Polycystic ovary syndrome (PCOS) affects many women of reproductive age, including ovarian and metabolic dysfunction. Major therapeutic goals include weight loss and improved insulin resistance. The effects of weight loss and increased insulin sensitivity of glucagon-like peptide-1 (GLP-1) receptor agonists provide another opportunity and pathway for the treatment of PCOS patients, especially those with metabolic abnormalities. This paper reviews the metabolism and reproductive outcomes about GLP-1 receptor agonists for PCOS by searching for literatures of clinical trials from PubMed in the past 10 years, in oder to provide new ideas and clinical evidence for clinical treatment of PCOS.
ObjectiveTo study how CD73 is shed from the retinal pigment epithelium (RPE) surface.MethodsCD73 shedding was induced by treating RPE with lipopolysaccharides (LPS) and TNF-α. After Phospholipase C (PLC) or pan matrix metalloproteinase (MMP) inhibitors were added, surface amount of CD73 was evaluated by flow cytometry (FACS). Then selective inhibitors or their corresponding siRNAs of MMP-2 and MMP-9 were applied to the treatments of RPE; and their effects on induced CD73 shedding were evaluated by FACS. By site directed mutagenesis, mutations were introduced to Lys547-Phe548 coding sites of CD73 cDNA, which was cloned in a pcDNA mammalian expression vector. Both wt-CD73 and mutated-CD73 were over expressed in CD73-/- RPE and their induced shedding was compared.ResultsLPS and TNF-α induced CD73 shedding from RPE was completely blocked by the addition of pan MMP inhibitor but not PLC inhibitor. Selective MPP-9, but not MMP-2, inhibitor or its siRNA blocked CD73 shedding. In CD73-/- RPE induced CD73 shedding was happened to overexpressed wt-CD73 but not Lys547-Phe548 sites mutant CD73.ConclusionMMP-9 is responsible for shedding CD73 from RPE through hydrolyzing its Lys547 -Phe548 sites.
Objective To observe the effect of ginsenoside Rg3 on the proliferation, migration, and tube formation of human retinal capillary endothelial cell (HRCEC) cultured in normal and hypoxia condition. Methods HRCEC was cultured in normal condition and treated with 0.0 mmol/L (group A), 0.1 mmol/L (group B) and 0.5 mmol/L (group C) ginsenoside Rg3. HRCEC was also cultured in hypoxia condition and treated with 0.0 mmol/L (group D), 0.1 mmol/L (group E) and 0.5 mmol/L (group F) ginsenoside Rg3. The effects of ginsenoside Rg3 on HRCEC proliferation were measured by methylthiazoletrazolium assay in 24, 48 and 72 hours after culture. In 24 hours after culture, the effect of cell migration was evaluated by transwell chamber; the effect of tube formation was evaluated by Matrigel; the expression of vascular endothelial growth factor (VEGF) protein and mRNA were detected by Western blot and real-time quantitative reverse transcription-polymerase chain reaction. Results Ginsenoside Rg3 could inhibit proliferation of HRCEC, depending on the concentration (F=30.331 and 33.402 in normal and hypoxia condition, respectively; P＜0.05) and time (F=85.462 and 136.045 in normal and hypoxia condition, respectively; P＜0.05). The number of cell migration was 103.33plusmn;3.54, 92..25plusmn;3.68, 78.64plusmn;4.66 in group A, B and C, the difference among three groups was statistically significant (F=28.801, P＜0.05). The number of cell migration was 125.76plusmn;3.11, 90.27plusmn;3.55, 77.81plusmn;5.01 in group D, E and F, the difference among three groups was statistically significant (F=117.594, P＜0.05). The number of tube formed in Matrigel was 24.3plusmn;2.2, 15.7plusmn;1.7, 10.1plusmn;2.3 in group A, B and C, the difference among three groups was statistically significant (F=35.364, P＜0.05). The number of tube formed in Matrigel was 26.2plusmn;1.9, 15.1plusmn;2.6, 8.6plusmn;1.9 in group D, E and F, the difference among three groups was statistically significant (F=50.989, P＜0.05). The expression of VEGF mRNA was 1.00plusmn;0.06, 0.79plusmn;0.06, 0.68plusmn;0.02 in group A, B and C, the difference among three groups was statistically significant (F=31.303, P＜0.05). The expression of VEGF mRNA was 3.88plusmn;0.12, 2.83plusmn;0.09, 1.15plusmn;0.05 in group D, E and F, the difference among three groups was statistically significant (F=682.668, P＜0.05). The expression of VEGF protein was 0.62plusmn;0.03, 0.41plusmn;0.02, 0.32plusmn;0.02 in group A, B and C, the difference among three groups was statistically significant (F=125.471, P＜0.05). The expression of VEGF protein was 0.91plusmn;0.03, 0.82plusmn;0.03, 0.71plusmn;0.02 in group D, E and F, the difference among three groups was statistically significant (F=41.045, P＜0.05). Conclusion Ginsenoside Rg3 can inhibit the proliferation, migration, and tube formation of HRCEC through the inhibition of VEGF expression.
