Volume 118  ·   Issue 22  ·  2005

Abstract：Background Protease activated receptor-2 is cleaved and activated by trypsin or mast cell tryptase and may play an important role in inflammation. However, it is unknown whetehr PAR-2 can mediate tryptase-induced inflammatory reaction. This study was conduct to investigate wheter PAR-2 could be the activated by mast cell tryptase and medicated the tryptase induced interleukin-8 expression in endothelial cells.Methods Protease activated receptor-2 expression was found in endothelial cell lines ECV304 cell by reverse transcription-polymerase chain reaction (RT-PCR) and Western blotting. Interleukin-8 stimulated by purified human mast cell tryptase was determined by RT-PCR and enzyme linked immunosorbent assay (ELISA). Data were analysed by the S-N-K one-way ANOVA test.Results The present study shows that mRNA and protein of protease activated receptor-2 could be expressed in ECV304 cells, and tryptase upregulated the expression levels of both interleukin-8 mRNA and protein. The increased expression of interleukin-8 was inhibited by an antiprotease activated receptor-2 monoclonal antibody, SAM11. An additional band was observed by Western blotting after the incubation of ECV304 cells with tryptase for 2 hours, which suggested that protease activated receptor-2 was activated. Conclusion Protease activated receptor-2 can mediate the mast cell tryptase stimulated expression of interleukin-8 in ECV304 cell。

Abstract：Background Nuclear factor-kappa B (NF-κB) is elevated in regulating transcription of many cytokines and inflammatory mediators. The purpose of this study was to investigate the activation and the significance NF-κB in lipopolysaccharide (LPS) induced keratitis.Methods LPS induced keratitis model was based on Wistar rats. At 0.5, 1, 3, 6, 12, 24 or 72 hours after LPS treatment, the rat corneas were observed with a slit lamp microscope, then the rats were sacrificed and their corneas were excised for routine histological analysis. The expression of NF-κB was detected with immunohistochemical staining. The change of tumour necrosis factors-α (TNF-α) mRNA expression was identified by reverse transcriptase polymerase chain reaction (RT-PCR).Results Histological findings demonstrated that LPS treated corneas showed significant changes in corneal structure. Corneal edema, pronounced inflammatory cells infiltration and inordinate collagen fibres were observed. Immunohistochemical results showed that the expression of NF-κB and its activation obviously increased after LPS treatment compared with the normal group and control group. Positive cells could be observed at 0.5 hour and peak expression of NF-κB was observed between 3 hours and 12 hours after infection, but returned to or approached normal level by 72 hours. RT-PCR showed that the level of TNF-α mRNA began to increase 0.5 hour after LPS treatment, peaked at 6 hours and then subsided by 72 hours. NF-κB had a positive correlation with the expression of TNF-α mRNA (r=0.964, P<0.01), both NF-κB and TNF-α had a strong positive correlation with the degree of inflammatory response in LPS treated corneas (r=0.929, P<0.01; r=0.587, P<0.05, respectively).Conclusions The activation of NF-κB was increased in LPS treated corneas and was elevated in LPS induced keratitis by promoting overexpression of TNF-α mRNA. NF-κB may play an important role in the pathogenesis of LPS-associated keratitis in rats。

