2008年·第121卷第10期

Abstract：Background Recent studies have suggested that susceptibility to major depressive disorder (MDD) might be related to the serotonin 1A receptor (5-HTR1A) C(-1019)G polymorphism. In this study, we aimed to assess the association between 5-HTR1A C(-1019)G polymorphism and MDD in the Northern Hart ethnic group of China.Methods The C(-1019)G of 5-HTR1A was detected with polymerase chain reaction (PCR) in 400 patients with MDD and 400 unrelated age-and sex-matched healthy control subjects. Association between the C(-1019)G and MDD was statistically analyzed.Results There was a statistically significant difference between MDD patients and controls in both the genotype distribution (X2=10.913, df=2, P=0.004) and the allele frequency (X2=10.379, dr=l, P=0.001), and a significant difference in the genotype distribution and the allele frequency was found both in the female subjects (Genotype distribution:X2=15.406, df=2, P=0.000; allele frequency: X2=15.552, df=l, P=0.000) and the late-onset subjects (Genotype distribution:X2=7.771, df=2, P=0.021; allele frequency: X2=8.007, df=l, P=0.005) in the two groups.Conclusion These results suggest that 5-HTR1A C(-1019)G polymorphism is probably associated with MDD and it is likely to be the susceptible gene locus for the female and late-onset MDD。

Abstract：Background Mechanical ventricular assistance is an important therapeutic method for severe heart failure patients. A variety of ventricular assist devices have been designed for use. The purpose of this report was to describe the experience of using Abiomed BVS5000 as a means of left ventricular support as a clinical treatment for heart failure patients.Methods From February 2004 to April 2006, 12 male patients were supported with Abiomed BVS5000 left ventricular assist device (LVAD) at Fu Wai Hospital. The average age was (55.2+9.6) years (range 39 to 68 years). The mean body surface area was (1.76±0.1) m2 (range 1.6 to 1.9 m2 ). Devices were inserted for post-cardiotomy shock after coronary artery bypass graft in 11 patients (92%) and in 1 dilated cardiomyopathy patient for acute cardiogenic shock. Modified cannulation methods by inserting the arterial cannulae in femoral artery and inserting the venous cannula in left atrium through a segment of bovine jugular vein were used in 7 patients. In this way, the device could be taken off without re-sternotomy when support was finished. A comparison was made between the modified method and routine left atrium-to-ascending aorta cannulating method.Results The median duration of support was 5 (3-43) days, with support flow rate of 3.8-4.5 L/min. There were 9 (75%)patients weaned from support and 8 (67%) patients discharged from the hospital. Four (33%) patients were dead. The most common morbidity was adverse neurological events. There is no statistical difference between modified and routine method on average in BVS5000 support duration, in assisted flow rate, in mechanical ventilation duration, in the intensive care unit stay and thoracic drainage.Conclusions The Abiomed BVS5000 is valuable to support patients with acute cardiogenic shock for short-term use.By the modified cannulating method, the weaning procedure can be effectively simplified. Optimization of inserting indication remains challenging and attributes to a successful assist program。

Abstract：Background Esophageal carcinoma is a common kind of malignant tumor and about 90% of which is esophageal squamous cell carcinoma (ESCC), and it has a high incidence in China. In recent years it has been argued that angiogenesis plays a key role in tumor growth and metastasis and it is a complex process influenced by many factors.This study was aimed to investigate the expression of PC cell-derived growth factor (PCDGF or progranulin) and vascular endothelial growth factor (VEGF) in ESCC tissue and their relationship with clinical pathological parameters of ESCC,clarify the role of PCDGF and VEGF in the angiogenesis of ESCC.Methods The expression of PCDGF and VEGF in 50 surgical specimens from patients with ESCC and 20 with normal esophageal mucosa were detected by immunohistochemistry. The vascular endothelial cells in tumor tissues were labeled by antibody to CD105 for counting microvessel density (MVD).Results The expression of PCDGF and VEGF in ESCC was significantly higher than that in normal mucosa.Expression correlated with the depth of tumor invasion, lymph node metastasis, and TNM (classification tumor, nodes,metastasis). In ESCC, both the expression level of PCDGF and VEGF had a positive correlation with MVD and the expression of PCDGF had a significant correlation with the expression of VEGF.Conclusions These results show that both of PCDGF and VEGE have higher expression in ESCC, which indicate that they have a close relationship with angiogenesis. They may be involved in tumor growth, infiltration and metastasis through promoting tumor angiogenesis and may be an important index reflecting biological behavior and prognosis of ESCC。

