[Obstructive sleep apnea-hypopnea syndrome in patients with pulmonary thromboembolism: clinical features and management].

OBJECTIVE: To describe the clinical features of obstructive sleep apnea-hypopnea syndrome (OSAHS) in hospitalized pulmonary thromboembolism (PTE) patients, and to explore its impact on the severity of disease and management among patients with PTE. METHODS: Demographic and clinical characteristics of 28 PTE patients complicated with OSAHS admitted to this hospital from January 2002 to December 2010 were analyzed. A total of 30 PTE patients without OSAHS served as a control group. RESULTS: PTE patients with OSAHS had a significantly lower age of onset of disease [(55 ± 11) yr vs (66 ± 11) yr, t = 3.230, P < 0.01], an increased body mass index (BMI) [(30.1 ± 2.8) kg/m(2) vs (26.1 ± 3.1) kg/m(2), t = -4.161, P < 0.001] and a higher smoking index [(19 ± 6) packs/yr vs (8 ± 4) packs/yr, t = -1.713, P < 0.05] when compared with PTE patients without OSAHS. PaO2 [(70 ± 8) mm Hg vs (79 ± 6) mm Hg, 1 mm Hg = 0.133 kPa, t = 4.233, P < 0.05] and involved lung segments [(8 ± 4) vs (5 ± 3), t = -2.496, P < 0.05] in PTE patients with OSAHS were more severe than those in PTE patients without OSAHS. All patients received anticoagulation and/or thrombolysis treatment, and continuous positive airway pressure (CPAP) ventilation was used in some PTE patients with OSAHS. CONCLUSION: PTE patients with OSAHS had a significantly earlier age of onset of disease and more severe conditions than PTE patients without OSAHS. Treatments including anticoagulation and CPAP should be used in these patients.

[Effect of retroviral vector mediating RNA interference on the release of tumor necrosis factor-alpha in lipopolysaccharide-stimulating macrophage].

OBJECTIVE: To explore the effect of small interfering RNA (siRNA) targeting NF-kappaB signal pathway on the expression level of tumor necrosis factor alpha (TNF-alpha) released by lipopolysaccharides (LPS)-stimulating-macrophages. METHODS: Human monocytic THP-1 cell was induced by phorbol myristate acetate (PMA) and transformed into macrophage. Two groups of macrophage were infected by siRNA retroviral expression vector specific to NF-kappaB functional subunit P65 (siRNA group) and Scramble control vector (Scramble control group) constructed by molecular cloning technology. Lipopolysaccharide (50 microg/ml) was used to treat the macrophages continuously. RT-PCR was performed to detect the expression level of NF-kappaB P65 mRNA and TNF-alpha mRNA at different time-points of LPS stimulation. Western blotting was used to analyze the protein level of NF-kappaB P65. Enzyme-linked immunosorbent assay was applied to analyze the expression level of TNF-alpha released by LPS-stimulated macrophages. RESULTS: At Hours 12 and 24 after LPS stimulation, the expression level of NF-kappaB P65 mRNA in siRNA group (0.97 +/- 0.02, 0.89 +/- 0.01) was significantly less than that in Scramble control group (1.01 +/- 0.03, 0.97 +/- 0.01, both P < 0.05). At Hours 24 and 72 after LPS stimulation, the expression level of NF-kappaB P65 protein in siRNA group (0.95 +/- 0.04, 0.94 +/- 0.01) was obviously less than that in Scramble control group (1.07 +/- 0.06, 1.03 +/- 0.05, both P < 0.05). At Hours 4, 8, 12 and 24 after LPS stimulation, TNF-alpha mRNA released by siRNA group macrophages was far less than that by Scramble control group macrophages (0.92 +/- 0.02 vs 0.98 +/- 0.01, 0.86 +/- 0.02 vs 1.00 +/- 0.01, 0.79 +/- 0.03 vs 1.01 +/- 0.01, 0.78 +/- 0.03 vs 1.02 +/- 0.01, all P < 0.05). At Hours 2, 4, 8, 24, 36, 48, 54 and 72 after LPS stimulation, the TNF-alpha content in culture medium supernatant in siRNA group macrophage was less than that in scramble control group (P < 0.05). CONCLUSION: NF-kappaB P65 siRNA inhibits the functional activity of NF-kappaB signal pathway in PMA-induced macrophage. Then it blocks the activation of macrophage and the excessive release of TNF-alpha due to endotoxin stimulation. The RNA interference technology may be applied to prevent and treat excessive inflammatory reaction in acute lung injury.

Current and future uses of skeletal stem cells for bone regeneration.

The postnatal skeleton undergoes growth, modeling, and remodeling. The human skeleton is a composite of diverse tissue types, including bone, cartilage, fat, fibroblasts, nerves, blood vessels, and hematopoietic cells. Fracture nonunion and bone defects are among the most challenging clinical problems in orthopedic trauma. The incidence of nonunion or bone defects following fractures is increasing. Stem and progenitor cells mediate homeostasis and regeneration in postnatal tissue, including bone tissue. As multipotent stem cells, skeletal stem cells (SSCs) have a strong effect on the growth, differentiation, and repair of bone regeneration. In recent years, a number of important studies have characterized the hierarchy, differential potential, and bone formation of SSCs. Here, we describe studies on and applications of SSCs and/or mesenchymal stem cells for bone regeneration.

[Clinical analysis of 62 cases of chronic thromboembolic pulmonary hypertension treated with pulmonary thromboendarterectomy without early and late deaths].

