2010年 · 第123卷第18期

Esophageal variceal bleeding (EVB), a severe complication and main mortality cause of portal hypertension, had reached a relatively mature stage in its research. The mortality rate of EVB within 5 days showed decreased tendency in recent years, which may be due to wide adoption of endoscopic variceal ligation (EVL) and endoscopic injection sclerotherapy (EIS).1 Endoscopic treatment had been widely used because of its simple procedure, high hemostasis rate and low recurrent bleeding rate, and had become a main measure in cease of first episode and prevention of recurrent bleeding. The technique of endoscopic procedures had less progress in the last 5 years. Recent studies on EVB mainly focused on further improvement of clinical outcome, including primary prevention by EVL, selection and combination of different hemostatic measures, minimizing complications, better long-term management and forecast of bleeding risk。

Abstract：Background Although the migration of hepatic stellate cells (HSCs) is essential for hepatic fibrotic response, the detailed mechanisms involved are poorly understood. The aim of this study was to examine the role of Rho GTPases (especially RhoA) in platelet-derived growth factor (PDGF)-BB-induced migration of HSCs.Methods The migration of primary rat HSCs was evaluated using transwell Boyden chamber, while cytoskeletal changes were visualized by immunofluorescence staining of intracellular actins and vinculin. Quantitative real-time PCR and Western blotting analysis were used to detect the expression of Rho GTPases (RhoA, Rac1 and Cdc42) within HSCs and their activation was determined by glutathione S-transferase pull-down assay. Finally, the effects of RhoA on PDGF-BB-induced cell migration and cytoskeletal remodeling were analyzed using HSC-T6 cells stably transfected with constitutively active (CA, Q63L) or dominant negative (DN, T19N) RhoA mutants. Data were analyzed using SPSS 16.0 software. Student's t test was used to analyze differences between two groups and one-way analysis of variance (ANOVA) was used among multiple groups.Results Rapid cytoskeletal remodeling led to a significant increase in the motility of primary rat HSCs after haptotactic (direct) and chemotactic (indirect) stimulation by PDGF-BB. PDGF-BB caused a dramatic elevation in the levels of both total and active RhoA protein. However, the levels of mRNA for Rho GTPases, including RhoA, Rac1 and Cdc42, were unaffected. Furthermore, PDGF-BB induced increased formation of stress fibers and focal adhesions in HSC-T6 cells transfected with CA-RhoA, but not in HSC-T6 transfected with DN-RhoA. Surprisingly, both CA- and DN-RhoA-transfected HSC-T6 cells showed decreased migratory potential in the absence or presence of PDGF-BB compared with controls.Conclusions PDGF-BB induced cytoskeletal remodeling in rat HSCs and promoted their migration via regulation of intracellular RhoA. RhoA may be one of the determinants in PDGF-BB-induced HSC migration。

Abstract：Background Medical ozone therapy system was reported to have certain effects on the treatment of severe hepatitis,but its mechanism is not very clear. One of the causes of death of severe hepatitis is complication of renal damage or hepatorenal syndrome. The present study aimed to observe effects of medical ozone therapy system on plasma renin activity (PRA), angiotensin Ⅱ (AⅡ), aldosterone (ALD), renal blood flow and renal function of patients with chronic severe hepatitis and explore mechanisms of medical ozone therapy in the treatment of severe hepatitis.Methods Eighty-five cases with chronic severe hepatitis were randomly divided into ozone therapy group (43 cases)and control group (42 cases). The patients in the ozone therapy group were treated with basic treatments plus ozone therapy system. Basic autohemotherapy was used. One hundred milliliter venous blood was drawn from each patient,and was mixed with 100 ml (35 μg/ml) medical ozone and then was returned the blood to the patient intravenously, once every other day for 20 days. Only the basic treatments were given to the control group. PRA, All, ALD, renal blood flow and damage to renal function of the two groups before treatment and 20 days after treatment were compared. Survival rates were also compared.Results Twenty days after the treatment, in ozone therapy group, PRA was (1.31±0.12) ng·ml-1·h-1, All (111.25±17.35)pg/ml, ALD (251.31 ±22.60) pg/ml, which decreased significantly compared with those before treatment (PRA (2.23±0.13)ng·ml-1 ·h1, AⅡ (155.18±19.13) pg/ml, ALD (405.31±29.88) pg/ml, t=4.67-14.23, P <0.01), also lower than those of control group 20 days after the treatment (PRA (2.02±0.11) ng·ml-1·h-1, All (162.21±15.32) pg/ml, ALD (401.20±35.02) pg/ml,t=4.97-15.61, P <0.01); renal blood flow was (175.15±28.20) ml/min, which increased compared with that before the treatment ((125.68±21.25) ml/min) and was higher than that of control group 20 days after the treatment ((128.59±23.15)ml/min, t=4.78, 4.61, P <0.01). Renal damage occurred in 2 cases (5%) in ozone therapy group, less than that in control group (9 cases, 21%) (X2=5.295, P <0.05). Thirty-three cases (77%) in ozone therapy group vs. 16 cases (38%) in control group survived (X2=12.993, P<0.01).Conclusions Basic treatment plus medical ozone therapy for patients with chronic severe hepatitis could decrease PRA, All and ALD levels significantly increase renal blood flow, prevent renal damage to certain extent and improve survival rate of the patients。

