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Purpose: Deep learning (DL) is widely used in dose prediction for radiation oncology, multiple DL techniques comparison is often lacking in the literature. To compare the performance of 4 state-of-the-art DL models in predicting the voxel-level dose distribution for cervical cancer volumetric modulated arc therapy (VMAT). Methods and Materials: A total of 261 patients’ plans for cervical cancer were retrieved in this retrospective study. A three-channel feature map, consisting of a planning target volume (PTV) mask, organs at risk (OARs) mask, and CT image was fed into the three-dimensional (3D) U-Net and its 3 variants models. The data set was randomly divided into 80% as training-validation and 20% as testing set, respectively. The model performance was evaluated on the 52 testing patients by comparing the generated dose distributions against the clinical approved ground truth (GT) using mean absolute error (MAE), dose map difference (GT-predicted), clinical dosimetric indices, and dice similarity coefficients (DSC). Results: The 3D U-Net and its 3 variants DL models exhibited promising performance with a maximum MAE within the PTV 0.83% ± 0.67% in the UNETR model. The maximum MAE among the OARs is the left femoral head, which reached 6.95% ± 6.55%. For the body, the maximum MAE was observed in UNETR, which is 1.19 ± 0.86%, and the minimum MAE was 0.94 ± 0.85% for 3D U-Net. The average error of the Dmean difference for different OARs is within 2.5 Gy. The average error of V40 difference for the bladder and rectum is about 5%. The mean DSC under different isodose volumes was above 90%. Conclusions: DL models can predict the voxel-level dose distribution accurately for cervical cancer VMAT treatment plans. All models demonstrated almost analogous performance for voxel-wise dose prediction maps. Considering all voxels within the body, 3D U-Net showed the best performance. The state-of-the-art DL models are of great significance for further clinical applications of cervical cancer VMAT.

Background: Pesticide resistance is a long-standing and growing problem in the chemical control of invertebrate pests. Molecular diagnostic methods can facilitate pesticide resistance management by accurately and efficiently detecting resistant mutations and their frequency. In this study, the kompetitive allele specific PCR (KASP) approach, a technology for high-throughput single nucleotide polymorphism (SNP) genotyping, is validated as a useful method for characterizing genotypes at a pesticide-resistance locus for the first time. We focus on the spinetoram resistance mutation of G275E in the nicotinic acetylcholine receptor alpha 6 (nAChR α6) subunit gene of Thrips palmi., Results: Of the 341 individuals of Thrips palmi tested, 98.24% were successfully genotyped, with 100% concordance with Sanger sequencing results. We then quantitatively mixed genomic DNA of known genotypes to establish 21 DNA mixtures with a resistant allele frequency ranging from 0 to 100% at steps of 5%. The linear discriminant analysis (LDA) showed that 75.8% of original grouped cases were correctly classified; six groups had no overlap in membership (resistant allele frequency: 0%, 5%, 10-75%, 80-85%, 90-95%, and 100%). When we chose 11 pooled samples with 10% steps for LDA, 84.4% of original grouped cases were correctly classified; seven groups had no overlap in membership (0%, 10%, 20-30%, 40-70%, 80%, 90%, 100%). The results indicated that KASP applied to pooled samples may provide a semi-quantitative estimate of resistance., Conclusions: Our study points to the suitability of KASP for high-throughput genotyping of genotypes affecting pesticide resistance and semi-quantitative assessments of resistance allele frequencies in populations. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Background: The two-spotted spider mite (TSSM), Tetranychus urticae (Acari: Tetranychidae), is a cosmopolitan phytophagous pest in agriculture and horticulture. It has developed resistance to many acaricides by target-site mutations. Understanding the status and evolution of resistant mutations in the field is essential for resistance management. Here, we applied a high-throughput Kompetitive allele-specific polymerase chain reaction (KASP) method for detecting six mutations conferring resistance to four acaricides of the TSSM. We genotyped 3274 female adults of TSSM from 43 populations collected across China in 2017, 2020, and 2021., Results: The KASP genotyping of 24 testing individuals showed 99% agreement with Sanger sequencing results. KASP assays showed that most populations had a high frequency of mutations conferring avermectin (G314D and G326E) and pyridaben (H92R) resistance. The frequency of mutation conferring bifenazate (A269V and G126S) and etoxazole (I1017F) resistance was relatively low. Multiple mutations were common in the TSSM, with 70.2% and 24.6% of individuals having 2-6 and 7-10 of 10 possible resistant alleles, respectively. No loci were linked in most populations among the six mutations, indicating the development of multiple resistance is mainly by independent selection. However, G314D and I1017F on the nuclear genome deviated from Hardy-Weinberg equilibrium in most populations, indicating significant selective pressure on TSSM populations by acaricides or fitness cost of the mutations in the absence of acaricide selection., Conclusion: Our study revealed that the high frequency of TSSMs evolved multiple resistant mutations in population and individual levels by independent selection across China, alarming for managing multiple-acaricides resistance. © 2023 Society of Chemical Industry., (© 2023 Society of Chemical Industry.)

Background: Known as the prerequisite component for the heterosis breeding system, the male sterile line determines the hybrid yield and seed purity. Therefore, a deep understanding of the mechanism and gene network that leads to male sterility is crucial. BS366, a temperature-sensitive genic male sterile (TGMS) line, is male sterile under cold conditions (12 °C with 12 h of daylight) but fertile under normal temperature (20 °C with 12 h of daylight)., Results: During meiosis, BS366 was defective in forming tetrads and dyads due to the abnormal cell plate. During pollen development, unusual vacuolated pollen that could not accumulate starch grains at the binucleate stage was also observed. Transcriptome analysis revealed that genes involved in the meiotic process, such as sister chromatid segregation and microtubule-based movement, were repressed, while genes involved in DNA and histone methylation were induced in BS366 under cold conditions. MethylRAD was used for reduced DNA methylation sequencing of BS366 spikes under both cold and control conditions. The differentially methylated sites (DMSs) located in the gene region were mainly involved in carbohydrate and fatty acid metabolism, lipid metabolism, and transport. Differentially expressed and methylated genes were mainly involved in cell division., Conclusions: These results indicated that the methylation of genes involved in carbon metabolism or fatty acid metabolism might contribute to male sterility in BS366 spikes, providing novel insight into the molecular mechanism of wheat male sterility., (© 2021. The Author(s).)

Background: DNA methyltransferase (DMT) genes contribute to plant stress responses and development by de novo establishment and subsequent maintenance of DNA methylation during replication. The photoperiod and/or temperature-sensitive genic male sterile (P/TGMS) lines play an important role in hybrid seed production of wheat. However, only a few studies have reported on the effect of DMT genes on temperature-sensitive male sterility of wheat. Although DMT genes have been investigated in some plant species, the identification and analysis of DMT genes in wheat (Triticum aestivum L.) based on genome-wide levels have not been reported., Results: In this study, a detailed overview of phylogeny of 52 wheat DMT (TaDMT) genes was presented. Homoeolog retention for TaDMT genes was significantly above the average retention rate for whole-wheat genes, indicating the functional importance of many DMT homoeologs. We found that the strikingly high number of TaDMT genes resulted mainly from the significant expansion of the TaDRM subfamily. Intriguingly, all 5 paralogs belonged to the wheat DRM subfamily, and we speculated that tandem duplications might play a crucial role in the TaDRM subfamily expansion. Through the transcriptional analysis of TaDMT genes in a TGMS line BS366 and its hybrids with the other six fertile lines under sterile and fertile conditions, we concluded that TaCMT-D2, TaMET1-B1, and TaDRM-U6 might be involved in male sterility in BS366. Furthermore, a correlation analysis showed that TaMET1-B1 might negatively regulate the expression of TaRAFTIN1A, an important gene for pollen development, so we speculated regarding an epigenetic regulatory mechanism underlying the male sterility of BS366 via the interaction between TaMET1-B1 and TaRAFTIN1A., Conclusions: Our findings presented a detailed phylogenic overview of the DMT genes and could provide novel insights into the effects of DMT genes on TGMS wheat.

Objective: To explore the role of platelet factor 4 (PF4) and β-thromboglobulin (β-TG) in patients with acute exacerbation of chronic obstructive pulmonary disease (AECOPD)., Methods: A total of 71 AECOPD patients and 50 chronic obstructive pulmonary disease (COPD) patients within a stable stage were admitted into Beijing Chaoyang Hospital from January 2008 to June 2010. And another 40 healthy volunteers were selected as control group. The data of demographics, arterial blood gas analysis and pulmonary function parameters was collected and analyzed. The plasma levels of PF4 and β-TG were measured by enzyme-linked immunosorbent assay (ELISA). Platelet count was measured by hematology analyzer. Statistical analysis was used for PF4, β-TG and platelet count. Spearman rank correlation was used for correlation analysis., Results: No differences in age and gender existed among the AECOPD, stable and control groups. The plasma level of PF4 in the AECOPD group (2.28 µg/L) was significantly higher than that of the stable group (2.01 µg/L) and control group (1.57 µg/L) (both P < 0.05). The level of β-TG in AECOPD was 2.32 µg/L and it was significantly higher than that of the stable group (1.85 µg/L) and control group (1.29 µg/L) (both P < 0.05). The differences in platelet counts were insignificant between the AEC OPD group ((196 ± 67) ×10(9)/L), stable group ((194 ± 50) ×10(9)/L) and control group ((190 ± 48) ×10(9)/L). AECOPD group was divided into moderate, severe and very severe groups by pulmonary function parameters. The levels of PF4 and β-TG in very severe group were significantly higher than those in moderate and severe groups (P < 0.05). A significant positive correlation was observed between PF4 and β-TG (r = 0.518, P < 0.01). The levels of PF4 and β-TG were negatively correlated with FEV1%, FEV1/FVC and PaO2 (all P < 0.05)., Conclusion: Abnormal platelet activation exists in AECOPD. And the levels of PF4 and β-TG may reflect the severity of AECOPD and can be used as the markers of estimating prethrombotic state.

Objective: To explore the effects of aerosolized earthworm fibrinolytic enzyme (EFE) on bleomycin-induced pulmonary fibrosis in rats., Methods: A total of 72 male SD rats were divided randomly into 3 groups of bleomycin (BLM) group with intratracheal BLM (5 mg/kg), control group with the same dose of normal saline, then after both receiving aerosolization of normal saline once daily instead of EFE, EFE group with EFE (2500 U/kg) by aerosolization once daily after BLM instillation. Lung histopathology, immunohistochemistry for transforming growth factor β(1) (TGF-β(1)), lung hydroxyproline contents, levels of urokinase PA (uPA), tissue plasminogen activator (tPA) and PA inhibitor 1 (PAI-1) in lung and blood were observed at Days 7, 14 and 28 of experiment, respectively., Results: Compared with BLM group, pulmonary fibrosis improved and the TGF-β(1) expression of lung tissue decreased (P < 0.01). Hydroxyproline content of lung tissue decreased in EFE group compared with BLM group ((5.8 ± 2.5) vs (9.6 ± 1.3), (6.7 ± 1.4) vs (9.7 ± 1.5), (7.5 ± 1.2) vs (9.7 ± 1.4) mg/L, P < 0.01). Compared with BLM group, the uPA levels of lung were elevated in EFE group at Days 7 and 14 ((1.04 ± 0.36) vs (0.72 ± 0.11), (0.90 ± 0.09) vs (0.75 ± 0.08) µg/L, P < 0.05). Moreover, the plasma levels uPA of increased at Days 14 and 28 ((0.32 ± 0.04) vs (0.25 ± 0.02), (0.36 ± 0.05) vs (0.28 ± 0.04) µg/L, P < 0.05). Consistently, compared with BLM group, the tPA levels of lung increased in EFE group ((4.70 ± 0.87) vs (3.01 ± 0.62), (5.72 ± 0.37) vs (3.00 ± 0.51), (6.73 ± 1.12) vs (3.18 ± 0.38) µg/L, P < 0.01) and the plasma levels of tPA also increased ((3.40 ± 0.36) vs (1.79 ± 0.38), (3.17 ± 0.37) vs (2.18 ± 0.17), (3.85 ± 0.56) vs (2.80 ± 1.06) µg/L, P < 0.01). However, compared with BLM group, the PAI-1 levels of lung decreased in EFE group ((6.04 ± 0.81) vs (8.52 ± 1.01), (6.78 ± 0.81) vs (9.81 ± 1.73), (7.63 + 0.99) vs (11.44 ± 2.54), P < 0.05) and the plasma levels of PAI-1 also decreased in EFE group ((4.82 ± 0.42) vs (6.89 ± 0.84), (5.73 ± 0.40) vs (7.30 ± 1.09), (5.64 ± 0.87) vs (7.98 ± 1.10) µg/L, P < 0.05)., Conclusions: Earthworm fibrinolytic enzyme may decrease bleomycin-induced pulmonary fibrosis and TGF-β(1) expression while increasing fibrinolytic activation. And fibrinolytic strategies are probably useful for the therapy of fibrotic lung diseases.

