Implication of epigenetic factors in the pathogenesis of type 1 diabetes / 中华医学杂志(英文版)

Type 1 diabetes (T1D) is an autoimmune disease that resulted from the severe destruction of the insulin-producing β cells in the pancreases of individuals with a genetic predisposition. Genome-wide studies have identified HLA and other risk genes associated with T1D susceptibility in humans. However, evidence obtained from the incomplete concordance of diabetes incidence among monozygotic twins suggests that environmental factors also play critical roles in T1D pathogenesis. Epigenetics is a rapidly growing field that serves as a bridge to link T1D risk genes and environmental exposures, thereby modulating the expression of critical genes relevant to T1D development beyond the changes of DNA sequences. Indeed, there is compelling evidence that epigenetic changes induced by environmental insults are implicated in T1D pathogenesis. Herein, we sought to summarize the recent progress in terms of epigenetic mechanisms in T1D initiation and progression, and discuss their potential as biomarkers and therapeutic targets in the T1D setting.

Effects of Genipin on the expression of uncoupling protein 1 in brown adipose and white adipose tissues in mice / 中国应用生理学杂志

OBJECTIVE@#To investigate the effects of genipin on promoting brown adipose tissue activation and white adipose tissue browning.@*METHODS@#The male C57BL/6J mice were divided into three groups: normal control group, genipin group and cold-stimulus group.Genipin group were treated consecutively with genipin at a dose of 15 mg/kg once a day for 9 days, normal control group were treated with the saline.The mice with cold-stimulus were exposed to 4℃ environment for 5 days.Daily food amount and body weight were measured.Morphological changes were observed in the subscapular region, inguinal region and epididymis around the adipose tissue.The expression of uncoupling protein 1 (UCP1) was determined by real-time PCR and Western blot respectively.@*RESULTS@#The wet weight of white fat in genipin-treated mice was decreased by 16% , and 28% in that of cold-stimulus mice, compared with the normal control group (P＜0.05).After treatments of genipin and cold-stimulus, the color of white adipose tissues was darker, and the size of lipid droplets in adipocytes was smaller, whereas the number was increased.Compared with the normal control group, UCP1 expression was increased obviously in fat tissues, including the subcutaneous and visceral white adipose tissues, and brown adipose tissue after treated with genipin and cold-stimulus (P＜0.05).@*CONCLUSION@#Genipin promoted activation of brown adipose tissue and browning of white adipose tissue by upregulating UCP1 expression, which could contribute to the loss of body weight against obesity.

Non-Hodgkin's lymphoma in the jaw: A report of 3 cases and literature review / 中南大学学报(医学版)

To investigate the clinical manifestations, imaging features, and diagnosis for non-Hodgkin's lymphoma in the jaw, we retrospectively analyzed 3 cases of non-Hodgkin's lymphoma in the jaw and reviewed relevant literature. Three patients' lesion occurred in the maxilla with early painless masses. Two patients were diagnosed as diffuse large B-cell lymphoma via biopsy, and one patient underwent maxillofacial resection with pathological examination which showed plasmaoblastoma lymphoma. Non-Hodgkin's lymphoma in the maxilla is rare and easily misdiagnosed due to the atypical clinical features. Biopsy at the early stage of the lesion and pathological examination can assist the diagnosis for non-Hodgkin's lymphoma.

Investigation on patient safety culture in standardized training for resident doctors / 中华医学教育探索杂志

Objective To investigate the cognition on patient safety culture of resident doctors re-ceiving standardized training in two affiliated hospitals, analyze the effectiveness of publicity and education in patient safety culture and put forward suggestions for improvements. Methods A total of 913 resident doctors receiving standardized training in the two affiliated hospitals during 2014 to 2016 were enrolled. Their cognition on patient safety culture were investigated using questionnaire surveys from May to October in 2016, and the main factors influencing the cognition on patient safety culture in standardized training were put forward through expert interviews. All statistical analyses were performed with SPSS 17.0 software with Chi-square test. Results The response rate of the questionnaire was 87.62％ (800/913). Three factors were involved in the patient safety system, including the hospital security objectives, security feedbackchannels, and adverse event warning mechanism. The cognitiive level of A hospital (68.96％, 62.52％, 62.81％) was higher than that of B hospital (52.99％, 46.16％, 47.01％), and the difference was statistically significant (P<0.05). The publicity of pre-service training, education in the department, and encouragement from teachers (82.13％, 84.48％, 78.33％) was better in A hospital than in B hospital (68.38％, 71.8％, 62.39％) (P<0.05). The reporting rate of adverse events in A hospital was higher than that in B hospital (P <0.05). Conclusion It is necessary for hospitals to further intensify the publicity and education on patient safety culture. We can improve students' cognition on patient safety culture to reduce medical errors by cre-ating a favorable atmosphere, establishing standardized admission education and training system, improving teachers' teaching ability, and strengthening the training for clinical skills.

