Diabetic macular edema(DME)and age-related macular degeneration(ARMD)are the leading causes of visual impairment and blindness worldwide, and their common pathological features are increased vascular permeability and abnormal neovascularization, in which cytokines such as vascular endothelial growth factor(VEGF)and angiopoietin-2(Ang-2)play an important role. Intravitreal injection of anti-VEGF agents significantly changed the clinical management of DME and ARMD, but limitations such as the non-responsive cases, the treatment burden and risks caused by frequent injections need to be overcome. Faricimab, a novel bispecific monoclonal antibody that simultaneously targets VEGF-A and Ang-2, can effectively reduce vascular permeability, decrease the number of neovascularization and alleviate retinal edema. Registered clinical studies have shown that Faricimab is effective in improving vision and reducing retinal edema, which is non-inferior to Aflibercept and Ranibizumab, maintains a long dosing interval, and has a high safety profile. This article reviews the latest advances in the treatment of DME and ARMD with Faricimab.

0.05],significantly higher than stage Ⅲ,Ⅳ[60%(6/10),50%(5/10);P

Adult ; Aged ; Brucellosis ; diagnosis ; therapy ; Female ; Humans ; Male ; Middle Aged ; Occupational Diseases ; diagnosis ; microbiology ; therapy

Alveolitis, Extrinsic Allergic ; Humans ; Occupational Diseases

Aim To investigate whether EGCG treat-ment ameliorates cognitive deficits in APP/PS1 trans-genic mice and, whether it has the ameliorating effect of p75 NTR signaling to neuronal apoptosis in the hippo-campus of APP/PS1 mice. Methods Morris water maze test and locomotivity test were used to predict be-havioral changes; further TUNEL staining and Fluoro-Jade B staining were applied to confirm the neuronal apoptosis and neuronal degeneration;Western blot was employed to detect protein expression levels of p75 NTR signaling in the hippocampus of APP/PS1 mice. Re-sults EGCG treatment dramatically ameliorated the cognitive impairments, and inhibited the neuronal ap-optosis in the APP/PS1 mice. Moreover, EGCG treat-ment dramatically inhibited the p75 NTR signaling by de-creasing the p75ICD expression, JNK2 phosphorylation, and cleaved-caspase 3 expression. Conclusion EGCG treatment dramatically ameliorates the cognitive impairments, and inhibits the neuronal apoptosis by in-hibiting the p75NTR signaling.

Objective To investigate the relationship between concentration change of serum 5‐hydroxy tryptamine and clinical symptoms improvement in primary premature ejaculation with the treatment of paroxitine .Methods 81 cases of lifelong PE and an intra‐vaginal ejaculation latency time (IELT ) ≤60 s were included in this study .Subjects were divided into 2 groups according to the IELT ,group A (IELT≤30 s) and group B (30 s

Aims To study the role of NGF/Trk A sig-naling pathway in Memantine ( MEM) improving APP/PS1 transgenic mice cognitive deficits and to explore its possible mechanisms. Methods Cognitive perform-ance was assessed by Morris water maze( MWM) , pas-sive avoidance test( PAT) and locomotivity test. Aβ1-42 protein levels were determined by immunohistochemis-try. The activities of AChE and ChAT were also exam-ined by ELISA and colorimetry. Western blot was used to detect the expression levels of NGF and its receptor TrkA and the downstream ERK pathway. Results MEM treatment significantly ameliorated the cognitive deficits, dramatically reduced the Aβ1-42 overexpres-sion. MEM increased the activity of choline acetyl-transferase( ChAT) , while decreased that of acetylcho-line esterase( AChE) . Moreover, MEM activiated NGF signaling by increasing the phosphorylation of TrkA fol-lowing the increased phosphorylation of c-Raf, ERK1/2 and downstream effector CREB after MEM treatment. Conclusion MEM treatment may activate the NGF/TrkA signaling in APP/PS1 mice to reduce amyloidosis and cognitive deficits.

