Diabetic retinopathy (DR) is one of the most serious complications of diabetes mellitus. Severe diabetic macular edema or proliferative retinopathy may lead to impaired vision or even blindness in diabetic patients. The glucagon-like peptide-1 receptor agonist (GLP-1RA) is now commonly used as novel glucose-lowering agents in the clinical management of type 2 diabetes, but the rapid glycaemic changes associated with the use of the GLP-1RA may aggravate the risk of an increase in the occurrence of short-term potential DR. Potential effects and mechanisms of DR include oxidative stress, vascular endothelial growth factor, inflammation, retinal neurodegeneration, and other cytokines.Whether GLP-1RA leads to the increased risk of DR remains controversial. More basic and clinical studies are needed with the aim of further clarifying the correlation between GLP-1RA and DR risk.
Ras homolog family (Rho)/ Rho-associated coiled-coil kinase (ROCK) signaling pathway widely exists in human and mammal cells, which is closely related to inhibition of repair after optic nerve damage. The expression level of Rho/ROCK signaling pathway-related proteins is up-regulated in glaucoma, and related with the death of retinal ganglionic cell (RGC) and the axon activity. ROCK inhibitors can protect the surviving RGC and promote axon extension with a dose-dependent manner. ROCK inhibitors also can inhibit glial scar formation, lower intraocular pressure and inhibit inflammatory response to some degrees. Rho/ROCK signaling pathway correlates with the optic nerve disease progression, and ROCK inhibitors hope to become a new therapeutic drug.
Objective To evaluate the effectiveness of GnRH antagonist on vitro fertilization-embryo transfer (IVF-ET). Methods We searched CBMdisc (1979 to 2010), Wanfang (1994 to 2010), CNKI (1994 to 2010), VIP (1989 to 2010), PubMed (1997 to 2010), PML (1997 to 2010), FMJS (2000-2010), and 9 related journals to identify randomized controlled trials (RCTs) on the comparison between GnRH antagonist (GnRHA) and GnRH agonist (GnRHa). The quality of included trials was critically appraised. RevMan 4.2.7 software was used for statistical analysis. Results Six published RCTs involving 1 208 participants were included. Compared with the GnRHa group, stimulation duration in the GnRHA group was lower (WMD= –1.07, 95%CI –1.38 to –0.76), dose of gonadotrophins (Gns) in the GnRHA group was slightly lower (WMD= –0.49, 95%CI –1.63 to 0.66), endometrial thickness at the time of HCG administration was no significant difference in the two groups (WMD= –0.09, 95%CI –0.42 to 0.24), number of oocytes retrieved in the GnRHA group was lower (WMD= –1.80, 95%CI –2.48 to –1.12), OHSS rate in the GnRHA group was slightly lower (Peto OR= 0.77, 95%CI 0.35 to 1.72), pregnancy rate in the GnRHA group was slightly lower (Peto OR= 0.83, 95%CI 0.65 to 1.05), miscarraige rate as no significant difference in the two groups (Peto OR= 1.49, 95%CI 0.79 to 2.82). Conclusions Compared with GnRHa, GnRHA requires shorter stimulation duration and less Gn, less affected the pregnancy rate, and reduces the incidence of OHSS. The use of GnRHA in clinical practice is relatively flexible with good acceptability. GnRHA for the superovulation IVF-ET offers an alternative treatment. The above conclusion still needs more well-designed, multi-center, and large-scale RCTs to confirm and update.
Objective The observe the effects of interferon-inducible protein-10 (IP-10) on proliferation, migration and capillary tube formation of human retinal vascular endothelial cells (HREC) and human umbilical vein endothelial cells (HUVEC). Methods The chemokine receptor (CXCR3) mRNA of HREC and HUVEC were quantified by reverse transcriptase polymerase chain reaction (RT-PCR). In the presence of the different concentrations of IP-10, the difference in proliferation capacity of HREC and HUVEC were analyzed by cell counting kit-8 (CCK-8) methods. Wound scratch assay and threedimensional in vitro matrigel assay were used for measuring migration and capillary tube formation of HREC and HUVEC, respectively. Results RT-PCR revealed both HREC and HUVEC expressed CXCR3. The proliferation of HREC in the presence of IP-10 was inhibited in a dosagedependent manner (F=6.202,P＜0.05), while IP-10 showed no effect on the inhibitory rate of proliferation of HUVEC (F=1.183,P＞0.05). Wound scratch assay showed a significant reduction in the migrated distance of HREC and HUVEC under 10 ng/ml or 100 ng/ml IP-10 stimulation (F=25.373, 23.858; P＜0.05). There was no effect on the number of intact tubules formed by HREC in the presence of 10 ng/ml or 100 ng/ml IP-10. The number of intact tubules formed by HREC in the presence of 1000 ng/ml IP-10 was remarkably smaller. The difference of number of intact tubules formed by HREC among 10, 100, 1000 ng/ml IP-10 and nonintervention group was statistically significant (F=5.359,P＜0.05). Conclusion IP-10 can inhibit the proliferation, migration and capillary tube formation ability of HREC and the migration of HUVEC.
