Study of Active Phytochemicals and Mechanisms of Cnidii Fructus in Treating Osteoporosis Based on HPLC-Q-TOF-MS/MS and Network Pharmacology.

INTRODUCTION: This study aimed to clarify the anti-osteoporosis mechanism of Cnidii Fructus (CF) via network pharmacology and experimental verification.\ Methods: HPLC fingerprints combined with HPLC-Q-TOF-MS/MS analysis confirmed common components (CCS) of CF. Then, network pharmacology was used to investigate the anti-OP mechanism of CF, including potential anti-OP phytochemicals, potential targets, and related signalling pathway. Molecular docking analysis was carried on investigating the protein-ligand interactions. Finally, in vitro experiments were performed to verify anti-OP mechanism of CF. RESULTS: In this study, 17 compounds from CF were identified by HPLC-Q-TOF-MS/MS and HPLC fingerprints and then were further screened key compounds and potential targets by PPI analysis, ingredient-target network and hub network. The key compounds were SCZ10 (Diosmin), SCZ16 (Pabulenol), SCZ6 (Osthenol), SCZ8 (Bergaptol) and SCZ4 (Xanthotoxol). The potential targets were SRC, MAPK1, PIK3CA, AKT1 and HSP90AA1. Molecular docking further analysis indicated that the five key compounds have a good binding affinity with related proteins. CCK8 assays, TRAP staining experiments, and ALP activity assays concluded that osthenol and bergaptol inhibited osteoclast formation and promoted osteoblast bone formation to improve osteoporosis. CONCLUSION: Based on network pharmacology and in vitro experiments analysis, this study revealed that CF possessed an anti-OP effect, and its potential therapeutic effect may be involved with osthenol and bergaptol from CF.

Molecular Targets and Associated Signaling Pathways of Jingshu Granules in Ovarian Cysts Based on Systemic Pharmacological Analysis.

BACKGROUND: More than a third of women could develop ovarian cysts during their lifetime. Jingshu granules are used for the treatment of gynecological disease of primary dysmenorrhea. However, the molecular mechanisms of Jingshu granules in ovarian cysts are still unreported. We aimed to find the active ingredients, molecular targets, and potential signaling pathways of Jingshu granules in ovarian cysts by using the systemic pharmacological analysis. METHODS: Firstly, the effect of Jingshu granules on female hormones and reproductive organs of young female rats was evaluated. Secondly, candidate pharmaceutical ingredients of Jingshu granules were retrieved from the traditional Chinese medicine systems pharmacology (TCMSP) database and analysis platform. Potential protein targets for the active ingredients in Jingshu granules were then identified according to the oral bioavailability and drug-likeness indices. Thirdly, ovarian cyst-related gene targets were screened based on different databases. Finally, enrichment analysis was used to analyze the potential biological function of intersection targets between Jingshu granules and ovarian cysts. RESULTS: In young female rats, Jingshu granules reduced the secretion of estradiol, progesterone, and prolactin and could affect the development of the uterus. This suggested that Jingshu granules played roles in hormone secretion and reproduction. From the TCMSP, a total of 1021 pharmaceutical ingredients of Jingshu granules were retrieved. After further screening, a total of 166 active ingredients and 159 protein targets of Jingshu granules were identified. In addition, 4488 gene targets of ovarian cysts were screened out. After taking the intersection, a total of 110 intersection targets were identified between potential protein targets of Jingshu granules and gene targets of ovarian cysts. In the functional analysis of 110 intersection targets, 8 signaling pathways including progesterone-mediated oocyte maturation (MAPK8 and CDK1 involved), GnRH signaling pathway (JUN involved), T cell receptor signaling pathway and Toll-like receptor signaling pathway (MAPK1 involved), NOD-like receptor signaling pathway (TNF, IL6, and IL1B involved), p53 signaling pathway (CDK2 and CDK4 involved), VEGF signaling pathway (MAPK14 involved), and PPAR signaling pathway (PPARG involved) were obtained. CONCLUSION: Our study revealed that Jingshu granules could function in patients with ovarian cysts through a number of molecular targets and signaling pathways. Our study may provide a new field into the mechanisms of Jingshu granules in ovarian cysts, from the molecular to the signaling pathway level.

