Expression of MMP-2 and TIMP-2 in laser-induced choroidal neovascularization in guinea pigs model with form-deprivation high myopia / 复旦学报（医学版）

Objective To establish the high myopic choroidal neovascularization (CNV) in guinea pigs and to investigate the role of (matrix metalloproteinase-2,MMP-2) and tissue inhibitor-2 of metalloproteinase (TIMP-2) in high myopic CNV.Methods Seventy-two 2-week-old guinea pigs were randomized into control group (n =36) and high myopia group (n =36).Right eyes were indued form deprivation high myopia for 6 weeks.Thirty guinea pigs were randomly selected in each group,and CNV were induced in the right eyes br the 532 nm laser.MMP-2 and TIMP-2 expressions were investigated by immunohistochemistry pre-laser and 7,14,21,28,35 days after laser induction,respectively,while MMP-2 and TIMP-2 relative expression levels in retinal pigment epithelium (RPE)-choroid-sclera complex were detected by real-time PCR.Integral opitical density (IODs) of positive expression and mRNA relative expression levels of these factors were performed by statistical analyses.Results The expressions of MMP-2 and TIMP-2 were up-regulated in the two groups after laser photocoagulation through immunohistochemistry and real-time PCR examinations.Expression of MMP-2 peaked at 21 d and TIMP-2 at 28 d,respectively.IODs of positive expression and mRNA relative expression levels of MMP-2 were higher in high myopia group than those in control group at each inspective time point,and the differences were statistically significant (P ＜ 0.05).TIMP-2 expression was significantly reduced in high myopia group compared with control group before laser photocoagulation (P＜0,05),while there was no significant difference between the two groups at each time point after laser photocoagulation.Conclusions MMP-2 and TIMP-2 were closely related to the formation of high-myopic CNV.Balance disorders of MMP-2 and TIMP-2 might participate in the occurrence and development of high-myopic CNV.

Quantitative evaluation of anterior chamber angle after laser peripheral iridotomy by spectral-domain anterior segment optical coherence tomography (AS-OCT) / 眼科新进展

Objective To quantitatively assess anterior chamber angle of primary angle-closure glaucoma (PACG) and primary angle-closure (PAC) patients after laser pheripheral iridotomy (LPI) by spectral-domain anterior segment optical coherence tomography (SD-AS-OCT),and investigate which parameters should be used in these patients and the clinical significance of these parameters in screening and follow-ups of glaucoma.Methods Fifty-five eyes of 40 patients diagnosed with PACG remission (11 eyes,8 patients),PAC (20 eyes,20 patients) or PAC suspect (24 eyes,12 patients) were examined.Each eye was examined by SD-AS-OCT at upper,lower,nasal,and temporal sides.Anterior chamber angle (ACA),trabecular iris angle (TIA),and trabecular iris space area (TISA500/750) were measured or calculated.All results were analyzed.Results The points from the inside to the corneal scleral spur 500 μm and 750 pm were selected,AOD,TIA,ACA,TISA at upper,lower,nasal,and temporal sides were measured,which were included into 500 series and 750 series.The mean values of TIA,ACA and AOD in the 500 series and 750 series were the largest in the temporal side and the lowest in the nasal side.The mean values of TISA measurement was the largest in the lower side and the smallest at the upper side.Pearson correlation analysis showed that TIA500 and ACA500 (r =0.799,P =0.00),TIA750 and ACA750 (r =0.799,P =0.00),TIA500 and TISA500 (r=0.919,P =0.00),TIA750 and TISA750 (r =0.920,P =0.00) had positive correlation.With TIA500 as independent variable x and TISA500 as dependent variable y,the regression equation was obtained:y =-0.300 + 0.005x (F =1195,P =0.00),which showed TISA500 and TIA500 were linearly positive correlated.With TIA750 as independent variable x,and TISA750 as dependent variable y,the regression equation was obtained:y =-0.440 + 0.009x (F =854,P =0.00),which showed TISA750 and TIA750 were linearly positive correlated.The coefficient of variation of the 750 series parameters were less than the 500 Series in the four directions.Conclusion SD-AS-OCT is an efficient tool for efficiency evaluation and follow-up during the course of PACG and PAC after LPI.For narrow angles,as the parameters of 750 series parameters have less variability,so 750 series are more recommended in clinical application.

