PTPRN mediates endocytosis of NaV1.2 sodium chan-nels and suppresses epileptogenesis in mice / 中国药理学与毒理学杂志

Epilepsy is a disorder of the brain charac-terized by abnormal neuron excitability.However,the underlying molecular mechanism of neuron excitability modulation remains elusive.With the help of bioinformatic methods,we have identified receptor-type tyrosine-pro-tein phosphatase-like N(PTPRN)as a critical gene dur-ing epileptogenesis.PTPRN recruits NEDD4L ubiquitin E3 ligase to NaV1.2 sodium channels,facilitating NEDD4L-mediated ubiquitination and endocytosis.Knockout of PTPRN endows hippocampal granule cells with augmented depolarization currents and higher intrinsic excitability,which is reflected by increased seizure susceptibility of transgenic mice.On the contrary,reduced neuron excit-ability and decreased seizure susceptibility are observed after PTPRN overexpression.Meanwhile,we find that a 133 aa fragment recaptures modulation effect of PTPRN full-length,and this fragment shows therapeutic potential towards epilepsy caused by NaV1.2 gain of function vari-ants.In brief,our results demonstrate PTPRN playsa criti-calroleinregulatingneuronexcitability,providing a poten-tial therapeutic approach for epilepsy.

Research progress on new operational quantities and the effects in area dose monitoring / 中国辐射卫生

@#Operational quantities, which are used to estimate protection quantities in the field of radiation protection, are important in area monitoring. The current operational quantities show certain limitations as the particle types and energy ranges are expanded. The International Commission on Radiation Units and Measurements Report 95 proposed a new system of operational quantities, where the definitions and phantoms of the operational quantities are consistent with the protection quantities, enabling better estimation of the protection quantities over wider ranges of particle types and energies. This paper focuses on the effects of the new recommended operational quantity system in area monitoring from the aspects of phantom application, conversion coefficient updating, and monitor design and calibration.

Effect of DC vaccine sensitized with CpG ODN combined with tumor antigen on murine melanoma / 药学学报

The potential application of dendritic cells (DC) sensitized with cytosine-phosphoric acid-guanine (CpG) oligodeoxynucleotide (ODN) and tumor antigen as a vaccine against murine melanoma was investigated with freshly isolated mouse bone marrow-derived dendritic cells. For the DC vaccine preparation, DC were sensitized with the B16 tumor antigen and CpG ODN was used to promote further maturation of the DC. The immunogenic activity of the vaccine was evaluated in vitro by determining the proliferation of T lymphocytes and the killing effect of cytotoxic T lymphocytes (CTL) on B16 tumor cells. The DC vaccine was injected intraperitoneally and tumor inhibition in mice bearing B16 xenografts was examined. All mice were cared for under an approved SIMM Institutional Animal Care and Use Committee (IACUC) protocol. In vitro, this DC vaccine promoted the proliferation of T lymphocytes and showed a potent killing effect on the target B16 cells. In vivo experiments showed that after treatment or pre-immunization both the tumor volume and weight were significantly decreased. The DC vaccine with CpG ODN and tumor antigen exhibited an inhibitory effect against melanoma, providing a potential method for melanoma cancer treatment.

Peak skin dose measurements for patients in neuro-interventional procedures using radiochromic film / 中华放射医学与防护杂志

Objective:To determine the peak skin dose (PSD) to patients from neuro-interventional procedures and evaluate the risk of the deterministic effect.Methods:Gafchromic XR RV3 films were used in a level A tertiary hospital in Beijing to measure the patients′ PSD from neuro-interventional procedures, mainly three common types of procedures, including vascular embolization, vascular angioplasty and vascular angiography. The films were scanned by Epson Expression 10000XL, read by ImageJ software, and analyzed by Film QA Pro?2014 software.Results:PSD was measured in 23 embolizations, 14 stentings and 12 arteriography. There were 20 patients whose PSD were equal or greater than 2 Gy, including 15 in vascular embolization and 5 in angioplasty. The PSDs to patients in cerebral arteriography were all below 2 Gy. The PSDs to some of the patients were higher than the threshold for deterministic effect recommended by ICRP Publication 118.Conclusions:There is a risk of deterministic effect in neurointerventional procedures. It is suggested that the patients be followed up to observe their radiation injury as well as to know in time the subsequent diagnosis and treatment.

