The Association Between Post-stroke Depression, Aphasia, and Physical Independence in Stroke Patients at 3-Month Follow-Up.

Objective: Few studies have examined the association between post-stroke depression (PSD), aphasia, and physical independence in Chinese patients. This study investigated the above association in stroke patients in China at 3-month follow-up. Methods: Altogether 270 patients within 14 days after ischemic stroke were recruited and followed up at 3 months. PSD, aphasia, and physical functional status were measured using the Stroke Aphasia Depression Questionnaire (SADQ), Western Aphasia Battery (WAB), and modified Rankin Scale (mRS), respectively. Patients with mRS total score >2 were considered as having "physical dependence." Results: Out of 248 patients at 3-month follow up, 119 (48%) were rated as having physical dependence. Multiple logistic regression analyses revealed that female (p = 0.04; OR = 2.2; 95% CI: 1.0-5.1), more severe stroke at admission (p < 0.01; OR = 1.4; 95% CI: 1.3-1.5), and more severe PSD at 3 months (p = 0.01; OR = 1.05; 95% CI: 1.01-1.1) were independently associated with physical dependence at 3 months. Conclusions: Greater PSD and stroke severity were independently associated with physical dependence at 3 months after stroke. Aphasia was also associated with physical dependence but the relationship was not significant. Early and effective depression screening, treatment and stroke rehabilitation appear to be important to improve the physical outcome and reduce the burden of stroke survivors.

Suicidal ideation at 1-year post-stroke: A nationwide survey in China.

OBJECTIVE: Few studies on suicidal ideation have been conducted in post-stroke patients in China. This national study examined suicidal ideation at 1-year post-stroke and explored its demographic and clinical correlates. METHODS: A total of 1418 patients with ischemic stroke were included in 56 hospitals nationwide. Demographic, clinical characteristics and neuro-imaging information were collected with standardized instruments, including assessment of stroke severity, depression, cognitive impairment, stroke recurrence, physical disability and insomnia. Suicidal ideation was measured using item 3 of the Hamilton Rating Scale for Depression. RESULTS: The frequency of suicidal ideation in this study was 6.6%. Multivariate analyses revealed that disability (OR=2.07, 95% CI=1.09-3.05), stroke recurrence (OR=4.13, 95% CI=1.74-9.77) and insomnia early (OR=1.87, 95% CI=1.03-3.39), middle (OR=2.66, 95% CI=1.46-4.85) and late (OR=2.35, 95% CI=1.31-4.19) at the 1-year follow-up and post-stroke depression (OR=2.16, 95% CI=1.23-3.82) were significantly associated with post-stroke suicidal ideation. CONCLUSION: Post-stroke depression, disability, insomnia and stroke recurrence are possible risk factors of suicidal ideation that warrant attention in clinical practice.

The Disability Rate of 5-Year Post-Stroke and Its Correlation Factors: A National Survey in China.

Few studies on long-term functional outcome have been conducted in post-stroke patients in China. The objective of this study was to conduct a nationwide survey in China to investigate the 5-year prevalence of post-stroke disability and its correlation factors. A total of 893 patients with ischemic stroke were included. Demographic, clinical and neuro-imaging information were collected with standardized instruments that assessed stroke severity, depression, cognitive impairment, stroke recurrence and physical disability. Disability was assessed with the modified Ranking Score (mRS), of which a cutoff score ≥2 indicates disability. Statistical analysis included chi-square tests, two independent samples t-tests, Mann-Whitney U test and multiple logistic regression analysis. The frequency of disability in this study population was 45%. Multivariate analyses revealed that older age, lower education level, previous history of stroke, stroke severity at admission, depression, cognitive impairment at 3 months, and stroke recurrence within 5 years follow up were all significantly associated with post-stroke disability. The disability rate in 5-year post-stroke was high in Chinese patients. Treatment of depression, secondary prevention of stroke and rehabilitation may benefit disabled patients with stroke in China.

Depression after minor stroke: the association with disability and quality of life--a 1-year follow-up study.

