2007年 · 第120卷第12期

The global prevalence of asthma ranges from 1% to 18% of the population in different countries.1 In China, while national data of asthma prevalence are still lacking, an epidemiological study in Beijing showed that the prevalence of asthma in occupational populations was 1.25%.2

Abstract：Background A bioactive compound from Paecilomyces tenuipes (BGPT) has an inhibitory effect on monoamine oxidase A (MAO-A) and monoamine oxidase B (MAO-B) in vitro and in vivo, which indicates BCPT may be a potential antidepressant. In this study we aimed to study the antidepressant effects of BCPT in the chronic unpredictable stress(CUS) model in rats and explore underlying mechanisms in the hypothalamic-pituitary-adrenal (HPA) axis.Methods The antidepressant effects of BCPT were studied in the chronic unpredictable stress model in rats. Animals were housed isolated, except the control group. Rats were exposed daily to different random stressors from day 1 to 21.Awarding response was detected by calculating the 24-hour consumption of sucrose water. Cortisol (CORT) and adrenocorticotropic hormone (ATCH) contents in serum and arginine vasopressin (AVP) contents in the pituitary body were detected by radio immunoassays. Total RNA of hippocampus or hypothalamus was extracted and subjected to reverse transcription-polymerase chain reaction (RT-PCR) for the measurement of corticotrophin releasing hormone(CRH) mRNA or mineralocorticoid receptor (MR) mRNA and glucocorticoid receptor (GR) mRNA levels. Statistical analyses were performed using one way analysis of variance (ANOVA) followed by Student-Newman-Keuls (SNK) test.Results Chronic unpredictable stress resulted in reduction of sensitivity to reward and abnormality in the HPA axis in the animal model. BCPT improved the reward reaction as measured by increasing sucrose consumption, remarkably reduced serum CORT and ACTH levels and the AVP content in the pituitary body in the CUS-treated rats, decreased the expression of CRH mRNA, enhanced the expression of hippocampus MR mRNA, GR mRNA and decreased the ratio of MR/GR.Conclusions BCPT has potentially antidepressant-like activity and normalized the HPA axis hyperactivity in a CUS model of depression in rats. This may be an important mechanism of its antidepressant effect。

Abstract：Background We investigated the role in electrical stimulations of paraventricular nucleus (PVN) on gastric mucosal cells and the activity of mitogen-activated protein kinases (MAPKs) family members induced by gastric ischemia-repertusion (Gl-R). And we elucidated the molecular mechanisms of the protection of PVN from GI-R injuries.Methods Sprague-Dawley rats were divided randomly into 4 groups: Group Ⅰ, the sham-operated GI-R control group;Group Ⅱ, the sham-operated electrical stimulations to PVN + sham-operated GI-R control group; Group Ⅲ, the GI-R group; and Group Ⅳ, the electrical stimulations to PVN + GI-R group. In all of the experiments, the PVN was stimulated prior to the induction of GI-R. The GI-R model was established by clamping the celiac artery for 30 minutes to induce ischemia and then was released to allow reperfusion for 30 minutes, 1 hour, 3 hours and 6 hours, respectively. The gastric mucosal cellular apoptosis, proliferation, and the expression and activity of MAPKs protein were observed by immunohistochemistry and Western blotting, respectively.Results Compared with the GI-R group, the application of electrical stimulations in the PVN significantly depressed gastric mucosal cellular apoptosis and enhanced gastric mucosal cellular proliferation following the 30-minute, 1-hour and 3-hour intervals of reperfusion; it also promoted the activation of p-ERK during the early phase of reperfusion but inhibited the activation of p-JNK1/2 and p-p38 following the 30-minute, 1-hour and 3-hour intervals of reperfusion.Conclusions The protection of PVN against GI-R injuries may attribute to the inhibition of apoptosis and the promotion of the proliferation of gastric mucosal cells during GI-R. This protective effect is mediated by activating the ERK pathway and depressing the JNK, p38 MAPK pathways of the gastric mucosal cells。