Abstract：Background Patients aged over 85 years have been under-represented in percutaneous coronary intervention (PCI)trials despite an increase in referrals for PCI. The long-term safety and efficacy of percutaneous coronary stenting in patients aged over 85 years with acute coronary syndrome (ACS) remain unclear. Moreover it is unknown whether there are differences between bare metal stent (BMS) and drug eluting stent (DES) in this special population.Methods A total of 80 patients with ACS aged over 85 years undergoing stenting (BMS group n=21 vs DES group n=59)were retrospectively studied. In-hospital, one year and overall clinical follow-up (12-36 months) of major adverse cardiac events (MACEs) including cardiac deaths, myocardial infarction, target lesion revascularization (TLR) and target vessel revascularization (TVR) as well as stroke and other major bleeding were compared between the two groups.Results In the entire cohort, the procedure success rate was 93.8% with TIMI-3 coronary flow post-PCI in 93.8% of the vessels and the procedure related complication was 17.5%. The incidence of in-hospital MACEs in BMS group was higher (14.3% vs 6.8%, P=0.30). The 1-year incidence of MACEs in DES group was 7.0% while there was no MACE in the BMS group. Clinical follow-up for 12-36 months showed that the overall survival free from MACE was 82.9% and the incidence of MACE in the BMS group was lower (5.3% vs 21.1%, P=0.20). Multivariate regression analysis showed that the creatinine level (OR:1.013; 95%C1: 1.006-1.020; P=0.004) and hypertension (OR:3.201; 95%C1: 1.000-10.663;P=0.04) are two major factors affecting the long-term MACE.Conclusions Percutaneous coronary stenting in patients aged over 85 years is safe and provides good short and long-term efficacy. Patients with renal dysfunction and hypertension may have a relatively high incidence of MACE。

Abstract：Background Gemcitabine plus cisplatin is a standard treatment for stages ⅢB and Ⅳ nonsmall cell lung cancer (NSCLC). This randomized phase Ⅱ study evaluated a 3-week versus a 4-week schedule of gemcitabine-cisplatin as first line treatment for Chinese patients with advanced NSCLC.Methods Patients were randomized to receive cisplatin 75 mg/m2 on day 1 plus either gemcitabine 1250 mg/m2 on days 1 and 8 of a 21-day cycle (3-week group) or gemcitabine 1000 mg/m2 on days 1,8 and 15 of a 28-day cycle (4-week group).Results One hundred patients were enrolled in this study. The response rate was 24% (12/51 patients) in the 3-week group and 27% (13/49 patients) in the 4-week group. There were no statistically significant differences between the two treatment groups in survival (hazard ratio: 1.19; 95% CI: 0.68-2.09) with a median survival of 12.1 months and 13.8 months in the 3-week group and the 4-week group respectively. The rate of grade 3/4 toxicity in the 3-week group was 55% compared with 86% in the 4-week group (P=0.001). The difference in the incidence of grade 3/4 haematological toxicities did not reach statistical significance (3-week: 37%, 4-week: 57%), however grade 3/4 drug related neutropenia (3-week: 27%, 4-week: 51%) and thrombocytopenia (3-week: 8%, 4-week: 31%) were significantly lower in the 3-week group. Grade 3/4 nonhaematological toxicities were less in the 3-week group (33% cf 63%; P=0.005).Conclusions The differences in the efficacy endpoints were all in favour of the 4-week schedule of gemcitabine plus cisplatin, however these differences did not reach statistical significance. Fewer grade 3/4 toxicities were observed in the 3-week group compared with the 4-week group。

