The mechanism of modified Gan Cao Fu Zi Decoction in the treatment of rheumatoid arthritis based on network pharmacology and experimental validation / 药学学报

We used network pharmacology to predict the mechanism in the treatment of rheumatoid arthritis (RA) via modified Gan Cao Fu Zi Decoction (GCFZ), and validated the results of the analysis and explored the pharmacodynamic effects of GCFZ through animal experiments. Firstly, TCMID, SymMap, HERB, STITCH and GEO databases were utilized to obtain the target genes of GCFZ for the treatment of RA, which yielded a total of 1 250 differentially expressed genes for RA, 534 genes for GCFZ targets and 83 intersecting genes. Then functional enrichment analysis of the intersecting genes was performed through GO and KEGG databases, and the results revealed that GCFZ and its active ingredients mainly functioned through cytokine pathways, where chemokine signaling pathway and tumor necrosis factor (TNF) signaling pathway were enriched with a high number of genes. Cytoscape 3.8.0 software was used to construct the drug-target-disease network and screen key proteins, which included TNF, C-X-C chemokine ligand 8 (CXCL8), C-X-C chemokine ligand 10 (CXCL10), C-C chemokine ligand 5 (CCL5), C-X-C chemokine ligand 2 (CXCL2) and C-X-C chemokine receptor type 4 (CXCR4). The molecular docking technology was used to confirm the binding ability of the main active ingredients of GCFZ to the core proteins. Additionally, the therapeutic effects of GCFZ in low (4 g·kg-1), medium (8 g·kg-1) and high (16 g·kg-1) dose groups were investigated by constructing the collagen-induced arthritis (CIA) rat model. X-ray imaging approach, HE staining and Safranin O-Fast Green staining showed that GCFZ treatment significantly improved bone destruction, synovial hyperplasia and cartilage damage in CIA rats, while immunofluorescence results showed that GCFZ treatment could regulate the expression of TNF, CXCL8 and CCL5. In summary, our results indicate that GCFZ contains a variety of small molecule pharmacodynamic substances, which can exert therapeutic effects via multiple targets and pathways, and obviously reduce the symptoms of arthritis in CIA rats. This animal experiment of our research was approved by the Experimental Animal Management and Ethics Committee of Bengbu Medical College.

Shengmai San for Treatment of Cardiotoxicity from Anthracyclines: A Systematic Review and Meta-Analysis / 中国结合医学杂志

OBJECTIVE@#To systematically evaluate the efficacy of Shengmai San in patients with cardiotoxicity of anthracyclines.@*METHODS@#Randomized controlled trials (RCTs) were identified by searching China National Knowledge Infrastructure (CNKI), Wanfang Database, Chinese Biomedical Literature Database (CBM), PubMed, Cochrane Library, and Embase Databases from the inceptions until December 2020. The Cochrane Handbook was used to evaluate the risk of bias in the included studies. Data analysis was conducted using RevMan 5.3 software.@*RESULTS@#Totally 19 RCTs with 2,331 participants were included in this review. Results showed that in improving arrhythmia (13 RCTs, n=1,877, RR=0.37, 95%CI 0.25 to 0.52, P<0.00001), the treatment group was superior to the control group. In terms of reducing left ventricular end-diastolic diameter (LVEDD, 2 RCTs, n=128, MD=-0.79, 95%CI -0.93 to -0.65, P<0.00001) and left ventricular end systolic diameter (LVESD, 2 RCTs, n=128, MD=-0.58, 95%CI -0.82 to -0.35, P<0.00001), the treatment group was also better than the control group. In reducing myocardial enzymes such as creatine kinase (CK) [(3 RCTs, n=256, SMD=-0.80, 95%CI -1.16 to -0.44, P<0.0001), (2 RCTs, n=126, SMD=-0.62, 95%CI -0.98 to -0.26, P=0.0007)], the treatment group was superior to the control group.@*CONCLUSION@#Shengmai San has a positive effect on the treatment of cardiotoxicity from anthracyclines. However, in the future, it is still necessary to conduct high-quality RCTs to verify its efficacy.

