Deng Y.,Guangdong Academy of Medical science
Zhonghua wei zhong bing ji jiu yi xue | Year: 2016
OBJECTIVE: To observe the axonal development in the corpus callosum of septic neonatal rats, and its effect on the neurological function after birth.METHODS: Forty-eight 1-day-old Sprague-Dawley (SD) rats were randomly divided into two groups: control group and sepsis group, with 24 rats in each group. The rat model of sepsis was reproduced by intraperitoneal injection of 1 mg/kg lipopolysaccharide (LPS), and the rats in control group were injected with an equal volume of phosphate buffered saline (PBS). The corpus callosum in brain was harvested at 7, 14, and 28 days after model reproduction, and double immunofluorescence staining and Western Blot were used to observe the expression of neurofilament heavy chain (NFH), neurofilament medium chain (NFM) and neurofilament light chain (NFL) in the corpus callosum. The morphology and number of axon were observed in the corpus callosum of rats at 28 days using electron microscopy. The number of myelin basic protein (MBP) positive cells in the corpus callosum of rats was determined by in situ hybridization.RESULTS: The immunofluorescence intensities of NFH, NFM, and NFL in the corpus callosum of rats at 7, 14, and 28 days after model reproduction in sepsis group were significantly lower than those of control group. In addition, it was revealed by Western Blot results that the protein expression levels of NFH, NFM, and NFL in sepsis group were significantly lower than those of control group [NFH (gray value): 0.16±0.03 vs. 0.34±0.04 at 7 days, 1.75±0.11 vs. 2.42±0.17 at 14 days, 3.39±0.25 vs. 5.11±0.23 at 28 days; NFM (gray value): 0.34±0.04 vs. 0.53±0.04 at 7 days, 0.74±0.04 vs. 1.12±0.07 at 14 days, 0.92±0.06 vs. 1.52±0.07 at 28 days; NFL (gray value): 0.12±0.02 vs. 0.26±0.14 at 7 days, 0.32±0.03 vs. 0.81±0.04 at 14 days, 0.85±0.08 vs. 1.81±0.05 at 28 days; P < 0.05 or P <0.01]. In the control group, an obvious myelination was found in the corpus callosum of rats on the 28th day after the birth, and the nodes of Ranvier were clearly distinguishable, with intact structure and smooth edges. The number of myelinated axons was reduced and the nodes of Ranvier were impaired in the corpus callosum of rats at 28 days after LPS injection. The expression of MBP in the corpus callosum of rats at 28 days after LPS injection was obviously decreased compared with control group (cells/LP: 23.67±3.21 vs. 35.00±3.61, P < 0.01).CONCLUSIONS: The axonal development in the corpus callosum of septic neonatal rats on the 28th day after the birth was impaired, and lead to reduced myelination and further deterioration of neurological function.
Huang J.,Guangdong Academy of Medical science
Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology | Year: 2011
To investigate the efficacy of Telbivudine and Entecavir for therapy of HBeAg positive chronic hepatitis B for 52 weeks. In this random and control study, the efficacy of Telbivudine and Entecavir treatments were compared in 180 patients with HBeAg positive chronic hepatitis B.The patients were randomly assigned to a daily 600 mg Telbivudine treatment group or daily 0.5 mg Entecavir group for 52 weeks. At week 52, HBV DNA undetectable rate was better in the Entecavir-treated group than in the Telbivudine-treated group, but didn't reach statistical significance. The viral breakthrough rates were significantly lower in the Entecavir-treated group than in the Telbivudine-treated group (x2 = 4.09, P <0.05). The clearance and seroconversion of HBeAg and the mean reductions of HBeAg from baseline at week 52 were significantly greater in the telbivudine-treated group than in the entecavir-treated group (x(2) clearance = 4.63, x(2) seroconversion = 4.80, (t-mean) reductions = 2.02; P < 0.05). The HBeAg seroconversion rates were not associated with both baseline ALT and baseline HBV DNA in both groups (P more than 0.05). In Telbivudine-treated group, the HBeAg decline is more than 2 log at week 24, HBeAg decline is more than 1 log at week 12 and the HBeAg baseline were independent factors correlated to HBeAg seroconversion rates at week 52 by Binary Logistic analysis, and also in entecavir-treated group the HBeAg decline is more than 2 log at week 24, HBeAg decline is more than 2 log at week 36 and the HBeAg decline is more than 2 log at week 12 were independent factors correlated to HBeAg seroconversion rates at week 52. Significant difference of HBeAg seroconversion rates at week 52 existed between Telbivudine-treated group and Entecavir-treated group. Entecavir is significantly superior to Telbivudine with less resistance to nucleosides. HBeAg decline is more than 2 log at week 24 is the best predicting factor for HBeAg seroconversion at week 52.