Abstract：Background Patients with sliding hiatus hernia (HH) and reflux esophagitis (RE) usually suffer from esophageal dysmotility. The aim of the present study was to investigate the role of acid reflux and duodenal gastroesophageal reflux (DGER), esophageal manometry, and esophageal dysmotility by applying the barium meal examination.Methods RE with HH was initially diagnosed using the reflux disease questionnaire, and was further confirmed by a barium meal examination and an endoscopy. The radiographic technique was used to test for spasms, strictures, and the coarseness of the mucosa, also was to study the types of reflux and clearance. Then, the esophageal manometry, the esophageal 24-hour pH, and the bilirubin monitoring were observed.Results Fifty-five patients were diagnosed as HH combined with RE and divided into two groups according to the severity of their esophagitis: group HH1 (grades A and B) and group HH2 (grades C and D). The barium meal examination revealed that the mucosa was either granular or nodular in all cases. The dump reflux and delayed clearance were more significant in patients in the HH2 group than those in the HH1 group (P＜0.05). The percentages of total, supine, and upright acid exposure time were greater in patients with HH than those in the control group (P＜0.01),but the differences between the HH1 and the HH2 groups were not significant. Lower esophageal sphictor pressure (LESP) was lower in the HH group than in the control group (P＜0.05). Three DGER parameters: the percentage of time with absorbance greater than 0.14, the number of bile reflux episodes, the number of bile refluxes lasting longer than 5 minutes were (28.43±93.34), (40.57±31.30), and (15.15±8.72), respectively in the HH2 group; these statistics were significantly higher than those for the HH1 (P＜0.05). The frequency and amplitude of peristalsis were all lower in HH patients than in the control (P＜0.05). Of all the patients, 54.3% (30 of 55) with acid reflux and DGER simultaneously in the HH group exhibited refluxes of barium from the stomach to the esophagus in the recumbent position, and 29.4% (5 in 17)with delayed clearance in the HH group were correlated with esophageal body peristalses. The result was that the frequency and amplitude of peristalsis were less and the duration of esophageal peristalsis was longer than those of control group.Conclusions Esophageal dysmotility may play an important role in the severity of RE combined with HH. Esophagealmotility results on a barium examination may coincide with esophageal manometry, 24-hour pH, and bilirubin monitoringin the RE and HH, but the radiologic method was the simplest to apply。

Abstract：Background The University of Wisconsin colloid based preserving solution (UW solution) is the most efficient preserving solution for multiorgan transplantation. Unfortunately, unavailability of delayed organ preserving solutions hindered further progression of cardinal organ transplantation in China. In this study, we validated an organ preserving Changzheng Organ Preserving Solution (CZ-1 solution) and compared it with UW solution.Methods A series of studies were conducted on how and how long CZ-1 solution could preserve the kidneys, livers,hearts, lungs and pancreas of New Zealand rabbits and SD rats. Morphology of transplanted organs was studied by visible microscopy and electron microscopy; biochemical and physiological functions and the survival rate of the organs during prolonged cold storage were studied.Results There was no significant difference between CZ-1 and UW solutions in preserving the kidneys, livers, hearts or lungs of rabbits; kidneys, livers, intestinal mucosa or pancreases of SD rats or five deceased donors' testicles. In some aspects, such as preserving rabbits' hearts, rats' intestinal mucosa and pancreases, the effect of CZ-1 solution was superior to UW solution. CZ-1 could safely preserve kidneys for 72 hours, livers for 24 hours, hearts for 18 hours and lungs for 8 hours for SD rats. Twelve kidneys preserved in cold CZ-1 solution for 22-31 hours were transplanted successfully and the mean renal function recovery time was (3.83±1.68) days.Conclusions CZ-1 solution is as effective as UW solution for organ preservation. The development of CZ-1 solution not only reduces costs and improves preservation of organs, but also promotes future development of organ transplantation in China。