Objective: To explore the changes and clinical significances of plasma D-dimer, factor X and tissue factor in acute exacerbation of chronic obstructive pulmonary disease (AECOPD) and analyze the in-depth changes of these indicators in AECOPD with co-current deep venous thrombosis (DVT)., Methods: A total of 56 AECOPD patients were divided into the DVT and non-DVT subgroups (n = 28 each). And 60 normal control subjects were recruited according to age and gender. For each subject, 2.7 ml whole blood was drawn and then the plasma levels of D-dimer, factor X and tissue factor were detected. The results were statistically analyzed with the software SPSS 13.0. And the analysis of variance was performed between the groups., Results: There was no significant difference between the distribution of the AECOPD group and the control group by gender and age. Therefore two groups were comparable. And in the AECOPD group, there was no significant difference between the distribution of DVT and non-DVT subgroups by gender and age. Therefore these two subgroups were comparable as well. The value of D-dimer in the AECOPD patients was significantly higher than that in the normal control [(0.76 ± 0.30) vs (0.29 ± 0.11) mg/L, P < 0.01]; and in the AECOPD group, the value of D-dimer in the DVT subgroup was significantly higher than that in the non-DVT subgroup [(0.85 ± 0.29) vs (0.67 ± 0.28) mg/L, P < 0.05]. In the AECOPD group, the value of tissue factor was (238 ± 68) mg/L and the value of factor X (1181 ± 337) mg/L. While in the normal control group, the values were (124 ± 30) and (998 ± 260) mg/L respectively. As for tissue factor and factor X, there were significant differences between two groups (all P < 0.01). Yet in AECOPD patients, neither indicator had significant differences between the DVT and non-DVT subgroups (all P > 0.05)., Conclusion: The blood of AECOPD patients is in a hypercoagulatory state. And an obvious rise in their plasma level of D-dimer suggests that it may be complicated with DVT.

Introduction: Endothelium derived nitric oxide (NO) is a key mediator of vascular homeostasis. Endothelial nitric oxide synthase (eNOS) gene, by affecting the expression and functional activity of the eNOS enzyme, thereby reducing NO availability, may be implicated in venous thromboembolism (VTE). We investigated the eNOS G894T polymorphism in VTE patients in the Chinese population., Materials and Methods: A case-control study was conducted in a general hospital. Blood samples, collected from 462 consecutive patients with VTE and 462 healthy controls, were used for DNA extraction. Single nucleotide polymorphisms (SNP) of eNOS (894G/T) were determined by allele specific-polymerase chain reaction (ARMS-PCR) analysis., Results: The eNOS 894G/T polymorphism alleles distribution was in agreement with the principle of Hardy-Weinberg equilibrium. The prevalence of homozygote, heterozygote and pathological homozygote for the eNOS G894T polymorphism in VTE patients was 79.7%, 18.1% and 2.2%, respectively (controls: 86.6%，12.3% and 1.1%). T allele distribution in the VTE (11.3%) and especially the male VTE patients (12.5%) was more common than in healthy controls (7.3%). The frequency of GT+TT genotype was significantly higher among the age≤55years patients in VTE group than in controls (20.1% vs. 12.2%, P=0.033)., Conclusion: Our result demonstrates that the 894G/T polymorphism variant of eNOS is a risk factor for VTE in Chinese population., (Copyright © 2010. Published by Elsevier Ltd.)

Objective: to explore the effect of simvastatin on alveolar epithelial cells and the expression of vascular endothelial growth factor (VEGF) in cigarette smoking-induced emphysema in rats., Methods: twenty-four, 12-week-old healthy male and female Wistar rats were randomly divided into 4 groups of 6 each: a control (W) group, a smoking (Sm) group, a simvastatin (St) group, and a smoking-simvastatin (SmSt) group. The rats were simultaneously fed, and kept in individual cages for 16 weeks. The VEGF level in lung tissue and bronchoalveolar lavage fluid (BALF) of each group was measured by ELISA. The expression of VEGF mRNA was determined by RT-PCR. The expressions of VEGF and proliferating cell nuclear antigen (PCNA) were determined by two-step immunohistochemistry assay. One-way ANOVA and LSD-t test were used for statistical analysis., Results: the percentage of PCNA-positively stained alveolar epithelial cells was significantly higher in the SmSt group [(10.3 ± 2.0)%] than in the Sm group [(4.8 ± 0.8)%]. The levels of VEGF in BALF and lung tissue homogenate of the SmSt group [(187 ± 15) ng/L and (6782 ± 50) ng/L] were similar to the W group [(200 ± 20) ng/L and (7558 ± 330) ng/L], but were significantly higher than that in the Sm group [(71 ± 16) ng/L and (4149 ± 110) ng/L]. VEGF expression in alveolar and bronchial epithelial cells of rats in the SmSt group [(67.7 ± 5.0)% and (49.0 ± 3.0)%], was similar to the W group [(68.3 ± 3.3)% and (51.3 ± 2.9)%]. But the level of VEGF expression was significantly increased as compared to that in the Sm group [(27.0 ± 5.9)% and (16.3 ± 2.7)%]. SmSt group vs Sm group t = 1.117 - 12.001, all P < 0.01., Conclusions: simvastatin ameliorated the development of cigarette smoke-induced COPD in rats, partly by promoting alveolar epithelial cell proliferation and up-regulating the expression of VEGF.

Objective: To establish a model of chronic periodontitis (CP) accompanied with chronic obstructive pulmonary disease (COPD) in SD rats and investigate the relationship between chronic periodontitis and COPD., Methods: Equal gender SD rats were randomly divided into 4 groups, A: control group, B: CP group, C: COPD group, D: COPD with CP group (n = 10, respectively). Each group was subjected to its predesigned intervention to establish a specific disease model. After 10 weeks, animals were sacrificed. The level of alveolar bone loss, lung function measurement, and the histopathological changes of periodontal and lung tissues were examined. The serum tumor necrosis factor (TNF)-α level was detected by enzyme-linked immunoabsorbent assay kits., Results: Bleeding index (BI) levels of group A and C were (0.25 ± 0.04) and (1.30 ± 0.25), respectively. Attachment loss was (0.43 ± 0.02) and (0.51 ± 0.02) mm. BI levels in group B and D were significantly higher than those in group A and C. Forced expiratory volume in 0.2 second to forced vital capital ratio (FEV(0.2)/FVC) values in group B, C and D were significantly lower than that in group A. Pulmonary function were worse in group D than that in group C (P < 0.05). The levels of serum TNF-α, a sensitive indicator of both diseases, were increased in all test groups compared with the control, and increased most in group D., Conclusions: The chronic periodontitis and chronic obstructive pulmonary disease model was established in SD rat. The chronic periodontitis may be a risk factor for promoting and inducing COPD.

Objective: To investigate the effects of asynchronous independent lung ventilation and synchronous independent lung ventilation with different levels of positive end-expiratory pressure (PEEP) and tidal volumes on hemodynamics and gas exchange in dogs with a hydrochloric acid induced acute lung injury., Methods: Twelve dogs with hydrochloric acid induced acute lung injury (left lung) were ventilated with volume controlled ventilation (VCV). The animals were randomly divided by random digit table into 2 groups. The first group (group NS, n = 6) received asynchronous independent lung ventilation with the left lung PEEP 10 cm H2O (1 cm H2O = 0.098 kPa), VT 3.5 ml/kg and the right lung PEEP 0 cm H2O, VT 5 ml/kg. The second group (group S, n = 6) received synchronous independent lung ventilation with the parameters as same as group NS. HR, mABP, mPAP, PAWP, CO and blood gas levels were measured during ventilation with different levels of PEEP (15, 20, 25 cm H2O) and VT (5, 7.5, 10 ml/kg) for 30 min., Results: (1) After 30 min ventilation, no significant differences for hemodynamics and gas exchange were found between group NS and group S when Left lung PEEP was 15 or 20 cm H2O and VT was 5 or 7.5 ml/kg. (2) After 30 min ventilation, HR, mABP, CO, PaO2/FiO2, SvO2 in group NS [(98 ± 8) beats/min, (84 ± 6) mm Hg (1 mm Hg = 0.133 kPa), (1.10 ± 0.13) L/min, (199 ± 14) mm Hg and (55 ± 6)%, respectively] were significantly lower than those in group S [(124 ± 9) beats/min, (103 ± 7) mm Hg, (1.52 ± 0.28) L/min, (221 ± 15) mm Hg and (62 ± 4)%, respectively] when PEEP was 25 cm H2O (all P < 0.01). (3) After 30 min ventilation, HR, mABP, CO, PaO2/FiO2, SvO2 in group NS [(92 ± 6) beats/min, (83 ± 9) mm Hg, (1.23 ± 0.08) L/min, (196 ± 8) mm Hg and (57 ± 2)%, respectively] were significantly lower than those in group S [(122 ± 10) beats/min, (104 ± 4) mm Hg, (1.56 ± 0.12) L/min, (216 ± 14) mm Hg and (63 ± 4)%, respectively] when VT was 10 ml/kg (all P < 0.01)., Conclusions: In this animal model, the hemodynamics kept stable when the difference between the left lung PEEP and the right lung PEEP was less than 20 cm H2O. Synchronous independent lung ventilation caused less hemodynamic compromise when higher PEEP (> 25 cm H2O) was used because of the marked asymmetry in the mechanics of the 2 lungs.