Abstract：Background Borderline gastrointestinal stromal tumors (GISTs) are intermediate tumors between benign and malignant variants; however, the clinical and pathological features of borderline GISTs remain poorly defined. This study aimed to characterize GISTs and to identify a set of borderline criteria for practical use.Methods Medical records and specimens of 840 patients from 12 hospitals were retrospectively examined. Totally 485 and 76 patients with any of the parameters predictive of either malignant or benign tumors were excluded. The Kaplan-Meier method was used to calculate disease-free survival and overall survival rates.Results Among the remaining 279 borderline GIST patients, 223 were followed up for 1 to 31.48 years. Two patients developed local recurrence, and both were cured by subsequent operations alone. The 5-year disease-free survival and overall survival rates were 99% and 100%, respectively. Morphologically, borderline GISTs typically exhibited moderate cellularity, and subsets of them also showed moderate atypia, low mitotic activities, or large tumor size. According to the National Institutes of Health (NIH) consensus criteria, the risk levels of the 279 GISTs were classified to be very low to high. However, the disease-free survival rates were not significantly different among these risk groups (P=0.681).Conclusions The proposed borderline GIST criteria in the current study may complement the existing NIH criteria,based primarily on tumor size and mitotic count, in the evaluation of the biological behaviors of GISTs. Since a subset of borderline GISTs with high risk level showed favorable outcome, the introduction of the borderline GIST system may avoid overdiagnosis and over therapy。

Abstract：Background Insulin-like growth factor binding protein-related protein 1 (IGFBPrP1) can activate hepatic stellate cells and increase extracellular matrix (ECM) in vitro. However, the effects of IGFBPrP1 in mice with hepatic fibrosis, and the mechanisms of these effects, are currently unknown. We aim to address these issues in this study.Methods Intraperitoneal injection of thioacetamide (TAA) is a classic method for establishing a mouse model of hepatic fibrosis. Using this model, we administered anti-IGFBPrP1 antibody, again via intraperitoneal injection. The morphological changes of liver fibrosis were observed with both HE and Masson stainning. The immunohistochemical assays and Western blotting were used to measure changes in IGFBPrP1, α-smooth muscle actin (α-SMA) and ECM in liver tissues, and the expression of transforming growth factor-β1 (TGF-β1) and Smad3. Data were statistically analyzed using one-way analysis of variance (ANOVA), the SNK-q test for inter-group differences.Results The Masson staining analysis showed that compared with normal control group, content of collagen fiber in TAA5w group was significantly increased (P <0.01), and it was significantly decreased in TAA5w/alGFBPrP1 group compared with in TAA5w group (P <0.01). The expression of hepatic IGFBPrP1, α-SMA, TGF-β1, Smad3, collagen I and fibronectin (FN) was significantly up-regulated in the TAA5w group (P <0.01). Anti-IGFBPrP1 treatment reversed these changes (P <0.01).Conclusions IGFBPrP1 plays an important role in the development of hepatic fibrosis. Anti-IGFBPrP1 prevents fibrosis in mice by suppressing the activation of hepatic stellate cells, inhibiting the synthesis of major components of the ECM (namely, collagen I and FN). The mechanism for this suppression of fibrosis is associated with the TGF-β1/Smad3 signaling pathways。