Abstract：Background Little is known about the role of dual angiotensin Ⅱ forming pathways during heart failure. In the present study, the changes of chymase and angiotensin converting enzyme (ACE) expressions in the failing hearts of hamsters were analysed.Methods Heart failure was induced by ligation of left anterior descending branch of the coronary artery. Chymase, ACE and angiotensin Ⅱ type 1 receptor (AT1R) mRNA levels were analysed by reverse transcription polymerase chain reaction (RT-PCR). The activities of chymase and ACE were determined by radioimmunoassay (RIA). Myocardial collagen fibre analysis was performed under optical microscope.Results Left ventricular systolic pressure (LVSP) and maximum left ventricular developed pressure increase rate (dp/dtmax, mmHg/s) gradually moved lower at 2, 3, 4 and 8 weeks after operation. On the other hand, left ventricular end-diastolic pressure (LVEDP) increased gradually after operation. Compared with the control group (3.55±0.06, 4.79±0.70), the heart weight/body weight ratio in operation group had increased significantly at 4 weeks and 8 weeks (4.28±0.43, 6.17±0.73) (P<0.01). Collagen staining showed that the quantity of myocardial collagen fibre increased significantly in the operation group. RT-PCR showed that the chymase mRNA level in the operation group was consistently greater than that in the control group. AT1R mRNA level was also increased significantly at 3 weeks and 4 weeks, both being 1.3 times that of the control group (P<0.01), whereas ACE mRNA level was not changed. Higher activity of chymase was detected in operation group, being 4, 8, 13 and 19 times that of the control group at 2, 3, 4 and 8 weeks (P<0.01), respectively. ACE activity was also significantly higher at the same time, being 7, 10, 10 and 3.5 times that of the control (P<0.01). Angiotensin Ⅱ (Ang Ⅱ) level in operation group increased significantly, being 2.5, 2.7, 3.5 and 2 times that of the control group at 2, 3, 4 and 8 weeks, respectively (P<0.01).Conclusions A dual Ang Ⅱ forming pathway from both ACE and chymase in the hamster hearts plays an important role during the development of heart failure. At the decompensatory stage, the reduction of AngII level may be associated with the decrease of ACE activity。

Abstract：Background Bacterial pneumonia in the recipients of liver transplantation (LTX) is a common postoperative complication influencing the prognosis greatly. In this article, the diagnosis and treatment of bacterial pneumonia in 33 LTX recipients are reported. Methods From February 1999 to January 2003, a total of 103 patients underwent allogeneic LTX at our center; afterwards, a retrospective analysis was made on their postoperative clinical manifestations, including symptoms (expectoration, panting and fever), sign (rale), results of laboratory examinations (white blood cell count and sputum culture of tracheal secretions or pleural fluid culture), and chest X-ray films. The following data of the pneumonia and non-pneumonia groups were collected, and the rank sum test (SPSS 11.0, Wilcoxon's method) was used to analyze the duration of postoperative respirator utilization and the volume of pleural effusion through pleurocentesis or pleural drainage.Results In the 103 patients, 33 experienced 53 episodes of bacterial pneumonia during their hospital stay after transplantation, 14 of them (42.42%) had more than three manifestations of the seven mentioned above. The pathogens causing bacterial pneumonia included Pseudomonas aeruginosa (17.48%), Klebsiella pneumoniae (15.53%), Acinetobacter baumannii (10.68%), and Staphylococcus aureus (7.77%). Amilkacin, tienam, ciprofloxacin, vancomycin, etc. were the antibiotics of choice against those bacteria. Acute rejection occurred during the treatment of bacterial pneumonia in 16 patients, and 5 of them died. Wilcoxon's rank sum test of the data indicated that the pneumonia group had longer duration of postoperative ventilator treatment and larger volume of pleural effusion than the non-pneumonia group (P<0.05).Conclusions The clinical manifestations of pneumonia after LTX might be atypical,and special attention should be paid to the respiratory symptoms and signs within 2 months after LTX. Whenever the diagnosis of bacterial pneumonia is confirmed, consideration should be given to reasonable use of antibiotics and regulation of immunity in addition to other routine therapies。