OBJECTIVE: Minor stroke is characterized by mild neurological functional impairment and relatively good outcome. Little is known about the association between post-stroke depression (PSD) and outcomes of minor stroke. The aim of this study was to investigate the association between PSD and disability and quality of life (QoL) at 1 year after minor ischemic stroke. METHODS: Patients with first-ever minor ischemic stroke (n = 747) were followed up at 14 ± 2 days, 3 months, 6 months, and 1 year after stroke. Depressive symptoms were assessed at each follow-up. Patients diagnosed with depression at 14 ± 2 days formed the early-onset PSD group; those who were diagnosed with depression at any subsequent follow-ups for the first time constituted the late-onset PSD group. The outcomes of minor stroke including disability (modified Rankin score ≥ 2) and QoL (Short Form-36 Health Survey) were assessed at the 1-year follow-up. RESULTS: A total of 198 (26.5%) patients were diagnosed with PSD over the 1-year follow-up; 136 and 62 patients were allocated to the early-onset PSD group and late-onset PSD group, respectively. Both early-onset and late-onset PSD were independently associated with disability and poor physical and mental health at 1 year after stroke. Recovery from depression (n = 112) within 1 year decreased the adverse impacts of PSD on functional outcome and QoL. CONCLUSIONS: Post-stroke depression was independently associated with disability and poor QoL at 1 year after first-ever minor ischemic stroke. Recovery from PSD decreased but did not eliminate the adverse impacts of PSD on outcomes of minor stroke.

The correlation between white matter hyperintensity and balance disorder and fall risk: An observational, prospective cohort study.

OBJECTIVE: The presence of an association between white matter hyperintensity (WMH) and the risk of falls in older people is uncertain, with little supporting prospective evidence available at present. We aimed to determine whether WMH was associated with dysfunctions of balance and gait, and other sensorimotor factors leading to falls, and the independent factors related to falls in older Chinese people. The protective effect of exercise against falls was also addressed. METHODS: In a representative sample of hospital-based individuals aged 50 years and older in China, the patients' history of falls, magnetic resonance imaging data, scores on the 9-item Berg Balance Scale (BBS-9) test and timed up-and-go test (TUGT), and sensorimotor measures of computerized dynamic posturography (CDP) were analyzed. Incident falls were recorded prospectively over a 12-month period. Using regression modeling, the association between the risk of falls and baseline WMH was estimated. RESULTS: Only individuals with severe WMH were at an increased risk of falls, and CDP was more sensitive than BBS-9 in detecting WMH-related balance and gait dysfunction. However, WMH was not an independent predictor of falls. Taller height and overweight or obese body habitus were identified as novel protective factors for falls. Female, fall history, and increased TUGT score were identified as independent risk factors for falls in older Chinese people. CONCLUSION: Although WMH was associated with an increased risk of falls, it was not an independent predictor.

Unfavorable Outcome of Thrombolysis in Chinese Patients with Cardioembolic Stroke: a Prospective Cohort Study.

BACKGROUND: Thrombolysis with alteplase is an effective and safe treatment for acute ischemic stroke (AIS). It is controversial whether the outcome of thrombolysis in cardioembolic stroke is different from that of other stroke subtypes. This study compares the outcomes at 3 months postthrombolysis in Chinese patients with AIS secondary to cardioembolism (CE) to the outcomes of those with large-artery atherosclerosis (LAA). METHODS: Using the Thrombolysis Implementation and Monitoring of Acute Ischemic Stroke in China (TIMS-China) cohort, we prospectively followed 827 patients treated within 4.5 h of onset symptoms with alteplase as an intravenous thrombolytic agent. CE and LAA were defined according to TOAST criteria. We compared symptomatic intracerebral hemorrhage (SICH), mortality, and functional outcome at 3 months using multivariables logistic regression analysis. RESULTS: In this cohort, 221 (19.6%) had CE and 606 (53.7%) had LAA. Approximately 2/3 of patients with CE had atrial fibrillation. Symptoms at onset were more severe in patients with CE than in those with LAA (NIHSS, 15.0 vs. 11.0; P < 0.0001); increased rate of SICH (5.9% vs. 0.8%; P < 0.0001); higher mortality (18.6% vs. 10.3%; P = 0.0015); and reduced functional independence (43.6% vs. 55.9%; P = 0.0018) at 3-month follow-up. After adjustment for baseline variables, the clinical outcome of patients with CE was worse than that of patients with LAA (OR, 0.62; 95% CI, 0.39 to 0.97, P = 0.0378). CONCLUSIONS: Patients with cardioembolic stroke had more SICH after thrombolysis, and worse clinical outcome at 3-month follow-up compared with those with LAA. This emphasizes the importance of preventing cardioembolism.

