Mar 2010, Volume 4 Issue 1
    

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  • Research articles
    Sai-Juan CHEN, Xiao-Ping CHEN, Guang-Biao ZHOU,
  • Research articles
  • Research articles
    Zhi-Ruo ZHANG PhD, Jian-Qing MI MD, Zhao-Jun WEN MA, Sai-Juan CHEN MD, PhD, Zhu CHEN PhD, Long-Jun GU MD, Jing-Yan TANG MD, PhD, Shu-Hong SHEN MD, PhD,
    China has been undertaking a profound reform on health care. Although more than 1.16 billion people have been covered by rural and urban medical insurance to date, the level of reimbursement from insurance is very limited, especially for critical diseases such as leukemia. This places heavy economic burdens on patients. Under these circumstances, systems innovation is imperative for the efficient utilization of limited funding. In this respect, certain valuable experience from other countries may prove helpful. The prospective payment system of Diagnosis-related Groups (DRGs), Clinical Paths, and the Comparative Effectiveness Analysis adopted by the National Institute of Health and Clinical Excellence (NICE, UK), can be fine tools to reduce medical costs and improve quality of services. Treatments of acute promyelocytic leukemia at Rui-Jin Hospital, and childhood acute lymphoblastic leukemia at Shanghai Children’s Medical Center, can be taken as suitable models to illustrate the crucial role of Clinical Paths in guaranteeing clinical and cost effectiveness of medical services for critical diseases, and to satisfactorily justify the feasibility of DRGs in China.
  • Research articles
    Jun-Jie XIAO MD, Yi-Han CHEN MD, PhD,
    Cardiovascular diseases (CVD) cause one third of all deaths in China, and the number is anticipated to double by 2020. They also greatly result in disability and adjusted life year loss. The prevalence of CVD has become a new burden for China, due to an aging population, smoking, and changes in dietary habits and lifestyles. As the largest developing country, China needs to tailor her own national policies for managing CVD with full consideration of epidemiology, local needs, and affordability. Smoking cessation, increased physical activity, control of hypertension and hypercholesterolemia, and maintenance of a “traditional Chinese” diet should be important strategies for reducing the burden of CVD in China. Health officials in China should take their responsibilities to implement educational and preventive measures seriously.
  • Research articles
    Wei-Li ZHANG MD, PhD, Ru-Tai HUI MD, PhD,
    Stroke is a major cause of adult death and disability worldwide. Epidemiological and animal studies have provided strong evidence that the pathogenesis of stroke is multi-factorial and induced by a combination of environmental and genetic risk factors, but the identification of individual causative variants remains little known. Genetic influences are likely to be polygenic with small effect sizes, and stroke itself consists of a number of different subtypes which may each have different genetic profiles. In addition, various ethnic populations may have different stroke risk, such as Asian race. The reasons for high risk of stroke among the Chinese, especially hemorrhagic stroke, remain unknown. Most human studies have taken a candidate gene approach using case-control methodology. To be reliably detected, small relative risks require large sample sizes, probably 1000 patients or more. Genome-wide association (GWA) study is an unbiased and comprehensive approach to identify common risk alleles for complex diseases. Recently, a multistage GWA study has identified three loci on chromosomes 2q, 8q and 9p to be associated with intracranial aneurysm in European and Japanese populations. Another GWA finding is the identification of risk variants for cardioembolic stroke on chromosome 4q25 in European populations. In this review, we mainly focus on the results from case-control association studies on genetic factors that play a role in the risk of ischemic and hemorrhagic stroke in Chinese population. The combined effects of multiple susceptibility genes for stroke risk are also summarized.
  • Research articles
    Chen WANG PhD, MD, Zhen-Guo ZHAI PhD, MD, Ying H. SHEN PhD, MD, Lan ZHAO PhD, MD,
    Venous thromboembolism (VTE), including deep vein thrombosis and pulmonary embolism, carries significant mortality and morbidity. The most important and effective way to reduce VTE incidence is to identify the patients at risk and give necessary prevention. VTE is a multifactorial and complicated disorder. Major risk factors for VTE include surgery and trauma, acute medical illness, active cancer and pregnancy. Genetic factors increase susceptibility to the disease and are useful in predicting the development of VTE. Gene-gene and gene-environment interactions alter and magnify the clinical picture in this disorder. This brief review summarizes some selected clinical and genetic risk factors for VTE based on the current research in China.
