2008年 · 第121卷第24期

Abstract：Background Congenital heart disease (CHD) is a common heart condition which does considerable harm to the health of children and adolescents. CHD epidemiological characteristics of Tibetan children whose ages ranged from 4 to 18 years were investigated in Qinghai Province. Methods A total of 32 578 Tibetan children, living at altitudes of 2535 m, 3600 m and 4200 m, were examined using a three-stage protocol: prescreening, rechecking and diagnosis using a color Doppler. The distribution of CHD at different altitudes was analyzed together with differences in occurrence according to age and gender. Results A total of 235 CHD cases were discovered. The total prevalence of CHD was 7.21%o. Prevalence of CHD has been shown to increase along with increase in altitude with 5.45%0 at an altitude of 2535 m, 6.80%0 at 3600 m and 9.79%. At 4200 m. There were no statistically significant differences between the prevalence at 2535 m and 3600 m 0(2=1.594, P ＞0.05). However, there was a significant difference between the prevalence at 2535 m and 4200 m (X2=7.002, P＜0.01). Also, apparent differences existed between the prevalence at 3600 m and at 4200 m (X2=5.540, P＜0.05). There was no statistically significant difference in prevalence according to age at an altitude of 2535 m, but the rate of CHD increased significantly along with increasing age at 3600 m and 4200 m. The total prevalence ratio of children aged from 16 to 18 years was significantly higher than that of children from 4 to 7, and from 8 to 12 with X2 values of 10.79 (P＜0.005), and 5.60 (P＜0.05) respectively. Within the constituent ratio of CHD, the prevalence of atrial septal defect (ASD) was the highest at 39.10%, followed by the prevalence of ventricular septal defect (VSD) at 32.8% and patent ductus arteriosus (PDA) at 24.7%. Furthermore the proportion of the four categories of CHD varied at different altitude levels: at 2535 m, of those diagnosed with CHD, the prevalence rate of VSD was the highest at 43.5%, at 3600 m ASD was the highest at 42.8% and at 4200 m, PDA was the highest at 50.8%. Conclusion The epidemiological characteristics of CHD in Tibetan children may be associated with altitude levels。

Abstract：Background The incidence of spinal injury with spinal cord contusion is high in developed countries and is now growing in China. Furthermore, spinal cord injury happens mostly in young people who have a long life expectance. A large number of patients thus are wheelchair bound for the rest of their lives. Therefore, spinal cord injury has aroused great concern worldwide. Despite great efforts, recovery from spinal cord injury remains unsatisfactory. Based on the pathology of spinal cord contusion, an idea of early neurosurgical intervention has been formulated in this study. Methods A total of 30 patients with "complete" spinal cord injury or classified as American Spinal Injury Association (ASIA)-A were studied. Orthopedic treatment of the injured vertebra(e), internal fixation of the vertebral column, and bilateral laminectomy for epidural decompression were followed directly by neurosurgical management, including separation of the arachnoid adhesion to restore cerebrospinal fluid flow and debridement of the spinal cord necrotic tissue with concomitant intramedullary decompression. Rehabilitation started 17 days after the operation. The final outcome was evaluated after 3 months of rehabilitation. Pearson chi-square analysis was used for statistical analysis. Results All the patients recovered some ability to walk. The least recovered patients were able to walk with a wheeled weight support and help in stabilizing the weight bearing knee joint (12 cases, 40%). Thirteen patients (43%) were able to walk with a pair of crutches, a stick or without any support. The timing of the operation after injury was important. An optimal operation time window was identified at 4-14 days after injury. Conclusions Early neurosurgical intervention of spinal cord contusion followed by rehabilitation can significantly improve the locomotion of the patients. It is a new idea of a therapeutic approach for spinal cord contusion and has been proven to be very successful。