Impact of libido at 2 weeks after stroke on risk of stroke recurrence at 1-year in a chinese stroke cohort study.

BACKGROUND: There were few studies on the relation between changes in libido and incidence of stroke recurrence. The aim of this study was to investigate the relationship between libido decrease at 2 weeks after stroke and recurrent stroke at 1-year. METHODS: It is a multi-centered, prospective cohort study. The 14 th item of the Hamilton Depression Rating Scale-17 was used to evaluate changes of libido in poststroke patients at 2 weeks. Stroke recurrence was defined as an aggravation of former neurological functional deficit, new local or overall symptoms, or stroke diagnosed at re-admission. RESULTS: Among 2341 enrolled patients, 1757 patients had completed follow-up data, 533 (30.34%) patients had decreased libido at 2 weeks, and 166 (9.45%) patients had recurrent stroke at 1-year. Multivariate logistic regression analysis showed that, compared with patients with normal libido, the odds ratio (OR) of recurrent stroke in patients with decreased libido was reduced by 41% (OR = 0.59, 95% confidence interval [CI]: 0.40-0.87). The correlation was more prominent among male patients (OR = 0.52, 95% CI: 0.31-0.85) and patients of ≥60 years of age (OR = 0.57, 95% CI: 0.35-0.93). CONCLUSIONS: One out of three stroke patients in mainland China has decreased libido at 2 weeks after stroke. Decreased libido is a protective factor for stroke recurrence at 1-year, which is more prominent among older male patients.

The relationship between frontal lobe lesions, course of post-stroke depression, and 1-year prognosis in patients with first-ever ischemic stroke.

BACKGROUND AND PURPOSE: Most studies on post-stroke depression (PSD) have focused on a certain time point after stroke instead of the time course of PSD. The aim of this study was to determine the relationship between frontal lobe lesions, course of PSD over a year following the stroke onset, and the 1-year prognosis in patients with first-ever ischemic stroke. METHODS: A total of 1067 patients from the prospective cohort study on the incidence and outcome of patients with post stroke depression in China who were diagnosed with first-ever ischemic stroke and attended 4 follow-up visits at 14±2 days, 3 months, 6 months, and 1 year after stroke onset, were enrolled in the study. PSD was diagnosed according to DSM-IV. The course of PSD was divided into the following two categories: persistent/recurrent depression and no/transient depression. Patients with any ischemic lesion responsible for the indexed stroke event located in the frontal lobe were defined as patients with frontal lobe lesions. Modified Rankin Scale (mRS) ≥2 at 1-year was considered to be poor prognosis. RESULTS: There were 109 patients with and 958 patients without frontal lobe lesions that formed the frontal lobe (FL) and no-frontal lobe (NFL) groups, respectively. After adjusting for confounding variables, frontal lobe lesion was significantly associated with persistent/recurrent PSD (OR 2.025, 95%CI 1.039-3.949). Overall, 32.7% of patients in the FL group had poor prognosis at 1- year compared with 22.7% in the NFL group (P = 0.021). Compared with no/transient depression, persistent/recurrent depression was found to be an independent predictor of poor prognosis at 1-year both in FL and NFL groups. CONCLUSIONS: Long-term and periodical screening, evaluation and treatment are needed for PSD after the onset of ischemic stroke, particularly for patients with frontal lobe infarction.

[The association between plasma neurotransmitters levels and depression in acute hemorrhagic stroke].

OBJECTIVE: To explore the relation between plasma neurotransmitters (Glutamic acid, GAA; γ-aminobutyric acid, GABA; 5-hydroxytryptamine, 5-HT; and noradrenaline, NE) and depression in acute hemorrhagic stroke. METHODS: Objectives were screened from consecutive hospitalized patients with acute stroke. Fasting blood samples were taken on the day next to hospital admission, and neurotransmitters were examined by the liquid chromatography-high resolution mass spectrometry (LC-HRMS). The fourth edition of Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) was used to diagnose depression at two weeks after onset of stroke. The modified Ranking Scale (mRS) was followed up at 1 year. Pearson test was used to analyse the correlation between serum concentration of neurotransmitters and the Hamilton Depression scale-17-items (HAMD-17) score. Logistic regression was used to analyse the relation of serum concentration of neurotransmitters and depression and outcome of stroke. RESULTS: One hundred and eighty-one patients were included in this study. GABA significantly decreased [6.1(5.0-8.2) µg/L vs 8.1(6.3-14.7) µg/L, P < 0.05] in patients with depression in hemorrhagic stroke, and there was no significant difference in GAA, 5-HT, or NE. GABA concentration was negatively correlated with HAMD-17 score (r = -0.131, P < 0.05); while concentration of serum GABA rose by 1 µg/L, risk of depression in acute phase of hemorrhagic stroke was reduced by 5.6% (OR 0.944, 95%CI 0.893-0.997). While concentration of serum GAA rose by 1 µg/L, risk of worse outcome at 1 year was raised by 0.1%, although a statistic level was on marginal status (OR 1.001, 95%CI 1.000-1.002). CONCLUSIONS: In patients with depression in the acute phase of hemorrhagic stroke, there was a significant reduction in plasma GABA concentration. GABA may have a protective effect on depression in acute phase of hemorrhagic stroke. Increased concentrations of serum GAA may increase the risk of worse outcomes at 1 year after stroke.