Identification of PD-1 small molecule inhibitors and validation in Panax ginseng / 药学学报

Tumor immune therapy has been remarkably successful in recent years and several kinds of PD-1/PD-L1 (programmed death-1/programmed death-ligand 1) antibody drugs have been approved by the FDA for treatment of advanced malignant neoplasms. However, as biomacromolecules these antibody drugs have certain drawbacks such as high cost, injection-only administration and immunogenicity; thus, we turned to small molecules that have lower immune risks and better modifiability. Considering the structural diversity of natural products, we chose to investigate the active components in Panax ginseng, a famous and highly valued traditional Chinese medicine. Nine compounds were separated and identified in this research using a HPLC-coupled MS system, and 3 PD-1 binding compounds were identified using the SPR method. The PD-1/PD-L1 inhibitory ability of ginsenoside Rg1, as a representative ginsenoside, was verified by cytopharmacological methods. This research provides a new method for the identification of immune blockade inhibitors in natural products.

Chronic phosphoproteomic in temporal lobe epilepsy mouse models induced by kainic acid / 北京大学学报(医学版)

OBJECTIVE@#To investigate functions of proteins and signaling pathways involved in epileptogenesis during the chronic stage of temporal lobe epilepsy in mouse models.@*METHODS@#Kainic acid-induced temporal lobe epilepsy models were conducted, when reaching stage 4 using racine scale, the mice of experimental group were supposed to be successfully established. Pentobarbital sodium was injected to stop epileptic seizure in case of death. Twenty-eight days after the kainic acid injection, when the experimental group generally turned into chronic spontaneous seizures, mice hippocampal tissues were extracted from the control and the experimental groups respectively for phosphoproteomic. Enriched phosphorylated proteins were detected using mass spectrometry, only the proteins whose density was greater than 106 were analyzed by matching the Gene Ontology (GO) database, Kyoto Encyclopedia of Genes and Genomes (KEGG) database and STRING database to detect proteins involved in epileptogenesis in protein functions, signaling pathways and protein-protein interaction respectively. After that, literatures were reviewed about the key proteins.@*RESULTS@#(1) Total of 12 697 phosphorylation sites of enriched proteins were detected by mass spectrometry, and there were 159 sites whose phosphorylation levels were significantly different from the control (P<0.001). (2) GO database showed that 35.7% of the 159 sites were about "catalytic activity", 39.5% were about "binding" and 20.8% were about "cell communication", and the 159 proteins also participated in many biological processes, such as "primary metabolic process" "response to stimulus" "developmental process" "localization" and "phosphate-containing compound metabolic process". (3) KEGG database showed that the 159 protein sites mainly involved in 10 signaling pathways: glutamatergic synapse, Ras signaling pathway, African trypanosomiasis, Cocaine addiction, Circadian entrainment, Amyotrophic lateral sclerosis (ALS), Long-term potentiation, Endocytosis, Gap junction, Nicotine addiction. (4) STRING database showed that the protein-protein interaction network formed by the 159 proteins was focused on Grin1/Dlg3, Arhgef 2/Arhgap33/Tiam1 and Sptnb1/3/4/Add3/Ank2 protein group respectively. (5) Phosphorylation levels of Grin1, Arhgef 2, Arhgap33, Tiam1, Sptbn1/2/4 and Ank2 in experimental group were significantly higher than in the control (P<0.001).@*CONCLUSION@#Phosphoproteomic illustrated integral distribution of phosphorylated proteins at the chronic stage of temporal lobe epilepsy in the mouse model. Literatures showed that most key proteins were closely related to epileptogenesis, suggesting that some proteins or signaling pathways may play a role in epileptogenesis, such as dopamine and Kir3.1.