Abstract：Background Lipopolysaccharide (LPS) forms outer membrane of the wall of Gram-negative cells. LPS can directly cause damage to epithelia of respiratory tract and is the major factor responsible for the chronic inflammation of respiratory passage. The mitogen-activated protein kinase (MAPK) signal transduction pathway of the airway epithelia is intimately associated with the action of LPS. The chronic inflammation of respiratory tract and smoking are interrelated and entwined in the development and progression of chronic lung diseases. This study was designed to examine the effects of cigarette smoke extract (CSE) and LPS on MAPK signal transduction pathway in order to further understand the roles CSE and LPS play in chronic lung inflammation.Methods Cultured primary human epithelial cells of airway were divided into four groups according to the stimulants used: blank control group, LPS-stimulation group, CSE-stimulation group and CSE plus LPS group. Western blotting was employed for the detection of phosphorylation level of extracellular-signal-regulated-kinase (ERK1/2), p38 MAPK and c-Jun N-terminal kinase (JNK). The expression of cytokines of MAPK transduction pathway (granulocyte-macrophage colony stimulating factor (GM-CSF) and mRNA of IL-8) in the primary epithelial cells of respiratory tract was also determined.Results Western blotting revealed that the phosphorylation levels of ERK1/2, p38 MAPK and JNK were low and 2 hours after the LPS stimulation, the phosphorylation of ERK1/2, p38 MAPK and JNK were all increased. There was a significant difference in the phosphorylation between the LPS-stimulation group and blank control group (P＜0.05); no significant difference was found between CSE-stimulation group and blank control group (P＞0.05); there was a significant difference between CSE + LPS group and blank control group and between CSE + LPS group and LPS group (P＜0.05). The phosphorylation of CSE-LPS group was higher than that of blank control group but lower than that of LPS group. In blank control group, the expression of IL-8 and GM-CSF mRNA was low in the epithelial cells of airway and the release of IL-8 and GM-CSF was also at a low level. One hour after LPS stimulation, the level of IL-8 mRNA increased (P＜0.05) and reached a peak after 2 hours. On the other hand, GM-CSF mRNA level increased 2 hours after the stimulation (P＜0.05)and reached the highest level 4 hours after the stimulation. Two hours after LPS stimulation, IL-8 and GM-CSF protein level began to rise (P＜0.05), and the level was the highest 8 hours after the stimulation (P＜0.01). Stimulation with CSE alone had no effect on the release of IL-8 and GM-CSF and expression of IL-8 mRNA (P＞0.05), but pre-treatment with CSE could delay the LPS-induced release of IL-8 and GM-CSF and the expression of IL-8 mRNA and its peak was lower.Conclusions LPS stimulation can significantly increase the phosphorylation of ERK1/2, p38 MAPK and JNK in the epithelial cells of airway and activate the MAPK transduction pathway, thereby can activate the downstream signal transduction pathway, and can ultimately result in the release of cytokines by the epithelial cells of airway. CSE can partially abolish the LPS-induced activation of MAPK signal transduction pathway and the expression of cytokines of the pathway, which might contribute to the development and progression of the inflammatory reactions in COPD patients。

Abstract：Background Shensong Yangxin (SSYX) is one of the compound recipe of Chinese materia medica. This study was conducted to investigate the effects of SSYX on sodium current (INa), L-type calcium current (ICa,L), transient outward potassium current (Ito), delayed rectifier current (IK), and inward rectifier potassium currents (IK1) in isolated ventricular myocytes.Methods Whole cell patch-clamp technique was used to study ion channel currents in enzymatically isolated guinea pig or rat ventricular myocytes.Results SSYX decreased peak INa by (44.84±7.65)% from 27.21±5.35 to 14.88±2.75 pA/pF (n=5, P＜0.05). The medicine significantly inhibited the ICa,L. At concentrations of 0.25, 0.50, and 1.00 g/100 mi, the peak ICa,L was reduced by(19.22±1.10)%, (44.82±6.50)% and (50.69±5.64)%, respectively (n=5, all P＜0.05). SSYX lifted the Ⅰ-Ⅴ curve of both INa and ICa,L without changing the threshold, peak and reversal potentials. At the concentration of 0.5%, the drug blocked the transient component of Ito by 50.60% at membrane voltage of 60 mV and negatively shifted the inactive curve and delayed the recovery from channel inactivation. The tail current density of IK was decreased by (30.77±1.11)% (n=5,P＜0.05) at membrane voltage of 50 mV after exposure to the medicine and the time-dependent activity of IK was also inhibited. Similar to the effect on IK, the SSYX inhibited IK1 by 33.10% at the test potential of -100 mV with little effect on reversal potential and the rectification property.Conclusions The experiments revealed that SSYX could block multiple ion channels such as INa ICa,L, Ik, Ito and IK1,which may change the action potential duration and contribute to some of its antiarrhythmic effects。

