AIM: To analyze the abnormal refractive status of infants and young children aged 6 to 48 months, and to provide basis for the correction of ametropia and the early prevention and treatment of amblyopia.METHODS: Infants and young children aged 6 to 48 months were examined for refraction by Spot vision screener for natural optometry. Clinical data of infants and young children with refractive abnormalities were collected, Ciliary muscle paralysis agent was used for retinoscopy and optometry, and the results were statistically analyzed.RESULTS: A total of 168 cases(336 eyes)with abnormal Spot refractive outcomes were collected, with a high proportion of hyperopia and astigmatism abnormalities, 38.4% and 28.6%, respectively, while the proportion of myopia was low(12.2%). There were 90 cases of anisometropia(≥1.00 D), among which 41 cases(45.6%)were astigmatic anisometropia, 33 cases(36.7%)were hyperopic anisometropia, and 16 cases(17.8%)were myopic anisometropia, accounting for the least proportion. A total of 109 infants and young children with Spot refractive abnormalities completed ciliary muscle paralysis retinal optometry. The analysis of the difference and correlation between Spot diopter and post ciliary muscle paralysis optometry results showed that the difference in astigmatism was 0.34±0.64 D(P<0.001), the difference in hyperopia was -2.10±1.27 D(P<0.001), and the difference in myopia was -0.43±0.91 D(P=0.023). Although there was a statistical difference between the two results, astigmatism, hyperopia, and myopia were highly positively correlated, respectively(r=0.694, 0.762, 0.909).CONCLUSION: The main refractive abnormalities in infants and young children aged 6 to 48 months are astigmatism, hyperopia, and anisometropia, with fewer abnormalities in myopia. For screening abnormalities, further ciliary muscle paralysis agent retinoscopy and optometry should be performed, and glasses correction should be given to effectively prevent refractive amblyopia in infants and young children.

Objective:To investigate whether astragaloside IV (AS-IV) exerts neuroprotective effects via zinc ion (Zn 2+) modulation of mitochondria-associated endoplasmic reticulum membranes (MAMs) and to elucidate the possible mechanisms. Methods:PC12 cells (rat adrenal pheochromocytoma cells) were routinely cultured; they were divided into 7 groups: control group (routinely cultured), 2-DG group (treated with 2-DG at 50 μmol/L for 30 min), astragaloside IV+2-DG group (treated with 50 μmol/L astragaloside IV for 20 min, and then treated with 50 μmol/L 2-DG for 30 min), astragaloside IV group (treated with 50 μmol/L astragaloside IV for 20 min), N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (a zinc chelator, TPEN)+astragaloside IV+2-DG group (treated with 10 μmol/L TPEN for 10 min, 50 μmol/L astragaloside IV for 20 min, and then 50 μmol/L 2-DG for 30 min); TPEN group (treated with 10 μmol/L TPEN for 10 min), TPEN+2-DG group (treated with 10 μmol/L TPEN for 10 min and then treated with 50 μmol/L 2-DG for 30 min). The expressions of glucose-regulated protein (GRP)78, GRP94, cysteine-containing aspartate proteolytic enzyme caspases-8, B cell receptor associated protein 31 (BAP31) and mitochondrial fission protein 1 (Fis1) were detected by Western blotting. Annexin V-FITC/PI kit was used to detect the apoptosis level. Immunofluorescence was used to detect the Fis1 protein expression, and mitochondrial fluorescence probe TMRE was used to detect the opening of mitochondrial permeability transition pore (mPTP).Results:(1) Compared with the control group, the 2-DG group had significantly increased expressions of GRP78, GRP94, Caspase-8, Bap31 and Fis1, and green fluorescent intensity of Annexin V-FITC ( P<0.05); compared with the 2-DG group, the astragaloside IV+2-DG group had significantly decreased expressions of GRP78, GRP94, Caspase-8, Bap31 and Fis1, and green fluorescent intensity of Annexin V-FITC ( P<0.05); compared with the astragaloside IV+2-DG group, the TPEN+astragaloside IV+2-DG group had significantly increased expressions of GRP78, GRP94, Caspase-8, Bap31 and Fis1, and green fluorescent intensity of Annexin V-FITC ( P<0.05). (2) Compared with the control group, the 2-DG group had significantly enhanced Fis1 protein fluorescent intensity ( P<0.05); the astragaloside IV+2-DG group had significantly decreased Fis1 protein fluorescent intensity compared with 2-DG group ( P<0.05); Compared with astragaloside IV+2-DG group, TPEN+astragaloside IV+2-DG group had significantly enhanced Fis1 protein fluorescence intensity ( P<0.05); compared with the control group, the TPEN+2-DG group had significantly enhanced Fis1 protein fluorescent intensity ( P<0.05). (3) TMRE fluorescence intensity in 2-DG group was significantly decreased compared with control group ( P<0.05); TMRE fluorescence intensity in astragaloside IV+2-DG group was significantly enhanced compared with 2-DG group ( P<0.05); TMRE fluorescence intensity in TPEN+astragaloside IV+2-DG group was significantly decreased compared with astragaloside IV+2-DG group (P<0.05); TMRE fluorescence intensity in TPEN+2-DG group was significantly decreased compared with the control group ( P<0.05). Conclusion:Astragaloside IV can exert neuroprotective effects through Zn 2+ inhibiting endoplasmic reticulum stress-induced apoptosis and preventing mPTP opening in PC12 cells, whose mechanism may be related to Fis1 and Bap31 expressions.