Huang W.H.,Guangdong Academy of Medical science
Zhonghua yi xue za zhi | Year: 2011
To compare the safety, efficacy and their impact on stent graft positioning between rapid artificial cardiac pacing induced hypotension and sodium nitroprusside induced hypotension during thoracic endovascular aortic repair (TEVAR). From September 2007 to February 2009, a randomized controlled trial as approved by the Ethics Committee of our hospital was conducted in 197 patients undergoing elective thoracic endovascular aortic repair of thoracic aortic dissection (n = 175) or aneurysm (n = 22). The patients were randomized into sodium nitroprusside group (n = 98) and rapid artificial cardiac pacing group (n = 99). During the localization and deployment of stent graft, hypotension was induced by intravenous sodium nitroprusside or rapid artificial cardiac pacing. Hemodynamics, landing precision (deviation from planned placement site), duration of procedure, renal function, neurocognitive function, incidence of endoleaks and paraplegia/hemiplegia were compared. Rapid artificial cardiac pacing was conducted without technical difficulty in all 99 patients. The level of hypotension (mm Hg, 1 mm Hg = 0.133 kPa) was most pronounced in the rapid artificial cardiac pacing group (47 ± 5 vs 82 ± 7, P = 0.003. Once rapid pacing ceased, blood pressure recovered more quickly to the preparing levels in the rapid artificial cardiac pacing group [(9 ± 2) s vs (481 ± 107) s, P < 0.01]. And the duration of procedure was also shorter in the rapid artificial cardiac pacing group [(94 ± 16) min vs (103 ± 24) min, P < 0.01]. Moreover, precise positioning and deployment was observed in rapid artificial cardiac pacing group versus to the sodium nitroprusside group (P < 0.01). There was no difference in renal function and neurocognitive function before and after the procedure in both groups. There was no difference in the incidences of endoleaks and paraplegia/hemiplegia between different groups (P > 0.05). As compared with sodium nitroprusside, rapid artificial cardiac pacing is safer in thoracic endovascular aortic repair. It shortens the endovascular procedure and enables more precise positioning and deployment of stent graft.
Liu Y.,Guangdong Academy of Medical science
Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences | Year: 2011
To investigate distribution of CYP2C9, CYP3A4, VKORC1 and GGCX gene polymorphisms in the Han population of Guangdong. The subjects included were 970 Chinese Han patients who received long-term warfarin anticoagulant therapy orally after valve replacement in Guangdong General Hospital between 2000 and 2008. By selecting and analyzing the 12 single nucleotide polymorphisms (SNPs) loci, rs12572351 G>A, rs9332146 G>A, rs4917639 G>T, rs1057910 A>C (CYP2C9*3), rs1934967 G>T, rs1934968 G>A, rs2242480 T>C, rs2246709 G>A, rs9923231 C>T (VKORC1-1639 G>A), rs2359612 G>A (VKORC1*2), rs10871454 C>T, and rs699664 T>C, in 4 genes including CYP2C9, CYP3A4, VKORC1 and GGCX that were possibly correlated with warfarin pharmacodynamics and pharmacokinetics through literature retrieval, the distribution of mutation frequencies of the 12 SNPs loci in Chinese Han population were obtained systematically. SNaPshot technique was used to detect gene SNPs, Hardy-Weinberg genetic equilibrium test was used to test population representativeness. The allelic mutation frequency at CYP2C9 gene rs12572351 G>A, rs9332146 G>A, rs4917639 C>A, rs1057910 A>C (*3), rs1934967 G>T and rs1934968 G>A loci was 32.53%, 2.16%, 8.25%, 3.61%, 19.18% and 37.37%, respectively; the allelic mutation frequency at CYP3A4 gene rs2242480 T>C and rs2246709 G>A loci was 29.07% and 40.41%, respectively; the allelic mutation frequency at VKORC1 gene rs9923231 C>T, rs2359612 G>A and rs10871454 C>T SNPs loci was 87.99%, 87.94% and 91.34%, respectively; the allelic mutation frequency at GGCX gene rs699664 T>C locus was 31.86%. It is of important clinical significance in individualized warfarin therapy to systematically study distribution of mutation frequencies at 12 polymorphisms loci in 4 genes including CYP2C9, CYP3A4 , VKORC1 and GGCX related to warfarin pharmacodynamics and pharmacokinetics in the Chinese Han population receiving valve replacement.