Association of Polymorphisms in CAV1/CAV2 Locus with Type 2 Diabetes in Chinese Han Population / 中山大学学报(医学科学版)

[Objective]To study the association of CAV1/CAV2 gene polymorphisms with type 2 diabetes in Chinese Han population.[Methods]14 single nucleotide polymorphisms(SNPs)of CAV1/CAV2 gene were genotyped in 272 pa-tients with type 2 diabetes mellitus(T2DM group)and 287 subjects with normal glucose tolerance(control group)by ma-trix-assisted laser desorption ionization-time of flight-mass spectrometry(MALDI-TOF-MS).Waist circumference,body mass index,plasma glucose,serum insulin and lipid profiles were measured.Homeostatic model assessment of insulin resis-tance(HOMA-IR)and β-cell function(HOMA-β)were calculated.[Results]The minor allele frequency(MAF)distri-butions of CAV1 rs926198,CAV2 rs2270188,and rs1052990 were significantly different between T2DM group and con-trol group(P=0.008,0.021,and 0.045,respectively). After adjusting for age,gender,and BMI,logistic regression analysis showed that minor allele carriers(CC/CT genotype)of CAV1 rs926198 displayed a particularly increased risk of developing T2DM compared to major allele homozygotes(TT genotype)(OR=2.240,95% CI=1.415-3.544,P=0.001). GG/GA genotype carriers of CAV1 rs3807986 had lower odds for T2DM than that of AA genotype(OR=0.640,95% CI=0.449-0.913,P=0.014). Compared with TT genotype,GG/GT genotype of CAV2 rs2270188 was a protective factor for T2DM(OR=0.616,95% CI=0.432-0.878,P=0.007). Significant genotype association with T2DM was also identified in CAV2 rs1052990(GG/GT versus TT genotype:OR=0.658,95% CI=0.453-0.956,P=0.028). Multiple linear regression showed that minor allele C of SNP rs926198 was associated with an increased level of HOMA-IR(beta=1.010,P<0.001) and minor allele G of SNP rs2270188 was associated with a decreased level of HOMA-IR(beta=-0.379,P=0.023). No significant association was identified between any SNP and HOMA-β.Allele G of CAV1 rs3807986 and CAV2 rs2270188 were also associated with a decreased level of LDL-C(P=0.033 and 0.030,respectively).[Conclusion]CAV1/CAV2 locus might be the candidate genes for conferring susceptibility to T2DM in the Chinese Han population.SNP rs926198, rs3807986,rs2270188,and rs1052990 in CAV1/CAV2 locus were associated with T2DM risk perhaps through insulin resistance pathway.

Application of Real-time Quantitative PCR in Detecting Atypical BCR/ABL mRNA Transcripts in Chronic Myelocytic Leukemia / 中国实验血液学杂志

<p><b>OBJECTIVE</b>To detect atypical BCR/ABL mRNA transcript by real-time quantitative PCR in CML patients without e13a2/e14a2,e19a2 or e1a2 transcripts, and investigate its value of clinical application.</p><p><b>METHODS</b>Twelve cases of CML with positive for t(9;22) translocation, but negative for common major and minor breakpoint cluster regions comfirmed by chromosome karyotyping or FISH analysis, were collected from July 2012 to December 2015. These 12 cases were then detected for b2a3(e13a3), b3a3(e14a3), e6a2, e8a2 and e1a3 fusion variants by real-time quantitative PCR.</p><p><b>RESULTS</b>Among 12 cases 4 variant transcripts were detected, including e1a3 in 1 case (8.33%), e8a2 in 2 cases (16.67%), b2a3 in 5 cases (41.67%) and b3a3 in 4 cases (33.33%), with total positivity of 100%, moreover b2a3 and b3a3 were predominant.</p><p><b>CONCLUSION</b>The detecting atypical BCR/ABL mRNA transcripts by real-time quantitative PCR is suitable for the diagnosis of CML negative for P210, P190 and P230 by standard real-time PCR test, and this detection is still the standard and economic method for monitoring minimal residual disease in CML patients with variants of BCR/ABL fusion gene.</p>