Efficacy of intrathecal injection of vancomycin and dexamethasone in treating refractory purulent meningitis in children / 重庆医学

Objective To observe and investigate the efficacy and safety of combining with intrathecal injection of vancomycin and dexamethasone based on intravenous meropenem for treating refractory purulent meningitis in children.Methods Ninety children cases of refractory purulent meningitis from June 2014 to March 2015 were randomized into the observation group (45 cases) and control group (45 cases) according to the random number table method.The control group was given intravenous meropenem therapy,on this basis the observation group was added with intrathecal injection of vancomycin and dexamethasone.The changes of serum inflammatory markers and clinical efficacies after 7 d treatment were compared between the two groups,and the incidence rate of sequelae in the two groups were recorded after 3-months follow up.Results The descend ranges of TNF-a,CRP and PCT after 7 d treatment in the observation group were (87.3±21.8)pg/mL,(47.9±10.7)mg/L and (348.9J67.3)pg/mL,which were significantly higher than (61.5±18.5)pg/mL,(33.0± 7.9)mg/L,(263.7 ± 61.5)pg/mL in the control group(P＜0.05).There was statistically significant difference in clinical efficacy between the two groups (Z=2.086,P=0.037),the total effective rate in the observation group was 93.3 ％,which was higher than 82.2 ％ in the control group (x2 =2.589,P =0.108);the average treatment duration in the observation group was(12.8 ± 3.9)d,which was significantly less than (16.7 ± 4.7)d in the control group,the difference was statistically significant(t=4.216,P＜0.01).There were no statistically significant differences in the incidence rate of adverse drug reactions and sequelae between the two groups (P＞0.05).Conclusion With intrathecal injection of vancomycin and dexamethasone based on intravenous meropenem therapy for treating purulent meningitis,can further inhibit the inflammatory reaction,and increases clinical efficacy without significantly increasing adverse drug reactions.

Construction of functional and concatenated dimers of two-pore-domain potassium channel TREK-1 / 军事医学

Objective To explore the feasibility of adding a flexible linker between two-pore-domain potassium channel TREK-1 (TWIK related K + channel 1)monomers to construct a tandem-linked dimer.Methods PCR was used to add a flexible linker between the two TREK-1 monomers.The cRNA obtained from in vitro transcription using the above vector was injected into Xenopus oocytes.After 24 -48 h,currents were recorded from these oocytes using a two-electrode voltage clamp.The effects of extracellular Ba2 + and pH on TdTREK-1 were observed and compared with those of native dimeric TREK-1.Results The tandem-linked dimeric TdTREK-1 was highly expressed in Xenopus oocytes.The currents through these channels were inhibited by extracellular Ba2 +and acidification.Furthermore,the responsiveness of the concatenated dimers to these extracellular stimuli was similar to that of native dimers.Conclusion Adding a flexible linker between the two monomers to construct the tandem-linked dimer does not affect the expression and gating properties of TREK-1, suggesting that the method be feasible.Such a method will allow the manipulation of a single subunit,which will help basis study the structure and function of TREK-1.

Effect of clopidogrel on development of chemically induced colitis-associated cancer in mice / 中国药理学与毒理学杂志

OBJECTIVE To investigate the effect of clopidogrel(Clog),a platelet aggregation inhibitor,on the development of colitis-associated colon cancer(CAC)and its possible mechanism. METHODS To establish a CAC model,male BALB/c mice were treated with single azoxymethane(AOM) 10 mg · kg-1 by ip. One week later,the mice drank 2.5% dextran sulfate sodium(DSS)for one week and water for two weeks,which lasted three cycles. From the first day mice received 2.5%DSS water, Clog 12.5,25.0 and 50.0 mg · kg-1 was ig administered once a day. Body mass,clinical symptoms,the number of colon tumor and tumor size in colon tissue were recorded. Hyperplasia of tumors was analyzed by HE staining. In the early inflammatory phase of the CAC model,the length of colons was measured, histological structure and epithelium cell proliferation of colon tissues were evaluated by HE staining and Ki67 staining,respectively. In the tumorigenesis and progression phase of the CAC model,epithe?lium cell proliferation of colon tissues was evaluated by Ki67 staining. The mRNA expression of tumor necrosis factor-α(TNF-α)was detected by real-time quantitative PCR. The expression of chemokine(C-X-C motif)ligand 2(CXCL2)and its receptor 2(CXCR2)in colon tissues was detected by PCR and immu?nohistochemistry. RESULTS Compared with model group,clinical symptoms of mice in Clog 12.5 mg · kg-1 group were alleviated,the size of colon tumors was decreased(P<0.05),and hyperplasia of tumors was reduced(P<0.05). During the inflammatory phase,the clinical symptoms of mice in Clog 12.5 mg·kg-1 group were significantly alleviated(P<0.05),the decrease of body mass was reduced(P<0.01),the colon shrinkage was ameliorated(P<0.01),the inflammatory injury and epithelium cell proliferation in colon tissues were reduced(P<0.05). During the tumorigenesis and progression phase,epithelium cell prolif?eration in colon tissues in Clog 12.5 mg·kg-1 group was reduced(P<0.01),and the mRNA and protein expression of TNF-α,CXCL2 and CXCR2 of colon tissues was decreased(P<0.05). CONCLUSION Clog can alleviate inflammation during the CAC early inflammatory phase and inhibit the formation of CAC. The antitumor effect of Clog may be related to the decrease in expression of CXCL2 and CXCR2.