  • Research articles
    Wen-Qiang CHEN MD, Yun ZHANG MD, PhD, FACC,
    Vulnerable atherosclerotic plaque rupture leading to thrombosis is the major cause of acute coronary syndrome (ACS). Studies on the pathophysiologic mechanism of both ACS and plaque stabilizing treatment are driving the development of animal models of vulnerable plaque. In our laboratory, we established animal models of plaque rupture and thrombosis in rabbits and mice that are similar to human plaque rupture. Potential mechanisms involved in plaque vulnerability were studied from the inflammation-immunity, proliferation-apoptosis, oxidative stress and biomechanics aspects. Imaging markers and biomarkers were used to detect vulnerable plaques, including high frequency duplex ultrasound, intravascular ultrasound (IVUS), intravascular ultrasound elastography, magnetic resonance imaging (MRI) and inflammatory markers. Effective gene and drug strategies to treat vulnerable plaques were explored.
  • Research articles
    You ZHOU MD, Chang-Kai SUN MD,
    Normal brain function requires continuous supply of oxygen and glucose in a strict manner. The close spatial and temporal relationship between neural activity and cerebral blood flow (CBF) is termed as neurovascular coupling, which is dependent or not dependent on astrocytes. The increase in flow evoked by brain activity is mediated by the concerted action of multiple mediators that originate from different cells and act at different levels of the cerebral vasculature. More studies are needed for further understanding the precise mechanisms underlying neurovascular coupling, especially the implications of astrocytes.
  • Research articles
    Xu WANG MS, Xiao-Wei GONG MD, PhD, Yong JIANG MD, PhD, Yu-Hua LI PhD,
    Mitogen-activated protein kinase (MAPK) signaling pathway, one of the most important signaling pathways in eukaryotic organism, is involved in multiple cellular events such as cell growth, differentiation, and apoptosis. MAPK is of great importance to the normal function of organisms, while its dysfunction results in various diseases. So far, inhibitors specifically against each subfamilies of MAP kinase have been developed, while more endeavors are needed to discover the compounds selectively targeting a particular subfamily member. Most of the kinase inhibitors exert their functions in an ATP-competitive way or a non-ATP-competitive way. Further studies on the effective mechanism of the MAPK inhibitors and their therapeutic roles in the treatment of diseases are helpful for the illumination of MAP kinase function, the development of novel inhibitors, and the therapy of diseases caused by the dysfunction of the MAPK pathway.
  • Research articles
    Jin-Nong ZHANG MD, Bo PENG BA, Jamile WOODS MD, Wei PENG MD, PhD,
    Severe sepsis and septic shock affect millions of patients and are major causes of mortality worldwide. Advancements in treatment and disease management led to a decline in in-hospital mortality from 27.8% (1979–1984) to 17.9% (1995 to 2000). In this article, we systemically review recent guidelines for the management of severe sepsis and septic shock published in 2008 by the International Surviving Sepsis Campaign Guidelines Committee. The 2008 Surviving Sepsis guidelines recommend protocolized resuscitation with goals to maintain central venous pressure≥8–12mmHg, mean arterial pressure≥65mmHg, urine output≥0.5mL·kg−1·h−1 and central venous oxygen saturation≥70% (or mixed venous≥65%). Further fluid administration, transfusion of packed red blood cells to achieve a hematocrit of≥30% and/or infusion of dobutamine max 20µg·kg−1·min−1 are advised if venous O2 saturations remain below 70%. In patients with decreased ventricular compliance or mechanical ventilation, a target central venous pressure of 12–15mmHg is recommended. Intravenous antibiotic administration within the first hour of recognizing severe sepsis and septic shock is essential, while use of corticosteroids in sepsis is controversial. The mechanisms by which activated protein C improves clinical outcomes in sepsis are unknown. Therapy with activated protein C is approved for patients with severe sepsis and an increased risk of death [Acute Physiology and Chronic Health Evaluation II (APACHE II)>25]. Bicarbonate therapy is discouraged. Intravenous insulin should be used to control hyperglycemia in patients with severe sepsis following stabilization in the intensive care unit.