Prospective cohort study of the predictive value of hemoglobin levels for non-alcoholic fatty liver disease / 中华肝脏病杂志

<p><b>OBJECTIVE</b>To assess the predictive value of hemoglobin (HGB) levels for non-alcoholic fatty liver disease (NAFLD) by performing a prospective cohort study of NAFLD incidence in a healthy population.</p><p><b>METHODS</b>A total of 2840 individuals in the Xinjiang province were enrolled in the study from 2008 to 2011, based on liver ultrasound showing no evidence of fatty liver disease and the discovery of no major risk factors upon interview. All participants completed an epidemiological questionnaire survey, a physical examination, an abdominal ultrasonography, and gave blood for biochemistry testing. The hazard ratios of NAFLD were compared when the participants were grouped according to HGB level (g/L in quintiles): Q1, less than or equal to 145 for males and less than or equal to 123 for females; Q2, > 145 to less than or equal to 151 for males and > 123 to less than or equal to 129 for females; Q3, > 151 to less than or equal to 155 for males and >129 to less than or equal to 134 for females; Q4, > 155 to less than or equal to 161 for males and > 134 to less than or equal to 139 for females; Q5, > 161 for males and > 139 for females. Between-group comparison of measurement data was carried out by t-test and of percentage or count data by chi-square test. Between group comparison of the HGB level was carried out by one-way ANOVA. The prospective association between HGB levels and NAFLD was assessed by conditioned logistic regression analysis.</p><p><b>RESULTS</b>The values of body mass index, blood pressure, and triglyceride level were significantly higher in the participants with elevated serum uric acid quartiles. Within the 3-year study period, NAFLD was newly diagnosed in 19.6% of the male participants and 10.1% of the female participants; the difference between males and females reached the threshold of statistical significance (X2 = 51.043, P less than 0.01). The incidence of NAFLD in the quintile groups was 6.10% in Q1, 10.50% in Q2, 13.13% in Q3, 16.95% in Q4, and 22.03% in Q5 (X2 = 70.495, P less than 0.01), and the increasing trend with elevated HGB quartiles was significant (P less than 0.01). In multivariate logistic regression analysis, with adjustment for sex, age, race, metabolic syndrome and its components, the hazard ratios for incidence of fatty liver comparing Q2 to Q5 of HGB concentration to Q1 were 1.125, 1.325, 1.516 and 1.982.</p><p><b>CONCLUSION</b>Elevated HGB concentration is predictive of NAFLD in otherwise healthy subjects and may be used for screening during a routine health check-up.</p>

Effects of Kangnao Liquid on Expressions of Pi3k mRNA and Akt mRNA in Focal Cerebral Ischemic-Reperfusion Injury in Rats / 天津医药

Objective To observe the therapeutically effect of kangnao liquid on Pi3k mRNA and Aktm RNA ex-pressions in rats with focal cerebral ischemia-reperfusion (I/R) injury. Methods 180 male SD rats were randomly divided into 6 groups:sham operated group, model group, three kangnao liquid groups (high-dose, medium-dose and low-dose) and nimodipine group. Rats in kangnao liquid groups were administrated with kangnao liquid of 24 g/(kg · d), 12 g/(kg · d) and 6 g/(kg · d), orally once a day. Rats in nimodipine group were given nimodipine 1 mg/(kg · d). Rats in model group and sham group were treated with the same volume of distilled water for 7 days. The animal model of middle cerebral artery occlusion (MCAO) was established by a monofilament method from right internal carotid artery. The neurological evaluation was per-formed 24 h after reperfusion. The in situ hybridization was used to investigate the expression levels of Pi3k mRNA and Akt mRNA in rats on 12 h, 24 h, 48 h, 72 h and 168 h after ischemia for 2 h. Results Compared with model group, neurological functions were improved significantly in kangnao liquid groups. The expression levels of Pi3k mRNA and Akt mRNA were al-so significantly higher in kangnao liquid groups than those of model group. The expression levels of Pi3k mRNA and Akt mRNA were significantly higher in nimodipine group than those of model group, but which were lower compared with those of high-dose and medium-dose kangnao liquid groups. Conclusion Kangnao liquid can protect nerve cells by enhancing the expressions of Pi3k mRNA and Akt mRNA in rats with cerebral ischemia-reprefusion injury.

