Inhibitory effects of S100A4 gene silencing on alkali burn-induced corneal neovascularization: an in vivo study.

OBJECTIVE: The purpose of this study is to explore the inhibitory effects of S100A4 gene silencing on alkali burn-induced corneal neovascularization (CNV) in rabbit models. METHODS: Sixty-five rabbits were used to establish alkali-induced CNV models. After the operation, rabbits were given daily antibiotic eye drops and an eye ointment to prevent infection. The models were assigned to either an S100A4 siRNA or an empty vector group. Thirty rabbits were selected as the normal control group. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the mRNA expression of S100A4, vascular endothelial growth factor (VEGF), and tumor necrosis factor-α (TNF-α) in corneal tissues. Immunohistochemistry was used to detect the protein expression of VEGF in corneal tissues, and an enzyme-linked immunosorbent (ELISA) assay was used to detect the protein expression of VEGF and TNF-α in the aqueous humor. RESULTS: The qRT-PCR results showed that S100A4 mRNA expression was lower in the S100A4 siRNA group than in the empty vector group at 1, 3, 7, 14, and 28 days after an alkali burn. When compared with the empty vector group, the expression of VEGF and TNF-α mRNA was downregulated in the S100A4 siRNA group. The immunohistochemistry results revealed that VEGF protein expression was downregulated in the S100A4 siRNA group when compared to the empty vector group at 1, 3, 7, 14, and 28 days after an alkali burn. The ELISA results suggest that VEGF and TNF-α protein expression is downregulated in the S100A4 siRNA group in comparison to the empty vector group at 1, 3, 7, 14, and 28 days after an alkali burn. CONCLUSIONS: These findings indicate that S100A4 gene silencing can inhibit alkali burn-induced CNV in rabbits.

Altered spontaneous brain activity patterns in patients with neovascular glaucoma using amplitude of low-frequency fluctuations: A functional magnetic resonance imaging study.

BACKGROUND: Neovascular glaucoma (NVG) can cause irreversible visual impairment and abnormal spontaneous changes in brain's visual system and other systems. There is little research on this aspect at present. However, amplitude of low-frequency fluctuations (ALFFs) can be used as an rs-fMRI analysis technique for testing changes in spontaneous brain activity patterns. PURPOSE: The aim of this study was to probe the local characteristics of spontaneous brain activity in NVG patients and analyze their correlation with clinical behaviors. METHODS: Resting-state functional magnetic resonance imaging (rs-fMRI) scans were obtained from eighteen patients with NVG (8 males, 10 females) and eighteen healthy controls (HCs; 8 males and 10 females) who were matched in age, gender, and education level. We evaluated spontaneous brain activity with the ALFF method. A receiver operating characteristic (ROC) curve was used to compare the average ALFF values for altered brain regions of NVG patients with those of HCs. RESULTS: Compared with HCs, NVG patients had lower ALFF values in the right cuneus, right middle occipital gyrus, left cingulate gyrus, right precuneus, and left medial frontal gyrus (p < 0.001). Higher ALFF values were observed in the right superior frontal gyrus and left middle frontal gyrus (p < 0.001). Analysis of the ROC curves of the brain regions showed that the specificity and accuracy of ALFF values between NVG and HCs in the area under the curve were acceptable (p < 0.001). CONCLUSION: The patients with NVG exhibited anomalous spontaneous activity in different brain regions; these finding should establish the foundation for a more comprehensive understanding of the pathological mechanisms of NVG. Furthermore, these abnormal variations in specific brain regions can be considered possible clinical indices of NVG.

Repeated cardiac arrest caused by an air embolism during hepatic resection: A case report.

RATIONALE: Although venous air embolism (VAE) during liver operation has been reported occasionally, fatal VAE in hepatic resection is uncommon. Prompt detection of VAE by transesophageal echocardiography (TEE) is crucial for effective therapy. We describe a case of fatal VAE that caused repeated cardiac arrest during hepatic resection and was confirmed by TEE. PATIENT CONCERNS: A 51-year-old woman with a body weight of 50 kg underwent partial liver resection due to intrahepatic duct calculus. She had a 1-year history of intrahepatic duct calculus without cardiopulmonary disease. The operation was performed under general anesthesia combined with epidural block. When the inferior vena cava was compressed, the PetCO2 level decreased abruptly from 30 to 10 mmHg, followed by a decrease in SpO2 and the development of hypotension. Her heart rate increased with ST interval elevation on electrocardiography monitoring. Ephedrine and phenylephrine were administered immediately but had little effect. Cardiac arrest occurred. DIAGNOSES: Air embolism was detected by TEE. INTERVENTIONS: Resuscitation was successful although cardiac arrest occurred repeatedly. OUTCOMES: The patient returned to consciousness 6 hours postoperatively but died of multiorgan dysfunction 10 days later. LESSONS: Fatal air embolism may happen during hepatic resection. Prompt detection of VAE by TEE is crucial for effective therapy and should always be available during hepatic resection.

Location- and Subunit-Specific NMDA Receptors Determine the Developmental Sevoflurane Neurotoxicity Through ERK1/2 Signaling.

It is well established that developmental exposure of sevoflurane (an inhalational anesthetic) is capable of inducing neuronal apoptosis and subsequent learning and memory disorders. Synaptic NMDA receptors activity plays an essential role in cell survival, while the extra-synaptic NMDA receptors activation is usually associated with cell death. However, whether synaptic or extra-synaptic NMDA receptors mediate developmental sevoflurane neurotoxicity is largely unknown. Here, we show that developmental sevoflurane treatment decreased NR2A, but increased NR2B subunit expression both in vitro and in vivo. Sevoflurane-induced neuronal apoptosis was attenuated by synaptic NMDA receptors activation or low dose of exogenous NMDA in vitro. Interestingly, these effects could be abolished by NR2A inhibitor PEAQX, but not NR2B inhibitor Ifenprodil in vitro. In contrast, activation of extra-synaptic NMDA receptors alone had no effects on sevoflurane neurotoxicity. In the scenario of extra-synaptic NMDA receptors stimulation, however, sevoflurane-induced neuronal apoptosis could be prevented by addition of Ifenprodil, but not by PEAQX in vitro. In addition, sevoflurane neurotoxicity could also be rescued by memantine, an uncompetitive antagonist for preferential blockade of extra-synaptic NMDA receptors both in vitro and in vivo. Furthermore, we found that developmental sevoflurane-induced phospho-ERK1/2 inhibition was restored by synaptic NMDA receptor activation (in vitro), low dose of NMDA (in vitro) or memantine (in vivo). And the neuroprotective role of synaptic NMDA activity was able to be reversed by MEK1/2 inhibitor U0126 in vitro. Finally, administration of memantine or NMDA significantly improved spatial learning and memory dysfunctions induced by developmental sevoflurane exposure without influence on locomotor activity. These results indicated that activation of synaptic NR2A-containing NMDA receptors, or inhibition of extra-synaptic NR2B-containing NMDA receptors contributed to the relief of sevoflurane neurotoxicity, and the ERK1/2 MAPK signaling may be involved in this process.