Interleukin-18 is an inactive precursor which lacks a signal peptide, it has a role in regulating retinal pathological angiogenesis. It also inhibits experimental choroidal neovascularization (CNV) via interferon-γand thrombospondin-1. Currently little is known about its mechanisms of inhibition for CNV, may be speculated to be due to effects of anti-angiogenesis, down-regulates vascular permeability and lower vascular endothelial growth factor (VEGF) levels via directly acting on the vascular endothelial cell and epithelial cells. Exogenous administration of mature recombinant interleukin-18 has no adverse effect on retinal pigment epithelial cell viability. In addition, the anti-VEGF role of interleukin-18 is tested to be safe and effective for humans. Interleukin-18 alone or in combination with anti-VEGF shows to be a good prospect for improving the prognosis of experimental CNV. However, more large clinical studies are required to confirm the exact efficacy of interleukin-18 for CNV.
Objective To assess the efficacy of medical expulsive therapy for ureteral calculi with tamsulosin. Methods We searched PubMed, MEDLINE, EMBASE, BIOSIS, International Pharmaceutical Abstracts (IPA) Database, The Cochrane Library and Chinese Journal Full-text Database from 1995 to September 2006, as well as the proceedings of urological scientific conferences from 2000 to 2006. Randomized controlled trials(RCTs) comparing tamsulosin and other therapies for ureteral calculi among adults were included. Data were extracted by two reviewers independently and synthesized by STATA 9.0 software. Results A total of 16 studies involving 1521 patients with distal or juxtavesical ureteral calculi were included. Compared with conservative therapy, tamsulosin showed higher expulsion rate [RR 1.50, 95%CI (1.20 to 1.87), Plt;0.0001], shorter expulsion time [SMD –1.29, 95%CI (–2.27, –0.31)] and fewer patients requiring ESWL or ureteroscopy [RR 0.40, 95%CI (0.27, 0.59), Plt;0.05]. Compared with conservative therapy, the combination of tamsulosin plus deflazacort also showed higher expulsion rate [RR 1.59, 95%CI (1.31, 1.93)], shorter expulsion time [SMD –0.8, 95%CI (–1.18, –0.42)] and fewer patients requiring ESWL or ureteroscopy [RR 0.13, 95%CI (0.06, 0.31), Plt;0.05]. Compared with deflazacort alone, the combination of tamsulosin plus deflazacort demonstrated similar expulsion rate [RR 1.31, 95%CI (0.78, 2.23), P=0.31], but significantly reduced the dosage of analgesics [SMD 15.20, 95%CI (14.98, 15.52)] and decreased the proportion of patients requiring ESWL or ureteroscopy [RR 0.09,, 95%CI (0.02, 0.47), Plt;0.05]. Compared with deflazacort plus nifedipine, the combination of tamsulosin plus deflazacort showed higher expulsion rate [RR 1.20, 95%CI (1.07, 1.35), P=0.002], but similar expulsion time [SMD –1.34, 95%CI (–3.47, 0.79)] and proportion of patients requiring ESWL or ureteroscopy [RR 0.34, 95%CI (0.05, 2.22), Pgt;0.05]. As for side effects, tamsulosin-based treatment and conservative therapy were comparable (Pgt;0.05). Conclusions Tamsulosin has a beneficial effect on the expulsion of ureteral calculi, especially for distal and juxtavesical ureteral calculi. Tamsulosin-based medical expulsive therapy at the dosage of 0.4mg daily is effective and safe for patients with distal ureteral calculi. More large-scale studies are required to define the efficacy of combination therapy of tamsulosin plus deflazacort.
Objective To systematically review the efficacy and safety of 3-month sustained releasing gonadotropin-releasing hormone agonist (GnRHa) (GnRHa 3M) and 1-month sustained releasing GnRHa (GnRHa 1M) in the treatment of pre-menopausal females with hormone receptor-positive breast cancer. Methods Databases including CNKI, WanFang Data, PubMed, EMbase and Web of Science were electronically searched to collect randomized controlled trials(RCTs) of GnRHa in the treatment of hormone receptor-positive breast cancer from inception to May 18th, 2021. Two reviewers independently screened literature, extracted data, and assessed the risk of bias of the included studies. The gemtc software package in R 3.6.1 software and Stata 15.0 software were used for network meta-analysis. Results A total of 11 RCTs including 7 484 patients were included. The network meta-analysis results showed that there was no significant difference between GnRHa 3M and GnRHa 1M in E2 level (MD=?1.3, 95%CI ?13 to 9.6), DFS (HR=1.2, 95%CI 0.88 to 1.7) and OS (HR=2.0, 95%CI 0.75 to 4.9). For safety, there was no significant difference between the two groups (RR=1.0, 95%CI 0.25 to 4.2). Conclusion Current evidence shows that the efficacy and safety of GnRHa 3M is similar to that of GnRHa 1M. Due to the limited quality and quantity of the included studies, more high-quality studies are needed to verify the above conclusions.