Abstract：Background Many studies have examined gender related differences in the presenting symptoms, management and prognosis of patients with acute coronary syndrome (ACS). Much data are available from industrialized countries, in which ACS is a major cause of morbidity and mortality, but relatively little information has been obtained from China,where an epidemic of cardiovascular disease is starting to emerge. The purpose of this study was to assess the differences in clinical practice in a national Chinese sample.Methods A total of 12 medical teaching hospitals participated in CRACE. Data collection began in 2001 and continued until 2004, 1301 patients with ACS were enrolled into the study. We compared the clinical demographics, different therapies and outcomes in hospitals between female and male patients with ACS.Results Patients had an average age of 63.13 years (ranging from 27 to 93 years) and 318 female and 983 male subjects were enrolled. Female subjects were older than male patients (67.23 years vs 61.80 years, P＜0.0001). The incidence of angina, heart failure, diabetes mellitus and hypertension in the female group was higher than in male group(73.6% vs 62.3%, P＜0.0001; 8.2% vs 5.7%, P=0.031; 30.8% vs 18.6%, P＜0.0001 and 66.4% vs 56.8%, P=0.001 respectively), but the incidence of smoking was less in the female group than in the male group (6.6% vs 66.2%,P＜0.0001). More male patients presented with ST-segment elevation myocardial infarction (STEMI) compared with female patients (48.5% vs 39%, P=0.002). With the exception of β-blocker administration, no differences were found among medications including aspirin, ACEI, lipid lowering agents and low-molecular-weight heparin (LMWH) between female and male patients presenting with ACS in hospitals. Compared with male patients with non-ST-segment elevation(NSTE) ACS, female subjects were more prone to receive β-blockers (75.1% vs 63.4%, P=0.001). Among STEMI and NSTE-ACS patients, fewer female subjects received reperfusion therapy compared with male subjects (37.1% vs 26.8%,P=0.013 for STEMI; 53.6% vs 37.2 %, P＜0.0001 for NSTE-ACS). Recurrent angina was more often seen in the female group of patients with the whole spectrum of ACS (25% vs 14.5%, P=0.005 for STEMI; 29.4% vs 20.2%, P=0.001 for NSTE-ACS) as was true for patients with congestive heart failure. There was no significant difference in in-hospital death rates between the two groups with ACS (5.6% vs 7.1%, P=0.2 for STEMI, and 2.1% vs 1.4%, P=0.738 for NSTE-ACS).Conclusions Female patients with ACS were older than male subjects and thus more often had concomitant diseases but less often had a history of smoking. They less often received reperfusion therapies and more often had higher in-hospital recurrent angina. However, there was no significant difference in in-hospital mortality between the female and male patients。

Abstract：Background Patients with melanoma metastasized to the central nervous system have a poor prognosis. Because the incidence of malignant melanoma in the Oriental is lower than that in the Caucasian population, brain metastases of malignant melanoma are rarely reported in Asia. Here we present our experience of brain metastasis of melanoma in an Asian perspective.Methods From 1990 to 2003, 369 patients with melanoma were treated in our hospital, 26 of them were diagnosed as having central nervous system involvement. Of the 26 cases, the clinical history, image, and pathologic findings of 23 patients were analyzed; the other 3 were excluded because of incomplete clinical data.Results Among the 369 patients with melanoma, 45% (167/369) developed lower extremity melanoma, and 27.1%(100/369) had acral lentiginous melanoma (ALM); while in the 23 patients with brain metastases, 34.7% (8/23) had lower extremity melanoma, and 34.7% (8/23) had ALM. Among the 23 patients, 17 had acute hemorrhage into the tumor,8 initially presented with a single cerebral metastatic lesion, and 15 had multiple brain lesions. Ten of them received surgery, 3 underwent stereotactic radiosurgery, and 16 received whole brain radiation. During follow-up, only 2 patients survived for more than 1 year, the median survival period was 5 months. The longest follow-up period was 11 years.Conclusions Compared with the Caucasian, Chinese patients with melanoma have a different proportion of melanoma subtype and higher incidence rates of lower extremities melanoma and ALM. However, their clinical presentation and prognosis are similar. The patients, who have excisable single or multiple brain lesions or limited extracranial disease and who are actively treated, may survive longer。