Objective: To study the expression of intercellular cell adhesion molecule-1 (ICAM-1), Interleukin-10 (IL-10) and the activation of transcription factor activator protein-1 (AP-1) in a rabbit model of ventilator-induced lung injury (VILI) and therefore to explore their possible role in VILI., Methods: The VILI model was established by mechanical ventilation with a large tide volum (V(T)) of 40 ml/kg. Forty healthy male New Zealand rabbits were randomly divided into 5 groups: a control group without mechanical ventilation, a conventional ventilation group, and injurious ventilation with large V(T) for 1 h group, 2 h group and 4 h group. The concentrations of soluble ICAM-1 (sICAM-1) and IL-10 in lung homogenates were measured by enzyme-linked immunosorbent assay (ELISA). The level of mRNA was measured by semiquantitative transcription-polymerase chain reaction (RT-PCR). The DNA-binding activity of AP-1 was measured by electrophoretic mobility shift assay (EMSA). The partial arterial blood pressure of oxygen (PaO2), myeloperoxidase (MPO) in lung homogenate, wet lung weight to dry lung weight ratio (W/D) were observed., Results: (1) The concentrations of sICAM-1 in large V(T) for 2 h group (23 ± 5) ng/L and 4 h group (35 ± 5) ng/L were higher than that in the conventional ventilation group (16 ± 4) ng/L (P all < 0.05), and that in the Large V(T) for 4 h group were higher than that in 1 h group (19 ± 4) ng/L and 2 h group (P all < 0.01). The concentrations of IL-10 in the large V(T) for 2 h group (24 ± 4) ng/L and 4 h group (26 ± 5) ng/L were higher than that in the conventional ventilation group (15 ± 2) ng/L (P all < 0.05), and that in the Large V(T) for 4 h group was higher than that in the 1h group (19 ± 4) ng/L(P < 0.05). The level of ICAM-1 mRNA in the large V(T) for 2 h group (1.18 ± 0.19) and 4 h group (1.29 ± 0.19) were higher than that in the conventional ventilation group (0.84 ± 0.13) (P all < 0.05), and that in Large V(T) for 4 h group was higher than that in 1 h group (0.96 ± 0.24) (P < 0.05). The level of IL-10 mRNA in the large V(T) for 4 h group (1.13 ± 0.17) was higher than that in the conventional ventilation group (0.84 ± 0.20) and Large V(T) for 1 h group (0.86 ± 0.12) (P all < 0.05). (2) The DNA-binding activity of AP-1 in the large V(T) for 2 h group (33.77 ± 8.23) and 4 h group (38 ± 9) were higher than that in the conventional ventilation group (23 ± 9) (P all < 0.01), and that in Large V(T) for 4 h group was higher than that in 1h group (25 ± 9) (P < 0.01). (3) Histopathological findings demonstrated that diffused alveolar damage induced by mechanical ventilation was worse with time, and after mechanical ventilation with large V(T) for 2 h, the level of MPO began to increase, and for 4 h the PaO2 reduced and the W/D increased., Conclusions: ICAM-1 and IL-10 took part in the inflammatory responses of VILI, and their up-regulation maybe due to the increase of their mRNA. Nuclear transcription factor AP-1 maybe involved in the transcriptional regulation mechanisms of these inflammatory mediators.

Aim: To investigate the role of chemokine receptor CXCR3 in cigarette smoking (CS)-induced pulmonary damage., Methods: CXCR3 knockout (CXCR3-/-) mice were used. Differences in airspace enlargement, mRNA expression of matrix metalloproteinases (MMPs), transforming growth factor (TGF) beta1, CXCL10 in lung homogenates, and CXCL10 content in bronchoalveolar lavage (BAL) fluids and homogenates were compared between CXCR3-/- mice and wild-type (WT) mice three days after three-day CS exposures., Results: The linear intercept was significantly less in CXCR3-/- mice than in WT mice (30.1+/-0.9 microm vs 40.3+/-2.4 microm, P<0.01). Morphologically, collagen was deposited less around airways and vessels in CXCR3-/- mice. The lung hydroxyproline content was significantly lower in CXCR3-/- mice than in WT mice (6.0+/-1.0 microg/mL vs 12.0+/-1.6 microg/mL, P<0.05). Profoundly lower mRNA expression of MMP2, MMP12, TGF beta 1, and CXCL10 was seen in lung homogenates from CXCR3-/- mice. CXCL10 concentrations in BAL fluid and lung homogenates were significantly lower in CXCR3-/- mice than in WT mice (BAL fluid: 19.3+/-1.4 pg/mL vs 24.8+/-1.6 pg/mL, P<0.05; lung homogenates: 76.6+/-7.0 pg/mL vs 119.5+/-15.9 pg/mL, P<0.05)., Conclusion: CXCR3 is important in mediating lung tissue damage and airway remodeling following a short-term CS insult, possibly through up-regulation of CXCL10 and inducement of mRNA expression of MMPs. Targeting CXCR3 may be helpful for prevention of CS-induced pulmonary pathology.

Background: Peripheral skeletal muscle dysfunction in patients with chronic obstructive pulmonary disease (COPD) may be due to the disease per se or as a result of concomitant confounding factors. Although the mechanistic basis for this functional impairment is uncertain, oxidative stress may play a role. The purpose of this study was to investigate whether local oxidative stress is associated with the reduced peripheral skeletal muscle performance in rats with emphysema., Methods: In situ mechanical properties of gastrocnemius were measured in Sprague-Dawley rats 5 months after intratracheal instillation of either elastase (EMP, n = 10) or normal saline (CON, n = 10). Lipofuscin inclusions, myocyte apoptosis and antioxidant enzyme activities were examined in the gastrocnemius muscle., Results: Lipofuscin inclusions were significantly higher in the gastrocnemius muscle of EMP compared with CON (3.2 + or - 0.4 vs. 1.7 + or - 0.4, P < 0.01). The activities of antioxidant enzymes were significantly increased in muscle homogenates of EMP as compared to CON. No significant differences were found in myocyte apoptosis between EMP and CON (1.2 + or - 0.9 vs. 1.0 + or - 0.8, P > 0.05). EMP decreased the fatigue endurance of gastrocnemius muscle (half-time to fatigue recovery: (150.0 + or - 55.4) seconds vs. (55.2 + or - 29.3) seconds, P < 0.01) and had no effect on maximal tetanic force ((467.4 + or - 36.6) g vs. (493.2 + or - 30.5) g, P > 0.05). A significantly positive correlation was found between the level of lipofuscin inclusions and the half-time to fatigue recovery of gastrocnemius muscle in EMP (r = 0.664, P < 0.05)., Conclusion: Local oxidative stress may have important functional consequences for peripheral skeletal muscle in rats with EMP.

Background: The body mass index, airflow obstruction, dyspnea, and exercise capacity (BODE) index was shown at predicting the risk of death, exacerbation and disease severity among patients with COPD, but few studies verified relationship between BODE index and health related quality of life (HRQoL) among Chinese COPD patients. The objective of this study was to evaluate the relationship between BODE index and HRQoL in cross-sectional and longitudinal association analyses., Methods: A multi-center prospective cohort study was initially conducted in 491 stable COPD patients in Beijing, China. Health status (HRQoL) was assessed by St. George's Respiratory Questionnaire (SGRQ); the BODE index was calculated for each patient; dyspnea was assessed using the 5-grade Medical Research Council dyspnea scale. Other measurements included socio-demographic, body mass index (BMI), lung function test and 6-minute-walk test (6MWT). Patients were then followed monthly for 12 months., Results: Only 450 patients completed the 1-year follow up and were enrolled in our present analyses. Mean age was (65.2 +/- 10.6) years, men 309 (68.7%). The BODE index was categorized into 4 subgroups: 0 - 2, 3 - 4, 5 - 6 and 7 - 10. At baseline BODE index was gradually increased with baseline total SGRQ and SGRQ subscales (P trend < 0.001). For individual components of BODE index, with the decrease of airflow limitation, and 6MWD, and with the increase of Medical Research Council (MRC) dyspnea grade, total SGRQ and SGRQ subscales were increased correspondingly, P trend < 0.05, respectively. Similar association patterns were found between baseline BODE index and its individual components and mean SGRQ scores at the end of 1-year follow up. By multiple linear regression analyses, baseline BODE index was not only significantly associated with SGRQ score at baseline but also with SGRQ score at the end of 1-year follow up after adjustment for age, male, current smoking, betas being 0.434 and 0.378, respectively., Conclusions: BODE index is associated with SGRQ score cross-sectionally and longitudinally among stable COPD patients. BODE index might have potential to be used as a sensitive tool to assess the status of quality of life and to monitor disease progression among stable COPD patients.

This study evaluated the accuracy of three-dimensional (3-D) ultrasound measurement of lymph node volume, and investigated the normal variations of cervical nodal volume. The volumes of 12 porcine neck lymph nodes were measured with 3-D ultrasound and calculated from two-dimensional (2-D) ultrasound using the ellipsoid formula, and compared with the volume measured by the water displacement method. 3-D ultrasound of cervical nodes was performed in 100 subjects, and the volumes of all ultrasound-detectable cervical nodes were measured. Results showed that the mean absolute errors of 3-D ultrasound and the 2-D ellipsoid formula method were 0.042 ml and 0.372 ml, respectively, and the mean percentage errors in measurement were 4.4% and 17.8%, respectively. In total, 830 nodes were detected in the subjects. Upper cervical nodes (0.48+/-0.47 ml) were significantly larger than submandibular nodes (0.39+/-0.24 ml) (p<0.05), and these two groups of lymph nodes were significantly larger than parotid (0.1+/-0.06 ml) and posterior triangle (0.1+/-0.11 ml) nodes (p<0.05). There was no significant variation of normal cervical node volume with advancing age (p>0.05). Men aged 20-29 years had significantly larger cervical nodes than women of the same age group (p<0.05), whereas there was no significant gender difference in nodal volume in other age groups (p>0.05). 3-D ultrasound measurement of cervical nodal volume is feasible. In vitro study showed that 3-D ultrasound had a lower mean error than the 2-D ellipsoid formula method in the measurement of cervical nodal volume. This study provides baseline information on the normal variations of cervical lymph node volume, as measured by 3-D ultrasound.

Objective: To explore the mechanism of Chinese medicinal therapy for nourishing blood and softening Gan in treating senile pruritus through observing the impact of Guishen Zhiyang Recipe (GZR) on serum levels of stem cell factor (SCF) and dynorphin (DYN) in patients suffered from the disease of blood-deficiency and Gan-hyperactive syndrome type (BDGH)., Methods: Sixty patients with senile pruritus were equally randomized into two groups, the patients in the treated group (33 cases) were treated by GZR, and those in the control group (28 cases) were treated by Fuyang Granule, all for 8 weeks. Changes of symptoms and skin lesions as well as blood levels of SCF and DYN were observed before and after treatment., Results: Three patients were rejected from the treated group. Twenty patients in the treated group were cured after treatment, the cure rate being 66.7%, which was significantly higher than that in the control group (10 patients, 35.7%, P < 0.05). Levels of SCF and DYN in the treated group significantly lowered after treatment (all P < 0.01), and were lower than those in the control group (P < 0.05 and P < 0.01, respectively)., Conclusion: GZR shows favorite effect in treating senile pruritus of BDGH type and it may be achieved by regulating SCF and DYN levels to improve the pruritus associated inflammatory media.

Objective: To observe the changes of the plasma soluble thrombomodulin (sTM) concentrations in patients with pulmonary thromboembolism (PTE) and assess the association between plasma sTM concentration and the risk of PTE., Patients and Methods: We measured plasma concentrations of sTM, protein C (PC) and protein S (PS) and examined the association between those plasma markers and the risk of PTE in 72 selected PTE patients and 70 controls., Results: Significant difference was identified in plasma sTM level between overall PTE patients and controls. Female PTE patients had statistically lower sTM concentrations than male patients. A positive linear correlation was found between plasma sTM concentration and age in female patients. Decreased plasma sTM concentration was associated with a continuously and progressively increased risk for PTE in women. The concentrations of plasma PC and PS did not differ between groups and no significant quantitative association was identified between the risk of PTE and the levels of plasma PC or PS., Conclusion: Decreased plasma sTM concentration is associated with an increased risk of PTE in women.

