As one of the serious complications of diabetes, diabetic retinopathy( DR) has become a main eye disease which causes blindness. The occurrence and development of DR is related to many factors. The pathogenesis is complicated, and the mechanism has not been clear. Early data suggest that the occurrence and development of DR has relations with many factors such as blood sugar level, diabetes duration and the environment. Among the factors, mitochondrial dysfunction and oxidative stress is the important mechanisms of DR and has become research focus in recent years. Consequences of mitochondrial dysfunction within cells include elevation of the rate of reactive oxygen species( ROS) production due to damage of electron transport chain proteins, mitochondrial DNA ( mtDNA ) damage, and loss of metabolic capacity. Clear understanding on the mechanism of mitochondrial functional change under high sugar level and oxidative stress response in the occurrence and development of DR is of great significance on prevention and cure of DR. ln this article, the development of mitochondrial metabolism and oxidative stress of DR is reviewed.

Objective To investigate the molecular mechanism of calreticulin ( CRT) transcription induced by HBV and its viral proteins. Methods The human hepatocellular cell line, HepG2, was trans-fected with pHBV1. 3 and eukaryotic expression plasmids of HBV viral proteins, respectively. The expres-sion of CRT was measured after transfection. A reporter plasmid of CRT promoter was constructed to analyze the induction of CRT promoter by pHBV1. 3 and HBV viral proteins. Furthermore, two truncated and one C/EBPα site deficient mutants were constructed to evaluate the regulatory effects of HBx on CRT promoter. Fi-nally, HepG2 cells were transfected with HBx expression plasmids and the cellular localization of C/EBPαwas analyzed. Results In this study, pHBV1. 3 could significantly up-regulate the expression of CRT at mRNA and protein levels as well as enhancing the activity of CRT promoter. Among the seven HBV viral proteins, HBx could enhance the activity of CRT promoter and the expression of CRT at mRNA and protein levels. HBx could not induce the transcription of CRT when the C/EBPα binding site was deleted from the CRT promoter. The expression of HBx could promote the nuclear translocation of C/EBPα. Conclusion HBV and its viral protein HBx could up-regulate the CRT expression at transcriptional level. The transcrip-tional factor C/EBPα played a critical role in HBx-induced transcriptional activation of CRT.

Extracellular single-unit discharge recording technique was used to examine the effects of Ginkgolide B (BN52021) on the discharges of neurons in CAI area of hippocampal slices and to elucidate the mechanisms involved.The results showed that:(1) In response to the application of ginkgolide B (0.1,1,10 βμmol/L; n =43) into the perfusate for 2 rain,the spontaneous discharge rates (SDR) of 42/43 (97.67%) neurons were significantly decreased in a dose-dependent manner; (2) Pretreatment with L-glutamate (L-Glu,0.2mmol/L) led to a marked increase in the SDR of all 10 (100%) neurons in an epileptiform pattern.The increased discharges were suppressed significantly after ginkgolide B (1 μmol/L) was applied into the perfusate for 2 rain; (3) In 8 neurons,perfusion of the selective L-type calcium channel agonist,Bay K 8644 (0.1 μmol/L),induced a significant increase in the discharge rate of 8/8 (100%) neurons.Ginkgolide B (1 μmoL/L) applied into the perfusate inhibited the discharges of 7/8 (87.5%) slices; (4) In 8 neurons,the broad potassium channels blocker,tetraethylammonium (TEA,1 mmol/L) completely blocked the inhibitory effect of ginkgolide B (1 μmol/L).These results suggest that ginkgolide B can inhibit the electrical activity of CAI neurons.The inhibitory effect may be related to the blockade of L-type voltage-activated calcium channel and may be concerned with delayed rectifier potassium channel (KDR),which indicated that ginkgolide B play a protective role on the central neurons.

AIM:To investigate the protective effect of nerve growth factor combined with Ginkgo biloba extract on retinal ischemia-reperfusion (RIR) injury in rabbits with experimental high intraocular pressure.METHODS:Establishment of rabbit glaucoma ischemia reperfusion model.Twenty-four New Zealand white rabbits were randomly divided into three groups:nerve growth factor group, Ginkgo biloba extract group and combination group.Respectively, in the continuous administration of 1, 7, 14d.We observed the morphological changes of the tissues of the retina.The levels of superoxide dismutase(SOD), nitric oxide(NO) and malondialdehyde(MDA) in retinal tissue were measured.RESULTS:Respectively, first, in the continuous administration of 1, 7, 14d, the contents of MDA and NO in Ginkgo biloba extract group and nerve growth group were higher than that in combination group (P<0.05).Secondly, the SOD content of Ginkgo biloba extract group and nerve growth group were lower than that of combination group at each time point (P<0.05).At each time point, the number of HE staining of retinal ganglion cells (RGCs) showed that the loss of RGCs in the combination group was significantly lower than that in the other groups, and the ganglion cell count showed that the Ginkgo biloba extract group and the neuronal growth group were lower (P<0.05).CONCLUSION:Nerve growth factor combined with Ginkgo biloba extract has better protective effect on retinal ischemia-reperfusion injury.The mechanism may be related to the decrease of free radicals and increase the activity of SOD in retinal tissue.

