Anti-tumor Effect and Mechanism of Kaempferol： A Review / 中国实验方剂学杂志

Cancer is a threat to human health. New treatments for cancer can significantly prolong the survival time of patients， but fail to improve the adverse reactions induced by chemoradiotherapy. Improving patient outcomes still requires the effort of cancer researchers. In recent years， the anti-tumor effects of active components from Chinese herbs have received wide attention. Kaempferol， a flavonoid mainly found in the medicinal plant Kaempferia galanga， can be used to treat obesity， cardiovascular diseases， diabetes and other diseases. It has also exhibited good efficacy in inhibiting the occurrence and development of liver cancer， colon cancer， lung cancer， ovarian cancer， and other malignant tumors. Kaempferol mainly exerts the anti-cancer effect by inducing apoptosis. Specifically， it promotes the production of intracellular reactive oxygen species （ROS） and triggers cell apoptosis through the mitochondrial pathway. Besides， it is capable of interfering with the cancer cell cycle， causing most cancer cells to arrest in the G2/M phase， and inducing cell autophagy， a programmed cell death， thus inhibiting cell migration and invasion and angiogenesis， synergistically improving chemotherapeutic drug efficacy， and reducing adverse effects. Kaempferol acts on a series of intracellular and extracellular targets to participate in the regulation of tumor cell signaling pathways， involving phosphatidylinositol 3-kinase （PI3K）/protein kinase B （Akt）， epidermal growth factor receptor （EGFR）， mitogen activated protein kinase （MAPK）， and Wnt signaling pathways， with the PI3K/Akt signaling pathway being most significant. In addition， kaempferol also plays an important regulatory role in tumor epigenetics. This paper reviewed the anti-tumor effect and mechanism of kaempferol， aiming to provide reference for in-depth study on its prevention and treatment of tumor and the development of new anti-tumor drugs.

Inhibition of Yiqi Jiedu formula on proliferation of nasopharyngeal carcinoma cells by MAPK/ERK signaling pathway / 中国中药杂志

To study the effect of aqueous extracts of Yiqi Jiedu formula (YQ) on the proliferation of CNE2 cells in human nasopharyngeal carcinoma, and investigate its mechanism to provide a new theoretical basis for the clinical application of YQ. CNE2 cells were treated with different concentrations (0.125, 0.25, 0.5, 0.25 g·L⁻¹) of YQ, positive control medicine (cisplatin 4.0 mg·L⁻¹), inhibitor PD98059 (50 μmol·L⁻¹), activator isoproterenol hydrochloride (20 μmol·L⁻¹), activator isoproterenol hydrochloride (ISO)+YQ 0.5 g·L⁻¹. Then cell labeling by using real-time analyzer (RTCA) and CCK 8 method were used to detect cell proliferation activity, and the half inhibitory concentration (IC₅₀) was calculated. The cell cycle distribution was detected by fluorescence double dye flow cytometry PI staining, and Western blot method was used to detect the expression levels of related protein and MAPK/ERK signaling pathway. The results of RTCA and CCK-8 test showed that as compared with the control group, YQ group could effectively inhibit the proliferation of CNE2 cells (<0.01), with a dose and time dependence, and 48 h IC₅₀ value was 0.5 g·L⁻¹. The results of cell cycle showed that after 48 h of water extract treatment, the cell cycle was significantly changed, the proportion of G₀/G₁ was reduced, the ratio of G₂/M increased, and the cell cycle was in G₂/M period (<0.01). Western blot results showed that after 48 h treatment with different concentrations of aqueous extract, cell cycle-related proteins cyclinD1, cyclinD3 and CDK2 expression levels were down-regulated; MAPK/ERK signaling pathway related protein p-c-Raf, p-MEK, p-ERK1/2 expression level significantly lower as compared with the control group (<0.05). After adding activator and inhibitor in MAPK/ERK signaling pathway on this basis, the results showed that after adding activator ISO, cell proliferation was significantly higher than that in the Control group; the cycle related proteins cyclinD1, cyclinD3, and CDK2 expression levels were increased; at the same time, key protein p-c-Raf, p-MEK, p-ERK1/2 expression levels in the signal pathways were relatively increased. While after the addition of inhibitor PD98059, the cell proliferation was significantly lower than that in the Control group, and the expression level of corresponding protein was decreased, which was significantly different from the Control group (<0.05). So YQ could block cell cycle and inhibit the proliferation of CNE2 cells mainly by reducing the expression of MAPK/ERK signaling pathway key protein p-c-Raf, p-MEK and p-ERK1/2.

