Prevalence of CYP2C19 gene mutations in patients with coronary heart disease and its biological activation effect in clopidogrel antiplatelet response / 中华心血管病杂志

Objective: The purpose of this study was to investigate the effects of CYP2C19 gene mutations on clopidogrel antiplatelet activity in the patients with coronary heart disease treated by percutaneous coronary intervention. Methods: Patients with coronary heart disease, who hospitalized in the Second Affiliated Hospital of Nanchang University from March 2011 to June 2019, and healthy individuals with matching genetic background, gender, and age as controls were included in this study. Basic clinical data were analyzed and blood samples of all research subjects were obtained for extraction of DNA, and Sanger first-generation sequencing method was used to detect CYP2C19 gene mutation from full exon and exon and intron junction. CYP2C19 gene variations in patients with coronary heart disease were compared with the 1000 Genomes Browse database and the sequencing results of healthy controls to determine whether the gene variation was a genetic mutation or a genetic polymorphism. After that, PolyPhen-2 prediction software was used to analyze the harmfulness of gene mutations to predict the effect of mutations on protein function. The same dose of CYP2C19 wild-type plasmid and the CYP2C19 gene mutant plasmids were transfected into human normal liver cells HL-7702. After transfection of 24 h, the expression of CYP2C19 protease in each group was detected. The liver S9 protein was incubated with clopidogrel, acted on platelets to detect the platelet aggregation rate and the activity of human vasodilator-activated phosphoprotein (VASP). Results: A total of 1 493 patients with coronary heart disease (59.36%) were enrolled, the average age was (64.5±10.4) years old, of which 1 129 were male (75.62%). Meanwhile, 1 022 healthy physical examination volunteers (40.64%) were enrolled, and the average age was (64.1±11.0) years old, of which 778 were male (76.13%). A total of 5 gene mutations of CYP2C19 gene were identified in 12 patients (0.80%), namely, 4 known mutations T130K (1 case), M136K (6 cases), N277K (3 cases), V472I (1 case) and one new mutation G27V (1 case), no corresponding gene mutation was found in healthy controls. It was found that T130K and M136K were probably damaging, G27V was possibly damaging, and N277K and V472I were benign mutations. In vitro, we demonstrated that the platelet aggregation rate of the M136K gene mutation group was 24.83% lower than that of the wild type (59.58% vs. 34.75%; P<0.05), and the phosphorylated VASP level was 23.0% higher than that of the wild type (1.0 vs. 1.23; P<0.05). However, the platelet aggregation rate and phosphorylated VASP level were similar between of G27V, T130K, N277K, V472I gene mutation groups and wild type group (P>0.05). Conclusions: In this study, 5 gene mutations are defined in patients with coronary heart disease, namely G27V, T130K, M136K, N277K, V472I. In vitro functional studies show that CYP2C19 gene mutation M136K, as a gain-of-function gene mutation, can enhance the activation of CYP2C19 enzyme on clopidogrel, thereby inhibiting the platelet aggregation rate.

Gefitinib plus Fuzheng Kang'ai Formula () in Patients with Advanced Non-Small Cell Lung Cancer with Epidermal Growth Factor Receptor Mutation: A Randomized Controlled Trial / 中国结合医学杂志

<p><b>OBJECTIVE</b>To evaluate the effect of Fuzheng Kang'ai Formula (, FZKA) plus gefitinib in patients with advanced non-small cell lung cancer with epidermal growth factor receptor (EGFR) mutations.</p><p><b>METHODS</b>A randomized controlled trial was conducted from 2009 to 2012 in South China. Seventy chemotherapynaive patients diagnosed with stage IIIB/IV non-small cell lung cancer with EGFR mutations were randomly assigned to GF group [gefitinib (250 mg/day orally) plus FZKA (250 mL, twice per day, orally); 35 cases] or G group (gefitinib 250 mg/day orally; 35 cases) according to the random number table and received treatment until progression of the disease, or development of unacceptable toxicities. The primary endpoint [progression-free survival (PFS)] and secondary endpoints [median survival time (MST), objective response rate (ORR), disease control rate (DCR) and safety] were observed.</p><p><b>RESULTS</b>No patient was excluded after randomization. GF group had significantly longer PFS and MST compared with the G group, with median PFS of 12.5 months (95% CI 3.30-21.69) vs. 8.4 months (95% CI 6.30-10.50; log-rank P<0.01), MST of 21.5 months (95% CI 17.28-25.73) vs. 18.3 months (95% CI 17.97-18.63; log-rank P<0.01). ORR and DCR in GF group and G group were 65.7% vs. 57.1%, 94.3% vs. 80.0%, respectively (P>0.05). The most common toxic effects in the GF group and G group were rash or acne (42.8% vs. 57.1%, P>0.05), diarrhea (11.5% vs. 31.4%, P<0.05), and stomatitis (2.9% vs. 8.7%, P>0.05).</p><p><b>CONCLUSION</b>Patients with advanced non-small cell lung cancer selected by EGFR mutations have longer PFS, MST with less toxicity treated with gefitinib plus FZKA than gefitinib alone.</p>

