2010年 · 第123卷第04期

Venous thromboembolism (VTE), composed of deep venous thrombosis (DVT) and pulmonary thromboembolism (PTE), has been recognized as worldwide health problem not only in the western countries but also in Asian-Pacific regions. Tremendous progress has been made in recent years in identifying the potential risk factors, understanding the pathogenesis and developing therapeutic approaches for VTE. However, most of the currently available data are from American and European populations. Limited data from Chinese population are validated. Efforts should be made to increase public awareness, and promote clinical and translational research of VTE in modern China。

Abstract：Background The main risk factor for chronic obstructive pulmonary disease (COPD) is cigarette smoking. However, only 10%-20% of chronic heavy smokers develop systematic COPD. We hypothesized that the inheritance of gene polymorphisms could influence the development of COPD, which was investigated by studying two single nucleotide polymorphisms (SNP) in exon 1 of the transforming growth factor-β1 (TGF-β1) gene.Methods We enrolled 219 patients with COPD as the research group and 148 healthy people as the control group, all of whom were Chinese Han people. The polymorphisms of the TGF-β1 gene, 869T/C and 915G/C, were analyzed using the method of amplification refractory mutation system-polymerase chain reaction (ARMS-PCR).Results The occurrence of the TGF-β1 gene 869T/C polymorphism in patients with COPD was significantly different from the control group (P <0.05), in which the relative risk of this disease increased in cases who had the C allele (OR: 1.131, 95% Cl:1.101-1.539). There was no increased frequency of TGF-β1 915G/C gene in COPD patients compared with control subjects (P >0.05).Conclusions The polymorphism 869T/C in TGF-β1 gene has a significant association with disease occurrence in COPD patients and the C allele might be a risk factor. The homozygous wild-type CC of 869T/C on TGFβ1 could be a predisposing factor in COPD and those who carry the C allele might have particularly susceptibility to developing COPD.

Abstract：Background It has been shown that neurohumoral factors other than mechanical obstruction are involved in the pathophysiology of acute pulmonary thromboembolism (APTE). The aim of this study was to investigate the effects of thrombolytic drugs, a selective endothelin-1 receptor (ET-1R) antagonist alone or their combination on APTE in a canine model.Methods Twenty dogs were randomly assigned to five groups: sham, model, urokinase (UK), BQ123, and combination (UK plus BQ123). The dogs in the sham group underwent sham surgery. APTE was induced in the other four groups by intravenous injection of autologous blood clots. Dogs in the UK, BQ123 and combination groups received UK, BQ123 (a selective ET-1R antagonist), or UK plus BQ123, respectively. The dogs in the model group were given saline. Mean pulmonary artery pressure (mPAP), serum concentrations of ET-1, thromboxane (TXB2), and tumor necrosis factor (TNF)-α were determined at different time points following the induction of APTE.Results UK and BQ123 alone markedly decreased mPAP in APTE. By comparison, the reduction was more significant in the combination group. Compared with the sham group ((-0.90±0.61) mmHg), mPAP increased by (7.44±1.04), (3.42±1.12) and (1.14±0.55) mmHg in the model group, UK alone and BQ123 alone groups, respectively, and decreased by (2.24±0.67) mmHg in the combination group (P <0.01). Serum ET-1 concentrations in the BQ123 and combination groups were (52.95±8.53) and (74.42±10.27) pg/ml, respectively, and were significantly lower than those in the model and UK groups ((84.56±7.44) and (97.66±8.31) pg/ml respectively; P <0.01). Serum TNF-α concentrations were significantly lower in the BQ123 group than in the model, UK and combination groups (P <0.05).Conclusions Our results indicate that the selective ET-1R antagonist BQ123 not only reduces the increase of mPAP and serum ET-1 level, but also inhibits the production of TNF-α, and attenuates the local inflammatory response induced by APTE. Selective ET-1R antagonists may be beneficial to the treatment of APTE, particularly when used in combination with a thrombolytic agent。