  • Research articles
    Dai-Hai YU PhD, Jian-Feng HUANG MD, Ji-Chun CHEN MS, Jie CAO MS, Shu-Feng CHEN PhD, Dong-Feng GU MD, PhD, for the GenSalt Collaborative Research Group, De-Pei LIU PhD, Lai-Yuan WANG PhD, Jing CHEN MD, MSc, Jiang HE MD, PhD, Cashell E. JAQUISH PhD, Dabeeru C. RAO PhD, Charles GU PhD, James E. HIXSON PhD, Chung-Shiuan CHEN MS8, Paul K. WHELTON MD, MSc9,
    Dietary potassium-supplementation has been associated with a decreased risk of hypertension and other cardiovascular outcomes. However, blood pressure (BP) responses to potassium supplementation vary among individuals. This study was designed to examine the association between 12 single nucleotide polymorphisms (SNPs) in the adducin 1 alpha (ADD1) and guanine nucleotide binding protein (G protein) beta polypeptide 3 (GNB3) genes and systolic BP (SBP), diastolic BP (DBP), and mean arterial pressure (MAP) responses to potassium-supplementation. We conducted a 7-day high-sodium intervention (307.8 mmol sodium/day) followed by a 7-day high-sodium with potassium-supplementation (60 mmol potassium/day) among 1906 Han Chinese participants from rural north China. BP measurements were obtained at the end of each intervention period using a random-zero sphygmomanometer. We identified significant associations between ADD1 variant rs17833172 and SBP, DBP, and MAP responses to potassium-supplementation (all P<0.0001) that remained significant after adjustment for multiple comparisons. In participants that were heterozygous or homozygous for the G allele of this marker, SBP, DBP, and MAP response to potassium-supplementation were −3.52 (−3.82, −3.21), −1.41 (−1.66, −1.15) and −2.12 (−2.37, −1.87), respectively, as compared to the corresponding responses of 1.99 (0.25, 3.73), −0.65 (−0.10, −0.21), and −0.23 (−0.37, 0.83), respectively, for those who were homozygous for A allele. In addition, participants with at least one copy of the G allele of rs12503220 of the ADD1 gene had significantly increased DBP and MAP response to potassium-supplementation (P = 0.0041 and 0.01, respectively), which was also significant after correction for multiple testing. DBP and MAP responses to potassium-supplementation were −1.36 (−1.63, −1.10) and −2.07 (−2.32, −1.82) for those with at least G allele compared to corresponding responses of 0.86 (−0.68, 2.40) and −0.45 (−1.74, 0.84) for those who were homozygous for A allele. In summary, our study identified novel associations between genetic variants of the ADD1 gene and BP response to potassium-supplementation, which could have important clinical and public health implications. Future studies aimed at replicating these novel findings are warranted.
  • Research articles
    Xin-Jian LI MD, Min-Na CHENG MPH, Yu-Heng WANG MD, Sun MIAO MPH, Zong-Qi ZHANG PhD, Yi-Sheng CHEN MD, Wei LU PhD,
    A community-based multi-center randomized controlled trial was conducted to evaluate the effectiveness of blood pressure control for hypertension patients in communities in urban Shanghai by integrated intervention. At present, patients (n=1395) from four communities have completed follow-up for one year, including the intervention group (n=921) and usual care group (n=474). The intervention programs included disease management by a care manager. Blood pressure of each patient was measured regularly. Compared with the control group, the net change of mean systolic blood pressure (SBP) was −6.75 (95% CI: −7.79 to −5.71, P<0.001) mmHg, mean diastolic blood pressure (DBP) was −4.29 (95% CI: −5.08 to −3.49, P<0.001) mmHg, and mean pulse pressure (PP) was −2.46 (95% CI: −3.50 to −1.43, P<0.001) mmHg in the intervention group. The net change extent was larger in patients with regular pharmacological treatment than in those with irregular pharmacological treatment or non-pharmacological treatment. The measures of integrated intervention for hypertension patients in communities can lower significantly not only SBP and DBP, but also PP. It is suggested that measures of integrated intervention can decrease the risk of cardiovascular diseases in hypertension patients.