Treatment of pulmonary hypertension based on inhibition of pulmonary vascular cell proliferation / 药学学报

Pulmonary hypertension is a rapidly progressing disease of the lung vasculature with poor prognosis, ultimately leading to right heart failure and death. The remodeling of small pulmonary arteries represents an important pathological characteristic of pulmonary hypertension. Pulmonary arterial smooth muscle cells (PASMCs) located in the middle layer of pulmonary artery exhibit hyperproliferation and resistance to apoptosis, which is the main initiator of pulmonary vascular remodeling and similar to that seen in tumor cells. In this review we focus on the signaling pathways that play a key role in PASMCs proliferation and the latest research progress on inhibitors targeting cell proliferation pathways to provide a new perspective for the treatment of PH．

A study on quality of Paridis Rhizoma and consideration on standards of Paridis Rhizoma in Chinese Pharmacopoeia / 中国中药杂志

Thin layer chromatography, high performance liquid chromatography and multivariate statistical analysis were integrated in current study to provide a basis for the quality evaluation and the standard improvement of Paridis Rhizoma(Chinese name: Chong-lou). The results demonstrated that the primary saponins in the two authorized sources of Paridis Rhizoma were polyphyllinsⅠ, Ⅱ and Ⅶ, while the rhizome of Trillium tschonoskii an adulterant of Paridis Rhizoma was rich of polyphyllin Ⅵ. Therefore, the apparent content of polyphyllin Ⅵ plays a determinant role towards the source authentication of raw materials and decoction slices of Paridis Rhizoma, whose adulterants frequently occur in the market. Moreover, the contents of polyphyllin Ⅵ in the two authorized sources could meet the requirements of Chinese Pharmacopoeia. Therefore, we suggested that polyphyllin Ⅵ should not be omitted from the quality standard of Paridis Rhizoma in the Chinese Pharmacopoeia, and on the other side, polyphyllinsⅠ, Ⅱ and Ⅶ should be the eligible quality indicators. The study aims to sound information and evidences for the quality evaluation of Paridis Rhizoma, and also to provide a theoretical basis for the standard revision of Paridis Rhizoma in the future Chinese Pharmacopoeia.

Performance of Hepatitis B Core-Related Antigen Versus Hepatitis B Surface Antigen and Hepatitis B Virus DNA in Predicting HBeAg-positive and HBeAg-negative Chronic Hepatitis

BACKGROUND: We examined changes in hepatitis B core-related antigen (HBcrAg) during the four sequential phases of chronic hepatitis B virus (HBV) infection: hepatitis B e antigen (HBeAg)-positive chronic infection (EPCI) and hepatitis (EPCH), followed by HBeAg-negative chronic infection (ENCI) and hepatitis (ENCH). We compared the performance of serum HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA in predicting EPCH and ENCH. METHODS: We enrolled 492 consecutive patients: 49 with EPCI, 243 with EPCH, 101 with ENCI, and 99 with ENCH. HBcrAg was detected by chemiluminescent enzyme immunoassays. HBsAg and HBeAg were detected by chemiluminescent microparticle immunoassays. HBV DNA was detected by real-time PCR. Predictive performance of HBcrAg, HBsAg, and HBV DNA was evaluated using ROC curves. RESULTS: Areas under ROC curves (AUCs) of HBcrAg, HBsAg, and HBV DNA for predicting EPCH were 0.738, 0.812, and 0.717, respectively; optimal cutoffs were ≤1.43×105 kU/mL, ≤1.89×104 IU/mL, and ≤3.97×107 IU/mL, with sensitivities and specificities of 66.3% and 77.6%, 65.0% and 93.9%, and 60.5% and 79.6%, respectively. AUCs of HBcrAg, HBsAg, and HBV DNA for predicting ENCH were 0.887, 0.581, and 0.978, respectively; optimal cutoffs were >26.8 kU/mL, >2.29×102 IU/mL, and >8.75×103 IU/mL, with sensitivities and specificities of 72.7% and 95.1%, 86.9% and 39.6%, and 89.9% and 92.1%, respectively. CONCLUSIONS: HBsAg and HBV DNA were the best predictors of EPCH and ENCH, respectively. HBcrAg is an important surrogate marker for predicting EPCH and ENCH.