Objective To investigate the clinical features and genetic basis of cryopyrin-associated periodic syndrome (CAPS). Methods The clinical manifestations, laboratory tests, and genetic tests of one case of CAPS were retrospectively analyzed. The related literatures were reviewed. Results A 7 year and eight month old male patient had recurrent fever for 7 years and his whole body was covered with patchy red rash which was itchy and faded with pressure. The limbs and joints were normal. The levels of high-sensitivity C-reactive protein, erythrocyte sedimentation rate, rheumatoid factors were increased. The patient had fundus arteriosclerosis, double conjunctival lesions and nerve deafness on both sides. There was no mutation found in NLRP3 gene coding region, but a heterozygous mutation (-2667G>T) had been found in 5 ' untranslated region. Compared with normal control, the mRNA level of NLRP3 increased 4.2 times and the expressions of IL-1βand IL-18 gene increased 2.2 (P=0.002) and 1.2 times (P>0.05). Conclusions The clinical features of CAPS can be recurrent fever, rash, and joint involved. The oph-thalmologic abnormalities and varying degrees of deafness may occur during the progression. The test of NLRP3 gene may help diagnosis.

Objectives To explore the clinical features and diagnosis of LMNA-associated congenital muscular dystrophy. Methods The clinical data from a case of muscular dystrophy caused by LMNA gene mutation were retrospectively analyzed. The related literatures were reviewed. Results A 8-month-old female infant suffered from weakness of raising head, eyelid droop, and motor development retardtion. LMNA gene was sequenced for the infant, her parents and the older sister. Heterozygous mutation of c. 94_96 del AAG (p. K 32 del) was found in the infant leading to the diagnosis of LMNA- associated congenital muscular dystrophy. No mutation was found in the infant’s parents and her older sister. The literature review showed that all ofLMNA- associated congenital muscular dystrophy patients had LMNA gene mutation, more than 80% patients mainly presented with weakness of raising head and may accompany with weakness of proximal limb, motor development retardation, and weakness of axial muscle. Conclusions Mutation analysis of LMNA gene is conducive to the diagnosis of congenital muscular dystrophy.

OBJECTIVETo explore the mechanisms involved in the ligustrazine alleviation of the pulmonary artery hypertension (PAH) in patients of chronic obstructive pulmonary disease (COPD) associated with chronic cor pulmonale (CCP) during exacerbation.

METHODSSeventy patients of COPD and CCP with acute exacerbation were randomly and equally divided into control group and treatment group. The control group received standard treatment with antibiotics, antiasthmatic and expectorant medications, and oxygenation; and the ligustrazine treatment group received ligustrazine treatment (80 mg/d; i.v.; for 2 weeks) in addition to the standard treatment. Before and at the end of 2 week treatment, the clinic responses of the two regimens were evaluated, plasma levels of endothelin-1 (ET-1) and nitric oxide (NO) were determined; arterial oxygen partial pressure (PaO2, mean pulmonary arterial pressure (mPAP), outflow tract of right ventricle (RVOT), and internal diameter of right ventricle (RV) were measured.

RESULTSGood clinic benefits were achieved in both the standard and ligustrazine regimens, plasma level of ET-1, values of mPAP, RV and RVOT decreased significantly, plasma level of NO and PaO2 values decreased (all P < 0.01 vs pre-treatment to all parameters). Compared with the control group, ligustrazine greatly enhanced the clinic efficacy from 77.1% to 97.1% (P < 0.05), and also resulted in more significant changes of all these parameters (P < 0.01 vs control group for all parameters). For both groups, the levels of plasma ET-1 were positively correlated with values of mPAP, RVOT, and RV (r = 0.710, 0.853, and 0.766, respectively, all P = 0.000), and negatively correlated with plasma NO and PaO2 (r = - 0.823, and - 0.752, respectively, all P = 0.000).

CONCLUSIONLigustrazine is effective in treating pulmonary artery hypertension during acute exacerbation of COPD and CCP in patients from the plateau area. The observed changes in the plasma levels of NO and ET-1 in response to ligustrazine treatment suggest that ligustrazine may act through the selective effect on pulmonary blood vessels to enhance the synthesis and release of NO and suppress those of ET-1 from lung vascular endothelial cells, thus reducing pulmonary artery pressure and decreasing pulmonary arterial hypertension.