Combination of Jianpi Liqi Yiliu Formula with Cytokine-induced Killer Cell Treatment for Advanced Hepatocellular Carcinoma / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the clinical efficacy of Jianpi Liqi Yiliu Formula (JLYF) combined with cytokine-induced killer (CIK) cells for treating patients with advanced hepatocellular carcinoma (HCC).</p><p><b>METHODS</b>Between January 2011 and January 2014, 60 advanced HCC patients were enrolled in this study, who were assigned to the treatment group and the control group according to their willingness for taking JLYF, 30 cases in each group. All patients received CIK cell treatment: 1 x 10⁹-3 x 10⁹ each time, by intravenous dripping from the 1st day to the 3rd day, once per day. Besides, patients in the treatment group took JLYF decoction, while those in the control group took Chinese medical decoction by syndrome typing. All patients received treatment of at least two cycles. The time to progression (TTP) , overall survival (OS), disease control rate (DCR), performance status scale (PS), Child-Pugh scale, and adverse reactions were observed, and subgroup analyzed.</p><p><b>RESULTS</b>To May 31, 2014, all patients reached the clinical endpoint. TTP was 3.5 months (95% Cl: 3.30-4.10) in the treatment group, better than that (2.5 months, 95% CI: 2.32-2.68) of the control group (P < 0.05). DCR was 36.7% in the treatment group and 30.0% in the control group (P > 0.05). OS was 5.2 months (95% CI: 4.53-5.87) in the treatment group and 4.6 months (95% CI: 4.06-5.14) in the control group (P > 0.05). The PS scale was 1.60 ± 0.10 after treatment, lower than that (1.80 ± 0.09) before treatment in the treatment group (P < 0.05). When the PS scale was 0-2 or Child-Pugh scale was class A, TTP was longer in the treatment group than in the control group (P < 0.05). No adverse reaction occurred in the two groups during the treatment course.</p><p><b>CONCLUSIONS</b>The combination of JLYF with ClK cell treatment could prolong advanced HCC patients' TTP, improve PS scale, as compared with syndrome typed Chinese medical decoction treatment group. Besides, when the PS scale was 0-2 or Child-Pugh scale was class A, it was a better treatment program for advanced HCC patients.</p>

Expression and significance of HSP90 in plasma of patients with multiple myeloma / 中国实验血液学杂志

This study was purposed to investigate the expression of heat shock protein 90 (HSP90) in peripheral blood plasma of patients with multipl myeloma (MM), and to explore its possible role in the pathogenesis of MM, and its relationship with treatment, prognosis and the outcome of patients. The peripheral blood samples from 58 patients with MM and 20 healthy volunteers were collected. The plasma concentration of HSP90 in patients and healthy volunteers was measured by ELISA. The results showed that the concentration of HSP90 in peripheral blood of patients with MM was significantly higher than that in the healthy volunteers [(32.398 ± 3.674) vs (25.762 ± 2.916) ng/ml] (P < 0.001). The concentration of HSP90 showed positively correlation with International Staging System(ISS) stage, therapeutic response, frequency of plasmocyte, globulin, immune globulin, M-protein, β2 micro-globulin, and light chain of MM patients (P < 0.05) ; while it showed little correlation with sex, age and type of MM patients (P > 0.05) . It is concluded that the HSP90 may be involved in the occurrence and development of MM. Detection of HSP90 in plasma would contribute to judge the clinical course, therapeutic efficacy and prognosis of MM patients.