Abstract：Background We investigated the possible association of the functional polymorphisms in the tumor necrosis factor (TNF) genes with susceptibility to esophageal squamous cell carcinoma (ESCC) and gastric cardiac adenocarcinoma (GCA). Methods The TNF-α-308G/A and TNF-β+252G/A single nucleotide polymorphisms (SNPs) were genotyped using polymerase-chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis, in 555 cancer patients (291 ESCC and 264 GCA) and 437 healthy controls in a high incidence region of North China. Results Among healthy controls, frequencies of the TNF-α 1/1, 1/2 and 2/2 genotypes were 89.4%,9.2% and 1.4% respectively, while frequencies of the TNF-β B1/B1, B1/B2 and B2/B2 genotypes were 12.6%,32.3% and 55.1%, respectively. No significant difference was found in the overall genotype and allelotype distribution of the TNF-α-308G/A and TNF-β+252G/A SNPs among cancer patients and controls. However, both the B1/B1 genotype and B1/B2 genotype significantly increased the risk of developing ESCC [the age and gender adjusted odds ratio (OR)=2.04 and 1.91, 95% confidence interval (CI)=1.04-4.43 and 1.14-2.60, respectively] and GCA (the age and gender adjusted OR=2.68 and 2.64, 95% CI=1.14-6.29 and 1.47-4.72, respectively) in individuals with negative family history of UGIC, in comparison with the B2/B2 genotype. When the two TNF polymorphisms were combined and analyzed, individuals with the TNF-β B1/B2 and TNF-α1/2 or 2/2 genotypes significantly reduced the risk of developing ESCC and GCA, in comparison with those harboring the TNF-β B2/B2 and TNF-α 1/1 genotypes (the age and gender adjusted OR=0.37 and 0.34, 95% CI=0.15-0.92 and 0.13-0.90, respectively).Conclusions Therefore, the TNF-α-308G/A and TNF-β+252G/A genotyping may be used as a stratification markers to predicate the risk of ESCC and GCA development in North China。

Abstract：Background Nowadays, there is a remarkable rise in resectability rate of periampullary adenocarcinoma and the mortality and morbidity of the pancreaticoduodenectomy procedure have been reduced remarkably, while the 5 year survival rates of patients with carcinoma of the head of the pancreas are still below 25%. We conducted this retrospective study to evaluate the clinical outcome of radical pancreaticoduodenectomy with extended retroperitoneal lymphadenectomy as a surgical therapy for adenocarcinoma of the head of the pancreas.Methods Twenty cases with adenocarcinoma of the head of the pancreas were treated by standard pancreaticoduodenectomy (removing only the peripancreatic lymph nodes en bloc with the tumour) from 1994 to 1997, and 46 cases with the same disease underwent extended retroperitoneal lymphadenectomy associated with standard pancreaticoduodenectomy from 1998 to 2002. The patients for whom there were insufficient follow-up data, or who had received postoperative adjuvant therapy, were excluded from the analysis. Clinical and pathological parameters of both groups were reviewed. The postoperative morbidity, mortality and survival data were compared statistically. Results Demographic and histopathological characteristics were similar in the two groups of patients. Performance of the extended lymphadenectomy lengthened the procedure. The mean total number of lymph nodes resected was significantly higher in the radical group (P< 0.05). Of the 46 cases in the radical group, 26% (12/46) had metastatic adenocarcinoma in the resected retroperitoneal lymph nodes. There was one perioperative death in the standard group, and two in the radical group. Postoperative diarrhoea and lymphatic leakage were only observed in the radical group. Transfusion requirements and postoperative morbidity rates did not differ between the two groups. The 1-, 2- and 3-year survival rates were 63%, 32% and 21% respectively in the standard group, and 66%, 38% and 21% in the radical group. No statistically significant difference was found between the groups. When subgroups of node positive patients were analysed, the 1-, 2- and 3-year survival rates were 42%, 17% and 8% respectively in the standard group, and 65%, 32% and 16% in the radical group. Better survival was observed in the first 2 years after operation in the radical group, but no survival differences were seen after 2 years post operation. Conclusions The addition of an extended lymphadenectomy to a pancreaticoduodenectomy did not significantly increase morbidity rates, but was associated with an early survival advantage.