Abstract：Background This study aimed to investigate multi-slice CT contrast-enhanced presentation of gastric cancer and its correlation with histo-differentiation and p53 and P-glycoprotein (P-gp) expression. Methods Sixty-six patients with gastric cancer in the present study underwent a multi-slice CT preoperative routine and dual-phase contrast-enhanced examination of the upper abdomen; postoperative specimens were used to determine histo-differentiation and the expression of p53 and P-gp. The correlation of multi-slica CT contrast-enhanced presentation with histo-differentiation and expression of p53 and P-gp was analyzed. Results The dual-phase contrast-enhanced ratio (CER) was not correlated with the histo-differentiation of gastric cancer (P＞0.05). Positive expression of p53 and P-gp was significantly higher in the cases of layered or heterogeneous enhancement than in the cases of homogenous enhancement (P＜0.05). Positive expression of p53 was also correlated with the arterial phase CER, tumor size and lymph node metastasis (P＜0.05), but not with infiltration thickness of the gastric wall, nor was it correlated with the portal phase CER (P＞0.05). Positive expression of P-gp was only correlated with the portal phase CER (P=0.005). Conclusions Differently enhanced pattern and CER of the arterial and portal phase in gastric cancer correlate with its different histo-differentiation and expression of p53 and P-gp respectively. In addition, tumor size and lymph node metastasis of gastric cancer relate to the expression of p53。

Abstract：Background The major difficulty in the research of DNA microarray data is the large number of genes compared with the relatively small number of samples as well as the complex data structure. Random forest has received much attention recently; its primary characteristic is that it can form a classification model from the data with high dimensionality. However, optimal results can not be obtained for gene selection since it is still affected by undifferentiated genes. We proposed recursive random forest analysis and applied it to gene selection. Methods Recursive random forest, which is an improvement of random forest, obtains optimal differentiated genes after step by step dropping of genes which, according to a certain algorithm, have no effects on classification. The method has the advantage of random forest and provides a gene importance scale as well. The value of the area under the curve (AUC) of the receiver operating characteristic (ROC) curve, which synthesizes the information of sensitivity and specificity, is adopted as the key standard for evaluating the performance of this method. The focus of the paper is to validate the effectiveness of gene selection using recursive random forest through the analysis of five microarray datasets; colon, prostate, leukemia, breast and skin data. Results Five microarray datasets were analyzed and better classification results have been attained using only a fewgenes after gene selection. The biological information of the selected genes from breast and skin data was confirmed according to the National Center for Biotechnology Information (NCBI). The results prove that the genes associated with diseases can be effectively retained by recursive random forest. Conclusions Recursive random forest can be effectively applied to microarray data analysis and gene selection. The retained genes in the optimal model provide important information for clinical diagnoses and research of the biological mechanism of diseases.

Abstract：Background Serum uric acid (UA), the final product of purine degradation, has been proposed to be a marker for the severity and a possible predictor of mortality in patients with pulmonary arterial hypertension (PAH). The objectives of this study were to elucidate whether serum UA level correlates with the clinical features and the hemodynamic variables in Chinese patients with PAH and to compare the difference of the correlates in patients associated with different etiologies. Methods Serum UA was assessed in 228 patients with three types of PAH (idiopathic PAH (IPAH), congenital heart disease related PAH (CHD-PAH) and connective tissue disease related PAH (CTD-PAH)) together with other clinical features. After the individualized treatment for at least 6 months, the UA levels and clinical features were re-evaluated in 88 patients. Results Serum UA was significantly elevated in patients with PAH compared with age-matched control subjects ((350.40±108.73) μmol/L vs (266.91±81.38) μmol/L), P＜0.001). Serum UA negatively correlated with cardiac output and mixed venous saturation (SvO<,2>) in all three types of PAH (all P＜0.05), positively correlated with the size of right ventricle in IPAH (P=0.002) and CTD-PAH (P=0.013) patients and with pulmonary vascular resistance just in CTD-PAH patients (P=0.001). Serum UA significantly decreased from (365.80±120.46) μmol/L to (333.67±117.56) μmol/L in 88 patients (P=0.006) with vasodilator therapy for at least 6 months, accompanied with a reduction in pulmonary vascular resistance from (15.13±6.96) Woods unit to (12.00±5.04) Woods unit (P=0.001) and an increase in cardiac output from (2.63±0.98) L/min to (3.08±1.04) L/min (P=0.005). Conclusions Serum UA increases in proportion to the clinical severity of all the three types of PAH, especially the CTD-PAH had a stronger correlations compared with IPAH and CHD-PAH. The serum UA levels also could partly reflect the response to the treatment in patients with PAH。