Abstract：Background Chronic obstructive pulmonary disease (COPD) is usually complicated with mucus overproduction in airway. Recently the increased expression of the human calcium-activated chloride channel 1 (CaCC1) was found to play an important role in mucus overproduction in the asthmatic airways. To investigate the relationship of CaCC1 and mucus overproduction in the airway of Chinese patients with COPD, the expressions of CaCC1, MUC5AC and mucus in bronchial tissues were examined.Methods Bronchial tissues were obtained from fiberoptic bronchoscopy and bronchial biopsy in West China Hospital from April to July in 2004. Twenty-five patients were diagnosed as the patients with COPD overproduction, and other 20 were the control subjects. The expressions of CaCC1, MUC5AC and mucin in bronchial tissues were detected by reverse transcriptase-polymerase chain reaction (RT-PCR), in situ hybridization with digoxigenin (DIG)-Iabeled RNA probe,immunohistochemical and alcian blue-periodic acid Schiff (AB-PAS) staining, respectively.Results Compared with the control group, the stronger expressions of CaCC1 were further detected throughout the bronchial tissues from patients with COPD (P＜0.01). Furthermore, the stronger expressions of the CaCC1 mRNA were related to the severity of airflow obstruction. Samples from COPD showed a stronger staining for MUC5AC than those in control subjects (P＜0.01) and AB-PAS staining revealed more mucins in COPD patients' submucosal gland comparing with that in control subjects (P＜0.01). Expression levels of the CaCC1 mRNA were respectively negatively correlated with the patients' forced expiratory volume in one second (FEV1) / forced vital capacity (FVC) data, FEV1% predicted data,V50% predicted data, V25% predicted data ( r=0.43, r=0.43, r=0.35, r=0.36, P＜0.01, P＜0.01, P＜0.05, P＜0.05). While the expression levels of the CaCC1 mRNA were well correlated with the expression levels of the MUC5AC mRNA of airway epithelium and the PAS-AB stained area of submucosal glands (r=0.39, r=0.46, P＜0.05, P＜0.01). Expression levels of the MUC5AC mRNA were negatively correlated with the patients' FEV1/FVC data (P=0.01), FEV1%pred data (P=0.01), V50% predicted data, V25% predicted data(r=0.53, r=0.53, r=0.48, r=0.43, P＜0.01, P＜0.01, P＜0.01,P＜0.01). While the expression levels of the MUC5AC mRNA were well correlated with the positively PAS-AB stained area of submucosal gland (P＜0.05), and the correlation coefficients were 0.43.Conclusion These results suggest that the stronger gene expression of CaCC1 exists, complicated with mucus overproduction in the airway of Chinese patients with COPD。

Abstract：Background Retroperitoneal sarcoma is a rare disease with poor prognosis. The aim of this study was to investigate the prognostic factors of the disease.Methods Between January 1988 and December 2003, 132 patients with retroperitoneal sarcoma were surgically treated in our hospital, 79 of them were followed up for 1-122 months (median: 19 months). Their clinicopathological data including tumor size, histological subtype, grade and resection margin status, were studied. The Kaplan-Meier method and log-rank test were used to analyze the disease-specific survival rates after the resection.Results Among the 132 patients, 98 (74.2%) received macroscopic complete resection, 29 (22.0%) incomplete resection, and 5 (3.8%) surgical biopsy. In the 79 patients who were followed up, macroscopic clear resection of retroperitoneal sarcoma (n=49) was associated with a significantly higher survival rate compared with unclear resection (n=30, P＜ 0.001). The median survival period was 31 months (95%C/, 20.09-41.91; actuarial 1-year survival, 85.7%) in the patients with the tumor completely resected and 11 months (95%C/, 6.71-15.29; actuarial 1-year survival, 46.7%) in those with incomplete resection. Patients with high-grade sarcomas had a significantly shorter survival time (n=39;median: 24, 95%C/: 5.71-42.29) than those with low-grade sarcomas (n=40; median: 15; 95%C/: 8.80-21.20; P＜0.01).Moreover, compared with the patients with the tumor sized ＜15 cm in diameter (n=53), the survival rate was lower in those with a sarcoma sized ＞15 cm (n=26). (Median: 12, 95%C/: 8.26-15.74 vs median: 24, 95%C/: 17.25-30.75; P＜0.05). Furthermore, the survival of the patients with liposarcomas (n=29, median: 29, 95%C/: 12.84-45.16),leiomyosarcomas (n=14, median: 11, 95%C/: 6.11-15.89), and others (n=36, median: 22, 95%C/: 14.95-29.05) varied significantly (P＜0.05)Conclusion Completeness of resection, tumor volume, grade, and subtype are prognostic factors of retroperitoneal soft tissue sarcomas。