In randomized clinical trials, pharmacologically inactive placebos can induce positive physiological responses in the human body, thereby relieving disease symptoms, known as the placebo effect. This article summarizes the research progress on the mechanism of the placebo effect, introduces the integrative framework theory, and focuses on the study of placebomics and molecular mechanisms of placebo effects. Molecules in signal systems, such as dopamine, opiate substances, 5-hydroxytryptamine, and endogenous cannabinoids, may be involved in the placebo effect. These signal systems are also involved in the occurrence and development of mental illnesses such as depression. It suggests that there may be common molecular mechanisms between the placebo effect and depression, providing new insights for clinical treatment and drug design for depression. Personalized placebos can be applied to replace conventional active drugs for treating depression, and specific medications for depression can be developed by avoiding common molecular mechanisms with placebo effects during the development of antidepressants.

In randomized clinical trials, pharmacologically inactive placebos can induce positive physiological responses in the human body, thereby relieving disease symptoms, known as the placebo effect. This article summarizes the research progress on the mechanism of the placebo effect, introduces the integrative framework theory, and focuses on the study of placebomics and molecular mechanisms of placebo effects. Molecules in signal systems, such as dopamine, opiate substances, 5-hydroxytryptamine, and endogenous cannabinoids, may be involved in the placebo effect. These signal systems are also involved in the occurrence and development of mental illnesses such as depression. It suggests that there may be common molecular mechanisms between the placebo effect and depression, providing new insights for clinical treatment and drug design for depression. Personalized placebos can be applied to replace conventional active drugs for treating depression, and specific medications for depression can be developed by avoiding common molecular mechanisms with placebo effects during the development of antidepressants.

Insomnia has become a common central nervous system disease. At present, the pathogenesis of insomnia is not clear. Animal models can help us understand the pathogenesis of the disease and can be used in transformational medicine. Therefore, it is very necessary to establish an appropriate model of insomnia. Clinical data show that insomnia patients with high levels of thyroxine and often accompanied by cardiovascular problems, a common mechanism underlying all of these physiological disruptions is the sympathetic nervous system. Combined with the characteristics of chronic onset of clinical insomnia, an insomnia model induced by long-term intraperitoneal injection of thyroid hormone has been created in our laboratory. In this paper, the insomnia-like state of the model was evaluated based on three validity criteria. Face validity has been demonstrated in metabolism, the Morris water maze, electrocardiogram (ECG) and electroencephalogram (EEG). Structure validity has been proved by the results of targeted metabolomics. After treatment with diazepam, a commonly used clinical anti-insomnia drug, the above physiological and pathological disorders were reversed. The results of comprehensive analysis show that the established thyrotoxicosis-associated insomnia model meets the validity requirement to establish an appropriate animal model of insomnia. The model presented in this article might help to study pathogenetic mechanisms of clinical insomnia, as well as to test promising methods of insomnia treatment.