The comparative study of left ventricular diastolic function and disease activity in rheumatoid arthritis / 中华风湿病学杂志

Objective To evaluate the change of left ventricular diastolic function and investigate the relation between left ventricular diastolic function and disease activity in rheumatoid arthritis (RA) without clinical manifestations of heart diseases. Methods Seventy consecutive active RA in-patients without clinical manifestations of heart disease were enrolled, while the control group was recruited from outpatient health physical check-up center and consisted of 60 age- and sex-matched healthy subjects. Cardiac related parame-ters were determined by echocardiography and the correlation between left ventricular diastolic function and the disease activity indexes were evaluated. Chi-square test, t test, Pearson or Spearman′s correlation test and Stepwise backward linear regression analysis were used for statistical analysis. Results RA patients had lower mitral inflow E/A ratio (1.2±0.4, 1.5±0.4, P<0.01), higher E/Em ratio (9.6±3.7, 7.8±2.0, P<0.01), longer isovolumetric relaxation time(IVRT)[(64±16) ms,(58±16) ms, P<0.05] than control group. Whilst, RA patients had higher pulmonary venous inflow A wave velocity-time integral (ArVTI) and A wave duration (DAr)[3.2±0.7,(2.8±0.6) cm; 117±11,(102±9) ms, P<0.05]. Moreover, the E/Em was positively corre-lated with C-reactive protein(CRP)(r=0.581, P<0.01), DAS28(r=0.456, P<0.01). Anti-CCP level was also associated with Em and early diastolic pulmonary venous inflow peak velocity(PVD)(r=-0.359, P<0.05;r=-0.305, P<0.05). In addition, multivariate analysis also revealed that there was linear regression relation-ship between E/Em and CRP, DAS28(t=3.266, P=0.002; t=2.949, P=0.005). Conclusion The study has revealed that left ventricular diastolic function is impaired in RA patients and the left ventricular diastolic function parameters is associated with the disease activity indexes. These results suggest that the decline of left ventricular diastolic function is associated with the inflammation activity in RA patients without clinical manifestations of heart disease.

Suppressing SNAP-25 and reversing glial glutamate transporters relieves neuropathic pain in rats by ameliorating imbalanced neurotransmission / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Neuropathic pain results from a lesion or disease affecting the somatosensory system at either the peripheral or central level. The transmission of nociception within the central nervous system is subject to modulation by release and reuptake of neurotransmitters, which maintain a dynamic balance through the assembly and disassembly of the SNARE complex as well as a series of neurotransmitter transporters (inhibitory GABA transporters GAT and excitatory glutamate transporters GT). Neuronal hyper-excitability or defected inhibition involved in neuropathic pain is one of the outcomes caused by imbalanced neurotransmission. SNAP-25, which is one of the SNARE complexes, can modulate the release of neurotransmitters. Glia glutamate transporter (GLT) is one of the two glutamate transporters which account for most synaptic glutamate uptake in the CNS. The role of SNAP-25 and GLT as well as GAT is not clearly understood.</p><p><b>METHODS</b>We used the rat chronic constriction injury (CCI) model for research, and degraded SNAP-25 by a single intrathecal administration of BoNT/A. The mechanical (MWT) and thermal withdrawal latency (TWL) were tested. The level of SNAP-25, GLT, and GAT-1 were assayed using RT-PCR and Western blotting.</p><p><b>RESULTS</b>SNAP-25 was suppressed by a single intrathecal administration of 0.01U BoNT/A and the reduction of SNAP- 25 was correlated with the relief of nociceptive responses in CCI rats. MWT and TWL returned to normal from the 5th to 14th day (P < 0.05) after the administration. On the 14th day after surgery, compared to the sham group, the upregulation of SNAP-25 in CCI rats was reversed after BoNT/A treatment (P < 0.05). The decreased GLT was reversed after BoNT/A treatment but increased GAT-1 was not influenced by BoNT/A treatment.</p><p><b>CONCLUSIONS</b>SNAP-25 and GLT play important roles in the development of neuropathic pain, and the mechanism may involve the imbalance of neurotransmission after peripheral nerve injury. Intrathecal administration of BoNT/A reversed the upregulation of SNAP-25 and downregulation of GLT after CCI, but had no significant effect on the expression of GAT-1.</p>

Establishment of the Chang liver cell line stably overexpressing human UCP2 gene and its effect on mitochondrial membrane potential and reactive oxygen species / 中华肝脏病杂志