Investigation on the relationship between the measured dose vs. the displayed dose in CT examinations for children / 中国医学装备

Objective: To establish the relationship between the measured dose and the displayed dose in CT scans for children, and assess whether the displayed dose could be used as the basis to monitor the actual dose so as to provide data support for establishing a fast estimation method of actual dose in CT examination for children. Methods: The CT equipments with 16 slices detectors and 64 slices detectors of two manufacturers that often were used in clinical practice were selected in the research. CT dosage phantom that suited to children was used and pencil-ionization chamber was adopted to measure CT dose indexes of head scan and breast scan for children under various scan parameters. At the same time, displayed dose of the equipment was recorded and the ratio of measured dose and displayed dose was calculated . Results: The measured doses of the two manufacturers for head of children were 1.30-1.39 times and 1.17-1.26 times of displayed dose, respectively. And on thorax sequence, the measured doses were 1.95-2.27 times and 1.75-1.97 times of displayed dose, respectively. Based on above results, the measured dose of head was more close to the displayed dose than that of thorax sequence. Conclusion: In the CT examination of children, the ratio of measured dose to displayed dose shows good consistency under the different exposure conditions of same CT device model, and thus provides possibility to rapidly estimate the real dose on children according to the displayed dose in CT examinations.

Effect of auxiliary radiological protective devices on reducing dose to the eye lens of interventional staff / 中华放射医学与防护杂志

Objective To establish a method for reducing the dose to the eye lens of interventional staff,and provide the data basis for improving radiological protection measures.Methods One piece of interventional equipment coupled with conventional auxiliary protective devices and two types of common neural interventional procedures were selected to monitor 46 and 35 procedures before and after the device modification.The doses to the eye lens of staff were measured with direct-reading dosimeters for analysis of dose trends.Results After modification of the devices,the average dose to the left eye lens decreased from (9.71 ±10.86) to (3.23 ±5.59) μSv for the first operator,from (9.51 ± 12.34) to (0.68 ± 0.78) μSv for the second in cerebral angiography;whereas the dose decreased from (14.83 ± 19.13) to (4.17±4.59) for the first operator and from (14.12±21.76) to (1.23 ±1.57)μSv for the second in embolization procedure,respectively.The left eye lens doses measured before and after the modification showed significant difference (U =-2.760,-2.467,-1.967,-2.655,P ＜0.05).Conclusions The modification of the auxiliary radiological protective devices may effectively reduce the dose to the eye lens dose.This method was shown to be feasible for the improvement of radiological protection of interventional staff.

Phenylpropanoids from Daphne aurantiaca / 中草药

Objective: To study the phenylpropanoids from Daphne aurantiaca. Methods: The constituents were separated by column chromatography, their structures were elucidated by spectral data analyses. Results: Thirteen phenylpropanoids were isolated from the EtOAc extract and were identified as caffeic acid tricosyl ester (1), caffeic acid eicosanyl ester (2), caffeic acid nonadecyl ester (3), caffeic acid octadecyl ester (4), caffeic acid heptadecyl ester (5), caffeic acid hexadecyl ester (6), caffeic acid tetradecyl ester (7), caffeic acid dodecyl ester (8), caffeic acid undecyl ester (9), caffeic acid isopentyl ester (10), ferulic acid (11), 3, 4-dimethoxy-cinnamaldehyde (12), and caffeic alcohol (13). Conclusion: The compounds are obtained from this plant for the first time.

Study of real-time measurements of occupational staff's eye lens doses by direct-reading dosimeters in interventional procedures / 中华放射医学与防护杂志

Objective To establish the methods for measuring the dose to occupational staff's eye lens in interventional procedures with direct-reading dosimeters,and to realize the real-time monitoring of eye lens dose and warning for high dose rate,thus providing the scientific basis of the staff radiological protection in interventional procedures.Methods Direct-reading dosimeters were calibrated with personal dose equivalent HP (3).The eye lens doses for occupational staff in different kinds of interventional procedures were measured by the devices with both single-and double X-ray tubes.The data obtained fromthe direct-reading dosimeters was compared to those obtained from TLDs.Results Direct-reading dosimeters showed good linear fitting with the calibration of HP (3),and the coefficients of variation were lower than 5％.The average eye lens HP (3) for the main operator in coronary arteriography and stent implantation in brain obtained by direct-reading dosimeters were 12.0 and 24.5 μSv,respectively,whereas those obtained by TLDs were 11.9 and 22.7 μSv,respectively.The direct-reading dosimeters gave similar t~nds as TLDs do so.The direct-reading dosimeters were able to provide eye lens HP (3) in each individual interventional procedure,and to monitor the real-time dose rate as well.Conclusions The calibration of HP (3) and the data gained by direct-reading dosimeters are reliable.Therefore,the methods for real-time measurement of eye lens dose for occupational staff in interventional procedures are successfully established.

