Sesquiterpene lactones of Aucklandia lappa: Pharmacology, pharmacokinetics, toxicity, and structure–activity relationship / 中草药·英文版

The medicinal part of Aucklandia lappa (Asteraceae) is its dried root, which is one of the commonly used Chinese medicinal materials. Here we reviewed sesquiterpene lactones isolated from A. lappa over the past ten years in the following aspects of pharmacological activities, pharmacokinetics, toxicology, structure–activity relationship. Pharmacological activities consist of anti-cancer, anti-inflammatory activity, anti-immunity activity, anti-oxidant activity, antimicrobial activity, spasmolytic activity and so on. The extractive, showing similar pharmacokinetics parameters, may exert their various biological activities by the interaction of their α-methylene-γ-butyrolactone moiety with the thiol groups of biomacromolecules through Michael-addition. However, the poor aqueous solubility, non-selective binding as a Michael acceptor at undesired targets limited clinical translation of this class. In order to evaluate the potential effect of the extractive applied in clinical trial, the present review outlines information on pharmacological activities, pharmacokinetics, toxicology, and structure–activity relationship, as well as the future research directions of the extractive for further development and utilization of A. lappa.

Preventive and therapeutic effects of rhEGF gel on radiation-induced oral mucositis:A clinical observation / 医学研究生学报

Objective Few studies are reported on the prevention and management of oral mucositis(OM) induced by post-operative radiotherapy in patients with oral cavity cancer.This study aimed to investigate the therateutic effect of the recombinant human epidermal growth factor(rhEGF) gel on radiation-induced OM. Methods Sixty-eight cases of radiation-induced OM after surgery for oral cavity cancer were randomly divided into an experimental and a control group of equal number,the former treated with rhEGF gel while the latter with borax mouthwash. Comparisons were made between the two groups of patients in the severity of oral cavity mucous membrane injury,the intensity of radiation-induced oral pain,the in-cidence of oral cavity infection, and the duration of radiotherapy. Results At 3 weeks of radiotherapy,the patients of the experimental group showed mainly mild and moderate OM while the controls chiefly moderate and severe OM,and at 6 weeks,the former exhibited mainly moderate while the latter chiefly severe OM, with statistically significant differences in the incidence rate between the two groups (P<0.01). The experimental group, compared with the controls, had a significantly higher incidence rate of grade-Ⅰ radiation-induced pain (47.1% vs 20.6%,P<0.01),but lower rates of grade-Ⅱ(17.6% vs 32.4%,P<0.01) and grade-Ⅲpain(2.9% vs 20.6%,P<0.01).The rates of oral infection and antibiotics medication were remarkably lower in the experimental group than in the controls(23.5% vs 38.2% and 11.8% vs 26.5%,P<0.05),and the duration of radiotherapy was markedly shorter in the former than in the latter ([42.37±3.14] d vs [48.47±4.39] d, P<0.05). Conclusion The rhEGF gel can significantly reduce the severity of radiation-induced oral mucositis,improve its symptoms,and shorten the time of postoperative radiotherapy for patients with oral cavity cancer.

Pharmacokinetics of magnolol and honokiol in Weichang'an pill / 中国中药杂志

To conduct multiple-reaction monitoring(MRM) quantitative analysis with high-performance liquid chromatography coupled with mass spectrometry method, establish the quantification method of magnolol and honokiol in blood sample under negative ion mode with ibuprofen as internal standard, investigate the pharmacokinetic process of lignans constituents after oral administration of Weichang'an pill(WCA) at different doses, and provide theoretical basis to further reveal the material basis of WCA's anti-diarrhea effect. In the plasma samples, the linear relationship was good over the concentration range of 5.25 to 1 344.00 μg•L ⁻¹ for magnolol and 10.08 to 2 580.00 μg•L ⁻¹ for honokiol. The results of precision, stability, and extraction recovery tests showed that the determination method of plasma concentration for such compositions was stable and reliable. Dose-dependence was shown for magnolol and honokiol in the plasma concentration-time profile. The results indicated that the time to reach the maximum plasma concentration(Tmax) for lignanoids was 0.55-1.42 h, when the maximum plasma concentration(Cmax) could reach 996.36-2 330.96,189.87-1 469.43 μg•L ⁻¹ respectively for magnolol and honokiol. The lignanoids could be absorbed rapidly in the blood after oral administration of WAC pills, providing experimental basis to prove rapid and long-acting anti-diarrhea effect of WAC pills after oral administration.