  • Research articles
    Wei HAN MM, Ming-Xing XIE MD, Qing LV MD, Xin-Fang WANG MD, Li ZHANG MM,
    The recent development of 2-dimensional strain (2D strain) imaging can provide a powerful alternative for assessing left ventricular (LV) torsion. This study was conducted to evaluate the global and regional left ventricular twist by 2D strain in patients with anterior wall myocardial infarction (AMI). A total of 55 AMI patients were divided into two groups according to their ejection fraction (EF) values (group A: LVEF≥50%; group B: LVEF<50%), and 35 normal people served as the control group. Using 2-dimensional strain software, global and regional LV rotation and displacement were obtained at two planes. Compared with the control group, patients of group A showed reduced peak LV twist of the anterior and anterior-septal wall (9.26±1.89vs 10.74±2.67; 9.71±1.71vs 11.36±2.29, both P<0.05), but the radial displacement and global twist were maintained (P>0.05). Differently, regional and global LV twist and radial displacement in patients of group B deceased significantly, especially in the anterior and anterior-septal wall, as compared with patients in the control or group A (both P<0.05). Moreover, a strong correlation was noted between peak twist and radial displacement; the twist-displacement loop was markedly distorted in patients of group B. This study demonstrated that 2D strain has a potential ability for quantification of left ventricular global and segment twist and radial displacement in patients with coronary artery disease.
  • Research articles
    Pei-Tu REN BM, Bao-Chun LU MM, Zhi-Liang CHEN MM, Hong FU MM,
    One hundred and twenty-six patients above 80 years old with biliary diseases undergoing operations in Shaoxing People’s Hospital from Jan. 2002 to Jan. 2007 were analyzed retrospectively. All patients performed a preoperative stair-climbing test, and the risks for cardiopulmonary €complications were evaluated with pair-matching and linear correlations analysis between stair-climbing height (h) and left ventricular ejective factor (EF), forced vital capacity (FVC) and forced expiratory volume in one second (FEV1). There was a significant difference in the incidence of cardiopulmonary complications among different stair-climbing heights. Stair-climbing heights were positively related with EF, FVC and FEV1. This suggests that the stair-climbing test is an effective and simple method for predicting cardiopulmonary complications in elderly patients with biliary diseases.
  • Research articles
    Dian-Ke YU PhD, Chen WU MD, Wen TAN MD, Dong-Xin LIN MD,
    Variation of individuals’ DNA repair capacity has been linked to cancer susceptibility. The xeroderma pigmentsum group F (XPF) plays a pivotal role in nucleotide-excision repair (NER) pathway. This study was to examine the functional significance of XPF promoter polymorphisms and their association with lung cancer risk. The function of XPF promoter polymorphisms was tested by a set of biochemical assays, and their effects on lung cancer risk were determined by a case-control analysis of 988 patients with lung cancer and 986 controls. The XPF−673T allele showed a significantly higher transcriptional activity as compared with the −673C allele. The −673TT genotype was associated with a decreased risk of lung cancer compared with the CC genotype (adjusted OR=0.62, 95% CI=0.42–0.91; P=0.015) and this effect was more significant among males (adjusted OR=0.55, 95% CI=0.35–0.86; P=0.009), elder subjects (adjusted OR=0.51, 95% CI=0.30–0.86; P=0.012), and light smokers (adjusted OR=0.35, 95% CI=0.14–0.88; P=0.026). These findings suggest that functional polymorphisms influencing DNA repair capacity may confer susceptibility to lung cancer.
  • Research articles
    Li-Feng LIU MD, PhD, Qiong CHEN MD, PhD, Ying CHANG MD, PhD, Ju-Sheng LIN MD, PhD, Jin-Liang ZHANG MM,
    This study aimed to identify functional single nucleotide polymorphisms in the cyclooxygenase-2 gene promoter and evaluate their effects on the risk of primary hepatocellular carcinoma (HCC) with hepatitis B virus (HBV) infection. We conducted a population-based, case-control study enrolling 630 Han Chinese people in Hubei province. Subjects included primary HCC patients with HBV infection (n=210), chronic hepatitis B cases (n=210) and healthy Han Chinese (n=210). -1195G/A polymorphism was analyzed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and sequencing analysis. We found-1195A allele carriers had a higher risk of HCC with HBV infection (OR, 0.72; 95% CI, 0.548–0.946). The-1195A allele might be used as a marker in screening individuals at high risk of HCC with HBV infection.