Efficacy of Recombinant Human Thrombopoietin and Recombinant Human Interleukin 11 for Treatment of Chemotherapy Indu-ced Thrombocytopenia in Acute Myeloid Leukaemia Patients / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To evaluate and compare the clinical efficacy and safety of recombinant human thrombopoietin(rhTPO) and recombinant human interleukin11(rhIL-11) for the treatment of chemotherapy-induced thrombocytopenia in adult acute myeloid leukaemia patients.</p><p><b>METHODS</b>Total of 96 adult acute myeloid leukaemia patients were divided into 3 groups according to randomized controlled method: rhTPO group, rhIL-11 group and control group, 32 cases in each group. The patients in rhTPO group and rhIL-11 received rhTPO of 15000 IU/d and rhIL-11 of 1.5 mg/d, respectively after the standard combined chemotherapy within 24 hours, and patients in control group, received nothing drugs to promote thrombocyte recovery. And rhTPO and rhIL-11 should be stopped when the Plt≥100× 10/L. After chemotherapy, the platelet recovery degree, duration of Plt<50× 10/L, ≥50× 10/L and ≥100× 10/L, the count of infusion thrombocytes, and incidence of adverse reactions all were compared.</p><p><b>RESULTS</b>The duration of Plt<50× 10/L was obviously less than that in control group(P<0.01). The duration of rhIL-11 was less than that in control group, but there was no statistical significance(P>0.05). As compared with that in control group, the Plt count in rhTPO and rhIL-11 groups can faster increase to Plt≥50× 10/L (P<0.01, P<0.05), among them the Plt count in rhTPO group faster increase, but there was no statistical signiticance. As compared with that in control group, the Plt count in rhTPO group and rhIL-11 group can increase to Plt≥100× 10/L (P<0.01), the Plt count in rhTPO group was more obviously increase than that in rhIL-11 group(P<0.05). The count of infusion Plt in rhTPO and rhIL-11 groups was lese than that in control group(P<0.01, P<0.05), and the count of infusion Plt in rhTPO group was less than that in rhIL-11 group(P<0.05). After using rhTPO and rhIL-11, the adverse reactions, such as low fever, induration of injection site, athralgia, nausea and vomiting occured in rhTPO group and rhIL-11 group, but all can be tolerated.</p><p><b>CONCLUSION</b>Both rhTPO and rhIL-11 can reduce the duration of thrombocytopenia and the amount of infused thrombocyte, promote platelet recovery in the patients with acute myeloid leukaemia after chemotherapy, to decreae the risk of bleeding, and reduce incidence of adverse reactions, both of them can be tolerated by patients, and rhTPO is more advantage than rhIL-11, worthy of clinical popularization and application.</p>

Potential mechanism of Huanglian Jiedu Decoction for treatment of hypertension based on network pharmacology / 中草药

Objective To study the mechanism of Huanglian Jiedu Decoction (HJD) in the treatment of hypertension by using network pharmacology. Methods Chemical components and targets related to the four herbs of Chinese meteria medica in HJD were searched through the traditional Chinese medicine systems pharmacology database and analysis platform (TCMSP) to construct the interaction network diagram of the target point of the compounds. The hypertension related targets were screened through OMIM, TTD, and PharmGkb databases; The interactive target of HJD and hypertension was constructed in PPI database; GO analysis of screened core targets between drug target and disease target was carried out using Davidv 6.8 database, and the related pathways of core targets were enriched using KEGG database. Results Using the oral bioavailability (OB) ≥ 30% and drug likeness (DL) ≥ 0.18 as screening condition for the compounds, combined with supplement literatures searched, 61 active components and 154 corresponding protein targets of HJD were screened out. A total of 118 enrichment results were obtained from 228 core targets of HJD in hypertension, including 59 biological processes, 31 molecular functions, and 28 cell compositions. The selected targets were enriched by KEGG database and 45 pathways playing an important role in hypertension were screen out. Conclusion The synergetic effect of HJD with multi-components and multi-pathway was confirmed by network pharmacology, and the main possible mechanism of HJD in treating hypertension was predicted, which lay a foundation for the identification of effective components, the mechanism of action, and clinical application.