Influence of Levetiracetam adjunctive therapy on cognitive function and life quality in school-age children with refractory epilepsy / 中国神经精神疾病杂志

Objective To examine the influence of LEV adjunctive treatment on cognitive function and life quality in RE school-age children. Methods Fifty-five cases of RE children were selected from our hospital from June 2013 to December 2015. Based on original treatment all children were added with LEV treatment for 16 weeks. The initial dose was 8~10 mg/(kg·d),and gradually increased to 50 mg/(kg·d). maintenance dose was 30 mg/(kg·d). Adverse drug reac?tions were recorded and clinical efficacies were determined after treatment. Wechsler Intelligence Scale for Children re?vised in China (WISC-CR) and quality of life in children with epilepsy (QOLCE) was used to evaluate children's cogni?tive function and children's life quality, respectvely. Results Average epilepsy attack frequencies after treatment (3.8± 1.3 vs. 6.6±2.3) times/month decreased significantly compared with before treatment (P<0.05). Clinical control ratio, ex?cellent ratio, effective ratio and ineffective ratio after treatment were 9.1%, 36.4%, 43.6%, 36.4%respectively and total effective ratio was 89.1%. The arithmetic score (10.9 ± 2.6 vs. 9.2 ± 2.1) and mapping score (15.1 ± 3.9 vs. 13.8 ± 3.3) in WISC- CR evaluation increased significantly (P<0.05). Life quality score (65.7 ± 5.7 vs. 62.8 ± 4.9) , cognitive function score (60.0 ± 5.7 vs. 57.4 ± 6.2) and social function score (65.0 ± 6.3 vs. 62.5 ± 5.5) after treatment in QOLCE evaluation in?creased significantly (P<0.05). During medication, the incidences of dizziness, fatigue, lethargy, irritability, euphoria and transient aminotransferase elevation were 12.7%, 9.1%, 20.0%, 9.1%, 3.6%and 3.6%respectively. Sixteen week medica?tion retention rate was 96.4%. Conclusion LEV adjunctive treatment can significantly reduce epilepsy attacks and im?prove cognitive function and life quality in RE children, but attention should be paid to LEV's influence on mental behavior.

Computerized optimization of high-performance liquid chromatographic method by using DryLab to test and isolate six cytochrome P450 probe substrates / 国际中医中药杂志

Objective DryLab software was used to assist high performance liquid chromatography (HPLC) method to test and isolate six Cytochrome P450 (CYP450) probe substrates.Methods Six CYP450 probe substrates were selected and the right HPLC method was developed and validated with the assistance of DryLab software.Results The new HPLC method with the assistance of DryLab software could test and isolate six probe substrates with degrees of isolation more than 2.00. The correlation coefficients (R> 0.999 8) indicated high linear correlation between the concentrations and the peak areas among six probe substrates. Recovery studies showed good results for all the probe substrat from 86.38% to 110.29%. And therelative standard deviation (RSD) ranged from 1.69% to 3.80% with its intra-day and inter-day precision ranging from 0.42% to 2.01%, and 1.36% to 2.29%, respectively.Conclusions The developed HPLC method with the assistance of DryLab could test and isolate six probe substrates with shortertime than the HPLC method alone.

