The chemometrics analysis and integrated pharmacology approach to decipher the effect and mechanism between raw and processed cistanche tubulosa.

ETHNOPHARMACOLOGICAL RELEVANCE: Cistanche tubulosa (CT) is the dried fleshy stem with scaly leaves of Cistanche tubiflora (Schenk) Wight, which has the effects of tonifying the kidney-yang, benefiting the vital essence and blood, and moisturizing the intestines and laxatives. There are differences in the activity of CT before and after processing, but the mechanism of processing is not clear. AIM OF THE STUDY: The study aimed to compare the strength of action of CT before and after yellow-wine processing in the treatment of constipation and kidney yang deficiency and to identify the active ingredients responsible for the differences in activity before and after yellow-wine processing. MATERIALS AND METHODS: This study established the fingerprints of CT and PCT using HPLC to identify their shared components. Then efficacy of KYDS and FC were carried out to compare the differences between CT and PCT in terms of efficacy. Next, this study established the spectrum-effect relationship between the shared chemical components and the medical effects of CT and PCT using the gray correlation analysis and entropy methods. Ultimately, the activity of the analyzed chemical components was verified using the zebrafish model. RESULTS: CT was more effective than PCT in promoting intestinal peristalsis, regulating gastrointestinal hormone levels, and thus treating FC. PCT was more effective than CT in improving the level of hormone indexes of the hypothalamus-pituitary-target gland axis, replenishing blood, and enhancing immunity. Through the analysis of the spectrum-effect relationship, it was finally found that 5, 6, 12 (tubuloside A), and 13 (isoacteoside) might be more closely related to the activity of tonifying kidney yang, and peaks 9, 10, and 11 (acteoside) are more closely associated with the treatment of constipation, and peaks 3 (salidroside), 4, 1, 2 (geniposidic acid), and 8 (echinacoside) were associated with both kidney yang tonic and treatment of constipation. At the same time, an activity verification experiment showed that echinacoside, geniposidic acid, and salidroside were effective in the treatment of FC and KYDS, while acteoside was very effective in the treatment of FC, and tubuloside A was significant in supplementing the blood, which validated the spectrum-effect relationship analysis. CONCLUSION: This study proved that the raw CT had a better laxative effect, while the yellow-wine processed CT had a better kidney-yang tonic effect; moreover, spectrum-effect relationships were established to analyze the chemical components leading to changes in the activity of CT before and after yellow-wine processing.

[Analgesic effect of combined therapy of medication and acupuncture in PVP for osteoporotic vertebral compression fracture: a randomized controlled trial].

OBJECTIVE: To evaluate the analgesic effect and application advantage of acupuncture combined with local anesthesia of lidocaine in percutaneous vertebroplasty (PVP) for the patients with osteoporotic vertebral compression fracture (OVCF). METHODS: A total of 60 patients with OVCF and receiving PVP at single vertebra under local anesthesia were selected and randomized into an acupuncture plus medication group and a simple medication group, 30 cases in each one. In the simple medication group, the local laying infiltration anesthesia with 1% lidocaine 30 mL was used. In the acupuncture plus medication group, firstly, filiform needles were used to stimulate Hegu (LI 4), Neiguan (PC 6), Jinmen (BL 63) and Yintang (GV 29) with reducing technique, and then the epidermal infiltration anesthesia was followed with 1% lidocaine 4 mL. The needles were retained till the end of operation. Successively, before operation (T0), during skin incision (T1), at the time of working channel completion (T2) and at the time of the injection of bone cement by half a dose (T3), as well as at the end of operation (T4), the mean arterial pressure (MAP), heart rate (HR), oxygen saturation (SpO2) and numerical rating scale (NRS) score were recorded. Besides, the key time of operation and adverse reactions during the operation were recorded, as well as the hospital stays after operation and the subjective satisfaction of the patients. RESULTS: In the acupuncture plus medication group, MAP and HR were lower than those in the simple medication group at T2, T3 and T4 respectively (P<0.05). NRS scores in the acupuncture plus medication group were lower than the simple medication group at T1 and T2 respectively (P<0.05). The key time of operation in the acupuncture plus medication group was shorter than the simple medication group (P<0.05). The incidence of adverse reaction in the acupuncture plus medication group was lower than the simple medication group (P<0.05) and the excellence rate of subjective satisfaction was higher than the simple medication group (P<0.05). CONCLUSION: Acupuncture combined with medication reduces the dose and adverse reactions of anesthetics, alleviates pain degree of patients, shortens the duration of operation and improves patients' subjective satisfaction in PVP for OVCF.

Systematic screen with kinases inhibitors reveals kinases play distinct roles in growth of osteoprogenitor cells.

Cancer treatment-related bone loss has become growing problematic, especially in breast and prostate cancer treated with hormone/endocrine therapy, chemotherapy and radiotherapy. However, bone loss caused by targeted therapy in cancer patients is largely unknown yet. In present study, a kinase inhibitors screen was applied for MC3T3-E1, a murine osteoprogenitor cell line, and seven kinase inhibitors (GSK1838705A, PF-04691502, Dasatinib, Masitinib, GDC-0941, XL880 and Everolimus) were found to suppress the cell viability with dose- and time-dependent manner. The most interesting is that many kinase inhibitors (such as lapatinib, erlotinib and sunitinib) can promote MC3T3-E1 cell proliferation at 0.01 µM. 4 out of 7 inhibitors were selected to perform the functional study and found that they lead to cell cycle dysregulation, treatments of PF-04691502 (AKT inhibitor), Dasatinib (Src inhibitor) and Everolimus (mTOR inhibitor) lead to G1 arrest of MC3T3-E1 cells via downregulation of cyclin D1 and p-AKT, whereas XL880 (MET and VEGFR inhibitor) treatment results in increase of sub-G1 and G2/M phase by upregulation of p53 protein. Our work provides important indications for the comprehensive care of cancer patients treated with some targeted drugs.