ObjectiveTo screen and identify an ideal lead compound with potential inhibitory effects on N-methyl-D-aspartate receptor (NMDAR) from the ZINC15 drug database, promoting drug design and development to improve epilepsy treatment. Methods Potential NMDAR inhibitors were identified through a series of computer-aided structural and chemical virtual screening techniques (Discovery Studio). Structure-based virtual screening was used to predict and further filter candidate compounds based on physicochemical, pharmacological, and toxicological properties. The binding affinity and chemical bond distribution between selected compounds and NMDAR were then analyzed, and the stability of the ligand-NMDAR complex in a natural environment was evaluated. Results The study identified one novel natural compound from the ZINC15 database, with ZINC000096085903 showing low rodent carcinogenicity, no Ames mutagenicity, no developmental toxicity, and ideal physicochemical properties. This compound demonstrated high binding affinity and favorable interaction energy, with the ZINC000096085903-NMDAR complex exhibiting more favorable potential energy than the complex formed by NMDAR and the reference ligand ketamine. Furthermore, molecular dynamics simulation indicated that this complex remains stable in vivo and can inhibit NMDAR similarly to ketamine. Conclusion ZINC000096085903 is an ideal lead compound for NMDAR inhibition. With higher binding affinity and stability when bound to NMDAR, as well as slower metabolism, ZINC000096085903 showed significant potential for long-term epilepsy treatment.
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.
ObjectiveTo compare the clinical outcomes of different pituitary down regulation protocols with gonadotropin-releasing hormone agonist (GnRH-a) in patients undergoing in vitro fertilization and embryo transfer (IVF-ET) treatment. MethodsThe clinical data of 358 IVF cycles in women at 40 years old or younger from November 2012 to January 2013 in the West China Second University Hospital were analyzed retrospectively. All the 358 cycles were divided into two groups, according to whether the leading follicle diameter was <14 mm (group A, 158 cycles) or ≥14 mm (group B, 200 cycles) after discontinuing the GnRH-a. The clinical outcomes were compared between the two groups. ResultsCompared with group B, the amount of gonadotropins used was significantly more, and the time of gonadotropin use was also significantly longer in group A (P<0.05). However, the serum level of estradiol (E2), progesterone (P) and Luteinizing hormone (LH), incidence of premature P rise, retrieved ovum number, the rates of implantation, clinical pregnancy, miscarriage and live birth did not significantly differ between the two groups (P>0.05). ConclusionDiscontinuing the use of GnRH-a in early stage of controlled ovarian stimulation can keep effective pituitary down regulation and it has the same optimal clinical outcomes in patients undergoing IVF-ET.
Objective To evaluate the effectiveness of GnRH antagonist in vitro fertilization-embryo transfer (IVF-ET) in polycystic ovary syndrome (PCOS) patients.Methods Such databases as PubMed (1997 to 2010), PML (1997 to 2010), FMJS (2000 to 2010), CBMdisc (1979 to 2010), CNKI (1994 to 2010), VIP (1989 to 2010), WanFang (1994 to 2010), and duxiu scholar searcher (www.duxiu.com), and nine relevant Chinese journals were searched for retrieving the randomized controlled trails (RCTs) on the effectiveness of GnRH antagonist versus GnRH agonist for IVF-ET in PCOS Patients. The studies were screened according to the inclusive and exclusive criteria by two reviewers independently, the data was abstracted and the quality was evaluated. The RevMan 4.2.7 software was used for Meta-analyses. Results Six grade-B studies involving 699 participants were included. The results of Meta-analyses showed that, compared with the GnRH agonist, there was no significant difference in the GnRH antagonist group about the stimulation duration (WMD= –1.23, 95%CI –2.76 to –0.31), dose of gonadotrophins (Gns) (WMD= –4.87, 95%CI –14.20 to 4.46), serum E2 value on the day of HCG administration (WMD= 31.37, 95%CI –263.40 to 326), number of oocytes retrieved (WMD= 1.34, 95%CI –1.02 to 4.70), clinical pregnancy rate (OR= 1.27, 95%CI 0.77 to2.10), and miscarraige rate (Peto OR= 0.67, 95%CI 0.38 to1.18). But the OHSS rate in the GnRH antagonist group was lower with a significant difference (Peto OR= 0.35, 95%CI 0.24 to 0.50). Conclusions Compared with the GnRH agonist protocol, the GnRH antagonist protocol can obviously reduce the incidence of OHSS, but has the same effect in Gn dose, retrieving oocytes and clinical pregnancy rate. Because the GnRH antagonist can decrease the treatment duration and cost, and has better safety, so it may be an ideal choice for PCOS patients to have IVF-ET therapy. For the quality and quantity limitation, and the methodology difference of the included studies, it is suggested that the conclusion from this study should be only served as a reference of clinical analyses, and should be revaluated and updated unceasingly.