To establish the Chang liver cell line stably overexpressing human uncoupling protein 2 (UCP2) and observe the effect of UCP2 on mitochondrial membrane potential (MMP) and reactive oxygen species (ROS). The Chang liver cell line was transfected with recombinant plasmid containing full-length human UCP2 cDNA (pcDNA3.1-hUCP2) or pcDNA3.1 empty vector. The stable cell line was established by antibiotic screening with Zeocin. UCP2 expression was detected by Western blotting and immunocytochemistry. The UCP2 overexpressing cells were pretreated with genipin at various doses (25, 50 and 100 munol/L). MMP and intracellular ROS were detected by fluorescence spectrophotometry. The total normalized protein content in UCP2 overexpressing cells was 1.6-fold higher than that in unmanipulated normal cells. The fluorescence intensities of Rhodamine123 and DCFH-DA in UCP2 overexpressing Chang liver cells (11.11+/-2.76 and 4.97+/-0.62, respectively) were significantly lower than those in unmanipulated normal cells (15.56+/-2.55, P less than 0.01 and 6.14+/-1.25, P less than 0.05, respectively) and in cells transfected with empty vector (16.11+/-2.93, P less than 0.01 and 6.23+/-1.13, P less than 0.05, respectively). Treatment of UCP2 overexpressing cells with 25, 50 and 100 munol/L genipin caused a dose-dependent increase in fluorescence intensities of Rhodamine123 (14.89+/-2.89, 17.89+/-2.93 and 24.00+/-2.55, respectively, all P less than 0.01) and DCFH-DA (9.16+/-0.78, 10.84+/-1.09 and 11.83+/-1.25, respectively, all P less than 0.01). The Chang liver cell line stably overexpressing UCP2 was established successfully. Using this cell system, UCP2 was found to play a role in mitochondrial function by regulating MMP and ROS.

Coverage on cataract surgery among adults aged 40 or above in a multiethnic rural district of high altitude area in Gongshan county, Yunnan province, China / 中华流行病学杂志

Objective To estimate the prevalence of cataract and its surgical coverage rate together with the burden related to bilateral cataract-blindness,among adults aged 40 or above in Gongshan county of Yunnan province and to evaluate the current cataract status and the efficacy of local cataract prevention program.Methods Cluster sampling was used.The protocol consisted of personal interview,pilot study,visual acuity checking,measuring the intraocular pressure; slit lamp microscopy and the fundus of the eye examination etc.Cataract was graded clinically using the Lens Opacity Classification System (LOCS) ]Ⅲ.Bilateral cataract-blindness burden,bilateral cataractblindness burden and cataract surgical coverage rate were calculated respectively,using two different criteria.Odds ratios (OR) were compared among different groups regarding age,gender,education,ethnic group and altitude of living area.Results Among the 1236 eligible residents,1116 (90.3％)were enrolled in the present study.The prevalence of cataract was 23.8％ among adults aged 40 or order.When the bilateral best refractive vision ＜3/60 was defined as the blindness criterion,the bilateral cataract-blindness burden showed as 1.3％,and cataract blindness surgical coverage rate was 50.0％.When the bilateral presenting vision ＜ 6/60 was defined as the blindness criterion,the bilateral cataract-blindness burden was 25.0％,and cataract blindness surgical coverage rate was 12.9％.The cataract surgical coverage rates were much lower and the bilateral cataract-blindness burden much higher in women,illiterates,living in high altitude areas and those who were aged 70 or above.Conclusion Cataract blindness was a serious public health problem in aged individuals and illiteracy in the residents of the studied areas.Poor prevention programs on cataract called for urgent action to be taken.