Abstract：Background Cancer-testis antigen (CTA) is a family of the most noticeable tumor antigens which could be potential tumor markers for cancer diagnosis. In this research we aimed to investigate the expression of SSX-1 and NY-ESO-1 mRNA, two members of the CTA family, in tissue and peripheral blood of patients with hepatocellular carcinoma (HCC) to assess their feasibility for the immunotherapy and diagnosis of HCC and the association of their expression levels with diverse clinical indicators.Methods Thirty-six north Chinese patients with HCC and 30 normal controls were enrolled in this study. Reverse transcription-polymerase chain reaction (RT-PCR) was used to detect the expression of SSX-1 and NY-ESO-1 mRNA in tumor tissues and corresponding levels in peripheral blood of patients.Results The positive rates of SSX-1 and NY-ESO-1 mRNA expression were 61.1% (22/36) and 11.1% (4/36),respectively, in cancer tissues; 38.9% (14/36) and 5.6% (2/36), respectively, in the corresponding peripheral blood samples. No positive expression of either SSX-1 or NY-ESO-1 mRNA was detected in the samples of cancer-adjacent tissues, cirrhotic tissues, normal liver tissue or the peripheral blood of control patients. No significant relationship was found between the expression of these two genes and clinical indicators such as age, gender, tumor size, extent of differentiation, serum α-fetoprotein (AFP) level or infection with hepatitis B virus (P＞0.05). The short term recurrence rate was 46.2% (6/13) in patients whose peripheral blood expressed SSX-1 mRNA, while the recurrence rate in patients with negative SSX-1 mRNA was 28.6% (4/14).Conclusions SSX-1 and NY-ESO-1 antigens might be new potentially promising targets for antigen-specific immunotherapy for HCC. High specific expression of SSX-1 and NY-ESO-1 mRNA suggested that we could apply them as tumor markers. The short term recurrence rate was significantly higher in patients whose peripheral blood expressed SSX-1 mRNA, suggesting that SSX-1 mRNA could be used as indicator for recurrence, metastasis and prognosis of HCC。

Abstract：Background So far, in China, there has been no effective or easy procedure to define the control of asthma. This study assesses the validity of Asthma Control Test in Chinese patients.Methods Three questionnaires (Asthma Control Test, Asthma Control Questionnaire and the 30 second asthma test)were administered to 305 asthma patients from 10 teaching hospitals across China. Spirometry was also used. Asthma specialists rated the control of asthma according to patients' symptoms, medications and forced expiratory volume in first second. The patients were divided into noncontrolled group and controlled group according to the specialists' rating.Reliability, empirical validity and screening accuracy were conducted for Asthma Control Test scores. Screening accuracy was compared among 3 questionnaires. The patients' self rating and the specialists' rating were also compared.Results The internal consistency reliability of the 5-item Asthma Control Test was 0.854. The correlation coefficient between Asthma Control Test and the specialists' rating was 0.729, which was higher than other instruments. Asthma Control Test scores discriminated between groups of patients differing in the percent predicted forced expiratory volume in first second (F=26.06, P＜0.0001), the specialists' rating of asthma control (F=88.24, P＜0.0001) and the Asthma Control Questionnaire scores (F=250.57, P＜0.0001). Asthma Control Test showed no significant difference with Asthma Control Questionnaire in the percent correctly classified, while the percent correctly classified by Asthma Control Test was much higher than 30 second asthma test. The patients' self rating was the same as assessment of the specialists (t=0.65, P=0.516).Conclusion The Asthma Control Test is an effective and practicable method for assessing asthma control in China。