Treating primary liver cancer patients by Pi-strengthening and Qi-regulating method: univariate and multivariate analyses of their prognoses / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate the prognostic factors in treating primary liver cancer (PLC) patients by Pi-strengthening and qi-regulating method (PSQRM), thus providing evidence and optimizing Pi-strengthening and qi-regulating program.</p><p><b>METHODS</b>Clinical data of 151 PLC patients treated by PSQRM at Oncology Department, Guangdong Provincial Hospital of Traditional Chinese Medicine from May 2007 to March 2009 were retrospectively analyzed. The univariate analysis was determined to analyze possible prognostic factors. Selected key factors were introduced into the COX proportional hazard model, and multivariate analysis was carried out.</p><p><b>RESULTS</b>The 1-year survival rate was 21.85%, the median survival time was 6.80 months, and the mean survival time was 8.98 months. The univariate analysis showed that Chinese medicine (CM) syndrome types, clinical symptoms at the initial diagnosis, ascites, tumor types, ratios of foci, portal vein tumor thrombus, intrahepatic metastasis, a-fetoprotein (AFP) levels, total bilirubin classification, albumin classification, Child-Pugh classification, and domestic staging of liver cancer were significant prognostic factors (P < 0.05). The statistic data of multivariate analysis indicated that CM syndrome types, ascites, tumor types, portal vein tumor thrombus, AFP levels, Child-Pugh classification, and domestic staging of liver cancer were independent factors influencing prognosis (P < 0.05).</p><p><b>CONCLUSION</b>The prognosis of PLC treated with PSQRM is determined by multiple factors including CM syndrome types, ascites, tumor types, portal vein tumor thrombus, AFP levels, Child-Pugh classification, and domestic staging of liver cancer.</p>

The distribution of Chinese medicine syndrome types in primary liver cancer and their differences of the survival time: a clinical study / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To explore the distribution of Chinese medicine (CM) syndrome types in primary liver cancer (PLC) and their differences of the survival time.</p><p><b>METHODS</b>From May 2007 to March 2009, recruited were 151 PLC inpatients at Department of Tumor, Guangdong Provincial Hospital of Traditional Chinese Medicine. Their survival time were statistically calculated. Patients' average survival time and median survival time were calculated using Kaplan-Meier method. The Log-rank test was used to analyze their differences of survival time among different CM syndrome types.</p><p><b>RESULTS</b>The proportion of CM syndrome types in PLC patients were ranked from high to low as follows: mutual accumulation of dampness and blood stasis syndrome [MADBSS, 43.0% (65/151)], Gan-stagnation Pi-deficiency syndrome [GSPDS, 34.4% (52/151)], qi stagnation blood stasis syndrome [QSBSS, 9.3% (14/151)], retention of damp-heat syndrome [RDHS, 8.6%(13/151)], and Gan-Shen yin deficiency syndrome [GSYDS, 4.6% (7/ 151)]. The median survival time of different CM syndrome types were ranked from longer to shorter as follows: GSPDS (14.77 months), QSBSS (6.13 months), RDHS (5.27 months), MADBSS (4.78 months), and GSYDS (0.80 months). The mean survival times were ranked from longer to shorter as follows: GSPDS (12.40 months), QSBSS (8.84 months), MADBSS (6.99 months), RDHS (7.08 months), and GSYDS (0.72 months). There was statistical difference in the difference of the survival time among different CM syndrome types (P < 0.05).</p><p><b>CONCLUSIONS</b>GSPDS and MADBSS were the most common CM syndrome types in PLC patients. There was difference in the survival time between GSPDS and MADBSS/between RDHS and GSYDS. There was difference in the survival time between MADBSS and GSYDS. Patients of GSPDS might get the best prognosis, while patients of GSYDS might get the poorest prognosis.</p>

Influence of Shenfu Injection on the quality of life of lung cancer patients receiving chemotherapy / 南方医科大学学报