Li A.,Guangdong Academy of Medical Science |
Gao H.-F.,Guangdong Academy of Medical Science |
Wu Y.-L.,Guangdong Academy of Medical Science
Expert Opinion on Therapeutic Targets | Year: 2015
Introduction: The mesenchymal-epithelial transition (MET) protein is the only known receptor for hepatocyte growth factor and has recently been identified as a novel promising target in several human cancers, including NSCLC. Activation of the MET signaling pathway can occur via different mechanisms. A number of compounds targeting MET have been evaluated in clinical trials, and recent clinical data have begun to afford some insight into the tumor types and patient populations that might benefit from treatment with MET pathway inhibitors.Areas covered: We review recent publications and information disclosed at public conferences and summarize the epidemiology of dysregulation of MET signaling, and the associations thereof with other driver genes and therapeutic inhibitors useful to treat NSCLC.Expert opinion: The MET pathway is emerging as a target for advanced NSCLC that is either resistant to EGFR tyrosine kinase inhibitors or that arises de novo. MET inhibitors currently being evaluated in clinical trials have yielded compelling evidence of clinical activities when used to treat various solid tumors, especially NSCLC. Remaining challenges are the identification of patient populations who might benefit from the use of MET inhibitors, and the most effective diagnostic methods for such patients. © 2015 Informa UK, Ltd.
Xie Y.B.,Guangdong Academy of Medical science
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2010
To study the status of and the factors contributing to Internet addiction among middle school students in Guangzhou. Cluster sampling method was used to recruit an urban middle school, a rural junior middle school and a rural senior high school to conduct the survey with the stressful life event questionnaire, the trait-oriented coping styles questionnaire and the Internet Addiction Test. The majority of respondents were classified as normal users of the Internet (n=1392, 89.2%), with 158 (10.2%) moderately and 10 (0.6%) severely addicted to the Internet. Fifty-eight students had never used the Internet. There were significant differences in gender, the father's education, the 4 dimensions of the stressful life event questionnaire and the coping styles between students with and without Internet addiction. Binary logistic analysis showed that the factors contributing to Internet addiction included passive coping styles, male gender and stressful life event experienced in family and interpersonal communication. The incidence of Internet addiction is high among middle school students in Guangzhou. Male students with stressful life events in family and interpersonal communication, poor education on the part of the father, and frequent use of negative coping styles are more likely to develop Internet addiction.
Xu D.,Guangdong Academy of Medical science
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2012
To compare the effects of propofol and inhalation anesthesia on the incidence of early postoperative cognitive dysfunction (POCD) in elderly patients undergoing noncardiac surgeries. PubMed, Cochrane Library, CBM, CNKI, Wanfang data and VIP Database (by October 2012) were searched for randomized controlled trials (RCTs) comparing propofol and inhalation anesthesia for their impact on the incidence of early POCD in elderly patients undergoing noncardiac surgeries. After data extraction and quality evaluation, Stata 12.0 software was used for statistical data analysis. Thirteen RCTs, including 2 comparing propofol with xenon, 7 comparing propofol with sevoflurane, and 4 comparing propofol with isoflurane were obtained, involving a total of 753 patients. The odds ratio of early POCD incidence between patients with propofol anesthesia and those with xenon anesthesia, sevoflurane anesthesia, and isoflurane anesthesia were 1.62 (95% CI 0.81-3.23, P=0.533), 0.67 (95% CI 0.39-1.14, P=0.830), and 0.20 (95% CI 0.08-0.50, P=0.925), respectively. Overall, the odds ratio of early POCD incidence between propofol anesthesia and inhalation anesthesia was 0.68 (95% CI 0.47-0.98, P=0.189). Egger's test showed a publication bias of the RCTs retrieved (P=0.011). Compared with inhalation anesthesia, propofol anesthesia is associated with a lower incidence of early POCD in elderly patients, but this conclusion needs to be further verified by more well-designed large-scale RCTs.
YU T.,Guangdong Academy of Medical science
Nan fang yi ke da xue xue bao = Journal of Southern Medical University | Year: 2011
To investigate the expression and functional role of the small conductance Ca(2+)-activated K(+) channels in human atrial myocytes. We collected the right atrial appendage tissues from 8 patients with congenital heart defect with sinus rhythm undergoing open-heart surgery. Immunohistochemistry was performed to identify the expression of 3 isoforms of SK channel (SK1, SK2 and SK3). Using the classical two-step enzymatic isolation method, perforated patch clamp and conventional voltage-clamp techniques were performed to record the action potentials (APs) and the whole-cell Ca(2+)-activated K(+) current (I(K, Ca)) in the single atrial myocyte. We compared the changes in action potential duration (APD) before and after the application of a specific SK channels blocker apamin (100 nmol/L). Human atrial myocytes showed positivity for all the SK1, SK2 and SK3 isoform channels. Patch-clamp recording confirmed the presence of I(K,Ca), and apamin significantly prolonged APD at 90% repolarization (APD(90)), but produced no obvious effect on APD(50). The three isoforms of SK channels are all expressed in human atrial myocytes. SK channels play a prominent role in the late phase of repolarization in human atrial myocytes, which is distinct from their functional roles in neurons where they mediate the process of afterhyperpolarization following APs.