Aim To explore the role of endoplasmic reticulum stress(ERS) in Astragaloside Ⅳ-induced cardioprotection in H9c2 cardiac cells, and to explore the potential mitochondrial mechanism.Methods Conventional culture was performed of rat heart tissue-derived H9c2 cells.Experiment was randomly divided into the control group, the ERS inducer 2-Deoxy-D-Glucose(2-DG) group, Astragaloside Ⅳ and 2-DG combination group, Astragaloside Ⅳ group.Confocal microscopy was used to observe the changes of TMRE fluorescence intensity so as to confirm the influence of ERS on the mitochondrial potential, and further speculate on the opening of the mitochondrial permeability transition pore(mPTP).Western blot analysis was applied to detect the expressions of ERS proteins GRP 78, GRP 94 and IRE1.Transmission electron microscopy was used to observe the ultrastructure of the cells.Results Different doses of 2-DG could mimic the mPTP opener atractyloside to induce the mPTP opening with the peak at 100 μmol·L-1;Astragaloside Ⅳ significantly reduced 2-DG-induced mPTP opening, the expression of GPR 78, GRP 94 and IRE1 and reduced injury of mitochondria and endoplasmic reticulum.Conclusions Endoplasmic reticulum stress could be induced by 2-DG.Astragaloside ⅳ-induced mitochondrial cardioprotection involves inhibition of the ERS through GRP 78, GRP 94 and IRE1 by prevention of the mPTP opening.

Objective To observe the neural protection of 3-n-butylphthalide (NBP) injection in focal cerebral ischemia-reperfusion rats. Methods 160 male Sprague-Dawley rats were randomly divided into sham group (n=10), ischemia-reperfusion group (IR group, n=50), high-dose NBP treatment group (high-dose group, n=50), middle-dose NBP treatment group (middle-dose group, n=25) and low-dose NBP treatment group (low-dose group, n=25). The later 4 groups were occluded the middle cerebral artery for 2 hours and reperfused. The sham group was sacrificed 24 hours after operation, and the other groups at 6, 12, 24, 48 and 72 hours after reperfusion, in which 5 of them were stained with TdT mediated dUTP Nick End Labeling (TUNEL) to observe the neuronal apoptosis, and immunohistochemistry to observe the expression of silent information regulation 2 homolog 1 (SIRT1) and peroxisome proliferator-activated receptorγcoactivator-1α(PGC-1α);the other 5 of sham group, IR group and high-dose group were observed with quantitative real-time PCR of SIRT1 and PGC-1α. Results Compared with the IR group, the number of apoptotic cells decreased and the SIRT1 and PGC-1αpositive cells increased in all NBP groups at each time (F>160.60, P<0.001), and it was the least of apoptotic cells and most of SIRT1 and PGC-1α positive cells in the high-dose group (P<0.05), while there was significant difference between the low-dose group and the middle-dose group, excluding 6 hours after reper-fusion (P<0.05). Compared with IR group, the expression of SIRT1 and PGC-1αmRNA increased in the high-dose group at each time (t>4.13, P<0.01). Conclusion NBP can protect brain from apoptosis in focal cerebral ischemia-reperfusion rats, which may relate to more ex-pression of SIRT1 and PGC-1α.