Effect of Tyrosine Phosphorylation Sites of Oncogenic Protein NPM-ALK on Cell Cycle and Its Related Mechanisms / 中国实验血液学杂志

<p><b>UNLABELLED</b>Objective：To explore the effect of tyrosine phosphorylation sites Tyr644 and Tyr664 in oncogenic protein NPM-ALK on cell cycle and its related mechanisms.</p><p><b>METHODS</b>Transiently transfected 293T cells and stably transfected Jurkat cells were used for analysis of cell cycle and protein after the transfection with the constructed recombinant plasmid pEGFP-N1, pEGFP-N1-NPM-ALK and pEGFP-N1-NPM-ALK(644, 664); soft agar assay for colony formation was performed to examine the different carcinogenicity of stable cell lines; cell viability of stable cell lines was examined by CCK-8 after the treatment with PPP.</p><p><b>RESULTS</b>The S arrest occurred in both NPM-ALK(644,664) transfected 293T and Jurkat cells; the susceptibility of NPM-ALK transfected Jurkat cells to PPP was highest among the 3 stable cell lines; the phosphorylated levels of AKT, ERK and STAT3 were decreased in NPM-ALK(644,664) cells compared with the NPM-ALK ones. Additionally, the double mutation induced the increase of CDK2 and the decrease of P27 (P<0.05).</p><p><b>CONCLUSION</b>The mutation of Tyr644 and 664 sites in NPM-ALK can induce cell cycle arrest in S phase and lower susceptibility to PPP that may be related with the phosphorylation change of cell growth related molecules in the downstream of NPM-ALK.</p>

Application of cultivating Yuan and clearing blockage method on HIV/AIDS / 中国中药杂志

According to HIV/AIDS being infectious and have a very long period of incubation, leading to immune system weakened and infected easily, we summarized its pathmechanism including Yuan Qi deficiency (vigour deficiency)and constraint (Qi depression,blood stagnancy, phlegm coagulation, poison accumulation), consequently treatment principle were raised--cultivates the Yuan and clear blockage. From viscera and Qi, blood, Yin and Yang perspective, we elaborate corresponding clinical application method and train of thought, that cultivating the Yuan method means tonify Qi firstly which emphasizes on the spleen and the kidney; Clear blockage method contains relieving liver for smooth Qi, invigorating spleen to remove phlem, promoting blood circulation and detoxification. In addition, cultivating the Yuan and clear blockage should cooperate closely based on traditional Chinese medicine diffrentiation, tonify deficiency should not used individually and vice verse.

Closed suction drainage or non-drainage for total knee arthroplasty: a meta-analysis / 中华外科杂志

<p><b>OBJECTIVES</b>To investigate the different effects of closed suction drainage and non-drainage for total knee arthroplasty(TKA) and to provide reference information for the choice of clinical treatment.</p><p><b>METHODS</b>Randomized controlled trials (RCTs) of closed suction drainage versus non-drainage for TKA were collected from the Cochrane Library, PubMed, EMBase, Springer, CBM, CNKI, VIP and WANFANG database. Methodological quality of the RCTs was independently assessed using the Consolidated Standards of Reporting Trials (CONSORT) checklist. Data analysis was performed by RevMan Version 5.1.6 based on the methods recommended by the Cochrane Collaboration.</p><p><b>RESULTS</b>Twenty-one RCTs without bias were finally enrolled, and 1920 enrolled knees were identified into drainage group (979 knees) and non-drainage group (941 knees). A lower incidence of soft tissue ecchymosis was demonstrated in the closed suction drainage group (OR = 0.30, 95%CI: 0.24 - 0.49); however, compared with the non-drainage group, more loss of blood (MD = 320.03, 95%CI: 235.31 - 404.76) and more need of homologous blood transfusion (OR = 1.83, 95%CI: 1.26 - 3.29) were found in the closed suction drainage group. In addition, there were no significant differences of postoperative infection (OR = 0.53, 95%CI: 0.22 - 1.32), deep venous thrombosis (OR = 1.00, 95%CI: 0.46 - 2.18), and the joint range of motion (MD = -0.04, 95%CI: -1.11 - 1.02) between the two groups.</p><p><b>CONCLUSION</b>Based on the current evidence, no obvious advantage is demonstrated for closed suction drainage, in comparison with non-drainage for TKA.</p>

Preparation, activity and targeting ability evaluation in vitro on folate mediated epigallocatechin-3-gallate albumin nanoparticles / 药学学报