Abstract：Background Late incomplete stent apposition (ISA) may occur after drug-eluting stent implantation, affecting long-term clinical outcomes. This study aimed to evaluate the impact of clinical presentations of coronary artery disease on late ISA after percutaneous coronary intervention (PCI) with sirolimus-eluting stents (SES) by means of three-dimensional volumetric intravascular ultrasound (IVUS) analyses. Methods One hundred and thirty-seven patients with coronary artery disease received SES implantation during PCI and had repeat angiography with IVUS examination. All patients were followed up one year after the procedure. Results In overall 219 treated lesions (137 patients), late ISA was identified in 25 lesions (16 patients). Clinical diagnosis of acute coronary syndrome (ACS) and use of long stents were more common in patients with than in those without late ISA. Patients with late ISA had greater external elastic membrane (EEM) area in stented segment ((15.34+5.44) vs (13.83=,-4.51 ) mm2, P=0.026), stented-to-reference segment EEM area ratio (1.13±0.22 vs 1.02±0.18, P ＜0.001), and plaque and media area ((8.43±3.93) vs (7.01±2.93) mm2, P =0.002) than in those without late ISA. Multivariate Logistic regression analysis showed that clinical diagnosis of ACS and use of long stents were independent risk factors for late ISA (OR 6.477, 95%C/ 2.297-18.263, P＜0.001; OR 3.680, 95%C/ 1.181-11.469, P =0.025; respectively). During one-year follow-up after IVUS examination, the rate of very late stent thrombosis tended to be higher in patients with than in those without late ISA (18.7% vs 3.3%, P=0.051). Conclusions The occurrence of late ISA after SES implantation may be related to clinical status, use of long stents, and marked positive vessel remodeling. Late ISA tended to increase the rate of very late stent thrombosis during follow-up, highlighting the importance of long-term dual antiplatelet therapy for these patients。

Abstract：Background Serum high sensitive C-reactive protein (hs-CRP), adiponectin levels and urine albumin excretion rate (UAER) are probably associated with inflammation and atherosclerosis. The aim of this study was to determine the three markers in coronary artery disease (CAD) subjects with different glucose tolerance status in a Chinese population and further explore the levels of the three markers in these subjects and the possible association of these markers with CAD risk factors and the severity of CAD as well. Methods A total of 242 subjects with angiographically documented CAD were recruited, and then assigned to three groups: the normal glucose tolerance (NGT) + CAD group, including 100 CAD patients with NGT; the impaired glucose tolerance (IGT) + CAD group, 40 CAD patients with IGT; the type 2 diabetes mellitus (T2DM) + CAD group, 102 CAD patients with T2DM. Serum hs-CRP, adiponectin levels as well as UAER were measured in all subjects. Results Serum hs-CRP levels were increased in the T2DM + CAD group compared with the NGT + CAD group (4.71±2.59) vs (3.60±2.46) mg/L, P=0.037. Serum adiponectin levels were gradually decreased from the NGT + CAD to IGT + CAD to T2DM + CAD groups, (5.99±1.84), (5.82±1.72) and (4.65±1.71) mg/L, P=0.002 and 0.040 for NGT + CAD and IGT + CAD groups vs T2DM + CAD group, respectively. While the UAER was gradually increased from the NGT + CAD to IGT + CAD to T2DM + CAD groups, (6.42±2.51), (6.89±2.94) and (15.03±4.22) pg/min (P＜0.001) for NGT + CAD and IGT + CAD groups vs T2DM + CAD group. Multiple linear stepwise regression analysis showed that waist-hip ratio (WHR) and low density lipoprotein cholesterol (LDL-C) were the significant determinants of serum hs-CRP levels; triglyceride (TG), high density lipoprotein cholesterol (HDL-C), age, WHR, T2DM, 2-hour serum insulin (2hlNS), sex, and apolipoprotein B were the significant determinants of serum adiponecUn levels; and systolic blood pressure (SBP), T2DM, and hemoglobin Alc (HbAlc) were the significant determinants of UAER in all subjects (R2= 0.070, 0.352, and 0.214, respectively). However, no significant correlation was seen for hs-CRP, adiponectin and UAER with the severity of CAD. Hs-CRP levels were significantly correlated with UAER. Conclusions There was a trend of increased serum hs-CRP levels from the NGT + CAD to IGT + CAD to T2DM + CAD groups, though it only showed significance in the T2DM + CAD group compared with the NGT + CAD group. Serum adiponectin levels were decreased and UAER was increased from the NGT + CAD to IGT + CAD to T2DM + CAD groups. Increased UAER and serum hs-CRP, and decreased adiponectin levels were associated with traditional CAD risk factors but failed to be correlated with the severity of CAD. Hs-CRP levels were significantly correlated with UAER。