Efficacy of herbal medicine (cinnamon/fennel/ginger) for primary dysmenorrhea: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To assess the efficacy of herbal medicine (cinnamon/fennel/ginger) for treating primary dysmenorrhea. METHODS: Relevant studies were searched in multiple databases. The weighted mean difference (WMD) was used as the effect indicator for measurement data, and each effect size was given estimates and 95% confidence intervals (CIs). RESULTS: Nine studies with 647 patients were selected. Compared with the results in the control group, pain intensity was significantly relieved in the trial group when assessed by the intervention (cinnamon vs. placebo: WMD = 1.815, 95% CI = 1.330-2.301; fennel vs. placebo: WMD = 0.528, 95% CI = 0.119-6.829; ginger vs. placebo: WMD = 2.902, 95% CI = 2.039-3.765), observation period (one cycle: WMD = 2.061, 95% CI = 0.815-3.307; one cycles: WMD = 1.831, 95% CI = 0.973-2.690), and study quality (high quality: WMD = 2.224, 95% CI = 1.488-2.960). Pain duration was significantly shorter in the trial group (cinnamon vs. placebo: WMD = 16.200, 95% CI = 15.271-17.129). No publication bias was observed for either outcome. CONCLUSIONS: For primary dysmenorrhea, cinnamon/fennel/ginger effectively reduced pain intensity, and cinnamon shortened the duration of pain. Further studies are needed to confirm our results.

[Hebei Province Ophthalmologists current situation survey 2013].

OBJECTIVE: This survey is conducted by Hebei Society of Ophthalmology to understand the current situation of the department of ophthalmology in Hebei province, in order to help the Branch to develop an effective, highly-targeted and practical continuing education program. METHODS: A questionnaire is used in this survey, which consists of 4 sections and 25 items, covering Basic Information, Hospital and Department, Personal Practice and Open-ended Questions. The questionnaire is distributed and collected by the Society of Ophthalmology of each region in Hebei province to all medical institutions in their area which have the ability to carry out ophthalmic clinical work. After the aggregation of the questionnaire and according to the omission, Hebei Society of Ophthalmology contacts the individuals who missed the survey by direct calls, letter post and email, etc. to finish the survey. RESULTS: This survey covers 121 counties and cities (coverage 85.8%), 305 medical institutions and 1 485 ophthalmologists. Results shows that trained ophthalmologists take a high proportion (84.3%) in all hospitals, the percentage of ophthalmologists who are eager to learn and improve is high (94.8%), the percentage of ophthalmologists having a Bachelor degree or above is high (68.9%). However, the percentage of ophthalmologists having a Master or Doctor degree is relatively low (19.6%), the talents who can independently carry out vitrectomy are insufficient (4.1%), the percentage of the medical institutions not having basic ophthalmic equipment is high (37.3%). CONCLUSIONS: The reasons restraining the development of Ophthalmology in Hebei province include the lack of professional talents and ophthalmic equipment. The contradiction between the increasing demand of the public for ophthalmological treatment and the limited medical service level we can provide is the primary contradiction in the departments of Ophthalmology in Hebei province. After the survey and according to the results, Hebei Society of Ophthalmology will organize more training to meet the desire and interest of the ophthalmologists in our province, to achieve the ultimately goal of improving the Ophthalmic medical level throughout the province.

Minor influence of sub-bowman keratomileusis on the posterior corneal surface at early stage.

PURPOSE: To evaluate the changes in posterior corneal surface (Q value and elevation) measured with Pentacam after femtosecond laser assisted Sub-Bowman Keratomileusis (SBK). METHODS: The Q values and elevation of posterior corneal surface were determined in 166 myopic/myopic astigmatism eyes of 88 patients using Scheimpflug imaging (Pentacam; Oculus, Wetzlar, Germany), which estimates asphericity and elevation for several areas of cornea analysed (Q value: 6, 7, 8 and 9 mm; elevation: 2, 4, 6 and 8 mm) before 1 and 3 months after SBK. The correlations between the changes of Q value or elevation and the mean preoperative spherical equivalent (SE), central corneal thickness (CCT), central ablation depth (AD), estimated residual bed thickness (RBT) and RBT/CCT ratio were investigated. RESULTS: Meridian and area differences in Q of posterior surface have been showed. Two major meridians (horizontal/vertical) present the change of significant negative direction before surgery (all p < 0.001), but the alteration of significant positive direction for all post-SBK follow-up visits (all p < 0.05). There was no statistically significant difference in posterior elevation at 2 mm zone (horizontal meridian: p = 0.439; vertical meridian: p = 0.233). Compared with preoperation, minor but significant forward displacements were found in posterior elevation at 4 and 6 mm areas of cornea analyzed (horizontal meridian: all p < 0.001; vertical meridian: p < 0.001, p = 0.024, respectively). However, posterior elevation in two meridians (horizontal/vertical) at 8 mm region was displayed significant backward shift (p = 0.001, p < 0.001, respectively). The Pearson correlation test showed no significant correlation between the changes in the Q values and elevation data in vast majority of areas of cornea analyzed and the SE, CCT, AD, RBT, and RBT/CCT ratio at 1 and 3 months after surgery (all p > 0.05). CONCLUSIONS: The posterior corneal surface showed central flattening and peripheral steepening at early stage post-SBK. To combine the asphericity with the elevation of the posterior corneal surface can overall and accurately understand the posterior corneal shape and its variations after refractive surgery.