ObjectiveTo observe the effect of complement receptor 1 (CR1) on barrier of cultured human retinal epithelial cells (hRPE) under complement-activated oxidative stress. MethodsThe third to fifth passage of hRPE cultured on Transwell insert were used to establish a stable hRPE monolayer barrier. The hRPE monolayer barrier was exposed to 500 μmol/L ten-butyl hydroperoxide and 10% normal human serum to establish the hRPE monolayer barrier model of complement-activated oxidative stress in vitro. hRPE monolayer barriers under complement-activated oxidative stress were divided into two groups including model group and CR1 treatment (1 μg/ml) group. Model group and CR1 treatment group were treated with 1 μl phosphate buffer solution (PBS) or CR1 for 4 hours. Normal hRPE monolayer barrier were used as control in transepithelial resistance (TER) measurement experiment. TER was measured to evaluate the barrier function of hRPE. The hRPE-secreted vascular endothelial growth factor (VEGF) and chemokine (C-C Motif) Ligand 2 (CCL2), together with complement bioactive fragments (C3a, C5a) and membrane-attack complex (MAC) in the supernatant were detected by enzyme-linked immune sorbent assay. ResultsStable hRPE monolayer barrier was established 3 weeks after hRPE seeded on Transwell insert. Complement-activated oxidative stress resulted in a sharp decrease of TER to 54.51% compared with normal hRPE barrier. CR1 treatment could significantly improve TER of barrier under complement-activated oxidative stress to 63.48% compared with normal hRPE barrier(t=21.60, P < 0.05). Compared with model group, CR1 treatment could significantly decrease the concentration of VEGF and CCL2 by 11.48% and 23.47% secreted by hRPE under complement-activated oxidative stress (t=3.26, 2.43; P < 0.05). Compared with model group, CR1 treatment could also decreased the concentration of C3a, C5a and MAC by 24.00%, 27.87%, 22.44%.The difference were statistically significant (t=9.86, 2.63, 6.94; P < 0.05). ConclusionsCR1 could protect the barrier function of hRPE cells against complement-activated oxidative stress. The underlying mechanism may involve inhibiting complement activation and down-regulating the expression of VEGF and CCL2.
Objective To evaluate the efficacy of long-term inhaled salmeterol / fluticasone combined with low-dose oral erythromycin in patients with bronchiectasis. Methods Sixty-two patients with bronchiectasis after exacerbation and maintained stable were randomly divided into three groups. Group A was treated with low-dose oral erythromycin, group B inhaled salmeterol/fluticasone, and group C inhaled salmeterol/fluticasone plus low-dose oral erythromycin. The study duration lasted for 6 months. The clinical symptoms, dyspnea scale, exacerbation frequency, and pulmonary function parameters were measured and compared. Results Fifty-four patients completed the whole study and 8 cases withdrew. The results showed that 6 months of low-dose erythromycin therapy can improve the clinical symptoms, whille exacerbation frequency was also decreased. Inhaled salmeterol/fluticasone improved lung function, however, had no effect on cough, expectoration and exacerbation frequency. Inhaled salmeterol/fluticasone combined with erythromycin was more significantly effective in improving lung functions as well as symptoms. Conclusions Long-terminhaled salmeterol/fluticasone combined with low-dose oral erythromycin can improve the clinical symptoms and lung function, decrease the frequency of exacerbation in patients with bronchiectasis. It may be as an alternative to the maintenance treatment of bronchiectasis.