The measurements of eye lens dose for occupational staff in interventional procedures / 中华放射医学与防护杂志

Objective To establish methods of measuring the eye lens dose to interventional staff,to obtain relevant dose data and to provide a scientific basis for reducing eye lens dose.Methods Two kinds of dosimeters,thermoluminescent dosimeter (TLD) and optically stimulated luminescence dosimeter (OSLD),were selected to measure the personal dose equivalent HP (3) to eye lens of occupational staff in several kinds of interventional procedures,including cardiovascular interventional procedures,cerebrovascular interventional procedures etc.Five types of Digital Subtraction Angiography (DSA) equipment were chosen in the study,including single tube equipment and double tube equipment.Results The eye lens dose HP (3) to interventional staff varied significantly with different interventional procedures.The lowest dose is shown in the coronary angiography procedure,while the highest dose shown in the cerebral stenting procedure.For the same type of interventional procedure,the eye lens dose to the primary interventionist was the highest.For same interventionist,the dose to the left eye was obviously higher than that to the right eye.In addition,the measured results of OSLD were apparently higher than that of TLD.Conclusions Both TLD and OSLD could be used to measure eye lens dose,and the ways of calibrating TLD to evaluate personal dose equivalent HP (3) were feasible.The reason of significant difference between the measured results of TLD and OSLD needs further research.

Impact on postoperative outcomes after red blood transfusion in coronary artery bypass graft surgey: a meta-analysis of current evidence / 中华胸心血管外科杂志

Objective To systemically assess impact on postoperative outcomes after red blood cell transfusion(RBCT) in coronary artery bypass graft surgey.Methods A meta-analysis was performed on the comparison and synthesis of findings from included studies published from January 1980 to January 2014.Pooled odds ratio(OR) and 95 ％ confidence interval(CI) were calculated using RevManS.3 software.Sensitivity analysis was conducted and possible publication bias was tested as well.Results Seven retrospective studies including 71 228 patients(33 872 RBCT cases,37 356 control cases) were eligible for inclusion.The pooled analysis revealed difference in the 30-day mortality OR =1.85 (95％ CI:1.35-2.54),1-year mortality OR =2.02 (95 ％ CI:1.44-2.84),shock OR =2.92 (95 ％ CI:1.96-4.35),renal dysfunction OR =7.67 (95 ％ CI:1.44-40.94),mediastinitis OR =2.26 (95 ％ CI:1.72-2.97),and myocardial infarction OR =3.53 (95 ％ CI:2.89-4.29).Conclusion Perioperative RBCT can incresase the risk of postoperative mortality and complications in coronary artery bypass graft surgey.High-quality randomized case cohort studies are still needed for the further proof of the risk.

Chemical constituents from Ganoderma philippii / 中国中药杂志

The chemical investigation on Ganoderma philippii led to the isolation of sixteen compounds by silica gel and Sephadex LH-20 column chromatography. On the basis of spectroscopic data analyses, their structures were elucidated as 2, 5-dihydroxyacetophenone (1), methyl gentisate (2), (S) -dimethyl malate (3), muurola-4, 10 (14) -dien-11beta-ol (4), dihydroepicubenol (5), 5-hydroxymethylfuran carboxaldehyde (6), ergosta-7, 22E-dien-3beta-ol (7), ergosta-7, 22E-dien-3-one (8), ergosta-7, 22E-diene-2beta, 3alpha, 9alpha-triol (9), 6/beta-methoxyergo-sta-7, 22E-dien-3beta, 5alpha-diol (10), ergosta-4, 6, 8(14), 22E-tetraen-3-one (11), ergosta4, 6, 8-(14), 22E-etetraen-3beta-ol (12), 5alpha, 8alpha-epidioxy-ergosta-6, 22E-dien-3beta-ol (13), 7alpha-methoxy-5alpha, 6alpha-epoxyergosta-8-(14), 22E-dien-3beta-ol (14), ergosta-8, 22E-diene-3beta, 5alpha, 6beta, 7alpha-tetraol (15), and ergosta-5, 23-dien-3beta-ol, acetate (16). All the compounds were obtained from this fungus for the first time, and compounds 4 and 5 were isolated from the Ganoderma genus for the first time.

Cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy / 药学学报

To develop a cell-penetrating chimeric apoptotic peptide AVPI-LMWP/DNA co-delivery system for cancer therapy, we prepared the AVPI-LMWP/pTRAIL self-assembled complexes containing a therapeutic combination of peptide drug AVPI and DNA drug TRAIL. The chimeric apoptotic peptide AVPI-LMWP was synthesized using the standard solid-phase synthesis. The cationic AVPI-LMWP could condense pTRAIL by electrostatic interaction. The physical-chemical properties of the AVPI-LMWP/pTRAIL complexes were characterized. The cellular uptake efficiency and the inhibitory activity of the AVPI-LMWP/pTRAIL complexes on tumor cell were also performed. The results showed that the AVPI-LMWP/pTRAIL complexes were successfully prepared by co-incubation. With the increase of mass ratio (AVPI-LMWP/DNA), the particle size was decreased and the zeta potential had few change. Agarose gel electrophoresis showed that AVPI-LMWP could fully bind and condense pTRAIL at a mass ratio above 15:1. Cellular uptake efficiency was improved along with the increased ratio of W(AVPI-LMWP)/WpTRAIL. The in vitro cytotoxicity experiments demonstrated that the AVPI-LMWP/pTRAIL (W:W = 20:1) complexes was significantly more effective than the pTRAIL, AVPI-LMWP alone or LMWP/pTRAIL complexes on inhibition of HeLa cell growth. Our studies indicated that the AVPI-LMWP/pTRAIL co-delivery system could deliver plasmid into HeLa cell and induce tumor cell apoptosis efficiently, which showed its potential in cancer therapy using combination of apoptoic peptide and gene drugs.

Wikstroelide M potently inhibits HIV replication by targeting reverse transcriptase and integrase nuclear translocation / 中国天然药物

AIM@#To evaluate the anti-HIV activity and mechanism of action of wikstroelide M, a daphnane diterpene from Daphne acutiloba Rehder (Thymelaeaceae).@*METHODS@#The anti-HIV activities of wikstroelide M against different HIV strains were evaluated by cytopathic effect assay and p24 quantification assay with ELISA. The inhibitory effect of wikstroelide M on HIV reverse transcription was analyzed by real-time PCR and ELISA. The effect of wikstroelide M on HIV-1 integrase nuclear translocation was observed with a cell-based imaging assay. The effect of wikstroelide M on LEDGF/p75-IN interaction was assayed by molecular docking.@*RESULTS@#Wikstroelide M potently inhibited different HIV-1 strains, including HIV-1IIIB, HIV-1A17, and HIV-19495, induced a cytopathic effect, with EC50 values ranging from 3.81 to 15.65 ng·mL⁻¹. Wikstroelide M also had high inhibitory activities against HIV-2ROD and HIV-2CBL-20-induced cytopathic effects with EC50 values of 18.88 and 31.90 ng·mL⁻¹. The inhibitory activities of wikstroelide M on the three HIV-1 strains were further confirmed by p24 quantification assay, with EC50 values ranging from 15.16 to 35.57 ng·mL⁻¹. Wikstroelide M also potently inhibited HIV-1IIIB induced cytolysis in MT-4 cells, with an EC50 value of 9.60 ng·mL⁻¹. The mechanistic assay showed that wikstroelide M targeted HIV-1 reverse transcriptase and nuclear translocation of integrase through disrupting the interaction between integrase and LEDGF/p75.@*CONCLUSION@#Wikstroelide M may be a potent HIV-1 and HIV-2 inhibitor, the mechanisms of action may include inhibition of reverse trascriptase activity and inhibition of integrase nuclear translocation through disrupting the interaction between integrase and LEDGF/p75.