Abstract：Background Two novel presenilin 1 (PS1) mutations, V97L and A136G, were recently found to be involved in the early-onset of Alzheimer's disease in two Chinese families. This research aimed to verify their pathological effects.Methods The human neuroblastoma SH-SY5Y cells stably transfected with these two Chinese presenilin 1 mutations were established to explore whether they are sensitive to, or influenced by, serum deprivation and protected by insulin-like growth factor-1 (IGF-1). Apoptosis rate, glucose uptake of the cells and the expression of glucose transport protein 1 (GLUT1) on cell membranes were examined.Results The V97L or A136G mutants significantly decreased the cells viability and increased the apoptosis rate when compare to PS1wt and mock transfected cells. IGF-1 was found to improve the viability of these two kinds of mutant cells significantly, and to show a protective effect for the mutants when they were treated with trophic deprivation. The glucose uptake of each transfected cell line increased to about 25% after IGF-1 treatment, GLUT1 expression on the cell membrane increased modestly by about 15%-20%.Conclusions Enhanced sensitivity to trophic withdrawal in the cells transfected with the two Chinese PS1 mutations may contribute to the neuron apoptosis. IGF-1 provided a protective effect to cells, possibly through an enhanced glucose transport and mitochondrial activities。

Abstract：Background Nasopharyngeal carcinoma (NPC) is endemic in Southern Asia. Radiation therapy remains the mainstay of treatment strategies for NPC. Although approximately 19%-56% of patients develop a recurrent disease 5 years after their primary treatment, recognition of post-radiation changes and early detection of relapse are important in improving the outcome of NPC. Our aim was to analyze the post-radiation changes and recurrent diseases related to NPC using computed tomography (CT) scans and to investigate their relationship.Methods CT scans of 510 pathologically proven NPC patients who have been followed up for more than 2 years after radiation were reviewed. The tumor's response to the radiation therapy and its relevance to recurrence were evaluated.Results For patients who were followed up for more than 2 years, their CT scans-obtained within 3 months, during the 4th to the 6th month, and beyond 7 months after radiation therapy, showed a normal nasopharyngeal cavity with a slight thickening in the wall in 93.5%, 95.0% and 84.8% of the patients respectively. The degree of tumor regression had no significant relevance to the risk of recurrence within the initial 3 months (P=0.094). During this term, the relapse rates in the cases in which the nasopharyngeal walls were displayed as normal, slightly or moderately thickening, or with obvious residual masses on CT scans were 7.1%, 11.7%, 23.5% and 23.1% respectively. The degree of tumor regression beyond 3 months after radiation therapy had a considerable reverse relevance to the risk of recurrence (P=0.000). The relapse rates were 13.2%, 14.1%, 10.2% and 2.1%, respectively, in the cases with a normal and a slightly thickening nasopharyngeal wall during the 4th to the 6th month, the 7th to the 12th month, the 13th to the 24th month, and beyond 25 months after radiation. In contrast, the percents in cases with moderate or more aggressive thickening walls in the corresponding periods were 62.5%, 88.9%, 100% and 100%. Within 6 months after radiation therapy, shown by CT scans,the metastatic lymph nodes disappeared, markedly decreased, slightly decreased, or enlarged in 37.4%, 51.8%, 4.7%,and 0.4%, respectively, of the patients. During 6 to 12 months after radiation therapy, the proportions were 78.5%, 19.2%,0.6% and 1.7% correspondingly. Beyond 12 months, the proportions were 83.7%, 7.9%, 0%, and 8.4%. The regression degree of the malignant nodes after radiation therapy showed a remarkable reverse relevance to the risk of recurrence in lymph nodes (P=0.000). In the cases with disappearing, markedly decreased, slightly decreased, or enlarged malignant nodes within six months after radiation, the relapse rates were 2.9%, 4.5%, 12.5% and 100%, respectively.Conclusions If the nasopharyngeal walls are shown to remain moderately thick on a CT scan beyond 6 months after radiotherapy, the risk of relapse will increase. The baseline images taken within 3 months after radiotherapy and regular follow-up studies are the key to pick up the tumor recurrences in an earlier stage。