Effect of intrathecal ketamine injection on protein kinase C expression in the spinal dorsal horn of rats with formalin-induced pain / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the expression of protein kinase C (PKC) in the spinal dorsal horn of rats with formalin-induced pain and the effect of intrathecal ketamine on PKC expression.</p><p><b>METHODS</b>Thirty-two SD rats were randomly divided into 4 equal groups, namely the control group, intrathecal saline group (NS), 50 µg ketamine group (K1) and 100 µg ketamine group (K2). The rats were anesthetized with 10% chloral hydrate, and a microspinal catheter was inserted intrathecally into the lumbar region. Five days later, the rats in groups, K1 and K2 were subjected to intrathecal administration of 50 and 100 µg ketamine (10 µl), respectively, followed by 10 µl saline, and those in NS group received 20 µl saline only. Thirty minutes later, 5% formalin (50 µl) was subcutaneously injected into the left hindpaw. The pain intensity score (PIS) was utilized to assess antinociceptive behavior within 1 h after formalin injection. Twenty-four hours later, the left hindpaw thickness was measured and the expression of PKC in the spinal dorsal horn in the L5 segment was assayed using immunohistochemistry.</p><p><b>RESULTS</b>Compared to group NS, groups K1 and K2 showed significantly decreased PIS (P<0.01) in the second phase of formalin-induced pain; 24 h later, the left hindpaw thickness of group NS increased obviously in comparison with that in the control group (P<0.01), whereas the thickness was significantly reduced in group K1 and K2 as compared to that in group NS (P<0.05). The number of immunoreactive cells and the immunohistochemical score of PKC in the spinal dorsal horn were significantly higher in group NS than in group C (P<0.01), but significantly lower in groups K1 and K2 than in group NS (P<0.05).</p><p><b>CONCLUSION</b>Intrathecal ketamine produces obvious antinociception against formalin-induced pain in rats and inhibits the enhanced PKC expression in the spinal dorsal horn in response to formalin-induced pain, suggesting the important role of PKC in nociceptive signal transmission and modulation in the spinal cord.</p>

Inhibition effect of PPARγ agonist on proliferation of human pterygium fibroblasts / 中华实验眼科杂志

Background Recurrence of pterygium is a common complication after the surgical excision of pterygium,and this procedure is related to cell proliferation,inflammation and neovascularization.Researches determined that rosiglitazone can suppress inflammation and neovaseularization and inhibit proliferation,hut few studies concerning the effect of rosiglitazone on pterygium were performed. Objective The aim of this study was to investigate the effect of peroxisome proliferator-activated receptor γ agonist on the proliferation and apoptosis of human pterygium fibroblasts(HPFs)in culture and search for a new drug to prevent and cure the recurrence after pterygium surgery. Methods Human pterygium samples were obtained during surgery and HPFs were cultured and purified using an explant method and 0.25%trypsin digestion,respectively.The identity of cultured HPFs was confirmed by immunohistochemistry using anti-vimentin and keratin antibodies.Rosiglitazone with the concentrations of 0(control),5,10,25,50,75,100,150,200,400μmol/L was then added in the culture medium for 12,24 or 72 hours.1%DMSO was used as blank control.The MTT method was used to assay the biologic effects of rosiglitazone on HPFs.Cell cycle distribution and apoptosis of HPFs after rosiglitazone treatment were studied by flow cytometic analysis.The expression of proliferating cell nuclear antigen(PCNA)mRNA in HPFs was detected by real-time PCR. Result Cultured HPFs radially migrated outward from the pterygium block,and then grew in long fusiform shape,showing positive response for vimentin and negative for keratin.The HPFs became round and thin with loose distribution after the addition of rosiglitazone.Following 25-125 μmol/L rosiglitazone administration for 12,48 or 72 hours,the A490 value of HPFs significantly declined with the increase of dosage(F=158.312,P=0.006)and lapse of time(F=1.924,P=0.135).Following the treatment of 25,75 or 125 μmol/L rosiglitazone for 24 hours,the number of HPFs in G0/G1 phase was markedly elevated;while the cell numbers in S phase decreased significantly in comparison with the control group(P＜0.05).The apoptotic rate of HPFs in the 25,75 and 125 μmol/L rosiglitazone groups significantly increased with the increase of rosiglitazone concentration(P＜0.05).Real-time PCR revealed that after 24 hours of rosiglitazone treatment,the expression of PCNA mRNA in HPFs was suppressed in a dose-dependent manner(F=3244.329,P＜0.05). Conclusion Rosiglitazone inhibits HPFs proliferation,arrests their cell cycle progression in G0/G1 phase,induces apoptosis of HPFs and depresses the synthesis of PCNA in a dose-and time-dependent manner.

Copy-number variations of SHANK3 and related clinical phenotypes in children with autism / 中华儿科杂志