Abstract：Background The true proliferation degree of bum and operation scars during their maturation was poorly defined. The objective of this study was to provide a quantitative evaluation of the proliferation degree of deep-partial thickness bum and surgical suture wound scars after wound healing and the accuracy of subjective judgment of scar types. Methods A total of 423 patients in the burn group and 667 patients in the suture wound group were enrolled in this study. Objective scar measurement (by negative-positive moulage) was carried out at 3, 6 and 12 months after wound healing in 1090 patients from different regions in China. The KruskaI-Wallis H test and chi-square test were used in the statistical analysis. Results The median degrees of scar proliferation were 0.03 cm at 3 months, 0.03 cm at 6 months and 0 cm at 12 months in the burn group and 0.05 cm, 0.04 cm and 0.04 cm respectively in the suture wound group. At 3 and 6 months post wound healing, there was no significant difference in scar proliferation between the groups (P＞0.01). After 1 year, burn scars displayed evidence of atrophy (P＜0.01). Although the degree of scar proliferation differed among the four scar types (P＜0.01), the ranges of scar height in the four scar types largely overlapped when judged in a subjective manner, especially in proliferation and superficial scars. Conclusions Scar atrophy occurs after one year in burns, but not in the surgical suture wound group. It is important to take anti-scar therapy for surgical wounds as well as burn wounds. The various scar types could not be judged precisely in a subjective manner。

Abstract：Background The diagnostic value of virtual imaging combined with three-dimensional computed tomographic angiography (3D-CTA) for intracranial aneurysms has not been fully elucidated yet. This study aimed to evaluate the value of combined application of virtual imaging techniques and 3D-CTA in diagnosing patients with aneurismal subarachnoid hemorrhage (SAH) at the acute stage. Methods Eighty patients with non-traumatic SAH received 3D-CTA examinations. The raw CT data of these patients were reconstructed and transferred into the 3D mode through the surgical plan system based on virtual reality (VR) image, and the 3D virtual images of skulls and brain blood vessels were acquired. The location, size and shape of aneurysms and their anatomic relationship with adjacent tissues were measured from many points of view. Results Seventy-three aneurysms were detected in 68 of the 80 patients, but 2 aneurysms were detected in 2 of the 5 patients who had been found free of aneurysms previously and had received 3D-CTA examinations for a second time one month later. The 3D virtual images produced by the virtual imaging system were clear and vivid, and they could reveal the location and size of the aneurysm and its relations to the parent artery and skull directly. Conclusions The imaging of 3D-CTA is convenient, reliable and fast in diagnosing intracranial aneurysms and can be regarded as the first choice for the diagnosis and treatment of ruptured intracranial aneurysms. Combined with the surgical plan system based on the VR image, 3D-CTA may obtain more imaging information about aneurysms。