Aim To explore the role of endoplasmic re-ticulum stress( ERS) in Astragaloside Ⅳ-induced car-dioprotection against ischemia/reperfusion injury in rats. Methods A model of myocardial ischemia 30 min followed by 120 min reperfusion was made by liga-ting coronary artery in male Wistar rats. Rats were di-vided randomly into 4 groups: sham group, ischemia/reperfusion group, ERS inhibitor TUDCA group, As-tragaloside Ⅳgroup. Myocardial samples were collect-ed from the risk zones during ischemia and reperfu-sion, ERS was determined by measuring levels of glu-cose regulated protein 78 ( GRP78 ) , an established marker of ERS with Western blot. Immunofluorescence study was used to test GRP78 intensity with laser scan-ning confocal microscopy, TTC method was used to measure the infarct size,hematoxylin-eosin staining was used to observe the changes of morphological changes of myocardium. Results There was no statistical difference in GRP78 expression during ischemia com-pared to the sham group, but was markedly increased upon reperfusion. Astragaloside Ⅳ could mimic TUD-CA and significantly decreased the GRP78 expression, reduced infarct size and improved the morphology of myocardial tissue with a significant statistical difference compared with the control group ( P<0. 05 ) . Conclu-sions ERS is induced upon reperfusion but not during ischemia in isolated rat hearts. Astragaloside Ⅳ pre-vents myocardial reperfusion injury presumably by the inhibition of ERS.

Objective Cerebral ischemic tolerance induced by cerebral ischemic preconditioning has become a hotspot in the researches of ischemic cerebrovascular disease, and its specific mechanism remains to be clarified.This study was to explore the brain protection mechanisms of cerebral ischemic preconditioning by observing the expressions of HIF-1αand VEGF in the cortex area sur-rounding the infarct locus in rats with focal cerebral ischemia /reperfusion ( I/R) after cerebral ischemic preconditioning. Methods A total of 130 male SD rats were randomly divided into three groups:sham operation, middle cerebral artery occlusion, and cerebral is-chemic preconditioning, the animals in the latter two groups subjected to 2, 6, 12, 24, 48 and 72 h of I/R.The expressions of HIF-1α and VEGF at different time points were detected by immunohistochemistry and Western blot. Results In the middle cerebral artery occlusion group, the expressions of HIF-1αand VEGF positive cells and proteins increased at 2 h after I/R, reached the peak at 24 h, and then gradually decreased to and at 72 h, but still higher than in the sham operation group (P<0.05).The expressions of HIF-1αand VEGF positive cells were significantly higher in the cerebral ischemic preconditioning than in the middle cerebral artery occlusion group (all P<0.05), so were the expressions of HIF-1αand VEGF positive proteins in the former group than in the latter (all P<0.05).The sham operation group showed only a little in-crease in the expressions of HIF-1αand VEGF positive cells and proteins. Conclusion Cerebral ischemia reperfusion injury induces the expressions of HIF-1αand VEGF, which can be further upregulated by brain ischemic preconditioning.

BACKGROUND:Studies have shown that human telomerase reverse transcriptase (hTERT) has the ability to enhance cel proliferation, maintain telomere length, prolonged cel life cultured in vitro. OBJECTIVE:To observe the effect of hTERT gene-modified bone marrow mesechymal stem cel transplantation on neural function recovery of rats with cerebral infarction. METHODS:Rat models of middle cerebral artery occlusion were established and randomized into model group, cel transplantation group and hTERT-modified cel transplantation group, with 20 rats in each group. Rats in the three groups were respectively injected via tail vein with 1 mL PBS, passage 9 bone marrow mesenchymal stem cel suspension (2.5×107/L) and hTERT-modified passage 9 bone marrow mesenchymal stem cel suspension (2.5×107/L), respectively. Modified neurological severity scores were determined before and after transplantation; RT-PCR and western blot assay were used to measure hTERT expression at gene and protein levels; TUNEL method was adopted to detect cel apoptosis in the brain. RESULTS AND CONCLUSION:hTERT-modified bone marrow mesenchymal stem cels had prolonged cel cycle, and with the increase in passage number, the cels showed good growth with no changes in morphology. The expressions of hTERT mRNA and protein were superior in the hTERT-modified cel transplantation group than the cel transplantation group, and there was a significant difference (P < 0.05). Modified neurological severity scores and number of apoptotic cels were decreased significantly in the hTERT-modified cel transplantation group compared with the other two groups (P < 0.05). These findings indicate that hTERT-modified bone marrow mesenchymal stem cels can promote neural functional recovery of rats with cerebral infarction.