Abstract：Background From late May 2009, sporadic imported cases of novel influenza A (H1N1) were continuously confirmed in Shanghai, but there were few reports on its clinical presentation in China. The aim of the study was to investigate the demographic and clinical features of the laboratory-confirmed cases and the treatment with oseltamivir.Method We performed a retrospective study in the Shanghai Public Health Clinical Center (SHAPHC), reviewing the medical records of the laboratory-confirmed patients derived from June 10 to July 20, 2009. Results Atotal of 156 cases were enrolled, of whom 152 had a history of recent travel. The mean age was 22.6 years and 89 cases (57.1%) were males. The most common symptoms were fever, cough, and sore throat, with children more likely to run a temperature above 38.5℃ than adults. The mean leucocyte count was 5.4×10~9/L, the mean neutrophil count 3.2×10~9/L and the mean lymphocyte count 1.4×10~9/L. Other findings included a normal range or elevated level of C-reactive protein (CRP) and glutamic-pyruvic transaminase and a normal or decreased level of prealbumin; the levels of prealbumin and CRP were significantly lower in the children than in the adults. Fifty-two patients had abnormal chest CT results, with small unilateral or bilateral pulmonary infiltrates, axillary and mediastinal lymphadenopathy and local pleural thickening, while no cases showed symptoms of hypoxia. All the patients received oseltamivir and recovered without complications, but the duration of fever and virus shedding were significantly longer in the children than in the adults. Conclusions Travel-related circulation may be an important reason for the H1N1 epidemic in the non-epidemic areas, and the virus caused mild respiratory symptoms. The infection in children was more severe in terms of prealbumin levels, temperature, the duration of fever and virus shedding. Oseltamivir was effective for H1N1, but more effective in the adults than in the children。

Abstract：Background High positive end-expiratory pressure (PEEP) and low tidal volume (VT) ventilation is thought to be a protective ventilation strategy. It is hypothesized that the stabilization of collapsible aiveoli during expiration contributes to lung protection. However, this hypothesis came from analysis of indirect indices like the analysis of the pressure-volume curve of the lung. The purpose of this study was to investigate isolated healthy and injured rat lungs by means of alveolar microscopy, in which combination of PEEP and VI- is beneficial with respect to alveolar stability (I-E%).Methods Alveolar stability was investigated in isolated, non-perfused mechanically ventilated rat lungs. Injured lungs were compared with normal lungs. For both groups three PEEP settings (5, 10, 20 cmH_2O) were combined with three VT settings (6, 10, 15 ml/kg) resulting in nine PEEP-VT combinations per group. Analysis was performed by alveolar microscopy.Results In normal lungs alveolar stability persisted in all PEEP-VT combinations (I-E% (3.2±11.0)%). There was no significant difference using different settings (P >0.01). In contrast, alveoli in injured lungs were extremely instable at PEEP levels of 5 cmH_2O (mean I-E% 100%) and 10 cmH_2O (mean I-E% (30.7±16.8)%); only at a PEEP of 20 cmH_2O were alveoli stabilized (mean I-E% of (0.2±9.3)%).Conclusions In isolated healthy lungs alveolar stability is almost unaffected by different settings of PEEP and VT. In solated injured lungs only a high PEEP level of 20 cmH_2O resulted in stabilized alveoli whereas lower PEEP levels are associated with alveolar instability。

