Liver regeneration is a rapid and concerted response to injury, in which growth factor-generated intracellular signals result in activation of transcription factors, DNA synthesis, and hepatocyte proliferation. However, the link between cytoplasmic signals resulting in proliferative response to liver injury remains to be elucidated. We show here that association of Gab1 adaptor protein and Shp2 tyrosine phosphatase is a critical event at the early phase of liver regeneration. Partial hepatectomy (PH) rapidly and transiently induced assembly of a complex comprising Shp2 and tyrosine-phosphorylated Gab1 in wild-type hepatocytes. Consistently, liver-specific Shp2 knockout (LSKO) and liver-specific Gab1 knockout (LGKO) mice displayed very similar phenotypes of defective liver regeneration triggered by PH, including blunted extracellular signalregulated kinase 1/2 (Erk1/2) activation, decreased expression of immediate-early genes, and reduced levels of cyclins A, E, and B1, as well as suppression of hepatocyte proliferation. In contrast, the Akt and interleukin-6/Stat3 pathways were up-regulated posthepatectomy in LSKO and LGKO mice, accompanied by improved hepatoprotection. Collectively, this study establishes the physiological significance of the Gab1/Shp2 link in promoting mitogenic signaling through the Erk pathway in mammalian liver regeneration.
BackgroundA wide range of organisms that enter the eye following ocular trauma can cause endophthalmitis. This study was to investigate the spectrum of pathogens and antibiotic susceptibility of bacterial isolates from a large cohort of post-traumatic endophthalmitis cases.MethodsA retrospective study of 912 post-traumatic endophthalmitis patients treated at a tertiary eye-care center in China was performed. The associations between risk factors and the most common isolated organisms were investigated by Chi square Test. The percent susceptibilities for the first 10 years (1990–1999) and the second 10 years (2000–2009) were compared by Chi square test. p < 0.05 was considered statistically significant.ResultsThree-hundred-forty-seven (38.1%) cases of endophthalmitis were culture-positive, and 11 (3.2%) showed mixed infections (Gram-negative bacilli and fungi), yielding a total of 358 microbial pathogens. Culture proven organisms included 150 (41.9%) Gram-positive cocci, 104 (29.1%) Gram-negative bacilli, 44 (12.3%) Gram-positive bacilli, and 60 (16.8%) fungi. The coagulase-negative staphylococcal (CNS) species S. epidermidis (21.8%) and S. saprophyticus (12.0%) were the predominant pathogens, followed by Bacillus subtilis (8.7%), Pseudomonas aeruginosa (7.8%), and Escherichia coli (6.4%). Delayed repair over 24 h (p < 0.001) and metallic injury (p < 0.01) were significantly associated with positive culture of CNS. The most frequent fungal species were Aspergillus (26/60), followed by yeast-like fungi (18/60). P. aeruginosa was relatively sensitive to ciprofloxacin (83.3%), cefoperazone (75%), tobramycin (75%), cefuroxime (75%), and ceftazidime (75%) during the second decade. Multi-drug resistance was observed in the predominant Gram-negative bacteria.ConclusionWe identified a broad spectrum of microbes causing post-traumatic endophthalmitis, with Gram-positive cocci the most frequently identified causative organism, followed by Bacillus species, fungi, and mixed infections. CNS infection was statistically associated with delayed repair and metallic injury. Variation in antibiotic susceptibility was observed among isolated bacteria and between different periods. Ciprofloxacin and ceftazidime in the first and second decades of the study, respectively, showed the highest activity against bacterial post-traumatic endophthalmitis. For infections caused by P. aeruginosa, a combination therapy of ciprofloxacin, tobramycin, and one of the cephalosporins might provide optimal coverage according to data from the second decade.
BackgroundThe baseline data pertaining to the national epidemiological survey of infectious keratitis remain scarce in China, and currently there is no corneal blindness control strategy developed by the nation.MethodsGeographically defined cluster sampling was used to randomly select a cross-section of residents from representative urban and rural populations in Hubei Province. Participants were selected from village registers, followed by door-to-door household visits. The assessment items included a structured interview, visual acuity testing, external eye examination, and anterior segment examination using slit lamp. Causes and sequelae of corneal disease were identified according to uniform customized protocol.ResultsThe prevalence of presenting corneal diseases was 0.8% (211/26 305), while the prevalence of infectious keratitis was 0.148% (39/26 305). The prevalences of viral, bacterial, and fungal keratitis were 0.065, 0.068, and 0.015%, respectively. There were no significant differences found between the prevalences of viral (accounting for 43.6%) and bacterial (accounting for 46.2%) corneal ulcers. cases of Acanthamoeba keratitis were not found. Infectious keratitis was the leading cause of corneal blindness (85.7%), and the prevalence of blindness in at least one eye resulting from infected corneas was 0.091% (95% CI: 0.067-0.127%).ConclusionsViral and bacterial mechanisms constitute the most important risk factors for infectious corneal ulcers in Central China. To reduce the rate and severity of infectious keratitis, he public health care policy should be focused on designing cost-effective strategies and operational programs for the prevention and prompt treatment of infectious corneal ulcers.
BackgroundTo evaluate the effects on vitrectomy with internal limiting membrane (ILM) peeling versus vitrectomy with inverted internal limiting membrane flap technique for macular hole-induced retinal detachment (MHRD).MethodsPubmed, Cochrane Library, and Embase were systematically searched for studies that compared ILM peeling with inverted ILM flap technique for macular hole-induced retinal detachment. The primary outcomes are the rate of retinal reattachment and the rate of macular hole closure 6 months later after initial surgery, the secondary outcome is the postoperative best-corrected visual acuity (BCVA) 6 months later after initial surgery.ResultsFour studies that included 98 eyes were selected. All the included studies were retrospective comparative studies. The preoperative best-corrected visual acuity was equal between ILM peeling and inverted ILM flap technique groups. It was indicated that the rate of retinal reattachment (odds ratio (OR) = 0.14, 95% confidence interval (CI):0.03 to 0.69; P = 0.02) and macular hole closure (OR = 0.06, 95% CI:0.02 to 0.19; P < 0.00001) after initial surgery was higher in the group of vitrectomy with inverted ILM flap technique than that in the group of vitrectomy with ILM peeling. However, there was no statistically significant difference in postoperative best-corrected visual acuity (mean difference (MD) 0.18 logarithm of the minimum angle of resolution; 95% CI −0.06 to 0.43 ; P = 0.14) between the two surgery groups.ConclusionCompared with ILM peeling, vitrectomy with inverted ILM flap technique resulted significantly higher of the rate of retinal reattachment and macular hole closure, but seemed does not improve postoperative best-corrected visual acuity.
Fireworks-related ocular injuries occur mainly in children, males and rural settings, are frequently severe and visually devastating. Therefore, preventive measures should be strengthened, including public education and legal restriction on the sale and use of fireworks.
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