Abstract：Background The few studies on MR colonography with air enema involved feasibility of bowel distention and imaging quality and lacked detection sensitivity of colorectal neoplasms. The purpose of this prospective study was to assess the detection sensitivity of colorectal neoplasms with the three-dimensional Fourier transform fast spoiled gradient-recalled MR colonography with air enema.Methods A total of 30 patients scheduled for optical colonoscopy due to rectal bleeding, positive fecal occult blood test results or altered bowel habits were recruited and successfully underwent entire colorectal examinations with three-dimensional Fourier transform fast spoiled gradient-recalled MR colonography and subsequent optical colonoscopy on the same day. Detection sensitivity of colorectal neoplasms with MR colonography was statistically analyzed on a per-neoplasm size basis by using findings from optical colonoscopy and histopathological examinations as the reference standards.Results Seventy-six neoplasms were detected with optical colonoscopy, consisting of 1 mm-5 mm (n=11), 6 mm-9 mm (n=29) and >10 mm (n=36) in diameter. Detection sensitivities of 1 mm-5 mm, 6 mm-9 mm, ≥10 mm and >6 mm colorectal neoplasms with MR colonography were 9.1%, 75.9%, 100% and 89.2%, respectively; overall detection sensitivity for all sizes colorectal neoplasms was 77.6%.Conclusions Detection sensitivity of three-dimensional Fourier transform fast spoiled gradient-recalled MR colonography with air enema is low for 1 mm-5 mm colorectal neoplasms, but the detection sensitivity is 89.2% for ≥6 mm neoplasms, and all ≥10 mm neoplasms could be detected。

Abstract：Background Previous studies have investigated the technique of linear ablation at the mitral isthmus (MI) in patients with idopathic atrial fibrillation (AF), but MI ablation in patients with prosthetic natural mitral valves (MVs) was not described in detail. Present study sought to summarize our initial experience of ablating MI in patients with prosthetic MVs Methods Patients with drug refractory AF and prosthetic MVs were eligible for this study, and the patients with natural MVs but received MI ablation served as control group. Left atrium (LA) mapping and ablation was carried out guided by CARTO system. The anatomy of MI was assessed via computer topography scan.Results During the study period, a consecutive of 19 patients (male/female=12/7, mean age of (48±-6) years) with prosthetic MVs (16 with metal valves, 3 with biologic valves) entered for AF ablation, other 35 patients served as control group. In study group, mapping along MI documented lower voltages ((2.0±1.0) vs. (3.1±1.3) mV, P=0.002), more fragmented potentials (19/19 vs. 20/15, P<0.001 ), and higher impedance ((132±34) vs. (110±20) Ω, P=0.004). After initial ablation, more residual gaps along the MI lesions were found in study group (2.4±0.4 vs. 1.7±0.3, P <0.001). The mean length of MI ((6.2±3.3) vs. (7.1±2.3) cm, P=0.25) was comparable between 2 groups, but the MI in study group was much thicker ((3.1 ±1.8) vs. (2.1±1.07) cm, P=0.01 ) and all were found as pouch type (19/19 vs. 2/35, P <0.001). The follow-up results were comparable (65.1% vs. 72.3%, P=0.30).Conclusion For patients with prosthetic MVs, linear ablation at MI could be successfully carried out despite anatomical and pathological changes。