Abstract：Background The number of Clare cells and the Clara cell 16-kDa protein (CC16) levels of the lung decrease in patients with chronic obstructive pulmonary disease (COPD). N-acetylcysteine (NAC) is a powerful antioxidant and can reduce the frequency of acute exacerbations of COPD. But the exact mechanism is unclear. The present study was designed to investigate the effects of NAC on Clara cells in rats with cigarette smoke exposure.Methods Eighteen adult male Wistar rats were randomly divided into 3 groups, 12 exposed to cigarette smoke (CS) thrice a day, 10 cigarettes for 30 minutes each time for 1 week, without (CS group) or with (CS+NAC group) oral intake of NAC 80 mg·kg~(-1)·d~(-1), and another 6 rats exposed to fresh air (control group). Clara cells were observed by an electron microscope. The Mrna expression of CC16 and CC16 protein in lungs were determined by reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry respectively. The glutathion (GSH) level in plasma and lung tissue were tested by fluorimetry assay.Results Compared with the controls, the pathologic score of small airways significantly increased in the CS exposed rats (20.3±14.7 vs. 53.7±11.5, P <0.05). The Clara cell particles in cytoplasm decreased in the CS group (P <0.05). The percentage of CC16-positive cells in bronchioles in the CS group (27.8±4.3 and 29.5±2.4 in terminal bronchioles and respiratory bronchioles, respectively) significantly decreased as compared with the control group (37.1±3.8 and 43.8±5.8 in terminal bronchioles and respiratory bronchioles, respectively) (P<0.05). No significant difference was observed in GSH level ((181±26) nmol/L in the control group vs. (170±18) nmol/L in the CS group) between the two groups. After treatment with NAC, the pathologic score of small airways (24.1±17.5) decreased (P <0.05). Clara cell particles in cytoplasm of Clara cells increased and GSH level in plasma ((213±40) nmol/L vs. (170±18) nmol/L in the CS group) increased too (P<0.05), while the increase in the proportions of CC16 positive cells in bronchioles (30.1±6.4 and 34.3±6.3 in terminal bronchioles and respiratory bronchioles, respectively) did not reach the statistical significance (P >0.05). No significant difference was found in the expression of CC16 Mrna among the three groups. Correlation analysis indicated that the percentage of CC16-positive cells in bronchioles negatively correlated with the pathologic score of small airways (r=-0.592, P<0.05), but not with GSH level.Conclusions One-week CS exposure decreased the number of Clara cells and the expression of CC16 in bronchioles in rats. NAC might provide protection of the Clara cells from oxidative damage and possibly through the elevation of the synthesis and secretion of CC16. These data indicate that NAC decreases airway inflammation induced by CS via induction of CC16。

Abstract：Background Congenital uterine anomalies are associated with the highest incidence of reproductive failure and obstetric complications. This study aimed to summarize the clinical characteristics and prenatal outcome of pregnancy in women with congenital uterine malformations.Methods This retrospective study evaluated the fertility and obstetric outcome of 116 inpatients with uterine malformations with pregnancy in Peking University Third Hospital from June 1998 to June 2009. A total of 270 randomly selected pregnant women with a previously confirmed normally shaped uterus as a control group. Student's t test and analysis of variance (ANOVA) were used to compare means for normally distributed variables. The analysis was carried out using the SPSS.Results Among 21 961 deliveries in Peking University Third Hospital, 116 (0.45%) were in women with uterine anomalies. A septate uterus was present in 43 (37.1%) and the uterus didelphys in 28 (24.2%) of the 116 women identified. Bicornuate uterus, arcuate and unicomate uterus were observed in 12 (10.3%), 18 (15.5%) and 15 (12.9%) patients, respectively. Patients with uterine anomalies had significantly higher rates of malpresentation (38.8%), preterm delivery (19.8%), and cesarean section (78.5%) compared with the group of women with a normal uterus. Patients with uterine anomalies had significantly lower mean birth-weight neonates and a significantly higher incidence of small for gestationalage (SGA) neonates; women with uterus didelphys more frequently required infertility treatment than patients with other uterine anomalies (P <0.001). The rate of malpresentation was significantly higher in patients with septated uterus in comparison with patients with uterus unicorns (P <0.05).Conclusions Women with congenital uterinemal formation usually have higher incidence of complications during pregnancy and delivery. A septate uterus appears to be associated with poorer obstetric outcomes。