Effect of Qiju Dihuang Pill on serum levels of IFN-gamma and IL-4 in pregnant women of Gan-Shen yin deficiency syndrome / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the effect of Qiju Dihuang Pill (QDP) on changes of Chinese medical syndrome types in pregnant women of Gan-Shen yin deficiency syndrome (GSYDS), and to explore the correlation between imbalanced cytokine levels and GSYDS.</p><p><b>METHODS</b>This was a random controlled trail. A total of 163 pregnant women of GSYDS at 12 -16 gestational weeks were randomly allocated into the experimental group (86 cases) and the control group (77 cases). Patients in the experimental group took QDP for 2 -4 weeks. Changes of Chinese medical syndrome types and serum interferon-gamma (IFN-gamma) and interleukin-4 (IL-4) levels were observed and compared between the two groups before and after treatment.</p><p><b>RESULTS</b>(1) Totally 41 patients (47.7%) in the experimental group were transformed to normal Chinese medical syndrome type. In the same period of the follow-ups, 9 patients (11.7%) in the control group were transformed to normal Chinese medical syndrome type, showing statistical difference (P < 0.05). (2) In the experimental group, the serum level of IFN-gamma and the ratio of IFN-gamma/IL-4 in the peripheral blood were obviously lower after treatment than before treatment (P < 0.01), and obviously lower than those in the control group (P < 0.01). The level of IL-4 after treatment in the experimental group was higher than that before treatment, and also higher than that in the control group, but with no statistical difference.</p><p><b>CONCLUSIONS</b>These results indicated that there was imbalanced IFN-gamma/IL-4 ratio in the peripheral blood of pregnant women of GSYDS. QDP might play a role in immunoregulation by affecting the IFN-gamma level.</p>

Multi-factoral analysis on the flap thickness influenced by laser operation in situ keratomileusis / 中华流行病学杂志

Objective To investigate the various factors that influencing the flap thickness after laser operation in situ keratomileusis (LASIK). Methods 369 LASIK eyes (192 cases;among them, 15 patients for surgery monocular) with M2 130 microkeratome heads, grouped by left or right eye were analyzed by Chi-square test and logistic regression analysis based on age, sex, occupation, family history of myopia and ophthalmologic examination results before and after LASIK. The result of analysis of one-way variance which P＜0.05 as the variance to described with logistic regression analysis. Results Results from logistic regression analysis showed that the flap thickness after LASIK of right eye group was related to two factors: the preoperative refractive power (P = 0. 017, OR = 0. 832,95% CI : 0. 715-0. 968), and the corneal thickness ( P = 0. 000, OR = 1. 023,95% CI : 1.011-1. 036) while left eye group was related to three factors: the preoperative astigmatism power (P = 0.044, OR = 2.094, 95% CI: 1.021-4.294),negative pressure suction time ( P = 0. 019, OR = 1. 418,95% CI : 1. 059-1. 898) and the corneal thickness(P = 0. 000, OR = 1. 049, 95% CI : 1. 025-1. 073 ). Conclusion Corneal thickness, the preoperative astigmatism power and the negative pressure suction time tended to make the flap thicker while the preoperative refractive power tended to make the flap thinner. Results showed that the flap thickness performed at the first time was more obvious than at the second time.[ Key words] Laser in situ keratomileusis; Flap thickness; Multi-factor analysis