Abstract：Background Bladder carcinoma is the most common malignant urological tumor in China. We present our preliminary experience and results of laparoscopic radical cystectomy (LRC) with orthotopic ileal neobladder in female patients with bladder carcinoma.Methods From February 2003 to February 2008, 14 female patients with bladder carcinoma underwent LRC with orthotopic ileal neobladder. Nine of these patients underwent hysterectomy and ovariectomy, and the other 5 had preservation of the uterus and ovarian appendage. Standard bilateral pelvic lymphadenectomy was followed by radical cystectomy that was completed laparoscopically with hysterectomy and ovariectomy when needed. The tumor was removed by a 4-5 cm lower midline abdominal incision, followed by the construction of ileal neobladder and the extracorporeal anastomosis of ureter-neobladder. The neobladder was anastomosed to the urethral stump under a laparoscope.Results The mean operative time and blood loss in the 14 patients were 350.2 minutes and 349.8 ml, respectively.Postoperative complications included uretero-pouch anastomotic stricture in 1 patient and pouch-vaginal fistula in 1 patient. Follow-up time of all patients ranged from 3 to 60 months, and 12 patients were followed up for more than 6 months and achieved micturition in half a year. One patient had occasional day-time urinary incontinence and 2 had night-time incontinence. Two patients who had undergone hystectomy and ovariectomy had voiding difficulties after one year, which was treated by intermittent self-catheterization. The mean volume of the neobladder and the residual urine were 333.6 ml and 31.2 ml, respectively. Surgical margins were tumor free for all patients. One patient had bone metastasis and died 11 months after the operation.Conclusions LRC with orthotopic ileal neobladder in female patients is a technically feasible, safe and mini-invasive procedure with a low morbidity and acceptable neobladder function. Long-term follow-up is required to confirm the neobladder function and oncological outcomes。

Abstract：Background The FIP1L1-PDGFRα fusion gene plays an important role in the pathogenesis of chronic eosinophilic leukemia (CEL) and is a direct therapeutic target of the tyrosine kinase inhibitor imatinib mesylate.Methods In 24 hypereosinophilic syndromes (HES) patients, using reverse transcriptase-polymerase chain reaction (RT-PCR), nested PCR and sequence analysis, we investigated the frequency of FIPIL1-PDGFRα and other abnormalities of tyrosine kinase family genes like PDGFRα, PDGFRβ, C-KIT, FGFR1, ABL and FLT3 as well as gene mutation "hotspots", like MPL515 and JAK2V617F, frequently involved in myeloproliferative diseases. Fluorescence in situ hybridization was used to confirm the 4q12 deletion.Results The FIPILI-PDGFRα fusion transcript was found in 8 (33%) of 24 patients with HES, corresponding to the chromosome 4q12 deletion identified by FISH. The FIP1L1-PDGFRα-associated patients diagnosed with CEL, frequently had hepatosplenomegaly, eosinophil-related tissue damage, anemia, thrombocytopenia, myelofibrosis and a short overall survival time. Nevertheless, imatinib mesylate induced rapid and complete hematological responses in treated FIP1L1-PDGFRα cases, followed by molecular remission and reversal of myelofibrosis. FIP1L1-PDGFRα fusion could co-exist with other mutations of tyrosine kinase family genes, like FLT3 or PDGFRβ. We also demonstrated that the SNPs of PDGFRβ were associated with selective splicing of exon 19 in case 20.Conclusions Correlating the CEL genotype with phenotype, FIPIL 1-PDGFRα emerges as a relatively homogeneous clinicobiological entity that co-exists with other abnormalities of tyrosine kinase family genes. It reflects the disease progression and there is a good response to imatinib. Detection of the FIP1L1-PDGFRα fusion gene is valid for both CEL diagnosis and therapy surveillance。