<p><b>OBJECTIVE</b>To explore possible relationship between copy-number variations (CNVs) in 15q11-13, 16p11 and SHANK3 gene by using multiplex ligation-dependent probe amplification (MLPA) and the phenotypes in children with autism and to further explore the clinical application of MLPA to make an etiological diagnosis of Autism.</p><p><b>METHODS</b>The diagnosed of autism was made according to the criteria of the ICD-10 and DSM-IV, with typical cluster of symptoms comprise social disability, communication impairments and repetitious behaviors. MLPA KIT P343-C1 AUTISM-1 was used to detect and describe the incidence of CNVs in these three domains.</p><p><b>RESULTS</b>Among 109 cases collected from 102 autistic pedigrees, 2 individuals had SHANK3 microdeletion, accounting for approximately 2% (2/109) of cases, suggesting the proportion of SHANK3 microdeletion might contribute to typical autism. The phenotypic traits of patients with SHANK3 microdeletions showed homogenicity in severe core symptoms and mental retardation.</p><p><b>CONCLUSIONS</b>SHANK3 microdeletion is an important genetics component for autism, which may explain 2% typical autism cases. SHANK3 microdeletion might explain autistic core symptoms and mental retardation. MLPA is a sensitive and a high throughput technique to detect CNVs in specific DNA segments, which is beneficial for further investigation of etiology of autism.</p>

Inhibitory effect of PPARγ agonist on the proliferation of human pterygium fibroblasts / 华中科技大学学报（医学）（英德文版）

The effects of DK2, a peroxisome proliferator-activated receptor γ agonist, on cultured human pterygium fibroblasts (HPFs) in virto were studied. The HPFs were incubated with 0-200 μmol/L DK2 for 12-72 h. The MTT method was used to assay the bio-activity of DK2 at different doses and time. The cytotoxic effect of DK2 was measured by LDH release assay. The cell cycle distribution and apoptosis were flow cytometrically detected. The expression of proliferating cell nuclear antigen (PCNA) in each group was detected by real-time PCR (RT-PCR) and Western blotting. The results showed that administration of 1-75 μmol/L DK2 for 12-72 h could significantly inhibit HPF proliferation in a dose- and time-dependent manner. DK2-treated cells did not release significant amount of LDH as compared with rosiglitazone-treated cells. After treatment with DK2 at concentrations of 15, 25 μmol/L for 24 h, the number of HPFs in G(0)/G(1) phase was significantly increased while that in S phase was significantly decreased (P<0.05), leading to arrest at G(0)/G(1) phase. The apoptosis rates of HPF cells in drug-treated groups were significantly higher than the rate of control group (P<0.05). At the dosage range between 15-25 μmol/L, DK2 could inhibit the expression of PCNA mRNA and protein in HPFs in a dose-dependent fashion (P<0.05). It was concluded that PPARγ agonist can significantly inhibit HPF proliferation, resulting in the arrest at G(0)/G(1) phase, induce the apoptosis of HPFs, and suppress the synthesis of PCNA, in dose- and time-dependent manners.

Inhibitory effect of PPARγ agonist on the proliferation of human pterygium fibroblasts / 华中科技大学学报（医学）（英德文版）

The effects of DK2, a peroxisome proliferator-activated receptor γ agonist, on cultured human pterygium fibroblasts (HPFs) in virto were studied. The HPFs were incubated with 0-200 μmol/L DK2 for 12-72 h. The MTT method was used to assay the bio-activity of DK2 at different doses and time. The cytotoxic effect of DK2 was measured by LDH release assay. The cell cycle distribution and apoptosis were flow cytometrically detected. The expression of proliferating cell nuclear antigen (PCNA) in each group was detected by real-time PCR (RT-PCR) and Western blotting. The results showed that administration of 1-75 μmol/L DK2 for 12-72 h could significantly inhibit HPF proliferation in a dose- and time-dependent manner. DK2-treated cells did not release significant amount of LDH as compared with rosiglitazone-treated cells. After treatment with DK2 at concentrations of 15, 25 μmol/L for 24 h, the number of HPFs in G(0)/G(1) phase was significantly increased while that in S phase was significantly decreased (P<0.05), leading to arrest at G(0)/G(1) phase. The apoptosis rates of HPF cells in drug-treated groups were significantly higher than the rate of control group (P<0.05). At the dosage range between 15-25 μmol/L, DK2 could inhibit the expression of PCNA mRNA and protein in HPFs in a dose-dependent fashion (P<0.05). It was concluded that PPARγ agonist can significantly inhibit HPF proliferation, resulting in the arrest at G(0)/G(1) phase, induce the apoptosis of HPFs, and suppress the synthesis of PCNA, in dose- and time-dependent manners.