Array analysis for potential biomarker of gemcitabine identification in non-small cell lung cancer cell lines.

Gemcitabine is one of the most widely used drugs for the treatment of advanced Non-small cell lung cancer (NSCLC), but modest objective response rate of patients to gemcitabine makes it necessary to identify novel biomarkers for patients who can benefit from gemcitabine-based therapy and to improve the effect of clinical therapy. In this work, 3 NSCLC cell lines displaying different sensitivities to gemcitabine were applied for mRNA and microRNA (miR) expression chips to figure out the biomarkers for gemcitabine sensitivity. Genes whose expression increased dramatically in sensitive cell lines were mainly enriched in cell adhesion (NRP2, CXCR3, CDK5R1, IL32 and CDH2) and secretory granule (SLC11A1, GP5, CD36 and IGF1), while genes with significantly upregulated expression in resistant cell line were mainly clustered in methylation modification (HIST1H2BF, RAB23 and TP53) and oxidoreductase (TP53I3, CYP27B1 and SOD3). The most intriguing is the activation of Wnt/ß-catenin signaling in gemcitabine resistant NSCLC cell lines. The miR-155, miR-10a, miR-30a, miR-24-2* and miR-30c-2* were upregulated in sensitive cell lines, while expression of miR-200c, miR-203, miR-885-5p, miR-195 and miR-25* was increased in resistant cell line. Genes with significantly altered expression and putatively mediated by the expression-changed miRs were mainly enriched in chromatin assembly (MAF, HLF, BCL2, and IGSF3), anti-apoptosis (BCL2, IGF1 and IKBKB), protein kinase (NRP2, PAK7 and CDK5R1) (all the above genes were upregulated in sensitive cells) and small GTPase mediated signal transduction (GNA13, RAP2A, ARHGAP5 and RAB23, down-regulated in sensitive cells). Our results might provide potential biomarkers for gemcitabine sensitivity prediction and putative targets to overcome gemcitabine resistance in NSCLC patients.

Poststroke depression and risk of recurrent stroke at 1 year in a Chinese cohort study.

BACKGROUND: Studies show that poststroke depression (PSD) increases mortality risk at 1 year. However, whether PSD increases the risk of recurrent stroke at 1 year remains unclear. This study was to investigate whether PSD at 2 weeks following a stroke could increase risk of recurrent stroke at 1 year. METHODS AND RESULTS: This was a multi-centered prospective cohort study. A total of 2306 patients with acute stroke were enrolled in our study. PSD was diagnosed according to the criteria set by the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). The outcomes of recurrent stroke were followed up via face-to-face or phone interview. A total of 1713 patients had complete follow-up data, with 481 (28.1%) cases of PSD and 158 (9.2%) cases of cumulative recurrent stroke at 1 year. Multivariate logistic regression analysis showed a 49% increase of OR of recurrent stroke at 1 year in patients with PSD, compared to patients without PSD following a stroke (OR=1.49, 95%CI: 1.03-2.15). There was no significant correlation between anti-depressant drugs and the risk of recurrent stroke at 1 year following a stroke (OR=1.96, 95%: CI 0.95-4.04). CONCLUSIONS: Based on the DSM-IV diagnostic criteria, nearly 3 out of 10 hospitalized stroke patients in China were diagnosed with PSD at 2 weeks following a stroke. PSD is associated with a higher risk of recurrent stroke at 1 year. Our study did not find benefit of anti-depressant drugs in reducing such risk.