  • Research articles
    Jing CHEN MD, Guang-Yuan HU MD, Guo-Qing HU MD, Hua WU PhD,
    This study was to investigate a better way to detect and differentiate primary, residual, recurrent nasopharyngeal carcinoma (NPC) lesions post-radiotherapy in patients with NPC by means of routine computed tomography (CT) in combination with 99Tcm-sestamibi single photon emission computed tomography (99Tcm-MIBI SPECT). Forty-eight patients with histologically confirmed primary NPC underwent 99Tcm-MIBI SPECT at the 3rd month before and after radiotherapy, and at the 6th month after radiotherapy. All patients had contemporaneous CT examinations. Histopathologic results and/or clinical follow-up data (over 18 months) were used as the golden standard for evaluating residual/recurrent lesions. The radioactive count ratio of nasopharynx to scalp was obtained as the MIBI uptake index (MUI). Receiver operating characteristic analysis was employed to define the cut-off value of MUI for malignancy. With MUI 2.15 as the cut-off point, the accuracy for detecting primary NPC was 94.12%. The mean MUI in the local-regional of the nasopharynx in such negative cases was 1.21±€0.12 at the 3rd month, while the mean MUI was higher in the other 15 patients with histologically confirmed recurrent/residual lesions (MUI=1.40€±€0.16, t=4.71, P<0.001). The optimal cut-off point of 1.33 of MUI was defined with 89.58% accuracy for differentiating residual/recurrent lesions from the benign process post radiotherapy, while CT evaluations showed an accuracy of 81.25%. A combination of CT and 99Tcm-MIBI SPECT for 37 NPC patients with congruent results showed an accuracy of 97.30% for differentiating residual/recurrent NPC from benign lesions. 99Tcm-MIBI SPECT plays a role in evaluating residual/recurrent lesions post-radiotherapy. The combination of CT and 99Tcm-MIBI SPECT can give more accurate diagnosis in the follow-up of NPC.
  • Research articles
    Qiong YU PhD, Xiang-Fei MENG PhD, Jie-Ping SHI, Ya-Qin YU PhD,
    Abnormal phospholipid metabolism in the brain plays an important role in neuropsychiatric diseases. Phospholipase A2 (PLA2) is a crucial element for normal neuro-physiological function. This study aims to investigate the genetic association between the polymorphism of cytosolic phospholipase A2 (cPLA2) family genes and schizophrenia among Han Chinese in the northern part of China. The polymerase chain reaction-based ligase detection reaction (PCR-LDR) was applied to detect the genotype ten single nucleotide polymorphisms (SNPs) of cPLA2 family genes among 201 pedigrees consisting of fathers, mothers and affected offsprings with schizophrenia. The pedigrees were collected from 2000 to 2006. Haplotype relative risk (HRR) test, transmission disequilibrium test (TDT), haplotype transmission analysis and multiple locus analysis were conducted to analyze the genotyping data. The genotypic frequency of cPLA2 gene did not deviate from Hardy-Weinberg equilibrium either in case or control group. HRR and TDT showed that the ten SNPs were not associated with schizophrenia (P>0.05). Analysis for haplotype transmission showed that no haplotype system was associated with schizophrenia (P>0.05). The conditioning on allele (COA) and conditioning on gene (COG) tests showed disease associations with the haplotype of rs2162886-rs1668589, rs891014-rs1668589 and rs2307279-rs7542180 (χ2=6.913, P=0.032; χ2=8.393, P=0.015; χ2€=8.447, P=0.038). Our data suggest that many loci in the cPLA2 family genes may be associated with schizophrenia.