Objective To investigate the effects of knocking down Rac1 gene (ras-related C3 botulinum toxin substrate 1) by small hairpin RNA (shRNA) on retinal neovascularization in a mouse model of oxygen-induced retinopathy (OIR). Methods One hundred and eight 7-day-old C57BL/6J mice were divided into three groups randomly.The OIR was induced by Smith protocol in 2 groups. OIR mice received an intravitreal injection of Rac1-shRNA plasmid or the nonsense plasmid in the geneintervention group and control group respectively at the age of postnatal day 11 (P11). Non-OIR mice also received an intravitreal injection of Rac1-shRNA plasmid at P11 as the blankintervention group which lived in the normoxic environment.Retinal neovascularization was investigated on flat-mounts after fluorescence angiography at P15 and P17. Endothelial cell nuclei breaking through the internal limiting membrane were counted on pathological section at P17.The expression of Rac1 and NF-kappa;B p65 subunit was measured by immuohistochemistry, Western blot, real-time polymerase chain reaction (RT-PCR) and in situ hybridization. Results Compared with the blank-control group,the level of Rac1 mRNA in the gene-intervention group decreased obviously（t=4.500，P=0.001）;the retinal non-perfusion areas,fluorescence leakage, neovascularization and the number of endothelial cell nuclei breaking through the internal limiting membrane were reduced significantly（t=6.521,P＜0.001）; the level of NF-kappa;B p65 nuclear translocation decreased（t=16.008,P＜0.001）while the expression of NF-kappa;B p65 mRNA was reduced obviously（t=3.354,P=0.006）, which was positively correlated with the expression of Rac1-mRNA (P=0.012).Conclusion Intravitreal injection of Rac1-shRNA with liposome in mice can effectively inhibit the expression of Rac1,and inhibit the retinal neovascularization under relative hypoxia via blocking the ROS-NF-kappa;B pathway.
Obesity is a chronic metabolic disease driven by multiple factors such as genetic susceptibility, environmental factors, and neuroendocrine system disorders. In recent years, the prevalence of obesity in China has been increasing year by year, and a series of obesity-induced diseases are a serious threat to public health. Glucagon-like peptide-1 receptor agonists, as a representative of the new weight loss drugs, have shown a therapeutic effect close to that of weight-loss metabolic surgery in clinical trials by targeting central appetite and metabolism and other synergistic effects, but they still face key problems such as significant differences in individual efficacy, limited evidence of the safety of long-term treatment, and regaining body weight after discontinuation of the drug. The mechanism of action and clinical evidence of several obesity drugs approved and listed in China are summarized, and the progress and challenges of obesity drug therapy in China in combination with recent advances in the development of multi-target agents internationally are discussed, with a view to providing a scientific basis for the clinical drug management of obesity and providing ideas for the research and development of obesity drugs in China as well as for the clinical transformation.
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.
Left ventricular thrombus (LVT) is a common complication of heart diseases such as myocardial infarction and heart failure. Vitamin K antagonist (VKA) is currently the main method for LVT, but its use requires frequent monitoring of coagulation indicators, which may lead to poor patient compliance. The novel oral anticoagulant (NOAC) is easy to administer and does not require monitoring of international normalized ratio or dietary restrictions. With the development of NOAC, the position of VKA for LVT may gradually be replaced in the future. This article provides a review of the comparative efficacy of NOAC and VKA for LVT in recent years, in order to provide new ideas for the clinical use of NOAC for LVT.
Objective To quantify the mRNA expression of NMDAR1 gene in the retina of eyes with acute elevation of IOP in rabbit． Methods Tweenty-six eyes of 16 rabbits were divided into three groups: Group 1: The IOP of one eye in 10 rabbits was elevated to 60 mm Hg by ante ri or chamber infusion． Group 2: The another eye of the same rabbit in group 1 was maintained the IOP to 20 mm Hg by anterior chamber infusion． Group 3: Unilat eral eyes of six rabbits were enucleated to evaluate the mRNA levels as normal control group． PCR product was identified by Southern blotting and the mRNA expression level was quantified by RT-PCR． Results The results revealed no significant difference between group 1 and group 2． Conclusion This implies that acute elevated IOP may not affect the mRNA expression level of NMDAR1 gene． (Chin J Ocul Fundus Dis, 2001,17:50-51)
Objective To observe the inhibitory effect of kallikrein-binding protein (KBP) on choroidal neovascularization. Methods Forty Brown Norway rats were randomly divided into the KBP groups and the control group, 20 rats in each group, the right eye as the experimental eye. The rats were photocoagulated by 532 nm laser to induce CNV model. One week after laser photocoagulation, the rats were received FFA examination. At the second day after FFA examination, the rats of KBP group were received an intravitreal injection of KBP 5 mu;l (4 mg/ml KBP). The same volume of deionized water was injected into the rats in the control group. The rats of two groups received FFA examination at one, two and three weeks after injection. The expressions of vascular endothelial growth factor and pigment epithelium derived factor were observed using hematoxylin and eosin stain and immunohistochemistry stain. CNV leakage area and the cumulative absorbance of laser spot area were analyzed by Image-Pro plus 6.0 software. Results FFA examination showed that there were CNV and fluorescence leakage at one week after laser photocoagulation; one, two and three weeks after injection, the leakage decreased gradually in KBP group, but increased with time in control group. Compared with control group, the spot area and CNV in KBP group reduced gradually, but CNV was always there in control group. The differences of VEGF (F=1.29) and PEDF (F=6.29) expressions at one week after laser photocoagulation were not statistically significant (P＞0.05). The differences of VEGF and PEDF expressions at one, two and three weeks after injection were statistically significant（VEGF:F=14.16,66.89,24.34; PEDF：F=4.22,62.04,233.05;P＜0.001）.Conclusion Intravitreal injection with KBP can inhibit CNV.
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.