<p><b>OBJECTIVE</b>To evaluate the influence of Shenfu Injection (SHF) on the quality of life of patients with advanced non-small cell lung cancer (NSCLC) receiving chemotherapy.</p><p><b>METHODS</b>A total of 133 patients with NSCLC receiving at least two cycles of chemotherapy with taxol plus cisplatin (TP)/vinorelbine plus cisplatin (NP) or gemcitabine plus cisplatin (GP) were randomized into SHF pre-treatment group (with SHF given only in the first cycle) and SHF post-treatment group (with SHF given only in the second cycle). The Quality of Life Questionnaire-Core 30 (QLQ-C30) and the Functional Living Index-Cancer (FLIC) were used to evaluate the quality of life of the patients after the treatments.</p><p><b>RESULTS</b>Both of the groups showed improved quality of life after the treatments (P<0.01), but the improvements were more obvious in SHF pre-treatment group (P<0.05). SHF showed favorable effects in relieving such adverse effects as fatigue, nausea, vomiting and diarrhea associated with the chemotherapy.</p><p><b>CONCLUSION</b>SHF can improve the quality of life in NSCLC patients receiving chemotherapies.</p>

Expression of regulatory T cells and Th17 cells in idiopathic thrombocytopenic purpura and its significance / 中华血液学杂志

<p><b>OBJECTIVE</b>To investigate the expression of regulatory T cells and Th17 cells in idiopathic thrombocytopenic purpura (ITP) and its significance.</p><p><b>METHODS</b>The quantity of CD4(+)CD25(+)T cells, CD4(+)CD25(high) T cells and CD4(+) IL-17(+)T cells in peripheral blood were measured with flow cytometry (FCM), the plasma level of IL-10 and IL-17 with ELISA and the expression of Foxp3 mRNA and RORc mRNA with RT-PCR in 29 newly diagnosed ITP patients and 28 healthy controls.</p><p><b>RESULTS</b>The ratio of CD4(+)CD25(+)T cells/CD4(+) T cells in the peripheral blood of ITP patients was significantly higher than that of the normal controls (P < 0.05). And the ratio of CD4(+)CD25(high) T/CD4(+) T cells in the patients was remarkably lower (P < 0.05). There was no difference in the percentage of CD4(+) IL-17(+)T/CD4(+) T cells between ITP patients and controls (P > 0.05). The ratio of Treg/Th17 was lower in ITP patients (P < 0.05). The plasma level of IL-10 in ITP patients was significantly decreased (P < 0.05), whereas no statistical difference was observed in the level of IL-17 (P > 0.05). The Foxp3 mRNA expression levels were largely reduced (P < 0.05), but the RORc mRNA expression was increased compared with that in controls (P < 0.05).</p><p><b>CONCLUSION</b>The imbalance of Treg/Th17 plays an important role in the pathogenesis of ITP.</p>

Treatment of advanced non-small cell lung cancer with extracorporeal high frequency thermotherapy combined with Chinese medicine / 中国结合医学杂志

<p><b>OBJECTIVE</b>To observe the clinical efficacy and benefit response of extracorporeal high frequency thermotherapy (EHFT) combined with Chinese medicine (CM) in the treatment of patients with advanced nonsmall cell lung cancer.</p><p><b>METHODS</b>The study adopted a prospective, small sample and randomized controlled method, and the advanced non-small cell lung cancer patients were assigned to two groups according to the table of random digits, one having the treatment of EHFT combined with CM (the treatment group), the other only with CM (the control group). The patients in the treatment group were treated with EHFT one hour once per day, together with CM differentiation decoction, 250 mL orally taken, twice daily for 14 days as one cycle, and 3-4 cycles was performed. The patients in the control group were treated only with CM differentiation decoction using the same dose as the treatment group. The efficacies were evaluated after three to four cycles of treatment. Primary endpoints were disease control rate (DCR) and time to progression (TTP). Secondary endpoints were overall survival time and 1-year survival rate.</p><p><b>RESULTS</b>Sixty-six patients accomplished the study. After the patients underwent different treatments, none of the patients got a complete response or partial response in both groups. In the treatment group, DCR was 72.2%, and 10 had progression of disease (28.8%), while the DCR of the control group was 63.3%, and 11 had progression of disease (36.7%); there was a significant statistical difference (P <0.05), suggesting that the combined regimen had superiority on the DCR. As for long-term efficacy, the median survival time (MST) of the treatment group was 7.5 months, TTP was 5.5 months, and 1-year survival rate was 21.4 %; in the control group, the results were 6.8 months, 4.5 months and 16.6% respectively. There was significant statistical difference on TTP (P <0.05), but no difference on MST or 1-year survival rate.</p><p><b>CONCLUSION</b>EHFT combined with CM differentiation has better tolerance and short-term efficacy in the treatment of patients with advanced NSCLC.</p>