Abstract：Background The present study was undertaken to replicate the associations of representative polymorphisms in three genes (complement factor H (CFH), complement factor B (BF) and HtrA serine peptidase 1 (HTRA1)) with exudative age-related macular degeneration (AMD) in a Hart Chinese population, and to test if the modifiable environmental factors affect AMD susceptibility associated with different type of genotype in these genes. Methods An age, gender and ethnicity matched case-control study was conducted to genotype the representative single neucleotide polymorphisms (SNPs) loci including rs1061170 and rs1410996 in CFH, rs641153 and rs4151667 in BF and rs11200638 in HTRA1 gene in 144 exudative AMD patients and 126 normal controls using PCR-RFLP and directresequencing. The demographic characteristics and behavioral risk factors were also recorded. Allelic and genotypic associations for individual SNP and joint associations with two loci were performed. The gene-gene and gene-environment interactions were analyzed using multivariate non-conditional Logistic regression analysis. Results The C risk allele frequencies for CFH Y402H (rs1061170) in cases and controls were 12.5% and 5.4% respectively, which were much lower than those in Caucasians (P＜0.001). Compared with TT homozygous genotype, the CT heterozygous genotype was positively associated with AMD with odds ratio (OR) of 3.23 (1.36-5.07). However, the population attributable risk (PAR) of C allele was only 3.3% (1.4%-4.3%). rs1410996 was also associated with AMD independent of Y402H. The ORs of exudative AMD for individuals carrying one copy risk allele and two copy risk alleles were 2.57 (1.21-5.45) and 4.76 (2.15-10.55) respectively, with correspondent PARs of 28.3% (2.0%-40.5%) and 38.2% (21.8%-45.4%). rs11200638 in HTRA1 was another susceptible locus for AMD and the risk homozygotes were significantly susceptible for exudutive AMD (OR=3.98, 1.88-8.43) with PAR of 38.9% (24.3%-45.8%). Education status and cigarette smoking were also related to exudative AMD. After controlling for environmental risk factors, CFH and HTRA1 SNPs were independently associated with exudative AMD, with OR of 3.50 (1.45-8.45) for CT genotype in Y402H, 3.34 (1.33-8.36) for GG genotype in rs1410996 and 3.85 (1.58-9.42) for AA genotype in rs11200638 respectively. The interaction analysis between gene and environmental factors showed that smoking synergistically increased susceptibility of AMD for heterozygotes of rs1410996, with ORinteraction of 7.33 (Pinteraction=0.029). Conclusions In a Han Chinese population, CFH and HTRA1 polymorphisms appear to be independently and possibly additivelv hereditary contributors to exudative AMD. Y402H polymorphism conferred a significant but relatively lower contribution in Chinese than in Caucasians with a low frequency of risk allele. The gene-environment interaction may be a best way to encourage those with a high genetic risk to prevent AMD by avoiding modifiable factors until there is effective treatment for AMD.

Abstract：Background As a model for both multistep and multipathway carcinogenesis, colorectal neoplastic progression provides paradigms for researching both oncogenes and tumor suppressor genes (TSGs). However, the mechanism of colorectal cancer (CRC) is not completely understood, and many genes may be involved in the colorectal carcinogenesis. The purpose of this study was to screen for the potential TSGs on chromosome lq31.1-32.1 in Chinese patients with sporadic colorectal cancer, to explore whether colorectal cancer in the Chinese population has unique genetic alterations and determine whether other putative TSGs exist and contribute to colon carcinogenesis. Methods Six polymorphic microsatellite markers, at a density of approximately one marker in every 1.6 cM, were chosen for refined loss of heterozygosity (LOH) mapping of lq31.1-32.1. Eighty-three colorectal cancer patients' tumor and normal DNA were analyzed via polymerase chain reaction (PCR) for these microsatellite markers. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.1 and Genotype 2.1 software were used for LOH scanning and analysis. On the basis of refined LOH mapping results, we undertook a microarray-based expression screening to identify tumor association genes in 19 of the CRC cases. Results The average LOH frequency of lq31.1-32.1 was 24.41%, with the highest frequency of 36.73% (18/49) at D1S2622, and the lowest of 16.42% (11/67) at D1S412. A minimal region of frequent deletion was located within a 2 cM genomic segment at D1S413-D1S2622. There was no significant association between LOH of any marker in the studied regions and the clinicopathological data (patient sex, age, tumor size, growth pattern, or Dukes stage). On the basis of refined mapping results, we chose 25 genes located in the D1S413-D1S2622 (lq31.3-32.1) region and presented a microarray-based high throughput screening approach in 19 sporadic CRC cases to identify candidate CRC related tumor suppressor genes. This study found 4 significantly down-expressed genes, including CSRP1, LMOD1, PPP1R12B and CFHL3. There was no significant association between expression levels of CFHL3, CSRP1, LMOD1, PPPIR12B and the clinicopathological data. By database searching, CSRP1 was hypothesized to be a colorectal cancer related tumor suppressor gene. Conclusions Through detailed deletion mapping, we found that the lq31.3-32.1 region might harbor one or more colorectal cancer related tumor suppressor gene(s). And by microarray-based high-throughput screening of candidate genes located in this region and by subsequent database searching, we present the first evidence that CSRP1 might be involved in the progression of CRC。