Abstract：Background Several candidate genes of ossification of the posterior longitudinal ligament (OPLL) susceptibility have been identified, but their polymorphisms account for only a small percent of the total variance. Bone morphogenetic protein-4 (BMP4) is a potent ectopic ossification inducing factor. BMP4 protein and mRNA are present in cells from OPLL patients, but not non-OPLL controls. A single nucleotide polymorphism of 6007C>T(rs17563) of BMP4 has been reported to affect bone density in postmenopausal women. Thus, BMP4 may function in OPLL development. Appropriately, the relationship between BMP4 polymorphisms and OPLL was investigated.Methods A case-control association study investigated the genetic etiology in 179 OPLL patients and 298 non-OPLL controls. Extent of OPLL was analyzed by radiologic examinations. Whether single nucleotide polymorphism (SNP) of -5826G>A(rs1957860) 5′ of the transcription start site and 6007C>T(rs17563) in exon 4 of the BMP4 gene were statistically associated with genetic susceptibility to OPLL in Chinese Han subjects was assessed.Results A significant statistical difference in genotype of 6007C>T polymorphism between male OPLL patients and male controls was evident, and the frequency of "TT" genotype in male OPLL patients was significantly higher than in male controls (P=0.039). The frequency of the "T" allele was also significantly higher in male OPLL subjects than in male controls (P=0.014, 0R=1.57). A significant difference was also observed between the 6007C>T polymorphism and the number of ossified cervical vertebrae in OPLL patients, while no statistical difference was apparent between the -5826G>A polymorphism and OPLL occurrence.Conclusions The T allele in the 6007C>T polymorphism may be a risk factor for male Han Chinese with ossification of the posterior longitudinal ligament in the cervical spine. Chinese Han male patients with CT and TT 6007C>T genotypes have a genetic susceptibility to OPLL and more extensive OPLL in the cervical spine。

Abstract：Background Target-controlled infusion (TCI) has been recently developed and successfully implemented in clinical practice. The current study was to estimate the population pharmacokinetics of rocuronium TCI in adult patients using nonlinear mixed-effects model (NONMEM), and to investigate the influence of relevant factors in adult patients.Methods Fourteen ASA Ⅰ-Ⅱ patients undergoing elective laparoscopy operation with general anesthesia were included.After induction, all patients received rocuronium by TCI system. The beginning target plasma concentration (Cpt) was 2.0 μg/ml, then increased Cpt according to the neuromuscular transmission monitoring. The endpoint of Cpt was determined when the T1 scale was blocked by 90%-95%. TCI rocuronium was stopped 30 minutes before the end of the operation.Arterial blood was drawn before anesthesia at 0, 2, 4, 6, 8, 10, 15, 20, 30, 45, 60, 120, 180, 240 and 360 minutes after the infusion of rocuronium was stopped for the analysis of plasma concentrations of rocuronium by liquid chromatography-mass spectrometry/mass spectrometry (LC-MS/MS). The population pharmacokinetics analysis was performed using NONMEM program.Results The pharmacokinetics of TCI rocuronium in adult patients was best described by a three-comparment model.Pharmacokintic parameters were clearance (CL)1=0.205 L/min, CL2=0.324 L/min, CL3=0.0292 L/min, volumes of distribution (V)1=4.00 L, V2=2.28 L, V3=4.26 L, Vdss=10.54 L. Both age and weight as covariates affected the pharmacokinetic parameters. V1 and CL1 were negatively correlated with patient age. CL1 was positively correlated with weight.Conclusions No pharmacokinetic change was noted when rocuronium was administered via TCI. Both age and weight as covariates affected the pharmacokinetic parameters。