Exploration of visual check approaches in clinical data management / 药学学报

Due to a great amount of data in clinical trials, the data cleansing needs to adopt a variety of measures, including the latest developed visual check approach. According to the different types of clinical data and the different stages in the course of clinical data management, this study reviews 8 types of visual graphics that show the relevance and trend among the data. The series of graphics can rapidly detect abnormal data, monitor clinical research in real-time, make the data management process much easier and improve the clinical trial efficiency and data quality.

Comparison of paper and electronic data management in clinical trials / 药学学报

Electronic case report forms (eCRFs) instead of the traditional paper case report forms (pCRFs) are increasingly used by investigators and sponsors of clinical research. We include a total of 14 phase III studies (8 pCRF, 6 eCRF) to compare paper and electronic data documentation both quantitatively and qualitatively in clinical studies. The result suggests that adaptions of electronic data capture (EDC) in clinical trials have the advantages in optimization of data capture process, improvement of data quality and earlier clinical decision compared to paper-based methods. Furthermore, the successful implementation of EDC requires accouplements with corresponding data management processes and reallocation of resources.

Quality control of clinical data management based on EDC / 药学学报

With the wide application of electronic data management (EDC), the data management is shifting to a new mode. In order to recognize the advantages of EDC, we choose 20 representative registered clinical trials, which involve 5 404 subjects and 321 sites. We found that EDC has many beneficial impacts on the course of clinical trial data management, including the process of data collection, data cleaning, data quality control and clinical trial decision-making. The result also provides a reference for the adoption of EDC in clinical trials.

Treating influenza patients of wind-heat affecting Fei syndrome by jinhua qinggan granule: a double-blinded randomized control trial / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To assess the effect and safety of Jinhua Qinggan Granule (JHG) in treating influenza patients of wind-heat affecting Fei syndrome (WHAFS).</p><p><b>METHODS</b>Totally 136 influenza patients of WHAFS were randomized by stratification into 3 groups, the high dose JHG group (44 cases, 10 g each time), the low dose JHG group (45 cases, 5 g JHG + 5 g placebo each time), and the placebo control group (47 cases, 10 g placebo each time). All medication was administered three times daily for 5 days. The fever disappearance time, the fever disappearance rate, efficacy of TCM syndrome, the disappearance rate of main symptoms and physical signs of flu, the negative rate of virus nucleic acid in the pharyngeal secretion, and safety indicators were assessed.</p><p><b>RESULTS</b>The median fever disappearance time was 32.8 h (95% CI: 22.5-41.0 h) in the high dose JHG group, 26.0 h (95% CI: 14.5-36.5 h) in the low dose JHG group, 39.5 h (95% CI: 29.0-46.0 h) in the placebo control group. There was statistical difference in the median fever disappearance time between the low dose JHG group and the placebo control group (P = 0.011). Three days after treatment, the markedly effective rate of TCM symptoms in the low dose JHG group was 66.7%, higher than that of the placebo control group (38.3%), and its effective rate was superior to that of the high dose JHG group (P = 0.043). Five days after treatment, the recovery rate of the low dose JHG group (42.2%) was higher than that of the high dose JHG group (25.0%, P = 0.026) and that of the placebo control group (14.9%, P = 0.002). The markedly effective rate of the low dose JHG group (86.7%) was higher than that of the placebo control group (55.3%, P = 0.001). Similar effects were obtained in the low dose JHG group and the high dose JHG group, but slightly poor in partial indicators of the high dose JHG group. There was no statistical difference in adverse reaction among these three groups (P > 0.05).</p><p><b>CONCLUSIONS</b>JHG was effective and safe in treating influenza patients of WHAFS. Routinely low dose was the optimal dosage of JHG.</p>

Limited sampling strategy models for estimating AUC for amlodipine in Chinese healthy volunteers / 药学学报