To study the preparation, activity and targeting ability evaluation in vitro on epigallocatechin-3-gallate (EGCG) bovine serum albumin nanoparticles targeting to PC-3 cells, the folate mediated EGCG bovine serum albumin nanoparticles (FA-EGCG-BSANP) were prepared by desolvation process. The morphology and particle size of the nanoparticles were determined by atomic force microscope (AFM). HPLC was used to analyse the entrapment efficiency and drug loading rate of EGCG The amount of folate conjugation on the BSANP was determined by quantitative ultraviolet (UV) spectrophotometer analysis. The targeting ability to PC-3 was observed using laser scanning confocal microscope (LSCM) and fluorophotometer microscope. And the activity of FA-EGCG-BSANP was mensurated by MTT method. The morphology and particle size distribution of FA-EGCG-BSANP were uniform and even with the mean particle size of 200 nm. The entrapment efficiency and loading rate of EGCG were (81.5 +/- 1.8) % and (29.3 +/- 0.6) %, respectively, and the amount of folate conjugation was 18.363 microg x mg(-1) BSA. The FA-EGCG-BSANP uptakes by cultured PC-3 cells were 23.65 times the amount of EGCG-BSANP in a concentration dependant manner. The lethality of PC-3 cells treated with FA-EGCG-BSA was 82.8%, while those treated with EGCG and EGCG-BSANP were 58.6% and 55.1%, respectively. And lethality of PC-3 cells was positively correlated with the nanoparticles uptake amount. FA-EGCG-BSANP can significantly promote EGCG to PC-3 cells sites and improve their efficacy, which is considered to an experimental foundation for further research on its activity, targeting ability and metabolism in vivo.

Analysis of the Relationship Between Era and YggG in E.coli by Double-promoter Expression Vector pDH2-YggG-P_(tac)-Era / 中国生物工程杂志

yggG, a Era-binding protein gene, was isolated and cloned from the E.coli genomic DNA library. Previous studies indicated that the product of yggG gene, YggG294(amino acids 1-294), strongly inhibited the growth of host bacteria and caused the death of bacteria cells. To elucidate whether Era is related to the death of bacterial cells expressed YggG294,A double promoter expression vector that can express YggG294 and Era proteins controllably in cells was constructed. Using this vector to express YggG294 and Era protein in the same E.coli cells, then analyzed the relation between YggG294 and Era. The results showed that the ratio of Era proteins to total proteins increased with the increase of induction time in E.coli cells without YggG294 expression and with little YggG294 expression;the ratio of Era proteins to total proteins seemed to be a constant level in E.coli cells overexpressing YggG294;but we could not detect any Era hydrolyzate in E.coli cells overexpressed YggG294 could not be detected. The results also showed that pre-expression of Era protein did not produce any effect on the growth inhibition of E.coli cells caused by YggG294. These results indicate that YggG294 can not hydrolyze Era protein in E.coli cells, and that YggG-Era interaction is not associated with the death of bacteria expressed YggG294. It is thus reasonable to draw a conclusion that Era is not associated with the growth inhibition of E.coli cells caused by YggG294. YggG294 inhibits the growth of bacteria by other way.

Oxymatrine-induced apoptosis of HepG2 cells:the possible mechanism / 第二军医大学学报

Objective:To investigate the effects of oxymatrine(OM)on the apoptosis of human hepatoma HepG2 cells and its possible mechanisms.Methods:HepG2 cells were treated with different concentrations of OM.The proliferation inhibition was measured by MTT assay and the apoptosis of HepG2 cells were examined by Hochest staining method.Flow cytometry was used to analyze the cell cycle distribution and apoptosis rate.The expression of caspase-3,Bcl-2,Bcl-x_L and Bax proteins was assayed by Western blotting assay.Results:OM inhibited HepG2 cells growth in a time-and dose-dependent manner.After treatment with OM for 24 hours,some cells appeared typical apoptotic characteristics and the apoptosis rate was increased. Treatment with OM also increased caspase-3 activity and Bax expression in HepG2 cells,and decreased the expression levels of Bcl-2 and Bcl-x_L.Conclusion:OM can induce HepG2 cell apoptosis,which may be related to the down-regulation of PI3K/Akt signal pathway,suppression of Bcl-2 and Bcl-x_L activity,and activation of caspase-3.