D-alanine (D-Ala) is an essential amino acid that has a key role in bacterial cell wall synthesis. Alanine racemase (Alr) is a unique enzyme that interconverts L-alanine and D-alanine in most bacteria, making this enzyme a potential target for antimicrobial drug development. Streptococcus mutans is a major causative factor of dental caries. The factors involved in the survival, virulence and interspecies interactions of S. mutans could be exploited as potential targets for caries control. The current study aimed to investigate the physiological role of Alr in S. mutans. We constructed alr mutant strain of S. mutans and evaluated its phenotypic traits and interspecies competitiveness compared with the wild-type strain. We found that alr deletion was lethal to S. mutans. A minimal supplement of D-Ala (150μg·mL?1) was required for the optimal growth of the alr mutant. The depletion of D-alanine in the growth medium resulted in cell wall perforation and cell lysis in the alr mutant strain. We also determined the compromised competitiveness of the alr mutant strain relative to the wild-type S. mutans against other oral streptococci (S. sanguinis or S. gordonii), demonstrated using either conditioned medium assays or dual-species fluorescent in situ hybridization analysis. Given the importance and necessity of alr to the growth and competitiveness of S. mutans, Alr may represent a promising target to modulate the cariogenicity of oral biofilms and to benefit the management of dental caries.

Qigui Tongfeng tablet (QLTFT) is a traditional Chinese medicine with good effect for treating gout. Here, network pharmacology method and molecular similarity analysis were utilized to study the effective substance basis and molecular mechanism of the QLTFT on the gout. The similarity to the medicinal compounds is reflected in the Tanimoto coefficient that gives the structural similarity of two compounds. Operationally, similar modifiers were described as pairs of concepts with a similarity score of 0. 500. The results of the molecular similarity analysis suggested that the flavonoids in QLTFT could be new leads for gout. Furthermore, complex biological systems may be represented and analyzed as computable networks. Two important properties of a network were degree and betweenness. Nodes with high degree or high betweenness may play important roles in the overall composition of a network. And the results of network analysis showed that dongbeinine, verticinone-N-oxide, verticine N-oxide, peimine, peiminine, isobaimonidine, dongbeirine, peimisine and simi-arenol which with high degree acted on xanthine dehydrogenase/oxidase, matrix metalloproteinase-9, an arachidonate 5-lipoxygenase-activating protein, tyrosine-protein kinase and etc. Inhibition of these targets can prevent the formation of uric acid, reduce inflammation by uric acid and regulate the body's immune response. Thus, these compounds may be the main effective substance basis. The research results not only reveals its molecular mechanism, but also provide a theoretical basis for the quality control of drugs and clinical application.
Gout ; drug therapy ; Humans ; Medicine, Chinese Traditional ; Pharmacology ; methods ; Tablets ; Technology, Pharmaceutical ; methods

Objective To compare the recurrence rate and long-term follow-up angiographic findings between stent-assisted coil embolization and simple coil embolization in treating large and giant intracranial aneurysms.Methods The clinical data and imaging materials of a total of 90 patients with large and giant intracranial aneurysms (＞10 mm,91 aneurysms in total),who were admitted to authors' hospital during the period from January 2004 to January 2016 to receive interventional embolization therapy,were retrospectively analyzed.Of the 90 patients,52 patients (52 lesions in total) received simple coil embolization (SCE group)and 38 patients (39 lesions in total) received stent-assisted coil embolization (SACE group).Postoperative recurrence rates of aneurysm were compared between the two groups,and recurrence risk factors were analyzed.Results The whole postoperative recurrence rate of aneurysm and re-treatment rate were 38.5％(35/91) and 20.9％(19/91) respectively;the recurrence rate and re-treatment rate of SACE group were 35.9％ (14/39) and 17.9％ (7/39) respectively,while those of SCE group were 40.4％ (21/52) and 23.1％ (12/52) respectively;the differences between the two groups were not statistically significant (P＞0.05).Multivariate logistic regression indicated that the recurrence risk factors of large or giant intracranial aneurysms included rupture of aneurysm (OR=0.284,95％CI=0.083-0.978,P=0.046),simple coil embolization (OR=5.03,95％ CI=1.04-24.44,P=0.045),concurrent hypertension (OR =0.13,95％ CI=0.036-0.51,P=0.003)and long time after operation (OR=1.002,95％CI=1.001-1.003,P=0.002).Conclusion Compared with simple coil embolization,stent-assisted coil embolization can reduce the recurrence rate of aneurysm.Rupture of aneurysm,simple coil embolization,long time after operation and concurrent hypertension are independent risk factors for recurrence of aneurysm after transcatheter arterial embolization.