  • Research articles
    Hong-Zhu LU MD, Dan LIU BM, Qi-Hong FAN BM, Jian-Hua ZHOU MD,
    Hepatitis B virus X protein (HBx), a 17-kd protein encoded by X gene of hepatitis B virus (HBV), has been shown to function as a transcriptional trans-activator of a variety of viral and cellular promoter/enhancer elements. The aim of the study is to investigate the extracellular regulated protein kinases (ERKs) pathway of HBx on glomerular mesangial cell (GMC) proliferation and tumor necrosis factor-α (TNF-α) expression. The HBV X gene was amplified by polymerase chain reaction (PCR), inserted into the eukaryotic expression vector pCI-neo and confirmed by restriction endonuclease digestion and sequence analysis. PCI-neo containing HBV X gene (pCI-neo-X) was then transfected into cultured GMC line via liposome. GMC proliferation, TNF-α and its mRNA expression were compared in the condition of with or without U0126 in culture media. HBx, ERK1/2 and p-ERK1/2 expression in GMCs was assessed by Western blotting. TNF-α mRNA expression was assessed by semi-quantitative reverse transcription-PCR (RT-PCR). TNF-α level in supernatants was measured by ELISA. GMC proliferation was detected by 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT) kit. The results showed that HBx expression was found in transfected GMCs and became prominent at 36th and 48th h after transfection whether with or without U0126 in culture media. TNF-α mRNA expression was significantly decreased in U0126 group compared with U0126-free group. TNF-α levels in supernatants in PCI-neo-X transfection without U0126 group were (189.0±18.1) and (172.3±24.3) pg/mL at 36th and 48th h after transfection, respectively. In contrast, TNF-α levels in supernatants with U0126 were (65.6±11.6) and (84.0±24.6) pg/mL at 36th and 48th h, respectively. The TNF-α levels in the latter groups were significantly lower than those in the former groups (P<0.05). GMCs proliferation was also lower in added U0126 group at 36th and 48th h after transfection. From above, we can conclude that HBx could induce GMC proliferation and increase TNF-α mRNA expression and its protein production. HBx upregulates TNF-α expression and induces cell proliferation of GMC line partly through ERK1/2 signal transduction pathway.
  • Research articles
    Zhou-Fang XIONG MD, Wei-Hong DONG MD, Ze-Hua WANG MD,
    We conducted a trial to assess the influence of closure or nonclosure of the peritoneum and subcutaneous tissue on the clinical outcomes of cervical cancer patients who underwent radical hysterectomy with lower abdominal cross incision. This randomized controlled trial was performed on 158 cervical cancer patients in our hospital between January 2002 and June 2004. Eighty-two patients were allocated to the “closure” group and 76 patients to the “nonclosure” group. Results showed that non-closure of the peritoneum and subcutaneous tissue could shorten operation time and febrile duration, reduce antibiotics requirement, increase the volume of drainage and decrease the incidence of liquefaction of subcutaneous fat (P<0.05). There was no difference in blood loss, postoperative complications, bowel function restoration and post-operative stay between the two groups (P>0.05). Our study revealed that closure of the peritoneum and subcutaneous tissue provides no immediate postoperative benefits while unnecessarily lengthening surgical time and anesthesia exposure. The practice of closure of the peritoneum and subcutaneous tissue at radical hysterectomy should be questioned.
  • Research articles
    Hui-Xia ZHOU MD, Zhi-Chun FENG MD, Hao MENG MD, Xiao-Guang ZHOU MD, Shuang LI BM, Jun WANG MM, Shi-Xi DAI BM,
    The surgical emergency treatments and curative effects of postrenal acute renal failure following obstruction due to upper urinary calculi in infants were evaluated. Of the 13 infants with postrenal acute renal failure following obstruction due to upper urinary calculi, 11 received retrograded catheterizations of the ureter with semi-rigid ureteroscopy (F 6.8), and two received open ureterolithotomy. The results showed that only one infant had anuresis and continuous reduction of hemoglobin 5h after the open ureterolithotomy and received exploration via excision and peritoneal dialysis, and the remaining 12 patients well recovered in this group. The renal function of all the patients was restored without postoperative complications. It is concluded that the retrograded catheterization of the ureter with ureteroscopy is a minimally invasive, safe and effective therapy for postrenal acute renal failure following obstruction due to upper urinary calculi in infants. For those infants whose urethras are thin and small, the open ureterolithotomy is a suitable method. But patients with bleeding tendency need to be corrected prior to the open ureterotomy to remove obstructions.