[Acute ischemic stroke in the very elderly outcome and predictive factors].

OBJECTIVE: To investigate the clinical characteristics, 3-month outcome and predictive factors in the very elderly patients with ischemic stroke. METHODS: A total of 305 acute ischemic patients aged 65 years and over were enrolled in the study. They were divided into two subgroups by age: 80 years old and over (n = 78), 65 - 79 years old (n = 227). The clinical outcome was assessed by the modified Rankin Scale (mRS) on (90 ± 7) days after stroke, and categorized as good (scoring 0 - 2) or poor (scoring 3 - 6) outcome. RESULTS: Significantly lower BMI [(23.62 ± 4.92) kg/m(2) vs (25.08 ± 3.69) kg/m(2), P = 0.005], lower frequency of dyslipidemia (56.41% vs 71.13%, P = 0.006) and alcohol intake (0% vs 6.61%, P = 0.043) were found in the very elderly group. The rates of poor functional outcome in the ≥ 80 years group and the 65 - 79 years old group were 56.41% (44/76) and 41.40% (94/224) respectively, with a P value of 0.015. Multivariate logistic regression analysis showed that higher National Institute of Health stroke scale (NIHSS) total score (OR 1.48, 95%CI 1.19 - 1.83) and lower albumin level (OR 0.73, 95%CI 0.55 - 0.95) were associated with poor outcome in ≥ 80 year old, whereas higher NIHSS total score (OR 1.38, 95%CI 1.24 - 1.53) and complications during hospital stay (OR 2.58, 95%CI 1.07 - 6.19) were predictive factors in the 65 - 79 years old group. CONCLUSION: Our study suggests that NIHSS scores, albumin level and complications during hospitalization are useful predictive factors for the short-term poor functional outcome in the patients of ≥ 65 years old and ≥ 80 years old patients have a worse prognosis.

Inhibition of survivin expression and mechanisms of reversing drug-resistance of human lung adenocarcinoma cells by siRNA.

BACKGROUND: Survivin, a member of the inhibitor of apoptosis protein (IAP) family, overexpresses in tumor cells and not expresses in terminally differentiated adult tissues. This study aimed to investigate the effects of survivin-specific siRNA on cell proliferation, apoptosis and chemosensitivity to cisplatin in vitro and in vivo and explore the mechanisms about decreasing expression of survivin in reversing cancer cells resistance to chemotherapeutic drug. METHODS: Survivin-specific siRNA was transfected into A549/DDP cells. The expression of survivin and lung resistance-related protein (LRP) mRNA levels were determined by RT-PCR, chemosensitivity of A549/DDP (cisplatin) cells to cisplatin was determined by MTT assay, and apoptosis and cell cycle were determined by flow cytometry (FCM). The protein expression levels of survivin, LRP, cyclin-D(1), caspase-3 and bcl-2 were determined by Western blotting analyses. The effect of survivin siRNA inhibition on tumor growth was studied in athymic nude mice in vivo. RESULTS: Survivin-specific siRNA efficiently down-regulated survivin expression. The cell cycle was arrested at G2/M phase, and apoptosis was obviously found. Inhibition of survivin expression could make the IC50 and drug-resistant index of cisplatin decrease, and enhance the cancer cells sensitivity to cisplatin. After transfection by survivin-specific siRNA, expression of LRP and cyclin-D1 were downregulated, caspase-3 expression was upregulated, bcl-2 expression had no obvious change. The animal experiment confirmed knockdown of survivin could inhibit the tumor growth. CONCLUSIONS: Survivin-specific siRNA can efficiently suppress the expression of survivin, increase apoptosis, inhibit cells proliferation and enhance the chemosensitivity to cisplatin in vitro and in vivo. Suppression of survivin expression helping to reverse drug-resistance may have relationship with downregulation of LRP and upregulation of caspase-3. Anti-tumor strategies based on the inhibition of survivin may be useful in targeting lung adenocarcinomas.

[Relationships between the expressions of intercellular adhesion molecule-1 and tissue inhibitor of metalloproteinase-1 and matrix metalloproteinase-9 in lung tissues of patients with chronic obstructive pulmonary disease].