Altitude ; Blood Gas Analysis ; Chronic Disease ; Endothelin-1 ; blood ; Humans ; Hypertension, Pulmonary ; drug therapy ; Nitric Oxide ; blood ; Pulmonary Artery ; physiopathology ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; Pyrazines ; therapeutic use ; Respiration

Objective To analyze the clinical features and gene mutation in mthylmalonic acidemia (MMA) accompanied by homocysteinemia (cblC), and review the relevant literatures. Methods The clinical features of 3 cases of MMA diagnosed by gene detection were retrospectively analyzed, and meanwhile the pertinent literatures of pathogenesis of MMA, especially combined with late-onset cblC and its gene detection, were reviewed. Results Patient 1 (26 days old) suffered from intermittent convulsions for 3 days, with isosuccinic acid 175.8 μmol/L, C3/C2 rate 1.363, homocysteine >?65 μmol/L and abnormal EEG. MMACHC gene detection found an exon deficiency (delEXON1), which has not been reported. Patient 2 ( 12 year old) was hospitalized for limb shaking, hyperspasmia and vomiting. His isosuccinic acid level was 334.3 μmol/L, C3/?C2 rate was 0.37, homocysteine >?65 μmol/L, and had abnormal EEG. MMACHC gene detection found the mutations of c.482G?>?A and c.609G?>?A. Patient 3 was hospitalized for intermittent convulsions for 20 days, whose isosuccinic acid, C3/?C2 rate, and homocysteine were increased. MMACHC gene detection found the mutations of c.394C?>?T and c.540del8 and c.540del8 had not been reported. Review of literatures discovered that MMA was combined with epileptic seizure in some patents, which further validate that the mutation in MMACHC gene c.482G?>?A may be related to the late-onset of cblC. Conclusions Gene detection contributes to the diagnosis of MMA; the mutation of MMACHC gene c.482G>A may be related to the late-onset of cblC; delEXON1 and c.540del8 are new mutations which have not been reported.

Objective To investigate the association of single nucleotide polymorphism (rs2295080) inmTOR gene with the susceptibility to acute leukemia (AL) in Chinese children.Methods A case-control study was performed by recruitment of 180 children with AL and 296 healthy children as controls. The genotype of this SNP was detected using PCR-RFLP. The data were analyzed by SPSS19.0.Results There was a signiifcant difference in genotypes in three groups (ALL, AML and con-trol) (P=0.026). And the SNP was associated with AL, with G allele being higher in AL group than that in controls (OR=1.413, 95%CI: 1.050-1.901,P=0.022). In ALL group, G allele was also higher than that in healthy group (OR=1.456, 95%CI: 1.052-2.015, P=0.023). However, no signiifcant association was observed in AML patients (P=0.302). In addition, ALL patients with GG gen-otype were associated with disease severity compared with patients with TT or GT genotype (OR=2.044, 95%CI: 0.569-7.341). ConclusionThe rs2295080 was associated with ALL, with G allele being a risk factor.

Objective To evaluate the efficacy and safety of telbivudine for pregnant women with hepatitis Be antigen (HBeAg)negative chronic hepatitis B(CHB). Methods Sixty-two cases of HBeAg negative CHB pregnant women were collected from May 2007 to May 2012,and they were divided into telbivudine group (n=31 ,600 mg per day by oral administration)and compound glycyrrhizin group (n=31 ,120 mg per day by intravenous administration).All neonates were given intramuscular injection of 200 IU hepatitis Bimmune globalin at birth immediately and 15 days after birth,and 20 μg genetically engineered hepatitis B vaccine at 0,1 and 6 months after birth.The serum alanine aminotransferase (ALT)level and hepatitis B virus (HBV)DNA titer were monitored.The HBV DNA negative conversion rate,the rate of intrauterine infection,duration of pregnancy,delivery mode,neonate weight and disability rate were compared between groups.All categorical data were analyzed using the chi-square test and comparison between groups was analyzed by t test.Results In telbivudine group,the HBV DNA level before delivery ([0.20±0.11]lg copy/mL)and 6 weeks after delivery ([0.22±0.13]lg copy/mL) were lower than that before treatment [(6.24±0.75 )lg copy/mL]and the differences were statistically significant (t=303.128 and 301 .321 ,respectively;both P <0.01).The negative conversion rate of HBV DNA in telbivudine group was 28 cases before delivery,while in compound glycyrrhizin group,no one had HBV DNA negative conversion.And statistical significant differences were achieved between these two groups before delivery and 6 weeks after delivery (t = -20.285 and -8.721 ,respectively;both P <0.01).In telbivudine group,the ALT levels before delivery and 6 weeks after delivery were (13.08±5.87) U/L and (25.97 ± 17.48)U/L,respectively,which were significantly decreased compared with that before treatment (205.95± 95.69 )U/L.The differences were statistically significant (t = 93.128 and 81.321, respectively;both P <0.01).In compound glycyrrhizin group,the ALT level before delivery ([104.15 ± 69.15]U/L)was lower than that before treatment ([209.60 ± 102.24]U/L)and the difference was statistically significant (t = 9.281 ,P =0.032).However,the ALT level was fluctuant 6 weeks after delivery (150.26± 86.43)U/L,which was not significantly different from that before treatment (t =2.821 ,P =0.122).The ALT levels before delivery and 6 month after delivery were significantly different in both two groups (t=-2.559 and -3.158,respectively;both P <0.05 ).There were no statistically significant differences between these two groups in the rate of intrauterine infection, duration of pregnancy,delivery mode,neonate weight and disability rate.Conclusion The using of telbivudine for pregnant women with HBeAg negative CHB can effectively control the hepatitis activation and reduce the virus titer.