Liposarcomas of the kidney are exceedingly uncommon and represent less than 1% of all malignant renal neoplasms. Here we report a case with liposarcoma presenting as a huge retroperitoneal mass of weighed 10 kg。

Pulmonary alveolar proteinosis (PAP) is an uncommon disease first reported by Rosen et al 1 in 1958, and characterized by the accumulation of surfactant proteins and phospholipids within the alveolar spaces. Acquired PAP is divided into two forms based on clinical features:idiopathic PAP and secondary PAP. Secondary PAP is reported to be associated with haematological malignancies, Pneumocystis carinii pneumonia and inhalation of silica or titanium, and the most frequent underlying disease of secondary PAP is haematological malignancy. The exact incidence of PAP in haematological malignancies is still obscure, since there have been only sporadic reports of secondary PAP. 2, 3

Dapsone syndrome is characterized by high fever, skin rash, methemoglobinemia, liver toxicity, and generalized lymphadenopathy. The incidence of the dapsone syndrome is increasing with the extensive application of dapsone. However it is rarely reported in pemphigus. We present a case of "infectious mononucleosis-like" dapsone syndrome in a patient with pemphigus vulgaris. The syndrome appeared when he was being treated methylprednisolone, which was commonly used as a treatment for dapsone syndrome。

Blood cyst is a rare primary cardiac tumor usually affecting the cardiac valves. Associated with severe occlusion-related complications, it is generally removed surgically. With a brief review of the literature, we present a case of pedunculated tumor in the left ventricular outflow tract identified by echocardiography。

To the editor: Intestinal invagination is uncommon in adults, and neoplasm is the main cause. Ileo-ileal invagination due to lymphoma in adults has been rarely reported in the literature.

With the developments of surgical skills and immunology, bile duct complications after liver transplantation have been reduced from half to less than one third, but the incidence of bile duct stenosis after transplantation is still as high as 17%.1,2 During liver transplantation, bile ducts may be damaged in several ways, most of which affect directly or indirectly peribiliary vascular plexus (PVP) and lead to bile duct complications after operation。

Asthma and chronic obstructive pulmonary disease (COPD) are the two commonest causes of adult airflow obstruction. The fundamental differences and similarities between the pathological mechanisms of asthma and COPD are well recognized.1

Abstract：Background Recent studies have showed that the fine mesh stents are associated with a significant reduction in both clinical and angiographic re-stenosis of the coronary arteries. To maintain a very satisfactory radio-opacity using the stents, Guidant of the USA has designed a new type of bare metal stents (BMS)-Multi-link (ML) Vision / ML MiniVision stents. The clinical outcomes of Asian patients with coronary artery disease (CAD) after implanting the Multi-link Vision or MiniVision stent were investigated in this study.Methods An observational, prospective, multi-center, non-randomized post marketing registry was conducted to demonstrate the efficacy of the BMS- ML Vision / ML MiniVision stents. The primary end point of the registry was clinical target lesion revascularization (TLR) at a 6-month follow-up. The major secondary end points included the rate of major adverse cardiac events (MACE) and serious adverse events (SAE) in hospital and at 6 months; and the rate of clinical TLR as a function of the type of angina. A total of 429 Asian people with 449 lesions from 14 centers were selected for this study. The average reference diameter of the lesions was (3.0±0.5) mm, and the mean length was (15.7±5.0) mm.Results The successful rate of the procedure was 99.3%. Twenty-five percent of the lesions were treated by direct stenting without pre-dilation. Eighty-six percent of the lesions were implanted with ML Vision stent. After the 6-month follow-up, the rate of clinical TLR was 1.4%. The MACE, SAE and target vessel revascularization (TVR) were 6.8%, 3.5%and 1.4% respectively.Conclusion The current registry showed the excellent 6-month clinical outcomes of ML Vision/ML MiniVision stents in Asian patients with CAD。