This study aims to save cost of sampling for estimating the area under the amlodipine plasma concentration versus time curve in 24 hours (AUC(0-24 h)). Limited sampling strategy (LSS) models was developed and validated by mutiple regression model within 4 or fewer amlodipine concentration values. Absolute prediction error (APE), root of mean square error (RMSE) and visual predict check were used as criterion. The results of Jackknife validation showed that fifteen (9.4%) of the 160 LSS based on regression analysis were not within an APE of 15% by using one concentration-time point. 156 (97.5%), 159 (99.4%) and 160 (100%) of the 160 LSS model were capable of predicting within an APE 15% by using 2, 3, 4 points, separately. Limited sampling strategies have been developed and validated for estimating AUC(0-24 h) of amlodipine. The present study indicated that the implemention of both 5 mg and 10 mg dosage could enable accurate predictions of AUC(0-24 h) by the same LSS model. This study shows that 12, 4, 24, 2 h after administration are key sampling time points. The combination of (12, 4), (12, 4, 24) or (12, 4, 24, 2 h) might be chosen as sampling hours for predicting AUC(0-24 h) in practical application according to requirement.

Enhancive effect of N,N'-dinitrosopiperazine on inducing precancerous lesion on nasal and/or nasopharyngeal epithelia of TgN(p53mt-LMP1)/HT mice / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

<p><b>OBJECTIVE</b>To investigate the enhancive effect of N,N'-dinitrosopiperazine (DNP) on induced carcinogenesis in nasal and/or nasopharyngeal epithelia among TgN(p53mt-LMP1)/HT transgenic mice to examine the underlying mechanism for the development of nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>TgN(p53mt-LMP1)/HT transgenic mice and the same strain of C(57)BL/6J wild-type mice both at the age of 5 months were randomly divided into 2 groups in parallel, respectively, i.e., TgN(p53mt-LMP1)/HT cancerous lesion-inducing group (TI), TgN(p53mt-LMP1)/HT control group (TC), C57BL/6J cancerous lesion-inducing group (CI), and C57BL/6J control group (CC). TI and CI mice were treated only with DNP for 16 weeks, twice each week, while TC and CC mice were given the same volume of saline as controls. At the end of treatment, animals were sacrificed to collect epithelial tissue samples from nasal cavity and nasopharynx for pathohistological evaluation by haematoxylin and eosin (HE) staining and for determination on the expression of TRAF2, c-Jun, and p16 by immunohistochemistry.</p><p><b>RESULTS</b>Atypical hyperplasia was more significant in the samples of TI than in those of TC, CI, and CC, with the rates of lesions being 90%, 10%, 0, and 0 (P<0.01) respectively, though DNP was used alone in a much shortened inducing period at less dosage and without the use of carcinogenic promoter 12-O-tetradecanoylphorbol-13-acetate as usual. The expressions of tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) and c-Jun in these samples were significantly up-regulated in TI (P<0.01), while the expression of p16 was significantly lower in TI than in the other groups (P<0.01).</p><p><b>CONCLUSION</b>TgN(p53mt-LMP1)/HT mice hold inherited constitutional defect in immune surveillance function, which can be aggravated by environmental carcinogens, such as DNP used even though in a much less strength. The enhanced carcinogenesis-inducing effect of DNP on TgN(p53mt-LMP1)/HT mice should be closely associated with abnormal signaling of activator protein-1 (AP-1) pathway, especially up-regulated expressions of TRAF2 and c-Jun, and down-regulated expression of p16.</p>

Correlation between TCM syndrome type and intracranial aggressive potentiality of untreated nasopharyngeal carcinoma / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To investigate the correlation between TCM syndrome type and intracranial aggressive potentiality of untreated nasopharyngeal carcinoma (NPC).</p><p><b>METHODS</b>Sixty untreated NPC patients of different syndrome types were treated conventionally and followed up for over one year. Correlation between the TCM syndrome type differentiated at the first consultation and the intracranial aggressive potentiality of the primary focus of NPC were analyzed.</p><p><b>RESULTS</b>The incidence of intracranial aggression was significantly higher in patients with Qi-Yin deficiency type than that in those with other two syndrome types during the follow-up period (P < 0.01).</p><p><b>CONCLUSION</b>The intracranial aggessive rate in the untreated NPC patients of Qi-Yin deficiency type was higher than in those of either Qi and blood coagulation type or fire-toxin stagnation type.</p>