Abstract：Background Ketanserin (KT), a selective serotonin (5-HT) 2-receptor antagonist, reduces peripheral blood pressure by blocking the activation of peripheral 5-HT receptors. In this study electrophysiological method was used to investigate the effect of KT and potassium ion on Kv1.3 potassium channels and explore the role of blocker KT in the alteration of channel kinetics contributing to the potassium ion imbalances. Methods Kvl.3 channels were expressed in xenopus oocytes, and currents were measured using the two-microelectrode voltage-clamp technique. Results KCI made a left shift of activation and an inactivation curve of Kv1.3 current and accelerated the activation and inactivation time constant. High extracellular [K+] attenuated the blockade effect of KT on Kv1.3 channels. In the presence of KT and KCI the activation and inactivation time constants were not influenced significantly no matter what was administered first. KT did not significantly inhibit Kv1.3 current induced by tetraethylammonium (TEA). Conclusions KT is a weak blocker of Kv1.3 channels at different concentrations of extracellular potassium and binds to the intracellular side of the channel pore. The inhibitor KT of ion channels is not fully effective in clinical use because of high [K+]o and other electrolyte disorders.

Pulmonary hypertension is a pathophysiologic process characterized by progressive elevation of pulmonary vascular resistance and right heart failure, which is a common complication of many diseases. Pulmonary hypertension with no apparent causes (unknown etiology) is termed primary pulmonary hypertension or, more recently, idiopathic pulmonary arterial hypertension (IPAH)。

Biliary papillomatosis (BP) is an extremely rare pathological condition, which is characterized by papillary proliferation of the bile duct epithelia. Although initially thought to be a benign entity, this tumor has been shown to have a tendency for malignant transformation。

The natural historv of HIV is defined as the untreated progression from the time of HIV transmission to death.1 The typical course of infection is characterized by three phases: acute or primary infection phase, the asymptomatic phase, and AIDS. Primary infection is often accompanied by a symptomatic acute retroviral syndrome starting 2-3 weeks after transmission and lasting an additional 2-4 weeks.1,2

Microscopic polyangiitis (MPA) is characterized by an inflammatory process of the vessel walls and is classified according to the smallest vessels involved. Diagnosis is based on clinical manifestations, anti-neutrophil cytoplasmic autoantibody (ANCA) testing, and histology. In this disease, pulmonary hemorrhage is seen in 30% of patients and is associated with an eight-fold increase in mortality. Classically, MPA involves the kidneys and upper and lower respiratory tracts. Due to the perceived risk of increased bleeding secondary to the use of systemic anticoagulation, extra corporeal membrane oxygenation (ECMO) is often not used to treat patients with hemorrhage suffered from MPA. Here we report a case of a 50-year-old woman with MPA that was successfully supported with ECMO。

Fetal aortopulmonary septal defect (APSD) is an extremely rare condition, accounting for 0.1%-0.2% of all cardiac defects in live births world wide.1 Hospital mortality is 13% and 33% for simple and complex APSD, respectively.2 This rare cardiac defect refers to a congenital malformation in the development of the arteriosus truncus septum, and is usually associated with a wide variety of other structural cardiac anomalies such as ventricular septal defect (VSD), pulmonary valve stegnosis and so on.3 Prenatal diagnosis of an APSD is possible by echocardiography。