinqi Jiangtang formula in clinic. The research ideas and key technologies for the mechanism of treatment of diabetes by Jinqi Jiangtang formula based on evidence-based medicine are formed, and it is expected to provide research reference for explaining the mechanism of dominant diseases in traditional Chinese medicine based on evidence-based medicine.
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Cancer-testis antigens (CTA) are a class of tumor-associated antigens, which are mainly located in X chromosome. CTA restrictively expressed in normal testis, ovary, placenta and so on. Their expression in other normal tissues is much lower, even can not be detected. However, their expressions are aberrantly high in human cancers. Based on CTA encoding immunogenic proteins, they can be regulated by epigentics, CTA provides very attractive targets for cancer immunotherapy. Multiple myeloma (MM) is incurable and has a low cureative rate and a high relapse rate. CTA have been detected in many MM cell lines and primary MM cells, they may be relaled to clinical prognosis. This reviews briefly summarized the research advances of CTA in the immune therapy of multiple myeloma, so as to provide a valuable therapeutic idea for myeloma.
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<p><b>OBJECTIVE</b>This study was aimed to detect the change of T-lymphocyte functional subsets marked by CCR7 and CD45RA in the aGVHD within 100 days after allo-HSCT and to explore its clinical significance.</p><p><b>METHODS</b>The peripheral blood of 42 patients after allo-HSCT was collected every two weeks since hematopoietic reconstitution. The expression of CD3, CD4, CD8, CCR7 and CD45RA-marked T-lymphocytes was detected by flow cytometry, the relationship between their expression and the prognosis of aGVHD was analyzed.</p><p><b>RESULTS</b>The percentage and the absolute count of CCR7(+) T lymphocyte were significantly reduced in aGVHD. The percentage of T(naïve), T(CM), T(EM) and the absolute count of T(naïve), T(EM), TTD were sharply reduced in aGVHD, moreover has changed correspondingly with outcome of aGVHD. The percentage of CD3, CD4, CD8-marked T-lymphocyte subsets did not significantly changed.</p><p><b>CONCLUSION</b>T-lymphocyte functional subsets marked by CCR7 and CD45RA are a valuable indicator to monitor early immune reconstruction for patients with the aGVHD after allo-HSCT.</p>