Study on Multicomponent Sequential Metabolism in Rats with Chuanxiong Rhizoma / 中国中医药信息杂志

Objective To study the multicomponent in vivo dynamic process in Chuanxiong Rhizoma;To elaborate in vivo metabolic profiling. Methods HPLC was used to establish the fingerprint of aqueous extract of Chuanxiong Rhizoma, and multicomponent changes were detected at the same time. Closed-loop intestine method was used to study the multicomponent changes of oral administration of Chuanxiong Rhizoma after stomach-intestine-liver process. Results Totally 17 components were detected in the fingerprint of aqueous extract of Chuanxiong Rhizoma and they were basically stable in the digestive juice. For in vivo metabolism, 4 components were metabolized by intestinal flora;3 components were metabolized by liver;2 new components were the metabolites of intestinal flora;1 component was the metabolite of liver. Conclusion Multicomponent sequential metabolism and closed-loop intestine method were used to clarify that multicomponent metabolic profiling was feasible, and it could provide experimental basis for the metabolism of traditional Chinese medicine.

The solubility, permeability and their interaction of daidzin and daidzein / 国际中医中药杂志

Objective The alm of this study was to determine the solubility and permeability of daldzin and daldzein and the interaction of these two components.Methods With the method inChinese Pharmacopoeia and in situ single-pass intestinal perfusion model we tested the solubility and permeability of daldzin, daldzein and their interaction.Results In pH 7.4 K-R buffer the solubility of daldzin was 6 times than daldzein and both the solubility of these two components were enhanced when they were determined together. In small intestine of rat, the permeability of daldzein was 3 times than daldzin. Daldzin could enhance the permeability of daldzein but the daldzein manifested an opposite trend.Conclusion When compared to daldzin, daldzein owned a lower solubility but a better permeability. When used together, both the solubility and permeability of daldzein would be enhanced. The solubility of daldzin could be enhanced slightly but its permeability would be reduced.

Development and evaluation of HEK293 cells stably expressing CRFR1 / 中国药理学通报

Aim ToconstructHEK293cellsstablyex-pressing corticotropin releasing factor receptor 1 ( CRFR1 ) , and evaluate its function by the cAMP as-say.Methods CulturedHEK293cellsweretransfect-ed with CRFR1-expressing vector by Lipofectamine 2000 and were selected by using G418 . CRFR1 ex-pression was detected by Western blot, RT-PCR and immunofluorescence.Results Westernblot,RT-PCR and immunofluorescence data revealed that the HEK293 cells expressed CRFR1 protein stably. The dose-responsive relationship experiment revealed that CRF induced a CRFR1-mediated cAMP production in HEK293 cells with EC50 =(5. 64 ± 0. 05) × 10 -10 mol ·L-1.Conclusion HEK293celllinesstablyex-pressing CRFR1 were constructed successfully, which would provide a cellular model to facilitate the research on the biological function of CRFR1 and CRFR1-targe-ted drug screening.

Effects of corticotropin releasing factor on dendritic development of hippocampal neurons / 国际药学研究杂志

Stress exerts profound effects on cognitive and emotional functions. As a regulator of response to stress,the corticotropin releasing factor (CRF) during stress impacts organism function through hypothalamic-pituitary-adrenal axis. Recent research has shown that dendritic branches were abnormal and dendritic spine was lost under stress. In contrast,stressed mice with CRF receptor 1 (CRFR1) deficiency or CRFR1 antagonist exhibited normal dendritic morphology of hippocampal neurons .The structure and related factors expression of hippocampal neurons were affected by CRFR1 as a G protein-coupled receptor(GPCR), but the molecular mechanism about CRF-induced direct injury effect on hippocampal neurons has been poorly understood. The paper reviews the research progress on the contribution of stress activated CRF-CRF receptor signaling to the structure and related factors of hippocampal neurons.

Antitumor activity of erythromycin on human neuroblastoma cell line (SH-SY5Y) / 华中科技大学学报（医学）（英德文版）

Antitumor effects of erythromycin and the related mechanism were investigated in the present study. Neuroblastoma cells (SH-SY5Y) were exposed to erythromycin at different concentrations for different durations. Cell proliferation was measured by cell counting, and cell viability was examined by MTT assay. Cell cycle phase distribution and the cytosolic calcium level were detected by flow cytometry. Mitochondrial membrane potential was measured by the JC-1 probe staining and fluorescent microscopy. The expression of an oncogene (c-Myc) and a tumor suppressor [p21 (WAF1/Cip1)] proteins was analyzed by using Western blotting. Erythromycin could inhibit the proliferation of SH-SY5Y cells in a concentration- and time-dependent manner. The cell cycle was arrested at S phase. Mitochondrial membrane potential collapsed and the cytosolic calcium was overloaded in SH-SY5Y cells when treated with erythromycin. The expression of c-Myc protein was down-regulated, while that of p21 (WAF1/Cip1) protein was up-regulated. It was concluded that erythromycin could restrain the proliferation of SH-SY5Y cells. The antitumor mechanism of erythromycin might involve regulating the expression of c-Myc and p21 (WAF1/Cip1) proteins.