Chemical constituents from Daphne acutiloba / 中国中药杂志

<p><b>OBJECTIVE</b>To study the chemical constituents from Daphne acutiloba.</p><p><b>METHOD</b>The constituents were separated by column chromatography, and their structures were elucidated by spectroscopic data analyses.</p><p><b>RESULT</b>Fifteen compounds were isolated from the EtOAc extract and identified as wikstroelide M (1), vesiculosin (2), prostratin (3), 7-hydroxy-coumarin (4), 7,8-di-hydroxy-coumarin (5), isodaphnoside (6), daphnorine (7), rutamontine (8), daphnolin (9), daphneticin (10), (+)-pinoresinol-beta-D-glucoside (11), oleodapnone (12), oleodaphnal (13), ergosterol peroxide (14) and cholest-5-en-3beta-ol (15).</p><p><b>CONCLUSION</b>All the compounds except for 4, 5 and 14 were obtained from the stems of this plant for the first time.</p>

Outcomes of patients with combined methylmalonic acidemia and homocystinuria after treatment / 中华儿科杂志

<p><b>OBJECTIVE</b>Combined methylmalonic acidemia with homocystinuria is a common form of methylmalonic acidemia in China. Patients with this disease can progress to death without timely and effective treatment. This study aimed to analyze the treatment outcomes of patients with combined methylmalonic acidemia and homocystinuria.</p><p><b>METHOD</b>From September 2004 to April 2012, 58 patients with combined methylmalonic acidemia and homocystinuria (34 males and 24 females) were diagnosed and treated in our hospital. Fifty cases were from clinical patients including 42 early-onset cases and 8 late-onset cases. Their age when they were diagnosed ranged from 18 days to 30.8 years. The other 8 cases were from newborn screening. All the patients were treated with vitamin B12, betaine, folic acid, vitamin B6, and L-carnitine. The physical and neuropsychological development, general laboratory tests, the levels of amino acids, acylcarnitines, and homocysteine in blood, and organic acids in urine were followed up.</p><p><b>RESULT</b>The follow-up period ranged from 1 month to 7.1 years. Three cases died (all were early-onset cases). In the other patients after treatment, the symptoms such as recurrent vomiting, seizures, lethargy, and poor feeding disappeared, muscle strength and muscle tension were improved, and general biochemical abnormalities such as anemia and metabolic acidosis were corrected. Among the surviving 55 cases, 49 had neurological impairments such as developmental delay and mental retardation. The median levels of blood propionylcarnitine and its ratio with acetylcarnitine, serum homocysteine, and urine methylmalonic acid were significantly decreased (P < 0.01), from 7.73 µmol/L (ranged from 1.5 to 18.61 µmol/L), 0.74 (ranged from 0.29 to 2.06), 97.3 µmol/L (ranged from 25.1 to 250 µmol/L) and 168.55 (ranged from 3.66 to 1032.82) before treatment to 2.74 µmol/L (ranged from 0.47 to 12.09 µmol/L), 0.16 (ranged from 0.03 to 0.62), 43.8 µmol/L (ranged from 17 to 97.8 µmol/L) and 6.81 (ranged from 0 to 95.43) after treatment, respectively.</p><p><b>CONCLUSION</b>Patients with combined methylmalonic acidemia and homocystinuria respond to a combined treatment consisting of supplementation of hydroxycobalamin, betaine, folic acid, vitamin B6 and L-carnitine with clinical and biochemical improvement. But the long-term outcomes are unsatisfactory, with neurological sequelae in most patients.</p>

Biflavans or biflavons from stems of Daphne acutiloba / 中草药

Objective: To study the chemical constituents from the stems of Daphne acutiloba. Methods: The constituents were separated by column chromatography and their structures were elucidated by spectral data analyses. Results: Fourteen biflavans or biflavons were isolated from the EtOAc fraction of 95% ethanol reflux extract in the stems of D. acutiloba and were identified as daphnodorin A (1), daphnodorin C (2), daphnodorin C' (3), daphnodorin F (4), daphnodorin E (5), wikstrol A (6), daphnodorin K (7), iso-chamaejasmin (8), (+)-chamaejasmin (9), daphnodorin D1 (10), daphnodorin H (11), 3-methoxyl daphnodorin H (12), daphnodorin K' (13), and daphnodorin B (14). Conclusion: All the compounds except 14 are obtained from the stems of this plant for the first time.