Background: Sepsis induced acute lung injury (ALI) as a common syndrome in clinical practice has a high mortality. Recombinant human activated protein C (APC) can significantly reduce the mortality of patients with severe sepsis. Several studies have implicated that APC may be protective in ALI., Methods: Twenty-one rabbits were operatively prepared and randomly divided into sham, control, or APC groups (n = 7 in each group). After a tracheotomy had been performed, ALI was produced in the control and APC groups by infusion of Escherichia coli endotoxin 100 microg/kg per hour intravenously for 1 hour. The sham group received only the vehicle, infusion of 20 ml of 0.9% saline. The rabbits were studied under anesthesia for 6 hours and were ventilated with 40% oxygen. Bovine APC (25 microg x kg(-1) x h(-1)) was intravenously administered. The infusion was initiated half an hour post-injury and lasted for 4 hours. The animals were resuscitated with Ringer's lactate solution., Results: In comparison with nontreatment in the control group, the infusion of APC significantly reduced the increase of thrombomodulin level (TM; control group was (0.68 +/- 0.06) ng/ml, vs APC group of (0.62 +/- 0.07) ng/ml at 6 hours, P < 0.05), and significantly attenuated the fall in protein S (PS; control group was (2.32 +/- 0.03) microg/ml at 2 hours, (2.24 +/- 0.06) microg/ml at 4 hours and (2.21 +/- 0.09) microg/ml at 6 hours, vs APC group (2.46 +/- 0.04) microg/ml at 2 hours, (2.40 +/- 0.05) microg/ml at 4 hours and (2.39 +/- 0.07) microg/ml at 6 hours, P < 0.01). In addition, APC limited the increase in plasminogen activator inhibitor-1 (PAI-1) both in plasma (control group was (0.68 +/- 0.12) ng/ml at 1 hour, (0.84 +/- 0.06) ng/ml at 2 hours, (0.87 +/- 0.08) ng/ml at 4 hours and (0.91 +/- 0.05) ng/ml at 6 hours, vs APC group (0.42 +/- 0.16) ng/ml at 1 hour, (0.43 +/- 0.04) ng/ml at 2 hours, (0.45 +/- 0.09) ng/ml at 4 hours and (0.45 +/- 0.14) ng/ml at 6 hours, P < 0.01) and in bronchoalveolar lavage fluid (at 6 hours: sham, (1.05 +/- 0.05) ng/ml; control, (1.13 +/- 0.06) ng/ml; APC, (1.06 +/- 0.06) ng/ml; P < 0.05). However, APC failed to prevent the decrease in PaO(2)/FiO(2) ratio. APC-treated rabbits showed no significant difference in platelet count and antithrombin but exhibited less D-dimer production than did the controls. Moreover, APC limited the histopathological score of lung injury (2.6 +/- 0.8 in control, vs 1.4 +/- 0.6 in APC group, P < 0.01)., Conclusion: Anti-coagulation and pro-fibrinolysis activity may be two of the possible mechanisms by which activated protein C attenuated endotoxin-induced ALI.

Aim: CXCR3, via binding its specific ligand CXCL10, plays an important role in cigarette smoke (CS)-induced pulmonary inflammation. CXCR3 is preferentially expressed in activated T cells (chiefly CD8+ T cells). The purpose of this study was to investigate the role of CXCR3 in CS-induced pulmonary injury using CXCR3 gene-deficient (CXCR3-/-) mice., Methods: Differences in the infiltration of inflammatory cells and CD8+ T cells and the expression of inflammatory mediators and chemokines in the bronchoalveolar lavage fluid and lungs at the mRNA and protein levels were compared between CXCR3-/- mice and wild-type (WT) mice at 2 h after 3 d of CS exposure., Results: Compared with their WT counterparts, the CXCR3-/- mice showed alleviated inflammation, as evidenced by fewer inflammatory cells, particularly cytotoxic CD8+ T cells, in bronchoalveolar lavage fluid and lung tissues. At both the mRNA and protein levels, there were significantly lower levels of inflammatory and chemotactic cytokines, including TNF-alpha, interleukin-8, interferon-gamma, transforming growth factor-beta1, and CXCL10 in the CXCR3-/- mice., Conclusion: Our data show that CXCR3 is important in recruiting inflammatory cells (particularly CD8+ T cells) into the airways and lungs, as well as initiating inflammatory and fibrotic cytokines release at 2 h following a short-term CS insult. CXCR3 could be a novel target for the treatment of pulmonary inflammation induced by CS.

Objective: To evaluate protective effect and its mechanism of prone position ventilation (PPV) combined with recruitment maneuver (RM) as a lung protective ventilation strategy on oleic acid-induced acute respiratory distress syndrome (ARDS) in dogs., Methods: Twenty-four oleic acid-induced ARDS dogs were ventilated with volume controlled ventilation (VCV): 16 cm H2O (1 cm H2O=0.098 kPa) of positive end-expiratory pressure (PEEP) and 10 ml/kg of tidal volume (VT). All dogs were randomly divided by random digit table into four groups: supine position (SP group), prone position (PP group), supine position+RM (SPRM group), and prone position+RM (PPRM group, 6 in each group), and ventilated by VCV for 4 hours and then sacrificed by exsanguination. The serum levels of inflammatory mediators were measured respectively at 0.5, 2 and 4 hours. After they were sacrificed, the levels of cytokines in left lung tissue homogenate were measured. The wet/dry weight ratio of right lung was determined and histological sections of the lungs were prepared and examined., Results: (1) At 4 hours, interleukin-8 (IL-8) in serum in the SPRM group was significantly higher than in other three groups (all P<0.05), tumor necrosis factor-alpha (TNF-alpha) in serum in the SPRM group was significantly higher than in the PP group and the PPRM group (all P<0.05). (2) IL-8 in lung tissue homogenate of the dorsal aspect of the lung in the SP group was higher than in the PP group and the PPRM group (both P<0.05). TNF-alpha in lung tissue homogenate at the dorsal aspect of the lung in the SPRM group was higher than in the PP group and the PPRM group (both P<0.05). (3) Wet/dry weight ratio of right lung in the PP group and the PPRM group were significantly lower than that in the SP group and the SPRM group (all P<0.05). (4)Pathology score of lung tissue at the dorsal aspect of the lung in the PP group and PPRM group was significantly lower than in the SP group and the SPRM group (all P<0.05)., Conclusion: Protective ventilation strategy combined with RM is safer in prone position than supine position, and it alleviates lung injury in dog with ARDS.

Objective: To evaluate the effects of prone position ventilation (PPV) combined with recruitment maneuver (RM) on oxygenation and intrapulmonary shunting in oleic acid-induced acute respiratory distress syndrome (ARDS) in canines while ventilated with lung protective ventilation strategy., Methods: ARDS was induced by oleic acid in 24 dogs, and the animals were ventilated with volume controlled ventilation (VCV), 16 cm H2O (1 cm H2O = 0.098 kPa) of positive end-expiratory pressure (PEEP) and small tidal volumes (V(T) 10 ml/kg). All the dogs were randomly divided by random digit table into 4 groups (6 each), a control group (supine position, SP group), a prone position group (PP group), a supine position + RM group (SPRM group), and a prone position + RM group (PPRM group), and then were ventilated by VCV for 4 h. Arterial and mixed venous blood gas analyses were measured. Data were analyzed using the SPSS for windows (version 11.5). Results were expressed as x +/- s. Homogeneity of variance test was performed. The differences in means were calculated using one-way ANOVA. Post-hoc multiple comparisons of means were performed using Least Significant Difference. Nonparametric tests for several independent samples were performed to compare differences between the ranks in the groups studied. P value of < 0.05 was considered statistically significant., Results: (1) At 15 min, PaO2/FiO2 in the SPRM group, the PP group and the PPRM group [(368 +/- 45) mm Hg (1 mm Hg = 0.133 kPa), (349 +/- 80) mm Hg, ( 423 +/- 43) mm Hg, respectively] was significantly higher than that in the SP group [(269 +/- 72) mm Hg, q = 2.77, 2.23, 4.31, respectively, all P < 0.05]. At 2 h, PaO2/FiO2 in the PP group and the PPRM group [(401 +/- 82) mm Hg, (416 +/- 23) mm Hg, respectively] was significantly higher than that in the SP group [(232 +/- 40) mm Hg, q = 3.99, 4.35, respectively, all P < 0.05]. At 4 h, PaO2/FiO2 in the PPRM group [(384 +/- 68) mm Hg] was significantly higher than that in the SP group [(256 +/- 75) mm Hg], that in the SPRM group [(267 +/-92) mm Hg] and that in the PP group [(284 +/- 83) mm Hg, q = 2.75, 2.56, 2.17, respectively, all P < 0.05]. (2) Intrapulmonary shunt (Q(S)/Q(T)) in the PP group was significantly decreased compared with that in the SP group from 30 min to 2 h [30 min (9.9 +/- 4.4)% vs (15.0 +/- 1.6)%, 1 h (9.7 +/- 4.5)% vs (16.0 +/- 2.0)%, 2 h (8.3 +/- 4.6)% vs (16.2 +/- 1.8)%, q = 2.86, 3.00, 3.65, respectively, all P < 0.05]. The Q(S)/Q(T), in the PPRM group was significantly decreased compared with that in the SP group from 30 min to 4 h [30 min (10.0 +/- 1.0)% vs (15.0 +/- 1.6)%, 1 h (10.4 +/- 2.7)% vs (16.0 +/- 2.0)%, 2 h (10.2 +/- 0.7)% vs (16.2 +/- 1.8)%, 4 h (10.1 +/- 1.1)% vs (15.7 +/- 1.7)%, q = 2.80, 2.67, 2.75, 2.99, respectively, all P < 0.05]., Conclusions: On the basis of small tidal volume lung and PEEP protective ventilation strategy, combining prone position and recruitment maneuver was more effective and showed a synergistic effect on improving oxygenation and intrapulmonary shunt.

The high molecular weight glutenin subunit (HMW-GS) pair 1Bx13 + 1By16are recognized to positively correlate with bread-making quality; however, their molecular data remain unknown. In order to reveal the mechanism by which 1By16 and 1Bx13 creates high quality, their open reading frames (ORFs) were amplified from common wheat Atlas66 and Jimai 20 using primers that were designed based on published sequences of HMW glutenin genes. The ORF of 1By16 was 2,220 bp, deduced into 738 amino acid residues with seven cysteines including 59 hexapeptides and 22 nanopeptides motifs. The ORF of 1Bx13 was 2,385 bp, deduced into 795 amino acid residues with four cysteines including 68 hexapeptides, 25 nanopeptides and six tripeptides motifs. We found that 1By16 was the largest y-type HMW glutenin gene described to date in common wheat. The 1By16 had 36 amino acid residues inserted in the central repetitive domain compared with 1By15. Expression in bacteria and western-blot tests confirmed that the sequence cloned was the ORF of HMW-GS 1By16, and that 1Bx13 was one of the largest 1Bx genes that have been described so far in common wheat, exhibiting a hexapeptide (PGQGQQ) insertion in the end of central repetitive domain compared with 1Bx7. A phylogenetic tree based on the deduced full-length amino acid sequence alignment of the published HMW-GS genes showed that the 1By16 was clustered with Glu-1B-2, and that the 1Bx13 was clustered with Glu-1B-1 alleles.