ObjectiveTo explore the effects of transthyretin (TTR) on biological behavior of retinal microvascular epithelial cell (RMVEC).
MethodsRMVEC was cultured in medium with 0 μmol/L and 4 μmol/L TTR. The proliferation, migration and healing abilities (0, 24, 48 hours) of RMVEC with different concentrations of TTR were measured by methyl thiazol tetrazolium (MTT) assay, transwell assay and scarification test.
ResultsMTT assay shows that RMVEC with the concentrations of 4 μmol/L TTR [absorbance (A) value=0.17±0.02] glows faster than with the concentrations of 0 μmol/L TTR (A value=0.40±0.03), the difference was statistically significant (t=15.47, P=0.000 1). The transwell assay shows RMVEC with the concentration of 4 μmol/L TTR [(140±7) cells] migrants faster than RMVEC with the concentration of 0 μmol/L TTR [(227±14) cells], the difference was statistically significant (t=5.44, P=0.000 6). The scarification test shows that the RMVEC with the concentration of 4 μmol/L TTR [(134.4±45.4) μm] heals faster than the RMVEC with the concentration of 0 μmol/L TTR [(330.0±23.1) μm], the difference was statistically significant (t=8.25, P<0.01). The cells in 48 hours and 4 μmol/L group were healed completely, but not healed in 0 μmol/L group.
ConclusionTTR can promote the proliferation, migration and healing abilities of RMVEC.
Objective To systematically assess the effectiveness and safety of 5-HT3 receptor antagonists in preventing propofol injection induced pain. Methods Databases including PubMed, EMbase, The Cochrane Library (Issue 1, 2012), CNKI, CBM, VIP and WanFang Data were searched from their inception to September, 2012 to collect the randomized controlled trials (RCTs) about 5-HT3 receptor antagonists in preventing propofol injection induced pain. Two reviewers independently screened the literature according to the inclusion and exclusion criteria, extracted the data, and assessed the quality of methodology. Then meta-analysis was performed using RevMan 5.2 software. Results A total of 15 RCTs involving 1 413 patients were included. The results of meta-analysis showed that: a) the incidence of propofol injection induced pain in the 5-HT3 group was obviously lower than the control group (RR=0.14, 95%CI 0.09 to 0.21, Plt;0.000 01); b) as to the severity of pain, there was no statistical difference between the two groups (RR=0.84, 95%CI 0.56 to 1.26, P=0.39); the 5-HT3 group was obviously lower that the control group in the incidence of both moderate pain (RR=0.25, 95%CI 0.19 to 0.34, Plt;0.000 01) and severe pain (RR=0.16, 95%CI 0.10 to 0.24, Plt;0.000 01); and c) as to the incidence of postoperative adverse reaction: the 5-HT3 group was obviously lower that the control group in the incidence of nausea and vomiting (RR=0.19, 95%CI 0.11 to 0.34, Plt;0.000 01) and shivering (RR=0.20, 95%CI 0.12 to 0.33, Plt;0.000 01) as well. Conclusion 5-HT3 receptor antagonists can effectively prevent the propofol injection induced pain, alleviate its severity, and reduce the postoperative adverse reactions. For the quantity and quality limitation of the included studies, this conclusion still needs to be further proved by performing more high quality studies.