Activation of auto-mesenchymal stem cells of skeletal muscle by bone morphogenetic protein for rescuing bone marrow failure / 中国医学科学院学报

<p><b>OBJECTIVE</b>To explore the effect of bone morphogenetic protein (BMP) to activate mesenchymal stem cells of skeletal muscle for rescuing bone marrow failure.</p><p><b>METHODS</b>The study was performed on lethal rat acute aplastic anemia model induced by combined 5-fluorouracil (5-FU) and busulfan. The rh-BMP-2 was implanted into the thigh muscle of the rats at 3 days before aplastic anemia was induced. In the control group the rats were implanted with agar into the thigh muscle. The blood picture, pathologic changes and the mortality in two groups were observed. At the same time, rh-BMP-2 were implanted into the thigh muscle of normal Kun-min mice for dynamic control observation of the implantation local morphological changes, colony forming units-spleen (CFU-S) and stem cell growth factor (SCF) expression of the stroma cells of ectopic ossicles induced by BMP.</p><p><b>RESULTS</b>At 7 days after BMP implantation in the mice the mesenchymal cells around BMP in muscle proliferated, and appeared in bone marrow to form an ectopic ossicles. The SCF expression of stroma cells in ectopic ossicles were higher than that of self-bone marrow. 56.3% of BMP-treated aplastic rats were survived over 3 months and its hematopoiesis was completely reconstituted and the histo-morphological picture of the spleen and bone marrow were recovered to normal. But in the control group only one of 23 rats was survived, the remainder died of hematopoietic failure.</p><p><b>CONCLUSIONS</b>BMP-implantation into the skeletal muscle could rescue the bone marrow hematopoietic failure. The mechanism might be related to the BMP activated auto-mesenchymal cells of skeletal muscles to direct hematopoietic cell differentiation. In our hands it might create a new pathway for utilization of auto-muscle derived mesenchymal cells to reconstitute hematopoiesis.</p>

Study of Low Dose Irradiation Enhancing the Effect of Chemotherapeutic Agents against Leukemia and Its Mechanism / 中国实验血液学杂志

For effectively enhancing the anti-leukemia effect of chemotherapeutic agents, and meanwhile decreasing the side effect of these agents, the study has been made to explore the synergistic effect of low dose irradiation (LDI) combined with Ara-C on murine leukemia and its mechanism. Firstly, an optimal scheme of low dose total body irradiation combined with Ara-C was established in L615 leukemia (T lymphocytic leukemia) mouse model. The machanism of the enhancing effect was explored by patho-morphological observation, examination of residual leukemia cells, the expression of GM-CSF on the surface of marrow stromal cells and in the bone marrow cultural supernatants. The results showed that the optimal scheme was 300 cGy irradiation at 4 days after inoculation of leukemic cells followed by Ara-C 30 mg/kg x 3 days in an interval of 1, 2 or 3 days after irradiation. The mean survival time of the L615 leukemia mice in LDI + Ara-C combined treatment groups was longer than that of control groups. The percentage of long-term survival mice (> 30 days) was the highest (58% - 72%), too. 17% of the mice were be cured. The numbers of blood leukocytes and marrow nucleated cells were transiently decreased in combined treatment group, and then recovered rapidly. Slight myelosuppression and marrow sinus dilation and congestion were seen after 300 cGy irradiation. The expression of GM-CSF either on the stromal cells or in marrow cultural supernatant after irradiation increased strikingly (P < 0.05). Therefore, LDI combined with Ara-C possesses synergistic effect. The mechanism is possibly related to three facts: LDI could increase the permeability of bone marrow sinus; LDI could promote marrow stromal cells to produce some cytokines (such as GM-CSF, etc.) which drive leukemia cells into cell cycle to make the cells more sensitive to chemotherapeutic agents; and LDI could augment Ara-C-induced cytotoxicity through the mechanism of apoptosis.