Objective: To investigate the effects of nitric oxide (NO) inhalation (iNO) on alveolar liquid clearance (ALC), alveolar permeability, and lung edema, and its possible mechanism., Methods: Eighteen male rabbits were challenged with endotoxin, and they were randomly assigned into three groups: mechanical ventilator (MV) group [volume control ventilation: tidal volume (V(T)) 15 ml/kg, respiration rate (RR) 40 beats/minute, positive end-expiratory pressure (PEEP): 5 cm H(2)O (1 cm H(2)O=0.098 kPa)], high; NO ( 40 x 10(-6) NO, HNO) group and low concentration; NO (10 x 10(-6) NO, LNO) group. Indexes including haemodynamics, blood gas analysis, and mechanics of breathing were determined after MV at different time points in each group. The rabbits were sacrificed after MV lasting for 4 hours. Wet/dry weight (W/D) ratio of the lung was calculated, and the condition of alveolar exudation was observed., Results: (1) Oxygenation index (PaO(2)/FiO(2)) in HNO group and LNO group were higher than those in MV group at 0.5 hour after treatment. (2) The peak pressure of airway (Ppeak) and plateau pressure of airway (Pplat) in LNO group were lower than those in MV group at 0.5, 2 and 4 hours after treatment (P<0.05 or P<0.01). Ppeak at 4 hours, Pplat at 2 hours and 4 hours were lower in HNO group as compared with those in MV group (P<0.05 or P<0.01). Pplat in LNO group was lower than that in HNO group at 2 hours and 4 hours (both P<0.01). (3) Alveolar exudation in HNO group and LNO group was milder than that in MV group (F=22.756, P<0.01). ALC in HNO group and LNO group were higher than that in MV group (F=3.965, P<0.05). The W/D ratio of lung in MV group was higher than that in HNO group, and the W/D rate in HNO group was higher than that in LNO group (F=11.740, P<0.01). (4) Lung injury score in HNO group and LNO group was higher than that in MV group, but without significant difference., Conclusion: iNO can reduce lung edema by increasing ALC and improving alveolar permeability, and the LNO may be more effective than HNO in treatment of early acute lung injury induced by endotoxin.

Objective: To study the changes of blood coagulative and fibrinolytic system and the function of pulmonary vascular endothelium in the course of acute pulmonary thromboembolism (PTE) and after anticoagulant or thrombolytic treatment., Methods: Twenty patients with acute non-massive PTE, 10 males and 10 females, aged (57 +/- 11) underwent anticoagulant treatment and 17 sex-, and age-matched acute massive PTE patients underwent thrombolytic treatment. The plasma level of D-dimer (D-D), thrombomodulin (TM), protein C (PC), protein S (PS), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1), and antithrombin-III (AT-III) activity were measured by ELISA before and after normal subjects severed as control group were included in the study. The plasma level of D-D, PS, PC, TM, t-PA and PAI-1 were measured by a method of ELISA before the treatment and six days after the anticoagulant treatment or 24 hours after the thrombolytic treatment. AT-III activity was measured by chromo-substrate method at the same time points. Forty sex- and age-matched healthy persons were used as controls., Results: The plasma levels of D-D, t-PA, PS, and TM level of the anticoagulant group were all significantly higher and the AT-III activity of the 2 treatment groups was significantly lower than those of the controls before treatment (all P < 0.05); the plasma levels of D-D, t-PA, PAI-1, PS, and TM of the thrombolytic group were ala significantly higher and the AT-III activity was significantly lower than those of the control group before the treatment (all P < 0.05). After anticoagulant therapy, the plasma levels of D-D, t-PA, PS, and PC were significantly lower than those before treatment (all P < 0.05), however, the plasma levels of PAI-1, TM, and AT-III activity after treatment did not differ significantly from those before treatment. The plasma levels of D-D, t-PA, PS, PC, and TM after treatment of the thrombolytic group were all significantly lower than those before treatment (all P < 0.05), however, the plasma levels of PAI-1, TM, and AT-III activity after treatment did not differ significantly from those before treatment., Conclusion: Apparent imbalance in the blood coagulative and fibrinolytic system and pulmonary vascular endothelium damage occur in the patients with acute PTE. Combination tests of plasma D-D, AT-III, PS, PC, TM, t-PA and PAI-1 can give a more comprehensive explanation of the imbalance in the blood coagulative and fibrolytic system. Anticoagulant treatment and thrombolytic treatment play important roles in the regulation of the imbalance of coagulative and fibrinolytic system and protection of the function of pulmonary vascular endothelium of PTE patients.

Objective: To observe the clinical effect of TCM treatment for dissolving phlegm and dispelling stasis (DP-DS) on acute cerebral infarction (ACI) and its influences on plasma protein C and S and soluble thrombomodulin (TM)., Methods: One hundred and twenty-two patients were randomly assigned to two groups, the treated group (62 cases) and the control group (60 cases). They were all treated with the conventional treatment, and DP-DS treatment was given to the treated group additionally. The treatment course was 14 days. The changes in scores of TCM syndrome and neurofunction impairment (NIHSS), levels of plasma protein C (PC), protein S (PS) and TM before and after treatment in the two groups were observed., Results: The total effective rate of TCM syndrome in the treated group was higher than that in the control group (P= 0.00). After treatment, NIHSS in the two groups was significantly different (P=0.00), and the score in the treated group was superior to that in the control group (P = 0.00). NIHSS score and levels of PC and PS were improved in both groups (P = 0.024, 0.028), and the improvement of PC in the treated group was superior to that in the control group respectively (P = 0.049). But no significant change of TM was shown after treatment., Conclusion: TCM DP-DS treatment shows significant effect in improving TCM syndrome and neurofunction impairment of the patients with acute cerebral infarction, and raise the levels of PC and PS.

Objective: To investigate the role of different ventilatory modes and spontaneous breathing (SB) in prevention of derecruitment in acute respiratory distress syndrome (ARDS)., Methods: Eighteen dog ARDS models were established by injection of oleic acid into the central vein and ventilated with volume controlled ventilation (VCV,) with the positive end expiratory pressure (PEEP) of 16 cm H(2)O, tidal volume (V(T)) of 10 ml/kg, and respiratory rate (RR) of 30 bpm, and the steady state in this mode was defined as baseline (0 min). After the baseline state was reached, all dogs accepted recruitment maneuver (RM) in pressure controlled ventilation (PCV) mode at the level of 15 cm H(2)O and PEEP of 35 cm H(2)O for 1 min, and then assigned into three groups and ventilated for 4 hs: VCV group (VCV with V(T) of 15 ml/kg), PCV group in which the peak inspiratory airway pressure was adjusted for keeping 15 ml/kg of V(T), and SB grouping which PCV with SB activity and inspiratory airway pressure were adjusted for keeping 15 ml/kg of V(T). PEEP of 10 cm H(2)O, RR of 20 bpm, and inspiratory/expiratory ratio of 1/2 were kept for all animals. Four hours later the dogs were killed and their lungs were taken out., Results: (1) The lower inflection points were identified as 16.1 +/- 1.9, 17.4 +/- 1.5, and 17.1 +/- 1.6 cm H(2)O for the VCV, PCV, and SB group respectively. (2) After RM, the PaO(2) levels of the PCV and SB groups were kept higher than baseline, but the PaO(2) level was as same as that in the baseline state in the VCV group. Compared with the VCV group, higher PaO(2) the PaO(2) level 30 min after RM in the SB group was found (P < 0.05). The intrapulmonary shunt 5 min, 30 min and 1 hr after RM in the SB group were all lower than those in the VCP group, however, not significantly (P = 0.077, 0.058, 0.076). (3) Compared with baseline levels, the plateau pressure and mean airway pressure in all animals were decreased significantly after RM. The plateau pressure in the SB group was significantly lower than that in the VCV group (P < 0.05)., Conclusion: PCV with spontaneous breathing activity can offset the effect of antiderecruitment for lower PEEP; it would be more safe and effective than VCV.

Objective: To study the effects of bone marrow mesenchymal stem cells (MSC) on pulmonary fibrosis., Methods: Bone marrow MSC were harvested from 6 week old male SD rats. Forty-eight female SD rats were randomly divided into six groups. The pulmonary fibrosis models were made by intratracheal instillation of bleomycin (5 mg/kg in 0.3 ml normal saline). The normal controls received intratracheal instillation of NS instead of bleomycin. On the 1st and 7th day after bleomycin administration, the rats received MSC infusion or a same amount of phosphate buffer solution (PBS) as controls via the tail vein, respectively. The rats were sacrificed by the 28 day of experiment, and the pathologic changes and hydroxyproline contents of the lung tissues were investigated. The sry gene of Y chromosome was detected by polymerase chain reaction (PCR)., Results: For rats receiving MSC on the 1st and 7th day after bleomycin administration, the lung fibrotic scores were 1.0 +/- 0.2 and 1.6 +/- 0.5, respectively, significantly decreased as compared with rats receiving no MSC (2.5 +/- 0.5 & 2.3 +/- 0.8, respectively). The hydroxyproline contents of lung tissue were (83 +/- 17) microg/mg and (96 +/- 20) microg/mg, also significantly decreased as compared with rats receiving no MSCs [(123 +/- 32) microg/mg & (127 +/- 34) microg/mg, respectively]. Earlier administration of MSCs resulted in more significant improvement of lung injury. The sry gene (322 bp) was detected in lungs of female rats receiving MSC on the first day of bleomycin induced lung injury., Conclusions: MSC may be involved in the repair of lung injury, especially in the early stage. MSCs are effective in preventing bleomycin induced lung injury and fibrosis.

Objectives: To investigate the changes of serum enzymes and cardiac troponin I (TnI) in patients with acute pulmonary thromboembolism (PTE). The relationships between these changes and the pulmonary artery pressure, the right ventricular function and the prognosis were evaluated., Methods: This prospective multi-centre trial included 519 patients with confirmed PTE from 24 collaborating hospitals, with 54 cases of massive PTE, 195 sub-massive PTE and 270 non-massive PTE. Thrombolytic treatment with urokinase or recombinant tissue plasminogen activator (rt-PA) was administered for massive and sub-massive PTE patients; anti-coagulative therapy with unfractionated heparin or low molecular weight heparin was used for non-massive PTE., Results: The values of serum ALT, AST, CPK and LDH before treatment in massive PTE [(74 +/- 33), (88 +/- 40), (157 +/- 75), (419 +/- 264) U/L] were significantly higher than those in sub-massive [(52 +/- 21), (43 +/- 18), (75 +/- 30), (284 +/- 176) U/L] and non-massive cases [(38 +/- 13), (35 +/- 11), (78 +/- 24), (239 +/- 178) U/L] (P < 0.05). The value of serum ALT at day 7 (84 +/- 39 U/L) in the unfractionated heparin sub-group of the non-massive PTE was significantly higher than that (67 +/- 26 U/L) in the low molecular weight heparin sub-group (P = 0.045). Of the 45 cases with high pulmonary pressure > 80 mm Hg (1 mm Hg = 0.133 kPa), 24 (54.4%) cases showed high serum LDH (P = 0.032) and 17 (41.5%) high serum ALT (P = 0.049). Of the 169 cases with right ventricular dysfunction, 68 (40.2%) cases showed high serum LDH (P = 0.049) and 76 (45.5%) high serum ALT (P = 0.037). Of the 48 cases with poor prognosis, 15 (30.8%) cases showed high serum LDH (P = 0.039) and 26 (54.5%) high serum ALT (P = 0.022). Of the 39 cases with TnI > or = 0.07 microg/L, 24 (63.3%) cases were complicated with decreased right ventricular function (P < 0.01) and 8 (24.2%) with poor prognosis (P = 0.034)., Conclusions: The values of serum ALT, AST, CPK, LDH and TnI are increased in acute PTE. Unfractionated heparin results in higher levels of ALT than lower molecular weight heparin. The increase of serum ALT, LDH and TnI is correlated with pulmonary artery pressure, right ventricular function and the prognosis of the PTE. These changes may be useful in the risk stratification of PTE patients.