Association between hemoglobin scavenger receptor CD163 expression and coronary atherosclerotic severity in patients with coronary heart disease / 中华心血管病杂志

<p><b>OBJECTIVE</b>To investigate the association between hemoglobin scavenger receptor (CD163) expression levels on monocytic surfaces and coronary atherosclerotic severity in patients with coronary heart disease (CHD) as well as the roles of CD163 in inflammation and lipidperoxidation.</p><p><b>METHODS</b>Eighty-four patients were diagnosed as CHD according to the results of coronary angiography and ACC/AHA diagnostic criteria. The patients were divided into 3 groups: acute myocardial infarction (AMI) group (n = 30), unstable angina (UA) group (n = 30), stable angina (SA) group (n = 24). Another 20 patients with normal coronary artery served as control. Expression levels of CD163 on monocytes were detected by means of flow cytometry, and the results were shown as mean fluorescence intensity (mfi). All patients underwent coronary angiography and the results were further evaluated by Jenkins score. Serum CRP and LDL-C were also measured.</p><p><b>RESULTS</b>The expression levels of CD163 on monocytes in peripheral blood were significantly higher in CHD patients compared to controls (P < 0.01) in the order of AMI group [(84.4 +/- 6.9) mfi] > UA group [(64.1 +/- 5.5) mfi, P < 0.01 vs. AMI] > SA group [(46.7 +/- 6.5) mfi, P < 0.01 vs. AMI and UA] > control group [(22.0 +/- 6.1) mfi, P < 0.01 vs. AMI, UA and SA]. The expression levels of CD163 on monocytes in patients with CHD were positively correlated with Jenkins score (r = 0.9107, P < 0.01), CRP (r = 0.766, P < 0.01) and LDL-C (r = 0.749, P < 0.01).</p><p><b>CONCLUSIONS</b>Expression levels of CD163 was significantly increased in patients with CHD and positively correlated with coronary heart disease severity and serum CRP and LDL-C.</p>

Progress in the biology of glucagon-like peptide 2 / 中国药理学通报

Glucagon-like peptide-2 (GLP-2) is a 33-amino acid peptide derived from the tissue-specific, post-translational processing of the proglucagon gene.GLP-2 is a newly discovered,specific for the intestine growth factor that affects gastrointestinal functions including epithelial growth of normal and developing intestinal preventing damage and facilitating intestinal repair in animal models and patients of intestinal disease. GLP-2 also inhibits gastrointestinal motility and gastric acid secretion, up-regulates intestinal blood flow and reduces food intake. The actions of GLP-2 are initiated by activation of the GLP-2 receptor (GLP-2R), a specific G-protein-linked membrane receptor. This review provides an overview of the physiological, pharmacological, and therapeutic actions of GLP-2 and GLP-2R signaling mechanism, with a focus on the most recent findings on the role of this peptide hormone in the normal and diseased gastrointestinal tract.

Three subanaesthetic dose ketamines mixed with butorphanol in the postoperative continuous intravenous analgesia / 中南大学学报(医学版)

OBJECTIVE@#To determine an optimal clinical dose of ketamine after comparing the efficacy and security of 3 low dose ketamines mixed with butorphanol in the postoperative continuous intravenous analgesia.@*METHODS@#Eighty ASA (American Society of Anesthesiologists) I-II patients scheduled for elective gynecological surgery under general anesthesia were divided randomly into 4 groups (n=20): Group B received butorphanol 3 microg/(kg x h);Group BK1 received butorphanol 2 microg/(kg x h) mixed with ketamine 60 microg/(kg x h); Group BK2 received butorphanol 2 microg/(kg x h) mixed with ketamine 90 microg/(kg.h); and Group BK3 received butorphanol 2 microg/(kg x h) mixed with ketamine 120 microg/(kg x h). Continuous intravenous infusion pump was used when the patients had obvious pain (visual analgesia scale of five), and the bolus infusion (4 mL) was given before the operation, and continuous infusion at 2 mL/h. In the postoperative period, pain was assessed using visual analogue scale (VAS) at 2,6,12,24, and 48 h.At the same time, Ramsay scores and adverse effects were recorded.@*RESULTS@#There was no significant difference in the adverse effects and the postoperative mean arterial pressure, heart rate, respiratory rate values, and pulse oxygen among the 4 groups. Postoperative VAS values in Group BK3 was the lowest, followed by Group BK2. There was no significant difference between Group BK1 and Group B. The incidence of somnolence in Group B was higher than that in Group BK1, BK2 and BK3(P<0.05).@*CONCLUSION@#Ketamine in subanaesthetic dose added to butorphanol for postoperative continuous intravenous infusion has a better postoperative analgesic effect and sedation. It can effectively spare butorphanol consumption without increasing adverse effects. The optimal combined dose is 90-120 microg/(kg x h).