OBJECTIVE: To evaluate the correlation between the expressions of intercellular adhesion molecule-1 (ICAM-1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) and matrix metalloproteinase-9 (MMP-9) in lung tissues of patients with COPD. METHODS: Lung tissues from patients with COPD (COPD group, n = 19) and those without COPD (smokers and nonsmokers with normal lung function, n = 11 and 9, respectively) were obtained from surgical excisions of lung cancer patients. The mRNA expression of ICAM-1, TIMP-1 and MMP-9 was detected using semi-quantitative RT-PCR. The protein expression of ICAM-1, TIMP-1 and MMP-9 was detected by using immunohistochemistry method. RESULTS: There were significant differences in FEV1% and FEV1/FVC% among smokers without COPD, nonsmokers without COPD and COPD patients. MMP-9 was highly expressed in alveolar epithelial cells, bronchial epithelial cells, vascular smooth muscle cells, alveolar macrophages, and interstitial cells in the COPD group, compared with smokers without COPD group and nonsmokers without COPD group (54.0 +/- 15.0), (1.2 +/- 0.7) and (1.4 +/- 0.8). Low level expression of TIMP-1 was detected in alveolar macrophages, alveolar epithelial cells and vascular smooth muscle cells in the COPD group, but no expression in smokers and nonsmokers without COPD. High level expression of ICAM-1 was detected in alveolar epithelial cells, and the expression was higher in the COPD group (52.1 +/- 13.4), (2.1 +/- 1.1) and (4.5 +/- 2.4). The mRNA level of MMP-9 showed significant difference among patients with COPD, smokers without COPD and nonsmokers without COPD (0.71 +/- 0.16), (0.20 +/- 0.08) and (0.17 +/- 0.05). The mRNA level of TIMP-1 was also significantly different among patients with COPD, smokers without COPD and nonsmokers without COPD (0.47 +/- 0.10), (0.26 +/- 0.08) and (0.20 +/- 0.06). ICAM expression was also significantly higher in patients with COPD as compared with smokers without COPD and nonsmokers without COPD (0.62 +/- 0.15), (0.44 +/- 0.12) and (0.37 +/- 0.11). Both the mRNA and the protein levels of MMP-9 were inversely correlated with FEV1 % and FEV1/FVC% (r= -0.759, -0.756, -0.772, -0.725, respectively, P <0.01). TIMP-1 mRNA level was inversely correlated with FEV1% and FEV1/FVC% (r = -0.675, -0.623, respectively P <0.01). Negative correlations were also noted between ICAM-1 expressions (both mRNA and protein) and FEV1% or FEV1/FVC% (r = -0.580, -0.531, -0.739, -0.756, respectively P <0.01). Interestingly, the mRNA expression of TIMP-1, MMP-9 and ICAM-1 was positively correlated (r = 0.576, 0.524, P < 0.01), while the protein levels of MMP-9 and ICAM-1 were positively correlated (r = 0.964, P <0.01). CONCLUSION: There was a significant correlation between over-expression of ICAM-1 and TIMP-land MMP-9 in lung tissues from COPD patients. Over-expressions of ICAM-1 in the lung may result in accumulation of inflammatory cells releasing certain inflammatory factors that could destroy the normal lung structure. In addition, highly expressed TIMP-1 and MMP-9 in lung tissues may also contribute to the destruction and reconstitution of the bronchial or/and alveolar wall, which is likely to play a major role in airway obstruction.

[Expressions of urotensin II and its receptor in pulmonary arteries in rats with chronic thromboembolic pulmonary hypertension].