Objective: This study was undertaken to evaluate the thickness, cross-sectional area, and length of Achilles tendons in asymptomatic subjects of different age groups and heights and between dominant and nondominant ankles., Methods: High-resolution sonographic examinations of Achilles tendons were performed in 40 healthy subjects (14 men and 26 women). The subjects were categorized into 4 age groups: (1) 20 to 29 years, (2) 30 to 39 years, (3) 40 to 49 years, and (4) 50 years or older. The thickness, cross-sectional area, and length of the Achilles tendons of both ankles were measured. All Achilles tendons were measured with the ankle in a relaxed, neutral position., Results: There was no significant difference in the thickness and length of Achilles tendons among subjects of different age groups (P>.05). The Achilles tendon cross-sectional area of subjects 50 years or older was significantly larger than that of subjects in the younger age groups (P<.05). There was a positive correlation between the height of the subjects and the length, thickness, and cross-sectional area of the Achilles tendons; however, the correlation coefficient was low (r=0.07-0.28; P>.05). Dominance of ankles did not affect the thickness and length of the Achilles tendons, whereas the cross-sectional area of the tendons was significantly larger in the dominant ankles (P<.05)., Conclusions: Sonography is a useful imaging tool in the evaluation of Achilles tendons. Normal variations of the tendon morphologic characteristics should be considered in the clinical diagnosis.

Objective: To explore the effects of polymorphonuclear cells (PMN) on lung ischemia-reperfusion (I/R) injury in a canine model of pulmonary thromboembolism., Methods: Fifteen dogs were divided into three groups: a sham group (n = 5), an ischemia group (n = 5) and a reperfusion group (n = 5). PMN in the whole blood were isolated with density gradient centrifugation. Apoptosis rates of the PMN was measured through flow cytometer after the cells were labeled by Annexin V-FITC before embolectomy and at 2, 4, 6 h after the operation. The myeloperoxidase (MPO) concentrations in lung homogenates were measured by ELISA. Alveolar PMN in the reperfusion lobar were observed by optical microscopy. The lung ultrastructure was studied by transmission electron microscopy., Results: Alveolar PMN infiltration and the concentrations of MPO in the reperfusion group were significantly higher than those in the ischemia group (PMN (31 +/- 11) vs (8 +/- 4)/ten high power fields, MPO (11.7 +/- 1.6) vs (9.1 +/- 0.5) microg/L, P < 0.05). In the reperfusion group, abundant inflammatory cell infiltration was observed, predominantly with PMN in the alveoli. Apoptosis rates of the blood PMN at 6 h after reperfusion were much lower than before reperfusion (3.0 +/- 2.5)% vs (7.4 +/- 4.5)%, P < 0.05). At 4 and 6 h after operation, the PMN apoptosis rates in the reperfusion group were significantly lower than the ischemia group (4 h: (4.8 +/- 2.6)% vs (9.3 +/- 2.0)%, 6 h: (3.0 +/- 2.5)% vs (8.0 +/- 1.6)%, P < 0.05). PMN attaching firmly to the alveolar septum were observed by electron microscope., Conclusion: PMN with enhanced activities and decreased apoptosis rate, are involved in the cellular mechanisms of the lung I/R injury in this model of pulmonary thromboembolism.

Volumetric measurement is useful in the clinical practice as it can accurately assess the size of organs and lesions, which aids diagnosis and monitoring of treatment response. This in vitro study was undertaken to evaluate and compare the accuracy of three-dimensional ultrasound (3D-US) volumetric measurements using different numbers of image planes for outlining the region-of-interest. A total of 20 tissue phantoms (10 with regular and 10 with irregular tissue specimens) with known volume (2.2 - 14.7 ml) were constructed. The tissue phantoms were scanned with a commercially-available ultrasound machine in conjunction with a 3D add-on system and the volume of the tissue specimen of the phantoms was measured by manual outlining of the boundaries using different numbers of image plane (16, eight, four and two image planes). Results showed that there was a high accuracy in 3D-US volumetric measurements, when 16 and eight image planes were used (best-fit slope between measured and true volume: 0.9224-0.9761 and 0.9099-0.956, respectively). Results also showed that there was no significant difference in the volume measured with 16 and eight image planes for both phantoms with regular- and irregular-shaped tissue specimens (p > 0.05). The measurement differences between 16 and eight image planes ranged from -0.07 to 0.14 ml for phantoms with regular-shaped tissue and from -0.24 to 0.1 ml for phantoms with irregular-shaped tissue. 3D-US has a high accuracy in volumetric measurements of regular- and irregular-shaped structures. Although highest accuracy in volume measurements was found when 16 image planes were used, similar level of accuracy can be achieved with eight image planes but the measurement time can be reduced by 50%. Therefore, in 3D-US volumetric measurements, the largest number of image planes may not be necessary for outlining the region-of-interest.

Objective: To determine the prevalence of polymorphisms in the plasminogen activator inhibitor-1 (PAI-1) promoter 4G/5G polymorphisms in Chinese Han population and to investigate whether they are associated with pulmonary thromboembolism (PTE)., Methods: Samples of peripheral venous blood were collected from 101 patients with PTE diagnosed by high probability of lung ventilation/perfusion scan and/or multi-slice CT pulmonary angiography (CTPA) as well as medical history and clinical manifestations, 67 males and 34 females, aged 48 +/- 15, and 101 age and sex-matched healthy controls from the same geographic area as controls. The genome DNA was extracted from the whole blood using potassium iodide-phenol-chloroform method. Polymerase chain reaction (PCR), denaturing high performance liquid chromatography (DHPLC), and sequence analysis were used to screen the single nucleotide polymorphisms and the genotype distribution of -675 4G/5G located in the promoter region of the PAI-1 gene., Results: The frequencies of the allele 4G of PAI-1 gene in the controls were 0.495, significantly lower than in the PTE patients (0.733, chi(2) = 24.060, P < 0.01). The frequencies of the allele 5G of PAI-1 gene in the controls were 0.505, significantly higher than that in the PET patients. The genotype frequency of 4G4G of the PET patients was 57.4%, significantly higher than that of the controls (30.7%, P = 0.000). The genotype frequencies of 4G5G and 5G5G of the PET patients were 31.7% and 10.9% respectively, not significantly different from those of the controls (37.6 and 31.7% respectively). The presence of 4G allele of PAI-1 gene was found to be a greater risk factor for PTE. In comparison with the controls, the OR of 4G4G + 4G5G, 4G4G, and 4G5G in the PET patients were 3.794 (1.786 - 8.060), 5.443 (2.416 - 12.260), and 2.450 (1.067 - 5.623) respectively with the P values of 0.001, 0.000, and 0.035 respectively., Conclusion: The 4G/5G and 4G/4G genotypes are associated with the pathogenesis of PET.T.

Objective: To investigate the effects of conventional ventilation, lateral position, asynchronous independent lung ventilation and synchronous independent lung ventilation on gas exchange, lung mechanics, hemodynamics, pulmonary perfusion and inflammatory mediators in dogs with a hydrochloric acid induced unilateral acute lung injury (ALI)., Methods: Twenty-eight dogs with hydrochloric acid induced unilateral ALI (the left lung) were ventilated with volume controlled ventilation. The animals were divided into four groups. The first group (group A, n = 7) received conventional ventilation in a supine position. The second group (group B, n = 7) received conventional ventilation in the healthy lung dependent position with the parameters as same as group A. The third group (group C, n = 7) received asynchronous independent lung ventilation. The fourth group (group D, n = 7) received synchronous independent lung ventilation with the parameters as same as group C. All the animals were observed for 4 h under the above described ventilation. Oxygenation, lung mechanics, hemodynamics and lung injury score were measured during the ventilation. The right and left pulmonary arterial blood flows were measured after 4 h ventilation., Results: (1) After 30 min ventilation, PaO2/FiO2 in group A [(180 +/- 25) mm Hg, 1 mm Hg = 0.133 kPa] was significantly lower than those in group B, group C and group D [(277 +/- 23), (296 +/- 31), (299 +/- 22) mm Hg respectively, all P < 0.01]. PaO2/FiO2 in group C [(348 +/- 34) mm Hg] and group D [(343 +/- 29) mm Hg] was significantly increased when compared with that of group B [(314 +/- 33) mm Hg] after 60 min ventilation (P < 0.05), but there was no significant difference between group C and group D. (2) After 120 min ventilation, C(st) in group B [(23 +/- 4) ml/cm H2O] significantly increased when compared with that of group A [(19 +/- 2) ml/cm H2O, P < 0.05]. After 60 min ventilation, C(st)-L in group C and group D increased significantly as compared to the beginning of the ventilation. (3) The left lung pulmonary arterial flow in group B, group C and group D [(31.3 +/- 4.6)%, (27.5 +/- 1.3)% and (27.3 +/- 2.8)%, respectively] significantly decreased when compared with that of group A (38.3 +/- 2.2)% after 4 h ventilation (P < 0.05 and P < 0.01)., Conclusions: Both lateral position and independent lung ventilation can improve gas exchange, while independent lung ventilation is better than lateral position ventilation. The improvement of oxygenation may be related to the effect on the distribution of pulmonary arterial flow.

Objective: To investigate the effects of different durations of thromboembolism on blood gases, hemodynamic parameters, pulmonary arteriography and thrombo-pathology in an animal model mimicking chronic pulmonary thromboembolism (PTE)., Methods: Sixteen dogs were embolized with five thrombi developed by autologous blood into the left lower pulmonary artery (n = 15) and the right lower pulmonary artery (n = 1, used to confirm the available method of selective embolization). The 15 dogs were divided into three groups: sham group (n = 5), one-week group (n = 5) and two-week group (n = 5) according to the different durations of embolization. Swan-Ganz catheter was used to guide a plastic duct, through which the thrombi were injected selectively into the left or right lower pulmonary artery by X-ray fluoroscopy. Local pulmonary arteriography of lower pulmonary arteries was taken. Blood pressure (BP), and blood gases were measured. Central venous pressure (CVP), mean pulmonary arterial pressure (MPAP), pulmonary arteriole wedge pressure (PAWP), and cardiac output (CO) were recorded, and pulmonary vascular resistance (PVR) was calculated. Each dog underwent muscular injection with tranexamic acid for one or two weeks to prevent thrombolysis. The lower lung lobe was dissected to confirm the thromboembolism after one or two weeks. The lung sections were stained with phosphotungstic acid hematoxylin (PTAH) to observe thromboemboli with optical microscopy., Results: In the PTE group, PaO(2)/FiO(2), MPAP and PVR changed significantly as compared to baseline values (P < 0.05) after one hour of embolization, with MPAP increasing from (15 +/- 3) mm Hg to (21 +/- 4) mm Hg, PVR increasing from (178 +/- 114) mm Hg.s/L to (404 +/- 260) mm Hg.s/L, and PaO(2)/FiO(2) decreasing from (508 +/- 58) mm Hg to (395 +/- 100) mm Hg; these parameters returned to the baseline values one or two weeks later. After embolization, pulmonary arteriography demonstrated lower lobar artery cut-off perfusion defects. One week later, pulmonary arteriography demonstrated irregularities and stiffness of the arterial wall, enlarged proximal part of lower pulmonary artery and cut-off perfusion defects. Poor filling at embolus site was evident after embolization for two weeks. In the 1-week PTE group, organized tissue covered with the blue-purple fibrin nest was observed in the thrombus with PTAH stain. In the two-week group, the well organized thrombi were partially recanalized and surrounded and invaded by hyperplastic tissues from pulmonary artery wall., Conclusions: A canine model mimicking chronic PTE can be established by the use of fibrinolytic inhibitor tranexamic acid. Different manifestations on pulmonary arteriography and varied degree of organization of thrombi are evident at different times after embolization.