The influence of age on retinal nerve fiber layer thickness in adults / 复旦学报（医学版）

Objective To evaluate the association of age and retinal nerve fiber layer (RNFL) thickness by means of scanning laser polarimetry in a sample of healthy Chinese eyes. Methods One hundred and fifty eyes of 150 healthy subjects underwent RNFL scan in two different modes (Variable Cornea Compensation,VCC;Enhanced Cornea Compensation,ECC) of Glaucoma Diagnosis Variable Cornea Compensation Nerve Fiber Analyzer.The parameters included temporal-superior-nasal-inferior-temporal (TSNIT) average,superior average,inferior average,TSNIT standard deviation,and nerve fiber indicator (NFI). Results Mean values of TSNIT average,superior average,inferior average,TSNIT standard deviation and NFI in VCC mode were (57.12±6.26),(69.35±4.21),(67.59±7.06),(25.46±4.02),(17.35±7.59),while the parameters' values in ECC mode were (56.15±5.32),(68.24±6.63),(66.90±2.40),(24.80±6.76),(18.84±8.51),respectively.The differences between the values of VCC and ECC modes were not statistically significant.The parameters' values of total subjects were associated with age.But there were no significant associations between age and parameter values in the eyes of those older than 40 years old subjects. Conclusions There are no significant differences between the RNFL values detected by VCC and ECC modes in 150 healthy Chinese eyes.Age has influence on RNFL thinning in 21-70 years old healthy eyes,but not in the eyes of older than 40 years old people.

Determination of the retinal nerve fiber layer thickness in diabetic patients with no manifested diabetic retinopathy / 复旦学报（医学版）

Objective To investigate whether there is a thinning of the retinal nerve fiber layer (RNFL) in the eyes of diabetic patients and to analyze the relationship between RNFL thickness and several diabetic risk factors. Methods Forty-two type 2 diabetes mellitus patients aged 47-70 years were enrolled in this study. All the subjects underwent ophthalmologic examinations and glaucoma diagnosis (GDx) nerve fiber analyzer scanning with two different modes: variable cornea compensation (VCC) and enhanced cornea compensation(ECC).The GDx parameters included the temporal-superior-nasal-inferior-temporal average (TSNITave), superior and inferior averages, the TSNIT standard deviation and the nerve fiber indicator (NFI). The receiver operating characteristic (ROC) was applied to study the diagnostic ability of indices. The association between risk factors and the NFI was studied. Results The area under the curve for the ROC of the NFI was the largest for both the ECC and VCC modes. There was a significant relationship between age and RNFL thinning. However, there was no significant association between diabetic duration and fasting blood glucose with RNFL thinning. The influence of age on NFI was greater in diabetic patients than in control subjects. Conclusions Age has an important influence on the NFI of diabetic patients. Diabetic patients with normal ocular fundus may have RNFL thinning.

Advancement in the study of relations between inflammation and dry eye / 复旦学报（医学版）

In the report of the definition and classification subcommittee of the International Dry Eye WorkShop (2007), inflammation was emphasized specially, and anti-inflammation therapy was also included in the treatment recommendations by severity level. Inflammation has been highly valued in the pathogenesis of dry eye recently. The management of dry eye through anti-inflammation therapy is also a hot point in recent years. What is the role of inflammation in the development of dry eye? This article mainly reviews the advancement of the study about their relevance in recent years.

Advances in the study of SR protein family / 基因组蛋白质组与生物信息学报·英文版

The name of SR proteins is derived from their typical RS domain that is rich in serine (Ser, S) and arginine (Arg, R). They are conserved in evolution. Up to now, 10 members of the SR protein family have been identified in humans. SR proteins contain one or two RNA binding motifs aside from the RS domain, and also possess special biochemical and immunological features. As to the functions of SR proteins, they facilitate the recruitment of the components of splicesome via protein-protein interaction to prompt the assembly of early splicesome; while in alternative splicing, tissue-specifically expressed SR protein along with the relative ratio of SR protein and heterogeneous nuclear ribonucleoprotein (hnRNP) is composed of two main regulative mechanisms to alternative splicing. Almost all of the biochemical functions are regulated by reversible phosphorylation.