Abstract：Background Prenatal diagnoses are extremely advantageous for pregnant women with high-risk indicators and can help prevent the birth of malformed infants. However, no large-scale statistical study analyzing the correlation between fetal chromosome disorders and abnormal indicators during pregnancy has been done in China. The objectives of this study were to diagnose and analyze fetal chromosome abnormalities, determine the feasibility of the various prenatal test methods and establish diagnostic guidelines for the early, middle, and late trimesters.Methods From January 2004 to May 2009, 2782 pregnant women at high-risk underwent prenatal diagnoses. Categorized data expressed as either actual counts or percentages were analyzed by the chi-square or Fisher's exact test. Chorionic villus sampling was performed in the early-trimester (10-12 weeks of gestation), amniocentesis in mid-trimester (16-28 weeks of gestation), and umbilical cord blood collection in mid- or late-trimester (16-37 weeks of gestation). In 51 cases either autopsy samples from intrauterine fetal deaths or placental tissues from aborted fetuses were tested.Results Chromosomal abnormalities were observed in 3.99% (111/2782) of the samples. Overall, the success rate of cytogenetic analysis for high-risk pregnancy groups was 98.17% (2731/2782). It was significantly less successful when used to analyze data from the chorionic villus sampling compared with that from amniocentesis and umbilical cord blood (P=0.000). Abnormal chromosome carriers had the highest percentage of abnormal chromosomes (67.86%) when compared with chromosomal abnormalities in patients with ultra-sonographic "soft markers" (11.81%), advanced maternal age (4.51%) and those who had positive serum screening results (P=0.000).Conclusions Invasive prenatal diagnostic techniques are feasible tools for confirming fetal chromosomal abnormalities. Abnormal chromosomes detected in one of the parents carrying abnormal chromosome, ultrasound soft markers, advanced maternal age or positive serum screening results were associated with a higher frequency of fetal genetic diseases。

Abstract：Background Human epidermal growth factor 2 (HER2) is one of the most important prediction factors, but only 25%-30% of breast cancer patients HER2 are positive. It is unknown whether there are other molecular markers that could be used to predict prognosis and recurrence in HER2 negative patients.This study investigated correlations of cyclin A2 and HER2 levels with clinical outcomes in 281 patients with invasive breast cancer in order to identify whether cyclin A2 can serve as a prognostic factor in HER2 negative patients.Methods Immunohistochemical staining was used to detect cyclin A2 and HER2 expression in 281 patients. Cyclin A2. and HER2 gene amplifications were analyzed using gene analysis and RT-PCR in 12 patients. Risk and survival estimates were analyzed using Log-rank, Kaplan-Meier, and Cox regression analysis; cyclin A2 and HER2 consistency with survival were analyzed using Kappa analysis.Results Patients with higher cyclin A2 and HER2 expressions had significantly shorter disease-free survival periods (P=0.047 and P=0.05, respectively). Kappa analysis performed that cyclin A2 and HER2 showed a low Kappa index (kappa=0.37), allowing us to conclude that cyclin A2 and HER2 detect different pathologies. Gene analysis and RT-PCR showed that cyclin A2 was upregulated in patients with early relapse; the average increase was 3.69-2.74 fold.Conclusions Cyclin A2 and HER2 are associated with proliferation and high recurrence, particularly when combined. Cyclin A2 is easily detected by nuclear staining and might be a useful biomarker for recurrence risk in HER2 negative patients。

Abstract：Background A study of prenatal genetic diagnosis for 22q11.2 mierodeletion, which has a wide phenotypic spectrum that involves almost all organs, is rarely reported in China. This study aimed to explore the prevalence of 22q11.2 microdeletion in congenitally malformed fetuses via the fluorescent in situ hybridization (FISH) technique and to investigate the feasibility of use of amniocytes to diagnose 22q11.2 microdeletion syndrome prenatally.Methods The study enrolled 23 cases of fetal cardiac malformation, as indicated by ultrasound in Beijing Anzhen Hospital and 14 cases of non-cardiac malformation, as determined by type-B ultrasound in Beijing Anzhen Hospital and other hospitals. Amniotic fluid was obtained by amniocentesis before odinopoeia, and the stillborn fetuses of the induced labor were preceded to autopsy. The amniotic fluid of 20 cesarean deliveries during the same period of time was used as a control. The TUPLE1 gene in the amniotic fluid of malformed and normal fetuses was assessed by the FISH method.Results The prevalence rates of the TUPLE1 gene deletion in the amniotic fluid cells from fetuses with cardiac deformations and fetuses without such malformations were 43.5% and 57.1%, respectively. The deletion of TUPLE1 was significantly associated with fetal malformation.Conclusion Chromosome 22q11.2 microdeletion is one of the major factors leading to fetal congenital malformations, and prenatal FISH screening for 22q11.2 microdeletion syndrome is technically feasible using amniocytes。