Objective: To investigate the inhibitory effect of vascular endothelial growth factor (VEGF) antisense oligonucleotides or/and dalteparin sodium (fragmin) on tumor growth and metastasis of mice Lewis lung cancer., Methods: 40 mice with Lewis lung cancer were randomizedly divided into five groups: control group, VEGF antisense oligonucleotides (ASODN) group, VEGF mismatch sense oligonucleotides (MSODN) group, low molecular weight heparin (LMWH) group, and combined group. Sodium chloride, VEGF-ASODN, VEGF -MSODN, fragmin, and VEGF-ASODN plus fragmin were given respectively (once every two days, 15 times altogether). The volume and weight of subcutaneous tumors were measured, and the rates of lung metastasis were detected by HE staining. The microvessel density (MVD) in tumor mass were measured by immunohistochemistry staining. VEGF protein level in tumor tissue were detected by Western blot assay., Results: After treatment, the tumor growth inhibitory rates were 47.34%, 27.31% and 59.03%, and the rates of lung metastasis were 37.5%, 37.5% and 25% in ASODN, LMWH, and the combined group, respectively. Tumor MVD and VEGF protein expression of the above three groups were lower than those of the control group. There was a significant difference in regard to the tumor growth inhibitory rates and MVD between the above three treated groups and the control group as well as the MSODN group (P < 0.05)., Conclusions: VEGF-ASODN and fragmin may down-regulate VEGF gene expression and inhibit angiogenesis, Combined use of fragmin can enhance anti- tumor effect of VEGF-ASODN.

Objective: To determine the prevalence of beta-fibrinogen gene -455G/A, -148C/T polymorphisms in Chinese Han population and to investigate whether they were associated with pulmonary thromboembolism (PTE)., Methods: The subjects consisted of 101 patients with PTE and 101 healthy controls matched with age and sex, from the same geographic area. All patients were diagnosed by high probability of lung ventilation/perfusion scan and/or multi-slice CT pulmonary angiography as well as medical history and clinical manifestations. Genome DNA was extracted from whole blood using KI-phenol-chloroform. Genotypes and allele frequencies of fibrinogen beta gene -455G/A, -148C/T polymorphisms were examined by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Restriction enzyme HaeIII and HindIII digestion were used for detecting -455G/A, -148C/T polymorphisms respectively., Results: Regarding fibrinogen beta gene -455G/A and -148C/, the allele frequencies G and A of fibrinogen beta -455 in the controls were 0.931, 0.069 while C and T of -148 were 0.777, 0.223 respectively, which were in good agreement with Hardy-Weinberg equilibrium. There was significant difference of -455G/A genotype frequencies distribution of AA, GA, GG between cases and in controls respectively, but no significant difference was found in the -148C/T polymorphisms. The frequencies of mutation allele -455A were 0.193, 0.169 in cases and in controls with P < 0.05 but there was no statistically significant difference of -148T allele. The presence of A allele of fibrinogen beta -455 was found to be a greater risk factor in cases than in controls. The odds ratio (OR) of GA and GA + AA were 3.723 (1.786 - 7.759), 3.749 (1.842 - 7.630), respectively. When compared with GG genotype, the P value was 0.0001., Conclusion: There was a complete linkage disequilibrium between fibrinogen beta -148C/T and -455G/A found. The frequencies of -455A, alleles in PTE disease were apparently higher than that of healthy adults but there was no difference in -148T alleles.

Objective: To investigate the mechanisms of alveolar derecruitment and titration of positive end-expiratory pressure (PEEP) and tidal volume (V(T)) after recruitment maneuver (RM) in acute respiratory distress syndrome (ARDS)., Methods: Eighteen dogs with oleic acid induced ARDS were ventilated with volume controlled ventilation [VCV, PEEP 16 cm H2O, V(T) 10 ml/kg, respiratory rate (RR) 30 breaths/min] and the steady state in this mode was defined as baseline (0 min). All animals accepted RM by using pressure controlled ventilation [PEEP 35 cm H2O and peak inspiratory pressure (PIP) 50 cm H2O for 1 min] and then randomly assigned into three groups and ventilated by VCV for 4 h: low V(T) and moderate PEEP group (LVMP group, V(T) 10 ml/kg, PEEP 16 cm H2O, RR 30 breaths/min), low V(T) and low PEEP group (LVLP group, V(T) 10 ml/kg, PEEP 10 cm H2O, RR 30 breaths/min) and moderate V(T) and low PEEP group (MVLP group, V(T) 15 ml/kg, PEEP 10 cm H2O, RR 20 breaths/min). Oxygenation, lung mechanics, hemodynamics and lung injury score were measured., Results: (1) The average lower inflection pressure (LIP) was identified as (16.0 +/- 2.1) cm H2O. (2) PaO(2) in the LVMP group [(371 +/- 64) mm Hg at 30 min and (365 +/- 51) mm Hg at 60 min] was higher than that in the LVLP and the MVLP group [(243 +/- 112), (242 +/- 97) mm Hg at 30 min and (240 +/- 108), (232 +/- 87) mm Hg at 60 min, respectively; all P < 0.05], but no significant differences were observed among three groups from the second hour after RM to the end of the experiment. Better ventilation profiles were observed in the MVLP group. (3) Compared with baseline, marked cardiac compromise with higher airway plateau pressure (Pplat) and lower static respiratory compliance (Cst) were found in the LVMP group, while improvement was observed in other two groups. Cst in the MVLP group was slightly higher than that in the LVLP group. (4) No significant differences of lung injury were found from bronchoalveolar lavage fluid (BALF) analysis., Conclusions: Higher PEEP close to LIP maybe useful in preventing alveolar recollapse and improving oxygenation, but harmful to hemodynamics and may increase the risk of lung jury. Lower PEEP combined with moderate tidal volume after RM may be a more reasonable approach than conventional lung protective ventilation.

Objective: To explore the changes of blood coagulative and fibrinolytic systems and functions of pulmonary vascular endothelium in patients with pulmonary thromboembolism (PTE)., Methods: Twenty patients with acute massive PTE, 40 patients with acute non-massive PTE and 40 control subjects without PTE were included in the study. D-Dimer (D-D), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor1 (PAI-1), plasma protein S (Ps), plasma protein C (Pc), thrombomodulin (TM), anticardiolipin antibody (ACA) and homocysteine (Hcy) were measured by the method of ELISA. Antithrombin-III (AT-III) activity was measured by chromo-substrate method., Results: The levels of D-D, t-PA, PAI-1, and TM were (1.46 +/- 0.62) mg/L, (11.4 +/- 6.9) microg/L, (88.2 +/- 27.5) microg/L, (6.8 +/- 1.1) microg/L respectively in patients with acute massive PTE and (0.92 +/- 0.27) mg/L, (6.6 +/- 1.5) microg/L, (60.1 +/- 26.1) microg/L, and (6.30 +/- 1.50) mg/L in patients with acute non-massive PTE. The levels of both PET groups were significantly higher than those of the control subjects [(0.38 +/- 0.10) mg/L, (4.7 +/- 1.4) microg/L, (35.7 +/- 9.2) microg/L, (3.0 +/- 0.5) microg/L and P < 0.05]. The levels of AT-III were (86.0 +/- 11.8)% in patients with acute massive PTE and (90.1 +/- 9.0)% in patients with acute non-massive PTE. The levels of AT-III in both groups were significantly lower than those of the control subjects, which were (102.6 +/- 9.2)% (P < 0.01 and P < 0.05 respectively). The levels of ACA-IgG, IgM and IgA in patients with acute massive PTE and non-massive PTE were also significantly higher than those in the control group (P < 0.05)., Conclusion: Imbalance of blood coagulation and fibrolytic systems and pulmonary vascular endothelium damage occur in patients with PTE.

Objective: To investigate the effects of thrombolysis and anticoagulation on the functions of vascular endothelial cells and coagulation and fibrinolysis in patients with pulmonary thromboembolism., Methods: Twenty-four patients with documented pulmonary thromboembolism and 20 normal subjects were included. Of the 24 patients with pulmonary thromboembolism, 7 were treated with recombinant tissue-type plasminogen activator intravenously, and 17 with low molecular weight heparin. The plasma levels of endothelin 1 (ET-1), tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), antithrombin III (AT-III) and D-dimer and the blood serum levels of nitrogen monoxide (NO) were measured in the control group and in the patients at different time points before and after therapies., Results: In patients receiving thrombolytic therapy, ET-1 [(103.7 +/- 26.6) ng/L] and D-dimer [(5.0 +/- 1.7) mg/L] increased significantly at 4 h after the treatment, and were higher than those at other time points (P < 0.05 and P < 0.01, respectively). The level of ET-1 was correlated positively with PaO(2) and D-dimer (r = 0.751, and 0.782 respectively, P < 0.05). In patients receiving anticoagulation therapy, compared with pretreatment data, NO and AT-III increased and ET-1 decreased significantly at 14 d after the start of low molecular weight heparin therapy, (48 +/- 14) micromol/L vs (66 +/- 24) micromol/L for NO, (90 +/- 7)% vs (99 +/- 4)% for AT-III, (72.0 +/- 18.3) ng/L vs (52.8 +/- 13.9) ng/L for ET-1, all P < 0.05., Conclusions: ET-1 and D-dimer changed significantly after thrombolytic therapy, while ET-1, NO and AT-III showed dramatic change after anticoagulation therapy. The change of ET-1 and D-dimer reflects the therapeutic effects. Thrombolytic and anticoagulation therapies are beneficial in keeping the balance between coagulation and fibrinolysis and protecting the functions of vascular endothelial cells in patients with pulmonary thromboembolism.

Objective: To investigate the relationship between vascular endothelial dysfunction and serum homocysteine (HCY) level in patients with coronary lesions., Methods: Serum HCY, serum nitric oxide (NO), plasma endothelin-1 (ET-1), and circulation endothelial cell (CEC) were measured in 76 patients who received coronary angiography. Fifty-four patients with a stenosis of 50% or more at least in one coronary atery were as coronary artery disease (CAD) group. Other 22 cases with no recognizable plaque and/or stenosis were as control group. HCY level was detected using an enzyme immunoassay kit. NO concentration was measured using a nitrate reductase kit. Radio-immunoassay was applied to analyse the ET-1 level, and CEC was measured by flow cytometry., Results: The levels of HCY, ET-1, and CEC in patients with coronary lesions were significantly increased in comparison with control group (P < 0.01), while NO level in CAD group was significantly lower compared with that in control (P < 0.01). Using a multivariate stepwise regression analysis, HCY level had a positive correlation with ET-1 level (r = 0.420, P < 0.05) and CECs number (r = 0.423, P < 0.05); and had a negative correlation with NO/ET-1 (r = -0.403, P < 0.05). But there was no significant correlation between HCY and NO levels., Conclusions: HCY might lead to endothelial cell injury, which would provide a plausible mechanism for the relationship between hyperhomocysteinemia and development of coronary artery disease. HCY can be considered as a predictor for preliminary or active coronary lesion.