The pandemic of human immunodeficiency virus type 1 (HIV-1) has been devastating for the last two decades in a number of developing countries and constituting a grand challenge to the public health.WHO/UNAIDS estimates that approximately 33.2million people were living with HIV-1 infection by the end of 2007 and almost 2.5 million new infections occurred in 2007. An unprecedented scientifc challenge for the AIDS vaccine community is how to develop an effective HIV vaccine that can block HIV transmission and consequently stop the continuing spread of HIV-1.The recent failure of Merck Phase Ⅱ B trial alerted the HIV vaccine community that new vaccine strategies need to be more exclusively explored. In this review, we outline the basics of HIV vaccine and retrospect the history of the road to HIV vaccine in last two decades,and highlight the challenges we are currently facing and new strategies to develop HIV vaccines in this field.The Institute of Biomedical Sciences, Fudan University, Shanghai

Abstract：Objective A systematic meta-analysis was performed to explore the role of cytotoxin-associated gene-A (CagA)seropositive strains of Helicobacterpylori (H. pylon) in the pathogenesis of atherosclerotic diseases.Data sources Data from Medline, EMBASE, CBMdisc, CNKI and the Cochrane Collaboration database were searched.Similar search strategies were applied to each of these databases.Study selection The review was restricted to the case-control studies on infective, chronic virulent CagA strains of H.pylori, involving the risk of ischemic stroke and coronary heart disease, ineligible studies were excluded. Two reviewers independently extracted the data and assessed study quality.Results Totally 26 case-control studies (11 studies on ischemic stroke and 15 studies on coronary heart disease) were retrieved and considered. The combined data revealed that the chronic seropositive virulent strains of H. pylori infection had a trend of increasing the risk of ischemic strokes and coronary heart diseases, yielding pooled Ors of 2.68 (95% CI: 2.20, 3.27)and 2.11 (95% CI: 1.70, 2.62), respectively. We also performed subgroup analyses, dividing the total population into Caucasian and Chinese subgroups. Through the subgroup analysis, no significant difference was found between the subgroups.Conclusions Our results support the hypothesis that CagA-seropositive strains infection is significantly associated with susceptibility to ischemic strokes and coronary heart diseases. The magnitude of the association with atherosclerotic diseases needs to be confirmed by prospective studies and the studies on CagA-seropositive strains eradication are more important。

Pancreatic cancer is one of the malignant tumor with a very poor prognosis. Both genetic and epigenetic alterations are involved in the pathogenetic mechanisms of pancreatic cancer. Hypermethylation and subsequent loss of expression of some tumor suppressor genes and tumor-related genes occur frequently in pancreatic cancer, such as loss of expression of pl6,1 RASSF1A,2 SOCS-1,3 and hMLH14 genes were repoted。

Testicular plasmacytoma is rarely reported. The diagnosis is mainly based on pathological examination. Orchiectomy, combined with chemotherapy and radiotherapy, is currently the main treatment strategy for testicular plasmacytoma. The prognosis of extramedullary plasmacytoma involving the testis is much better than multiple myeloma involving the testis.Herein we present a case of a 62-year-old man who was diagnosed with testicular plasmacytoma。

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder with variable phenotypic expression.Epilepsy is the most common neurological complication and up to 80%-90% of the individuals with TSC suffer from epilepsy at some point in their lifetime.Developmental delay, intellectual impairment, autism,behavioral problems, and neuropsychiatric disorders occur commonly in individuals with TSC and may be associated with poorly controlled epilepsy.1 In this paper we reported a case report of TSC, focusing on the patient's clinical symptom, surgical aspects and neuropathology through a comprehensive analysis。