Chronic central serous chorioretinopathy (CSC) usually demonstrates frequent recurrence, diffuse leakage and persistent subretinal fluid, which cannot be absorbed, thus lead to photoreceptor damage and poor visual acuity. As glucocorticoids have been implicated in the pathogenesis of chronic CSC, various anti-glucocorticoids oral drugs were used in the clinic to promote retinal fluid absorption and reduce the central retinal thickness of the macula and improve the vision outcomes. In addition, the 5α-reductase-specific inhibitor finasteride, the P450-3A4 inducer rifampicin, circadian rhythmic regulator melatonin, and systemic anti-inflammatory drug methotrexate have also been put into clinical trials for chronic CSC, and achieved certain effects. However, most of the clinical studies on these oral drugs were case reports, but not multi-center randomized clinical trials. The long-term effects of these oral drugs need to be observed and studied further.
We correct some misunderstandings of hypertension therapy and update the knowledge of hypertensive drugs by reviewing the progress of evidence-based research of hypertension in 2004.
Obesity is closely related to thyroid function. The concentration of thyroid stimulating hormone (TSH) in obese patients is higher than that in the general population, and TSH will decrease accordingly after weight loss. Leptin is a bridge linking obesity and thyroid hormones, which can affect the release of TSH. There are many kinds of weight-reducing drugs that target the thyroid gland. Among them, thyroid hormone receptor-specific agonists may be potential drugs for future obesity treatment, but further studies are still needed.
Objective To investigate if lactic acid can promote the expression of vascular endothelial growth factor (VEGF) in the rat retinal explants.Methods The retinas of two-week neonatal SD rats were placed onto the culture plate inserts and incubated with Dulbeccoprime;s modified Eagleprime;s medium （DMEM） plus 2% fetal bovine serum (FBS) containing 10,20,30 mmol/L of lactic acid, respectively. Each group had 24 retinas. At 24 hours after incubation, the retinas were sectioned for light microscopy and the expression of VEGF was measured by real time PCR and Western blot. Results The cultured retinas maintained intact construction, and no cytolysis and apoptosis were observed under light microscope. RT-PCR showed the levels of VEGF mRNA were 0.74plusmn;0.06 for 10 mmol/L lactic acid group, 0.99plusmn;0.12 for 20 mmol/L group, and 1.45plusmn;0.17 for 30 mmol/L group respectively. VEGF expression was 0.34plusmn;0.15 for 10 mmol/L, 0.54plusmn;0.16 for 20 mmol/L, and 0.93plusmn;0.23 for 30 mmol/L group respectively by Western blot. Both PCR and Western blot showed 30 mmol/L of lactic acid significantly increased the levels of VEGF mRNA and VEGF expression. Conclusion The induction of retinal VEGF by lactic acid is concentration-dependent.
ObjectivesTo evaluate and compare the clinical impact of different methods of trigger in polycystic ovary syndrome (PCOS) with high ovarian response undergoing in vitro fertilization-embryo transfer (IVF-ET) cycles.MethodsA total of 323 PCOS patients with high ovarian response in an gonadotrophin-releasing hormone antagonist protocol in our reproductive medical center from January 1st, 2017 to December 31st, 2017 were included. Then they were divided into two groups based on the different trigger modes: Group A: gonadotrophin-releasing hormone agonist (GnRH-a) with low dose human chorionic gonadotrophin (HCG); Group B: HCG as trigger. Analysis and comparison of the general data of the two groups of patients, ovulation induction cycle treatment, embryo laboratory indicators and resuscitation cycle treatment outcome were performed retrospectively.ResultsThere were no significant differences in baseline such as ages, BMI, startup dose of Gn, the total dosage of drugs, promote ovulation days and so on (P>0.05). The serum E2 level on trigger day in group A was significantly higher than those in group B (7 256.94±2 031.92 vs. 6 200.26±1 001.44, P<0.05). There were no significant differences in the retrieved oocytes (23.90±7.99 vs. 23.81±7.15), binuclear fertilization rate (58.19% vs. 56.30%), and the number of frozen embryos (12.81±5.45 vs. 11.07±5.36) between two groups (P>0.05). There were also no significant differences between two groups in the incidence of moderate to severe OHSS (5.98% vs. 7.87%), clinical pregnancy rate (59.28% vs. 57.53%), implantation rate (41.05% vs. 38.24%), miscarriage rate (9.28% vs. 8.22%) and live birth rate (47.42% vs. 41.10%) during the frozen-thawed cycles (P>0.05).ConclusionsFor high responders of PCOS patients with GnRH antagonist protocol, using GnRH-a with low dose HCG as trigger maybe could decrease the incidence of moderate to severe OHSS. Embryo resuscitation and transfer cycle can also obtain ideal outcome.