Abstract：Background Detection rate of retropharyngeal lymph node metastasis in patients with nasopharyngeal carcinoma (NPC) needs to be improved. The purpose of this study was to compare three magnetic resonance (MR) sequences for detecting lymph nodes in patients with NPC.Methods Between July 2007 and March 2008, MR staging of pre-treated tumor was conducted on 120 patients with pathologically confirmed NPC. The outcome of three different sequences for MR NPC staging were compared: coronal short TI inversion recovery (STIR), axial proton density fat-suppressed (PDWl fs), and coronal contrast enhanced fast spin echo T1 weighted fat-suppressed (CE FSE T1WI fs). Nodal classification method (1999) was applied to count the number of retropharyngeal and cervical lymph nodes discovered by each MR sequence. Paired t tests were used for statistical analysis.Results A total of 2575 lymph nodes were found using coronal STIR sequence; 1816 lymph nodes for coronal CE FSE T1WI fs sequence and 2638 lymph nodes for axial PDWI fs sequence. Significant differences existed in the number of lymph nodes detected by axial PDWI fs and coronal CE FSE T1WI fs sequence (paired t test, P <0.05), with the former sequence getting higher numbers. Statistical differences also existed between coronal STIR and coronal CE FSE T1WI fs sequence (paired ttest, P <0.05), with the former sequence getting higher numbers. No significant difference was found between coronal STIR sequence and axial PDWI fs sequence (paired t test, P >0.05).Conclusions For the detection of retropharyngeal and cervical lymph nodes, coronal STIR sequence and axial PDWI fs sequence have similar performance and both sequences showed better detection than CE FSE T1WI fs sequence. Furthermore, by combining coronal STIR sequence and axial PDWI fs sequence, we can improve the detection of lymph nodes in NPC N-staging before treatment, especially for lymph nodes located in the thoracic entrance。

Venous thromboembolism (VTE), including deep vein thrombosis (DVT) and pulmonary thrombo-embolism (PTE), carries significant mortality and morbidity. As a result of the increasing awareness and improvement in diagnostic facilities, the hospital admissions have increased dramatically in China. Recent publications have reported the increasing incidences of PTE and DVT in hospitalized patients.~(1-3)

Chronic obstructive pulmonary disease (COPD), one of the most common public health problems worldwide, is the fourth leading cause of death in the world. In China, respiratory diseases (of which COPD is a major component) are the third leading cause of death in rural areas and the fourth leading cause of death in urban area, accounting for 1 million deaths and over 5 million disabilities each year. COPD ranks first among the burdens in China.~1

Pulmonary Langerhans' cell histiocytosis (PLCH) is an isolated form of Langerhans' cell histiocytosis that usually develops in cigarette smokers.~(1,2) PLCH usually has typical light microscopic morphology with a spectrum of progressive changes.~(2-4)

Rhabdomyolysis is one of the identified uncommon but potentially lethal complications of isoniazid intoxication, which can be secondary to severe muscle exertion due to generalized seizures or can be caused by direct toxicity of either the drug or one of its metabolites on muscles.~(1,2)

In February 2005, Gefitinib (Iressa), a small-molecular epidermal growth factor receptor and tyrosine kinase inhibitor, was approved in China as an anticancer agent for patients with advanced (local or metastatic) non-small cell lung cancer (NSCLC), who failed prior chemotherapy. The common adverse events of the drug include acne-like skin rash, paronychia, pruritus, diarrhea, nausea/vomiting, anorexia, hepatitis, and hyperbilirubinemia.~1

Broncholithiasis, a rare disorder of the respiratory system, is usually caused by pulmonary fungal infection and tuberculosis occurring in the early years of its victims. Pulmonary fungal infection and tuberculosis can lead to calcification of the hilar and mediastinal lymph nodes; the calcified lymph nodes erode the nearby bronchi and cause clinical and imaging abnormalities。

In 1977, Carney originally described the association of gastric epithelioid leiomyosarcoma, pulmonary chondroma and extra-adrenal paraganglioma, and this unusual syndrome was subsequently called "Carney triad"。

A total of 770 000 deaths from tuberculosis(TB)were avoided over the past eight years in China thanks to a large-scaleTB control project,it was announced on January 20,2010。