[Mechanism of Wuwei Ganlu in treatment of knee osteoarthritis:a study based on network pharmacology and molecular docking].

Wuwei Ganlu, a formula for medicated bath, consists of medicinal materials of Ephedra sinica, Platycladus orientalis, Myricaria squamosa, Artemisia carvifolia, and Rhododendron anthopogonoides, which is effective in inducing perspiration, resisting inflammation, relieving pain, regulating yellow water disease, and activating blood circulation. On this basis, a variety of formulas for Tibetan medicated bath have been derived for the treatment of diseases in internal organs, joints, nerves, etc. Modern studies have confirmed that Wuwei Ganlu has a good therapeutic efficacy on knee osteoarthritis(KOA). The present study explored the mechanism of Wuwei Ganlu in treating KOA based on network pharmacology and molecular docking. Firstly, the chemical components of Wuwei Ganlu were obtained through literature mining and database retrieval, and corresponding potential targets were predicted according to the BATMAN-TCM database. The protein-protein interaction(PPI) network was obtained after the potential targets were input into the STRING database. The network function modules were analyzed by the Molecular Complex Detection(MCODE) algorithm, and the functions of the modules were annotated to analyze the action mode of Wuwei Ganlu. Secondly, the related targets of KOA were collected through the DisGeNET database, and the overlapping targets were confirmed to analyze the mechanism of Wuwei Ganlu in treating KOA. Finally, the key targets were selected for molecular docking with the main components of Wuwei Ganlu to verify the component-target interaction. A total of 550 chemical components and 1 365 potential targets of Wuwei Ganlu were obtained. PPI analysis indicated that this formula could exert the effects of oxidation-reduction, inflammation resistance, bone absorption, bone mineralization, etc. Nineteen common targets were obtained from the intersection of potential targets of Wuwei Ganlu and KOA disease targets. It was found that the Wuwei Ganlu mainly acts on nuclear factor-κB(NF-κB), interleukin-1 beta(IL1ß), tumor necrosis factor(TNF), IL6, IL1 receptor antagonist(IL1 RN), and prostaglandin-endoperoxide synthase-2(PTGS2) to treat KOA. Among the 550 chemical components of Wuwei Ganlu, 252 potential active components were docked with TNF and 163 with PTGS2, indicating good binding of the components with potential key targets. The study preliminarily explored the mechanism of Wuwei Ganlu in treating KOA to provide a reference for the further development and utilization of Tibetan medicated bath that has been included in the UN Intangible Cultural Heritage.

Characteristics of Cerebral Stroke in the Tibet Autonomous Region of China.

It is well known that cerebrovascular disease has become an important cause of adult death and disability. Strikingly, the Tibet Autonomous Region (TAR) ranks on the top in China for the incidence of stroke. To help explain this phenomenon, we have searched for and analyzed stroke-related literature for the TAR in the past 2 decades and have referenced reports from other regions at similar altitudes. This article focuses on epidemiology features, risk factors, and pathogenesis of stroke in the TAR in an effort to generate a better understanding of the characteristics of stroke in this region. The special plateau-related factors such as its high elevation, limited oxygen, the high incidence of hypertension, smoking, and the unique dietary habits of the region are correlated with the high incidence of stroke. In addition to these factors, the pathogenesis of stroke in this high-altitude area is also unique. However, there is no established explanation for the unique occurrence and high incidence of stroke in the TAR. Our study provides an important rationale not only for the clinic to prevent and treat this disease, but also for the government to develop appropriate health policies for the prevention of stroke in the TAR.

[Speciation Distribution and Risk Assessment of Heavy Metals in Typical Material Roof Dusts].

With the modified BCR sequential extraction procedure, the chemical speciation and risk for 10 heavy metals (Ba, Co, Cr, Cu, Mn, Ni, Pb, Sb, Sr and Zn) in roof dusts were investigated. The subjects of this study were collected from four typical material paved roofs (i. e., ceramic tile, concrete, metal and asphalt) in southeast China. The results indicated that the average contents of heavy metals in roof dust significantly exceeded road dust. The analysis of chemical fraction showed that the acid soluble/exchangeable fraction of Zn was much higher than other elements, the existence of Pb and Cu was mainly in oxidization fraction, while other heavy metals dominated by the residual fraction. The mobility sequence percentages for all roof dust samples decreased in the order of Pb > Zn > Cu >>Mn > Co >>Sr > Sb > Ni > Ba > Cr, and it should be noted that Pb, Zn, Cu, Mn and Co all have more than 50% proportion in mobility sequence. Based on environmental risk assessment, the highest values of contamination factors (Cf) and risk assessment code (RAC) consistently was observed in Zn, which indicated that Zn had relatively high ecological risk. Health risk assessment showed that the non-carcinogenic hazard indexes (HI) of heavy metals decreased in the order of Pb > Cr > Sb > Zn > Mn > Cu > Ba > Ni > Co > Sr, the HI of heavy metals for adults were lower than safe value while the HI of Pb for children was higher than safe value, suggesting that they will not harm the adult's health except Pb for children. The carcinogenic risk for Cr, Co and Ni were all below the threshold values, which indicated that there was no carcinogenic risk.

[Integripetal rhodiola herb attenuates high altitude-induced pulmonary arterial remodeling and expression of vascular endothelial growth factor in rats].