Abstract：Background This is a prospective clinical study based on a large sample gathered from multiple centers in China,subordinating to 10th Five-Year Plan of National Science & Technology Progression. We analyzed the high-risk factors inducing hypertensive disorders in pregnancy (HDP) and estimated the potential effect of anti-oxidants administration,including vitamin C (VC), vitamin E (VE) and Salvia Miltiorrhiza L (SML), a Chinese herb medicine, in amelioration of the high-risk factors in pregnancy.Methods From April 2005 to July 2006, 4814 pregnant women from 24 national wide cooperative hospitals were involved in this prospective research. The participants were randomly divided into two groups: 1607 cases were in anti-oxidants group with administration of vitamins and SML; 3207 cases were in control group without any medicine given. Every participant was under monitoring for the morbidity of HDP and the high-risk factors were investigated in HDP cases in each group.Results (1)The morbidity of HDP was 3.55% in anti-oxidants group vs. 4.18% in control group. No statistical difference existed between the two groups (P>0.05). (2) In anti-oxidants group, the HDP morbidities among three subgroups: VC +VE + SML, VC + VE and SML only, were 5.51%, 3.05% and 5% respectively. It showed no statistical difference among three remedies (P>0.05). (3) The related index of factors affecting HDP showed in intensity sequence as follows: family HDP history > profession > education level > age > body weight. The incidence of HDP in normal population was 3.51%,and the incidence of HDP in high-risk pregnant women (family HDP history, heavy physical labor, low education level (middle school and below), age >40, body mass index ≥24) was 5.84%, which was obviously higher than that in normal population (P <0.01). In anti-oxidants group, the probability of HDP in women with high-risk factors was 3.81%, which was obviously lower than that in control group with high-risk factors at 7.14% (P<0.01). (4) In control group, the morbidity of HDP in women with family HDP history (especially with sisters'), heavy physical labor, middle school and below, age ≥35 was: 50.00%, 15.22%, 6.33%, 26.28% and 5.75%, respectively, and that in anti-oxidants group was 0, 7.69%, 3.74%,9.27% and 2.67%, respectively, which was obviously lower than that in control group.Conclusions The high-risk factors prone to induce HDP included: family history of HDP, heavy physical labor, low education level, aging and obesity. No impressive effect of anti-oxidants application was found in preventing HDP in general population but the remedy demonstrated positive effect on preventing HDP in pregnant women with high-risk factors。

Abstract：Background Antibodies against acetylcholine receptor, acetylcholinesterase, ryanodine receptor and titin have been found in patients with myasthenia gravis. However, the relations between these antibodies and character of myasthenia gravis are unknown. This study aimed to detect multiple antibodies in myasthenia gravis and to investigate its clinical significance.Methods These antibodies were detected by enzyme-linked immunoabsorbent assay in 89 cases of myasthenia gravis,66 cases of other neurological diseases and 66 healthy controls. The incidences of antibodies were compared using the chi-square test.Results Acetylcholine receptor, acetylcholinesterase, titin and ryanodine receptor antibodies were detected in 53.9%,20.2%, 64.0% and 55.0% of myasthenia gravis patients respectively, higher than in patients of other neurological diseases and controls groups. The combination of the four antibodies assays provided 94.4% sensitivity and 84.0% specificity for the diagnosis of myasthenia gravis. Acetylcholinesterase antibody occurred more frequently in acetylcholine receptor antibody negative patients with adverse reactions to neostigmine test. Titin antibody provided 82.1% sensitivity and 52.5% specificity for myasthenia gravis with thymoma. Incidences of titin and of ryanedine receptor antibody were higher in late onset myasthenia gravis than in early onset myasthenia gravis. The proportion of titin antibody positive patients increased with the severity of myasthenia gravis as graded by a modified Osserman scale.Conclusions Testing for acetylcholine receptor, acetylcholinesterase, titin and ryanodine receptor antibodies can offer a better diagnostic method for myasthenia gravis than each antibody test alone. Titin antibody combined with computed tomography was better for the diagnosis of thymoma. Titin antibody occurred most frequently in severe myasthenia gravis。