Objective: To identify the risk factors of deep venous thrombosis (DVT) in hospitalized patients with acute stroke, under a perspective case-control study., Methods: 488 cases with stroke, identified by CT or MRI and admitted to the department of neurology and neurosurgery in Beijing Chaoyang Hospital between December 2001 and December 2002 were consecutively studied. There were 328 male and 160 female patients (95.5% Hans) with a mean age of 65 +/- 11 years, ranging 22 - 93 years. The procedure of study would include: (1) General condition, possible risk factors, symptoms of DVT physical check-up to every eligible patient on first day of admission but the plasma concentrations of D-dimer (ELISA), thrombomodulin, antithrombin-III and blood routine examination were measured on the next morning. (2) The ultrasonography (US) was used for detecting both lower extremities at 7 - 10 days after the onset of stroke, and D-dimer and AT-III tests were repeated on the same or next day that the US was taken. (3) The ultrasound examination was repeated after a week in patients with high suspicion of DVT. (4) The therapy of stroke was recorded before the end of the study. Data of stoke patients with DVT was compared with those without DVT to identify the DVT risk factors. The effect of each variable on DVT was assessed by logistic regression analysis., Results: The prevalence of DVT was 21.7% among the patients. In multivariate analysis, age >/= 65 years old (OR = 1.655, 95% CI: 1.005 - 2.725), being male (OR = 1.993, 95% CI: 1.221 - 3.253), bedridden (OR = 3.275, 95% CI: 1.653 - 6.486) and DVT assessment scores >/= 2 (OR = 5.019, 95% CI: 2.685 - 9.381) were independently associated with DVT in all the stroke patients. Being male (OR = 2.828, 95% CI: 1.242 - 6.438), white blood cell count > 10.0 x 10(9)/L (OR = 2.032, 95% CI: 0.897 - 4.602) and DVT assessment scores >/= 2 (OR = 8.809, 95% CI: 3.081 - 25.188) were the independent risk factors of DVT in hemorrhagic stroke group. Age >/= 65 years old (OR = 2.167, 95% CI: 1.072 - 4.381), bedridden (OR = 3.008, 95% CI: 1.435 - 6.307) and DVT assessment scores >/= 2 (OR = 2.600, 95% CI: 1.077 - 6.278) were the independent risk factors of DVT in ischemic stroke group., Conclusion: Patients hospitalized with acute stroke were under high risk of DVT. Data suggested that old age, female, bedridden and high DVT assessment scores >/= 2 were independent risk factors for DVT in acute stroke patients that called for supervision and prophylaxis on DVT.

Objectives: To study the functional changes and the significance of coagulation, fibrinolysis and pulmonary vascular endothelium before and after experimental pulmonary thromboembolism in rabbits., Methods: Rabbit pulmonary thromboembolism models by injection of auto-blood clots into femoral vein were used to observe the dynamical changes of activity of coagulation and fibrinolysis and endothelin-1 (ET-1), nitrogen monoxide (NO), von Willebrand factor (vWF) in blood., Results: Petechial and patchy hemorrhages were observed on the surfaces of embolic lungs. The injected blood clots and secondary thrombosis in the pulmonary arteries, inflammatory cell infiltration around alveoli, local hemorrhages in the alveoli and interstitial tissue could be found by microscopy. The concentration of D-dimer, ET-1 and vWF in blood were significantly elevated, and the tissue-type plasminogen activator (t-PA), NO and antithrombin III (AT-III) decreased significantly after embolism (P < 0.05). After administration of urokinase, the pathological injuries relieved, and the concentration of D-dimer was higher at 1 h and 2 h after embolization than that before embolization (P < 0.05), and reduced to the level of pre- embolization at 4 h after embolization. The levels of t-PA, NO and AT-III after embolization were lower than those before embolization (P < 0.05). The level of ET-1 was higher at 2 h after embolization (P < 0.05) and reduced to the level of pre-embolization at 4 h., Conclusions: PTE has important impacts on coagulation, fibrinolysis and pulmonary vascular endothelial function. Thrombolysis with urokinase could keep the balance between coagulation and fibrinolysis and protect pulmonary vascular endothelial function.

Objective: To evaluate the effects of simvastatin combined with omega-3 fatty acids on high sensitive C-reactive protein (HsCRP), lipidemia, and fibrinolysis in coronary heart disease (CHD) and CHD risk equivalent patients with mixed dyslipidemia., Methods: A randomized, double-blind placebo controlled and parallel group trial was conducted. Patients with CHD and CHD risk equivalents with mixed dyslipidemia were treated with 10 or 20 mg simvastatin for 6-12 weeks. Following with the treatment of patients whose low-density lipoprotein cholesterol (LDL-ch) reaching goal level (< 100 mg/dL) or close to the goal (< 130 mg/dL), while triglyceride (TG) > or = 200 mg/dL and < 500 mg/dL, was combined with omega-3 fatty acids (3 g/d) or a placebo for 2 months. The effects of the treatment on HsCRP, total cholesterol (TC), LDL-ch, high-density lipoprotein cholesterol (HDL-ch), TG, lipoprotein (a) [LP (a)], apolipoprotein A1 (apoA1), apolipoprotein B (apoB), plasminogen activator inhibitor-1 (PAI-1), and tissue plasminogen activator (tPA) were investigated. Forty patients finished the study with each group consisting of twenty patients., Results: (1) There were significant reductions of HsCRP, TG, TC, and TC/HDL-ch, which decreased by 2.16 +/- 2.77 mg/L (38.5%), 94.0 +/- 65.4 mg/dL (31.1%), 13.3 +/- 22.3 mg/dL (6.3%), 0.78 +/- 1.60 respectively in the omega-3 fatty acids group (P < 0.01, < 0.001, < 0.05, < 0.05) compared to the baseline. HsCRP and triglyceride reduction were more significant in omega-3 fatty acids group compared to the placebo group (P = 0.021 and 0.011 respectively). (2) In the omega-3 fatty acids group, the values and percentage of TG reduction had a significantly positive relation with HsCRP reduction (r = 0.51 and 0.45, P = 0.021 and 0.047 respectively)., Conclusion: In CHD and CHD risk equivalent patients with mixed dyslipidemia, dyslipidemia's therapeutic effect using simvastatin and omega-3 fatty acids may result from not only the combination of lipid adjustment, but also enhancement of their own nonlipid influences.

Background: Cigarette smoking is the major risk factor for chronic obstructive pulmonary disease (COPD). However, only 10% - 20% of chronic heavy cigarette smokers develop symptomatic disease. COPD is most likely the result of complex interactions between environmental and genetic factors. Genetic susceptibility to COPD might depend on the variations in enzyme activities that detoxify cigarette smoke products, such as microsomal epoxide hydrolase (mEH) and glutathione S-transferase (GST). In this study, we investigated the relationship between polymorphisms in the genes encoding mEH and glutathione S-transferase P1 (GSTP1) and COPD in a Chinese population., Methods: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was performed to find mEH polymorphism in exon 3 (Tyr113-->His), exon 4 (His139-->Arg) and GSTP1 polymorphism in exon 5 (Ile105-->Val) in 100 COPD patients and 100 age- and sex-matched healthy controls., Results: The proportion of mEH exon 3 heterozygotes was significantly higher in patients with COPD than that in the control subjects (42% vs 32%). The odds ratio (OR) adjusted by age, sex, body mass index (BMI) and cigarette years was 2.96 (95% CI 1.24 - 7.09). There was no marked difference in very slow activity genotype versus other genotypes between COPD patients and the controls. When COPD patients were non-smokers, the OR of very slow activity genotype versus other genotypes was more than 1.00; and when COPD patients were smokers (current smokers and ex-smokers), the OR was less than 1.00. There was no significant difference in GSTP1 polymorphism adjusted by age, sex, BMI and smoking between COPD patients and the controls., Conclusions: mEH exon 3 heterozygotes might be associated with susceptibility to COPD in China. The interaction might exist between mEH genotype and smoke. The gene polymorphism for GSTP1 might not be associated with susceptibility to COPD in the Chinese population.

Objective: To investigate the prevalence and the clinical manifestations of DVT in hospitalized patients with acute stroke, and to evaluate the short-term prophylaxis effect of low molecular weight heparin (LMWH) to prevent DVT., Methods: 488 cases with stroke admitted to the department of neurology and neurosurgery in Beijing Chaoyang Hospital between December 2001 and December 2002 were consecutively investigated. The diagnosis of stroke was identified by CT or MRI. The patients (95.5% Hans) were comprised of 328 male and 160 female, with a mean age of (65 +/- 11) years, ranging 22 approximately 93 years. The procedure of investigation: (1) A detailed history was taken and a physical examination was performed to every eligible patient. (2) The ultrasonography (US) was used for detecting both lower extremities at 7-10 days after acute stroke. (3) The ultrasound examination was repeated after a week in patients highly suspected of DVT., Results: (1) The prevalence of DVT was 21.7% among the patients. (2) DVT was the most frequent (28.0%) in the patients ranging 70 approximately 79 years. (3) A higher incidence of DVT was observed in female than in male (29.4% vs 18.0%, P = 0.004). (4) The incidence of DVT in severely paralyzed patients was 25.9%. (5) Leg edema was the most common symptoms of DVT with the frequency of 13.3%, but there was a poor correlation between the symptoms and the location of DVT. And 74.5% patients were asymptomatic. (6) Most DVTs occurred in distal extremities. The DVTs in proximal veins and in distal veins were in a ratio of 1.0 to 2.3. Fibular veins were most frequently attacked (30.4%). The presence of a filling defect on ultrasound images was described in 77.3% of the DVTs. (7) A 40.0% reduction of DVT incidence was caused by LWMH treatment in ischemic stroke patients., Conclusions: (1) The hospitalized patients with acute stroke were the crowd with high risk of DVT. (2) Most DVTs were asymptomatic; the signs were nonspecific, which indicated the diagnosis of DVT couldn't depend merely on clinical manifestation. (3) Most DVTs were in distal extremities. Filling defect was the most common manifestation of ultrasonography in DVT. (4) The incidence of DVT could be reduced by using LMWH in acute ischemic stroke patients.

Objective: To compare the thrombolytic effects of the two dosing regimes with urokinase (UK) in a canine model of pulmonary thromboembolism induced by radioactive blood clots., Methods: Seventeen dogs were randomly assigned into three groups: the control group, the UK(2h) group (UK infused over 2 hours) and the UK(12h) group (UK given over 12 hours). The thrombolytic differences was investigated among the three groups. Thrombolysis was assessed by continuously counting over both lung fields with single photon emission computed tomography (SPECT) and calculated by regions of interest (ROI) technology and by counting radioactivity in the lung in vitro. The extent of thrombolysis was calculated as the difference between the radioactivity originally incorporated in the clot (decay-corrected) and the radioactivity in the lung in vitro., Results: In three groups, the lysis rates measured by ROI technology were (6.2 +/- 4.0)%, (39.5 +/- 13.9)%, and (16.9 +/- 8.9)% respectively, and (6.0 +/- 2.7)%, (42.8 +/- 12.4)%, and (17.7 +/- 9.3)% by the method in vivo. The thrombolytic ratio of the UK(2h) group was significantly higher than that of the other two groups (P < 0.01), and there was no marked difference between the control group and the UK(12h) group. There was a thrombolytic peak in the UK(2h) group at the first four hours after infusion of agent., Conclusions: For the fresh thrombi, the UK(2h) regime is superior to the UK(12h) due to its higher thrombolytic ratio and prompt thrombolytic property. The model and methods are highly reliable.

Objective: To investigate the association between polymorphisms in the microsomal epoxide hydrolase (mEH) gene and susceptibility to chronic obstructive pulmonary disease (COPD) in a Chinese population., Methods: Polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) were performed to genotype mEH polymorphisms in exon3 (Tyr113-->His) and exon4 (His139-->Arg) in 100 COPD patients and 100 age and sex matched healthy controls., Results: (1) The proportion of mEH heterozygotes in exon3 was significantly higher in the patients with COPD than that in the control subjects (42% vs 32%). The odds ratio (OR) adjusted by age, sex, body mass index (BMI) and cigarettes years was 2.96 (95% CI 1.24 - 7.09). (2) There was no marked difference in very slow activity genotype versus other genotypes between COPD patients and controls. (3) When COPD patients were nonsmokers, the OR of very slow activity genotype versus other genotypes was more than 1.00, and when COPD patients were smokers (Current smokers and ex-smokers), the OR was less than 1.00., Conclusions: (1) mEH heterozygotes in exon3 might be associated with the susceptibility to COPD in China. (2) The interaction might be existed between mEH genotype and smoke.