Effects of rosiglitazone on the IMTc and serum MMP-9 levels in newly diagnosed type 2 diabetic patients / 中南大学学报(医学版)

OBJECTIVE@#To investigate the change of carotid intima-media thickness (IMTc) and serum matrix metalloproteinases-9 (MMP-9) levels in newly diagnosed Type 2 diabetic patients, and to analyze the relationship between MMP-9 and IMTc; at the same time, to assess the effect of rosiglitazone on IMTc and MMP-9 levels.@*METHODS@#Fifty-eight patients with Type 2 diabetes mellitus were selected in our study, and 25 healthy adults served as normal controls. Diabetic patients were divided into 2 groups: Group A (31 subjects) were treated with rosiglitazone (4 mg/d), and Group B (27 subjects) were treated with metformin alone (500 approximately 1,500 mg/d). They all received the treatment for 3 months. The IMTc was measured by high resolution ultrasonography, and the serum MMP-9 was determined by enzyme linked immunosorbent assay (ELISA) to assess the relationship between IMTc and MMP-9.@*RESULTS@#The mean level of serum IMTc and MMP-9 in Type 2 diabetic patients was significantly higher than that in healthy adults (P < 0.05). After treatment with rosiglitazone and metformin, IMTc and serum MMP-9 levels decreased significantly (P < 0.05). There was no obvious change in IMTc and serum MMP-9 levels in group B before and after the treatment (P = 0. 071, P = 0.065). Using multiple linear stepwise regression analysis, the significant correlation between IMTc and HbA1C, BMI, WHR, HDL-C, MMP-9 were discovered.@*CONCLUSION@#IMTc and MMP-9 levels increase in newly diagnosed Type 2 diabetic patients, suggesting that there is closely relationship between serume MMP-9 levels and early diabetic macrovascular disease. IMTc and MMP-9 can be reduced significantly in the newly diagnosed diabetic patients after being treated with rosiglitazone, which may be one of the protective mechanisms of vascular vessels.

Effect of plasma glucose on the vascular endothelial function and analysis of relevant factors / 中南大学学报(医学版)

OBJECTIVE@#To compare the flow-mediated dilatation (FMD) among the newly diagnosed impaired glucose tolerance (IGT), type 2 diabetes mellitus (T2DM), and the normal controls (NC) and to analyze relevant factors under different glucose levels.@*METHODS@#The study included IGT (n=34), DM1 (n=52), DM2 (n=33) and NC (n=25). Levels of fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (PPG), fasting insulin (FINS), 2-hour postprandial insulin (PINS), triglyceride (TG), total cholesterol (TC), and hemoglobin A1C (HbA1C) were determined in all participants. High resolution ultrasound examining FMD was performed to measure vascular endothelial function subsequently.@*RESULTS@#There was statistically significant difference between IGT, DM, HG and NC group in FMD (P=0.008). Partial correlation analysis found that a significant negative correlation existed between FMD and homeostasis model assessment-index (HOMA-IRI), difference of plasma glucose (DPG), FPG and PPG (P<0.01), and a negative correlation between FMD and HbA1C (P<0.05). Setting FMD as dependent variable to conduct multiple linear stepwise regression, in IGT group it was the waist/hip ratio (WHR) and HOMA-IRI that entered the regression equation; in DM1 group it was HOMA-IRI, PPG and DPG that entered the regression equation; in DM2 group it was FPG and HOMA-beta that entered the regression equation.@*CONCLUSION@#There exists a flow-mediated vasodilatation dysfunction in patients of newly diagnosed IGT and T2DM. Effect of relevant factors on FMD differs with different glucose levels.