Abstract：Background Globally, 180 million people suffer from diabetes mellitus. Islet transplantation is believed to be an almost ideal therapy for insulin-dependent patients. How to maintain the viability and the function of isolated human islets is a challenge in clinical practice. Sertoli cells are considered ‘nurse cells'in the seminiferous tubules and have been used in cell graft protocols for neurodegenerative diseases and diabetes in many studies. Many researchers have used immature murine testes as the primarily source of Sertoli cells in islet transplantation because they are easily purified. Mature human Sertoli cells have been seldom investigated. In the present study, we developed a method for the isolation and culture of Sertoli cells derived from adult human testes, and investigated their effects on the function of allogeneic islets when they were cultured together in vitro. Methods Adult Sertoli cells were prepared successfully by two-step enzyme digestion with trypsin, collagenase and hyaluronidase. They were identified by morphological characteristics and their activity was determined by MTT colorimetry over a 28-day culture time in vitro. A glucose-stimulated insulin secretion test was performed to detect the effects of Sertoli cells on allogeneic islets' function when they were co-cultured for 21 days in vitro. Results In cultured cells, mature human Sertoli cells accounted for more than 90% of total cells. The activity of Sertoli cells reached 95% and they remained highly cytoactive for a long time in vitro (P>0.05). Compared with the islets cultured alone, the co-cultured islets with allogeneic Sertoli cells maintained higher sensitivity to glucose stimulation for the duration of the experiment (P<0.01). Conclusions A method of isolation and culture of Sertoli cells from adult testes has been established. Sertoli cells could enhance allogeneic islets' function when they were co-cultured in vitro. They could be a helper cell in islet transplantation。

Abstract：Background Live attenuated hepatitis A vaccine (H2 strain) is widely applied in prevention of hepatitis A epidemic in China and other countries now. It is essential to observe and confirm the vaccine immune efficacy, population antibody level and its persistent efficacy after mass immunization.Methods A total of 220 children with negative anti-HAV antibody (aged 1-3 years) were taken for follow-up assay to observe seroconversion and geometric mean titre(GMT)level 2 months, 12 months, 6 years, and 10 years after inoculation. Another survey sampled from subjects of different age groups (3, 6, 9, 15, 18, 25 and 35 years) to compare anti-HA antibody positive rate before and after inoculation performed 10 years previously. Epidemiological observations were taken for 10 years to evaluate the relationship between vaccine coverage and hepatitis A morbidity. Serum antibody to HAV was detected by enzyme linked immunoassay (ELISA, calibrated by WHO international reference) and ABBOTT Axsym HAVAB microparticle enzyme immunoassay. Results Seroconversion in follow-up assay 2 months and 10 years after inoculation was 98.6% and 80.2% respectively. For children, the vaccination anti-HA antibody positive rates were significantly different before and after 10 years, 7.69% cf 70.45% (aged 3 years) and 52.58% cf 71.78% (aged 18 years). When vaccine coverage rose from 57% to 74%, there were no any HA epidemics. When vaccine coverage reached 85%, there were no any HA cases. With vaccine coverage between 85% and 91%, there were no any HA cases in cohorts from the age of 1 year to 15 years during the 10 years. Conclusions Live attenuated hepatitis A vaccine has an obvious long-term effectiveness in prevention and control of HA epidemics through mass vaccination。

Iodine is an important constituent for the synthesis of thyroid hormone. Deficient or excessive iodine intake may affect thyroid size and function.1 The strategy of Universal Salt Iodination (USI) has been implemented in China since 1996. The median urinary iodine (MUI) was 330 μg/L in 1997, and 306 μg/L in 1999. We conducted a cross-sectional epidemiological study in three counties (rural communities) in 1999 to investigate the effect of iodine intake on the prevalence of hypothyroidism。