The aim of this study was to investigate the effect of integripetal rhodiola herb on pulmonary arterial remodeling and expression of vascular endothelial growth factor (VEGF) in high altitude pulmonary hypertension in rats. Fifty healthy male Wistar rats were divided into five groups randomly: Plain control group (LC group), 10-day plateau group (H(10) group), 30-day plateau group (H(30) group), 10-day rhodiola-treated plateau group (R(10) group), and 30-day rhodiola-treated plateau group (R(30) group). Each group included 10 rats. The rats in LC group were kept in Chengdu (500 meters above sea level), and rats in H and R groups were kept in Lhasa (3 700 meters above sea level). The rats in R group were daily treated with integripetal rhodiola herb extract (24%, 10 mL/kg) intragastrically for 10 d or 30 d, while rats in LC and H groups were treated with the same volume of saline. Mean pulmonary arterial pressure (mPAP) was detected via a catheter in the pulmonary artery by pressure waveform monitoring. The ratio value of right ventricle weight to left ventricle plus septum weight [RV/(LV + S)] was measured. The microstructure of pulmonary arterioles was examined by electron microscopy. The expression of VEGF in the lung was investigated using immunohistochemistry. The results showed that mPAP and [RV/(LV + S)] in H(10) group and H(30) group were higher than those in LC group (P < 0.05); but there was no significant difference between H(10) group and R(10) group (P < 0.05); and mPAP and [RV/(LV + S)] in H(30) group were lower than those in H(30) group (P < 0.05). Electron microscopy showed that compared to LC group, arteriolar endothelial cells were arranged in a columnar or palisading form, protruding into the lumen, accompanied with luminal stenosis, irregular internal elastic membrane, and proliferation of vascular smooth muscle cells in H groups, which was more obvious in H(30) group than in H(10) group; while these pathological changes were attenuated in the R groups compared to H groups. The levels of VEGF protein in H groups were also higher than those in LC group (P < 0.05); while the expression of VEGF in R(30) group was lower than that in H(30) group. In summary, the results show that the integripetal rhodiola herb can attenuate high altitude-induced pulmonary arterial remodeling in rats, and the inhibition of VEGF protein expression by rhodiola may be one of the mechanisms.

Laser Doppler flowmeter study on regional cerebral blood flow in early stage after standard superficial temporal artery-middle cerebral artery bypass surgery for moyamoya disease.

BACKGROUND: Standard superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery is an effective treatment for moyamoya disease, but recent evidence suggests that postoperative cerebral hyperperfusion can occur. In this study, the trendline of changes in regional cerebral blood flow (rCBF) after surgery were continually monitored near the site of anastomosis in order to investigate both the efficacy of the procedure for improving rCBF and the possible risk of hyperperfusion. METHODS: Standard STA-MCA bypass surgery was performed on 13 patients. rCBF was measured continually using laser Doppler flowmetry (LDF) until the 5th day after the operation with the LDF probe implanted adjacent to the area of the anastomosis. The trendline of rCBF changes postoperatively was recorded for the analysis performed using SPSS 13.0. RESULTS: The baseline LDF value of cortical rCBF was (84.68 + or - 14.39) perfusion unit (PU), which was linear relative to absolute perfusion volume before anastomosis and (88.90 + or - 11.26) PU immediately after anastomosis (P > 0.05). The value changed significantly from before to after anastomosis (P < 0.05); it was (417.72 + or - 21.35) PU on the 1st day after surgery, and (358.99 + or - 18.01) PU, (323.46 + or - 17.38) PU, (261.60 + or - 16.38) PU and (375.72 + or - 18.45) PU on the following 4 days, respectively. The rCBF decreased gradually from the 2nd day until the 4th postoperative day, but still was at a high level (P < 0.05). However, on the 5th postoperative day the rCBF increased again to the second highest level, which was significantly different compared with the baseline value (P < 0.05), but not significantly different compared with the values on the other 4 days (P > 0.05). CONCLUSIONS: STA-MCA anastomosis improves the cerebral blood supply significantly in the early stage after surgery, however, the risk of symptomatic hyperperfusion may exist, which may possibly occur on the 1st day and 5th day after surgery. A LDF is useful for postoperative monitoring for both the efficacy of bypass and possible risk of neurologic deterioration or bleeding from hyperperfusion.

[Effects of traditional tibetan medicine, Fructus Lonicerae microphyllae on phagecytosis and cytokines production of murine macrophages].

OBJECTIVE: To explore the effects of traditional Tibetan medicine, Fructus Lonicerae microphyllae (FLM) on phagecytosis and cytokines production of murine macrophages. METHOD: The phagecytosis of murine macrophages was analyzed by neutral red phagecytosis assay. The activities of IL-1 and TNF-alpha were measured by biological methods. The mRNA of TNF-alpha and INF-gamma expressed by macrophages was detected by RT-PCR. RESULT: The phagecytosis of murine macrophages was significantly enhanced by FLM at a concentration from 1 microg x mL(-1) to 100 microg x mL(-1) and the secretions of IL-1, and TNF-alpha from macrophages were markedly induced by FLM. Meanwhile, FLM also increased the expression of TNF-alpha mRNA and INF-gamma mRHA from macrophages in vitro. CONCLUSION: FLM could promote phagecytosis and cytokines production of murine macrophages.