OBJECTIVE: To investigate the expressions of Urotensin II (UII) protein and mRNA and its receptor (UT) mRNA of medium and small pulmonary arteries of rats with chronic thromboembolic pulmonary hypertension. METHODS: The Wistar rats were injected thrombi through the jugular vein 2 times in 2 weeks and tranexamic acid was injected peritoneally once daily during the experiment to prevent thrombolysis. The mean pulmonary artery pressure (mPAP) was measured using right cardiac atheterzation. The expressions of UII protein in pulmonary arteries were studied by immunohischemistry with a polycolonal antibody. The expressions of UII mRNA and UT mRNA were detected by in situ hybridization using UII and UT oligonuclear probes. The changes of structures in pulmonary vessle were observed, including relative medial thickness of pulmonary artery (PAMT) and vessle wall area/total vessle area (WA/TA). RESULTS: The mPAP of the 4 weeks to the 12 weeks groups were (19.9 +/- 6.2) mm Hg (1 mm Hg = 0.133 kPa), (23.8 +/- 4.1) mm Hg and (27.4 +/- 5.4) mm Hg, higher than that of the control group (F = 13.75, P < 0.01, respectively). The PAMT of the 4 weeks to the 12 weeks groups were (42.6 +/- 11.16)%, (47.82 +/- 10.02)% and (53.79 +/- 10.41)%, and WA/TA of the 4 weeks to the 12 weeks groups were (22.75 +/- 6.79)%, (25.32 +/- 4.90)% and (27.05 +/- 7.71)%, both changed significantly as compared to the control group (F = 5.52 and 6.61, P < 0.01, respectively; P < 0.05 in 4 weeks group; P < 0.01 in 8 weeks and 12 weeks groups, respectively). The expressions of UIIprotein, UII mRNA and UT mRNA in the 4 weeks to the 12 weeks groups were obviously higher than the control group (F = 30.39, 30.78 and 14.49, P < 0.01, respectively), and their expressions were more marked in the small pulmonary arteries than in medium pulmonary arteries. The expressions of UIIprotein, UII mRNA and UT mRNA were positively correlated with mPAP and PAMT. The pulmonary vascular remodeling was time-dependently aggravated after embolism (r: 0.822, 0.866 and 0.846; 0.675, 0.712 and 0.756, P < 0.01, respectively). CONCLUSIONS: The expressions of UII protein, UII mRNA and UT mRNA of pulmonary arteries in the animal models were higher than those in the control group. These dynamic changes of UII mRNA, UIIprotein and UT mRNA may contribute to the development of pulmonary hypertension and vascular remodeling after pulmonary thromboembolism.

[Expressions of and the effect of smoking on vascular endothelial growth factor and induced nitric oxide synthase in lung tissues of chronic obstructive pulmonary disease patients].

OBJECTIVE: To investigate the expressions of and the effect of smoking on vascular endothelial growth factor (VEGF) and induced nitric oxide synthase (iNOS) in lung tissues of chronic obstructive pulmonary disease (COPD) patients. METHODS: The peripheral lung tissues were obtained from 46 patients with lung carcinoma. They were divided into three groups according to their habit of smoking and lung function, 19 smokers with moderate COPD, 12 smokers and 15 nonsmokers with normal lung function. The expression of VEGF and iNOS was detected by immunohistochemistry. RESULTS: Expressions of VEGF and iNOS were increased in lung tissues of smokers without COPD (1.50 +/- 0.39, 1.45 +/- 0.41) compared with nonsmokers without COPD (1.18 +/- 0.33, 1.09 +/- 0.41) (each P < 0.05), and were significantly increased in lung tissues of smokers with moderate COPD (2.19 +/- 0.51, 2.39 +/- 0.45) compared with nonsmokers without COPD (each P < 0.01). The expression of VEGF in lung tissues was significantly correlated with the expression of iNOS (r = 0.78, P < 0.01), but was inversely correlated with FEV(1) (r = -0.67, P < 0.01). CONCLUSIONS: Expressions of VEGF and iNOS were upregulated in lung tissues of smokers and patients with moderate COPD. Overexpression of iNOS and VEGF may participate in the mechanism of airway and vascular remodeling, and airflow limitation in COPD.

[Analysis of gene expression profile in lung adenocarcinoma, tumor adjacent tissue and fetal lung tissue].

OBJECTIVE: To investigate the gene expression profiles in lung adenocarcinoma (LA), tumor adjacent tissue (TAT) and fetal lung tissue (FLT) by cDNA microarray technique. METHODS: Total RNA from LA, TAT and FLT was extracted and purified. The cDNA was made by RT-PCR, and then labeled with Cy5 and Cy3 fluorescence as probes which were hybridized with the whole gene chips. Subsequently, the signal images were scanned by ScanArray 4000 fluorescence scanner and analyzed by Gene Pix PRO3.0. RESULTS: In 4 cases with LA and TAT, 25 genes were screened out for differences in gene expression level, among which 3 were upregulated and 22 downregulated; in FLT and TAT cases, 316 genes were screened out, among which 192 were upregulated and 124 downregulated; 16 genes were found to be differentially expressed genes in common in LA, TAT and FLT, among which 12 were upregulated and 4 downregulated. CONCLUSION: The 25 differentially expressed genes in LA and TAT may be related to occurrence and development of lung cancer, while the 316 genes in FLT and TAT may be related to fetal developmental. The 16 differentially expressed genes may be related to the initiation of lung cancer.