Nasopharyngeal carcinoma (NPC) is rare in most countries,especially in Europe and North America (incidence rate below 1/100 000 people per year). However, it has a high incidence in several southern areas in China, especially in the Cantonese region, including Guangzhou city, where the incidence rate is approximately 30-80/100 000 people per year.1 In the high incidence areas, more than 95% NPCs are poorly differentiated (WHO types 2 and 3), which are sensitive to radiotherapy and chemotherapy. Besides its special epidemiological and pathological characteristics, NPC differs from other head and neck cancers in terms of its unique clinical development features. The advanced NPCs can be divided into three clinical types:2 (a) cranial type (A or ascending type) is characterized by direct extension of the tumor toward the base of skull with involvement of the cranial nerves Ⅰ, Ⅲ, Ⅳ, Ⅴ1 and Ⅵ and/or destruction of the bone, but without cervical lymphadenopathy. About 12.4% patients belonged to this type; (b) generalized cervical lymphadenopathy type (D or descending type) has the special feature of extensive metastasis in the cervical lymph nodes on one or both sides with a large mass of 8 cm×8 cm, yet without affecting the cranial nerves (42.2%); (c) mixed type (AD or ascending-descending type) shows the features of both the above 2 types, but cervical lymphadenopathy usually remains localized for a long time and the size of the mass rarely reaches 8 cm×8 cm (30.0%). A representative example of type A and type D patients is shown in Fig. 1. Different clinical subsets have different biological behaviors, different treatment outcomes, and deserve different therapeutic plans. Therefore, defining NPC clinical types is useful for the individualized therapeutic planning.

Choroidal neovascularization (CNV), a major cause of vision loss, is the result of the increased vascular endothelial growth factor (VEGF) expression in human retinal pigment epithelial (RPE) cells. It is important to inhibit the expression of VEGF protein in RPE cells。

The global campaign "Vision 2020: The Right to Sight" was officially launched in Geneva by Dr. Gro Harlem Brundtland, the Director General of World Health Organization (WHO) in February 1999. This represents the global initiative for the elimination of avoidable blindness by the year 2020.1 Seven months later, the International Agency for the Prevention of Blindness (IAPB) General Assembly was held in Beijing, China. During the IAPB General Assembly, the Chinese Ministry of Health, China Disabled Person's Federation together with WHO launched the national campaign "Vision 2020: The Right to Sight" in China.2

Pulmonary function tests provide an objective means to verify ventilatory dysfunction and to estimate its severity in respiratory disorders. Measurement of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) is considered to be the basic tests for the assessment of airway obstruction. Although they are useful diagnostically and prognostically, the results of FEV1 and FVC are strongly dependent on the cooperation of the patient. Lack of collaboration is particularly present in elderly patients because of mood alterations, fatigability or cognitive impairment.1 The forced oscillation technique (FOT) and the interrupter resistance technique are the two methods of measuring respiratory resistance during tidal breathing, they are of special interest because both of them are noninvasive, requires minimal cooperation, takes little time and can be easily repeated, especially in children and elderly subjects who cannot accomplish forced expiratory maneuvers in a reproducible manner.2

Carotid body tumor (CBT) is a rare tumor, which is composed of chromaffin cells, groups of cells associated with the autonomous system, occurring at the carotid bifurcation. This tumor grows slowly, usually with a history of several years and seldom undergoes malignant transformation. The majority of CBT are benign, only few cases of malignant CBTs were reported in the literature.1-3 Over a period of 10 years (1993-2004), 28 patients with CBT were diagnosed and surgically treated in the Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, School of Stomatology, Shanghai Jiaotong University, only one was proven both clinically and histopathologically to be malignant CBT. This paper reports this unusual patient with recurrent malignant carotid body tumor as well as cervical lymph node metastases and reviews the relevant literature。

Lhermitte-Duclos disease (LDD), or dysplastic gangliocytoma of the cerebellum, is a rare hamartomatous lesion characterized by a slowly enlarging mass within the cerebellar cortex. The disease reveals unique appearance on magnetic resonance imaging (MRI). Recognition of the imaging features makes the correct diagnosis possible even without a pathological examination. Three cases are presented and analyzed in this report。