Zhang B.,Guangdong Academy of Medical science
Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association | Year: 2012
The urokinase receptor (uPAR) and its soluble form play a key role in the pathogenesis of focal segmental glomerulosclerosis (FSGS). The modification of uPAR pathological actions on podocytes will become an important task for the development of improved nephroprotective therapeutics. Here we show that podocyte uPAR expression can be reduced using amiloride. Amiloride has a significant role in the reduction of podocyte cell motility in vitro and proteinuria in mice. Amiloride inhibited the induction of uPAR protein and PLAUR messenger RNA (encoding uPAR) and with that it reduced uPAR-mediated β3 integrin activation in lipopolysaccharide (LPS)-treated podocytes. Transwell migration assay and wound healing assay showed that directed and random podocyte motility of LPS-treated podocytes were increased and substantially reduced by amiloride. The off-target effect of amiloride was independent of its function as epithelial sodium channel blocker and different from triamterene. Amiloride was also effective in the LPS mouse model of transient proteinuria (LPS mice) and in the 5/6 nephrectomy rat FSGS model (NTX) by significantly inhibiting podocyte uPAR induction, reducing proteinuria. In addition, amiloride attenuated glomerulosclerosis, as determined by glomerulosclerotic index. Thus, our observations show that amiloride inhibits podocyte uPAR induction and reduces proteinuria in NTX rats and LPS mice. Given the pathological relevance of the uPAR-β3 integrin signaling axis in FSGS, amiloride may be utilized in patients with FSGS.
Li L.,Guangdong Academy of Medical science
Zhonghua er ke za zhi. Chinese journal of pediatrics | Year: 2011
To acquire more knowledge about neonatal lupus erythematosus (NLE). Seven cases with neonatal lupus erythematosus who were seen in this hospital from 1990 to 2009 are reported in this paper and 87 cases reported previously from 1980 to now in China were reviewed. The clinical manifestations, serum autoantibodies, treatment and results of long-term follow-up are analyzed and summarized. Totally 94 cases were summarized. Male/female ratio was 48/46; 73 cases had skin rash; 23 had heart abnormality, among whom 13 had cardiac conductive problems including 8 cases of atrioventricular blockage (AVB) (3 degree I, 3 degree II and 2 degree III) and 5 cases of right bundle branch block cases (RBBB). Nine cases had anatomical abnormality including 5 cases of atrial septal defect (ASD), 2 cases of ventricular septal defect (VSD) and 2 cases of atrial enlargements. Forty-four cases had hematological problems including 28 with thrombocytopenia, 11 with leukocytopenia and 34 with anemia. Thirty cases had hepatic abnormality, including 24 liver dysfunction, 22 hepatomegaly, 6 splenomegaly and 3 cholestasis. Three cases had nephropathy; 3 had elevated creatine kinase; 2 had nervous disorder. Among the 94 cases, 86 (91.5%) were positive for anti-SSA, 51 (54.3%) anti-SSB, 16 anti-ds-DNA, 14 anti-U1-RNP, 13 anti-Sm (+), 6 anti-RNP and 4 anti-rRNP(+). Among the corresponding mothers, 39 cases (44.8%) were asymptomatic before pregnancy, 35 had SLE, 5 had SCLE, 3 had Sjogren syndrome, 2 had chilblain, photosensitivity and arthralgia, respectively, 1 had rheumatoid arthritis and 1 had psoriasis. During pregnancy, 8 mothers developed SLE. Totally 48 mothers (51.1%) suffered from LE. Together with 15 mothers who had transient skin rash during the pregnancy, there were 23 mothers (59%) who had new clinical manifestation among the 39 asymptomatic mothers. Twenty NLE cases accepted glucocorticoid treatment, 4 of them were treated with intravenous immunoglobulin. Sixty-eight cases were followed up for up to 12 years, 58 cases were healthy, 5 cases improved and 3 died. Two cases still had grade III AVB without pacemaker. NLE is a rare acquired autoimmune disease. Although nearly half of the mothers were asymptomatic before pregnancy, more than half of them developed LE or other symptoms. The clinical presentations in Chinese cases include a transient rash, cardiac lesion while grade III AVB was rare, hematological changes and liver impairments which were common but not serious. Anti-SSA and/or anti-SSB were the most related autoantibody. Most patients with NLE have relatively good prognosis.