Abstract：Background Post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) is regarded as one of the worrisome complications of endoscopic retrograde cholangiopancreatography (ERCP). Results of randomized controlled trials evaluating the preventive effect of ulinastatin and gabexate mesylate (GM) on PEP are contradictory. The present study was designed to evaluate the prophylactic effect of ulinastatin and GM on PEP with meta-analyses of randomized controlled trials (RCTs).Methods Five electronic databases were searched for RCTs evaluating the preventive effect of ulinastatin and GM on PEP. Summary effects were assessed with the methods recommended by the Cochrane Collaboration.Results Twelve studies involving 5105 participants were included in our meta-analyses. Administration of ulinastatin decreased the incidence of PEP only at sufficient doses (OR, 0.39; 95% CI, 0.19 to 0.81; P=0.01). Number needed to treat (NNT) was 6. And administration of ulinastatin also reduced the incidence of post-ERCP hyperamylasemia (PEHA)(OR, 0.40; 95% CI, 0.28 to 0.58; P<0.000 01). Slow infusion of high-dose GM was effective for PEP prevention (OR, 0.44;95% CI, 0.25 to 0.79; P=0.006), and rapid infusion of low-dose GM also showed efficacy for PEP prophylaxis (OR, 0.37;95% CI, 0.20 to 0.69; P=0.002). NNT was 7 and 6 respectively. However, administration of GM at low doses and by slow infusions was ineffective (OR, 0.99; 95% CI, 0.64 to 1.55; P=0.98). Administration of GM had the tendency to reduce PEHA rate, but not to a statistical significance (OR, 0.86; 95% CI, 0.73 to 1.01; P=0.06). When low-quality studies were excluded, the meta-analysis with two high-quality studies indicated that ulinastatin did not reduce the rate of PEP (OR,0.63; 95% CI, 0.32 to 1.26; P=0.19) and PEHA incidence (OR, 0.80; 95% CI, 0.31 to 2.07; P=0.64). The meta-analysis with six high-quality studies showed that GM administration decreased PEP incidence (OR, 0.52; 95% CI, 0.29 to 0.91;P=0.02), while was not efficacious for PEHA prevention (OR, 0.88; 95% CI, 0.74 to 1.04; P=0.12).Conclusions Ulinastatin and GM may be of value for the prophylaxis of PEP. GM should be administered at high doses and by rapid infusions. And the doses of ulinastatin should be sufficient. However, the conclusions are not overwhelming.More large-sample size and high-quality RCTs are still needed to elucidate whether administrations of the two drugs really have prophylactic effect on PEP。

Deep skin wounds heal by scar formation with a loss of its original appearance, structure and function.However, when the same damage occurs to the skin of an early gestational fetus, complete regeneration can be observed. Despite significant research in the field of skin regeneration, many mysteries remain, such as the loss of wound healing ability with maturity, the differences in healing at different parts of the body, and the presence of hypertrophic scars and keloids in some races but not in others. The finding of HOX genes in the skin provides new explanations to these conundrums。

Intra-atrial reentrant tachycardia (IART) is not uncommon after surgical correction of congenital heart disease (CHD). The patients with IART are often refractory to antiarrhymic agents and present with severe symptoms. Current treatment approach to IART has shifted largely to interventional procedures which have a good short-term success rate, however, late recurrence rate is still high. With the development of mapping technique especially the application of three-dimensional electroanatomic mapping, the exact mechanisms of IART have become clear。

Gastrointestinal bleeding is a common acute clinical emergency, with a mortality rate of 5%-12%.1 Most gastrointestinal bleeding is self-limited, but a small number of cases are difficult to treat due to an untraceable site and cause of bleeding, massive bleeding, serious illness, or other complications. Conservative treatment usually cannot achieve effective hemostasis.2 Blind exploratory laparotomy is risky and often leads to delayed postoperative recovery. In some cases, the bleeding site cannot be revealed even with surgery, which makes surgical treatment futile. In contrast, interventional therapy, a diagnostic and therapeutic technique secondary to traditional medical therapy and surgery, can be used to diagnose unexplained bleeding while simultaneously achieving immediate hemostasis。

Laparoscopic procedure as a minimally invasive surgery has been introduced into many abdominal surgeries. Smaller incisions of the abdominal wall reduce postoperative pain and the risk of wound complications,and provide an excellent cosmetic result compared with open surgery. Natural orifice transluminal endoscopic surgery (NOTES), a no-scar surgery, is a hot spot of modern surgery.

Chondrosarcoma is the most common malignant primary ches t wall tumor, only 20% of these cases involve sternum.1 Current therapy for chondrosarcoma requires adequate surgical excision and radiation therapy,2chemotherapy have not been yet proved to be effective.However, reconstruction of the defect is difficult, the problems of providing soft tissue coverage additionally complicating the surgery and even potentially limit the ability to achieve clear margin. Titanium internal fixation system can provide proper chest stability, ensure wide surgical margin and reduce hurts。

Endoleaks are defined as the persistence of blood flow outside the lumen of the endoluminal graft but within an aneurysm sac or the adjacent vascular segment being treated by the graft and classified into 5 categories.1,2 Although type Ⅲb endoleaks (fabric defect) have been reported to occur in some divices,3-6 it has never been previously reported with the AnacondaTM endograft (Vascutek, Terumo, Scotland) after endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA). Here we report a delayed type Ⅲb endoleak of AnacondaTM endograft after EVAR for AAA。