OBJECTIVE: To retrospectively evaluate the effects of pulmonary thromboendarterectomy (PTE) on chronic thromboembolic pulmonary hypertension (CTEPH). METHODS: Sixty-two cases of CTEPH operated with PTE from October 2002 to September 2008 at Anzhen Hospital were retrospectively reviewed and were assigned into either proximal CTEPH group (n = 46) or distal CTEPH group (n = 16). RESULT: No early death was reported. 15 had residual pulmonary hypertension and 23 had pulmonary reperfusion injury postoperatively. And reperfusion injury was recovered with the support of ventilation or ECMO. Between pre and post-procedure, the pulmonary artery systolic pressure changed from 91 +/- 38 mm Hg to 53 +/- 21 mm Hg, the pulmonary vascular resistance from 916 +/- 548 dynxsxcm(-5) to 368 +/- 302 dynxsxcm(-5) (t = 6.896, P = 0.0001), and the arterial partial pressure of oxygen (PaO(2)) from 51 +/- 7 mm Hg to 90 +/- 7 mm Hg and the arterial oxygen saturation (SaO(2)) from 87.0% +/- 3.9% to 96.1% +/- 3.3%, P < 0.05. With the follow-up of (24.8 +/- 14.6) months (cumulative follow-up was 121.6 patient-years), there was no late death and 38 were in NYHA functional class I, 20 class II, 2 class III and 2 class IV. According to Kaplan-Meier actuarial curve, the freedom from reembolism at 3 years was 96.7% +/- 2.8%. The linear bleeding rate related to anticoagulation was 2.47% patient-years, and the linear thromboembolic rate related to anticoagulation is 1.64% patient-years. CONCLUSION: The early and mid-long term survival rate of PTE procedure on CTEPH is acceptable and the complication rate related to anticoagulation with warfarin is relatively low.

Multi-agent-based bio-network for systems biology: protein-protein interaction network as an example.

Recently, a collective effort from multiple research areas has been made to understand biological systems at the system level. This research requires the ability to simulate particular biological systems as cells, organs, organisms, and communities. In this paper, a novel bio-network simulation platform is proposed for system biology studies by combining agent approaches. We consider a biological system as a set of active computational components interacting with each other and with an external environment. Then, we propose a bio-network platform for simulating the behaviors of biological systems and modelling them in terms of bio-entities and society-entities. As a demonstration, we discuss how a protein-protein interaction (PPI) network can be seen as a society of autonomous interactive components. From interactions among small PPI networks, a large PPI network can emerge that has a remarkable ability to accomplish a complex function or task. We also simulate the evolution of the PPI networks by using the bio-operators of the bio-entities. Based on the proposed approach, various simulators with different functions can be embedded in the simulation platform, and further research can be done from design to development, including complexity validation of the biological system.

[The role of disequilibrium of expression of matrix metalloproteinase-2/9 and their tissue inhibitors in pathogenesis of hyperoxia-induced acute lung injury in mice].

OBJECTIVE: To investigate the role of matrix metalloproteinase-2/9 (MMP-2/9) and their tissue inhibitors (TIMP-1/2) in pathogenesis of acute lung injury (ALI) induced by hyperoxia. METHODS: Seventy-two C57BL/6 mice were randomly divided into normal control group, hyperoxia for 24 hours group, hyperoxia for 48 hours group, and hyperoxia for 72 hours group, with 18 mice in each group. The mice in hyperoxia groups were exposed to >98% oxygen in sealed cages, and the normal control group were placed outside of the cage to breathe room air. At the end of the exposure time the animals were euthanized, the right lung was removed and phosphate buffer solution (PBS) was used to lavage the lung through the endotracheal catheter. The wet/dry weight ratio, broncho-alveolar lavage fluid (BALF) protein content and the volume of pleural fluid were measured, the severity of lung injury was assessed; the expression of MMP-2/9 and TIMP-1/2 mRNA in lung tissue at 24, 48 and 72 hours of hyperoxia were assessed by reverse transcript-polymerase chain reaction (RT-PCR); the amount of MMP-2/9 and TIMP-1/2 protein in lung tissue were measured by enzyme-linked immunosorbent assay (ELISA). RESULTS: Hyperoxia caused ALI as evidenced by the increase in lung wet/dry weight ratio, BALF protein content and the volume of pleural fluid as compared with the normal control group (P<0.05 or P<0.01). RT-PCR study showed increased expression of MMP-2/9 and TIMP-1 mRNA in lung tissues (P<0.05 or P<0.01), and ELISA assay also demonstrated upregulation of MMP-2/9 and an increase in TIMP-1 amount in BALF compared with their normal control group (P<0.05 or P<0.01). The ratios of both MMP-2 mRNA/TIMP-2 mRNA and MMP-2 protein/TIMP-2 protein were all increased in hyperoxia groups as compared with their normal control group (all P<0.01). CONCLUSION: Hyperoxia causes ALI in mice, and disturbance of MMP-2/TIMP-2 balance plays an important role in the development of hyperoxia-induced ALI in mice.

[The clinical analysis of 54 cases for the surgical treatment of pulmonary embolism].

OBJECTIVE: To evaluate the results of surgical procedures for pulmonary embolism. METHODS: Fifty-four patients of pulmonary embolism received surgical treatment from October 1994 to June 2007, of which 9 were acute pulmonary embolism underwent pulmonary embolectomy and 45 patients were chronic thromboembolic pulmonary hypertension (CTEPH) underwent pulmonary thromboendarterectomy. RESULTS: The mortality rate was 44.4% in acute pulmonary embolism group and 13.3% in CTEPH group (P < 0. 05). Thirteen patients had residual pulmonary hypertension and 23 patients had severe pulmonary reperfusion injury postoperatively. The pulmonary artery systolic pressure changed from (89.4 +/- 36.3) mm Hg (1 mm Hg =0.133 kPa) preoperative to (55.6 +/- 22.4) mm Hg postoperative. The pulmonary vascular resistance changed from (89. 7 +/- 56.7) kPa L(-1) S(-1) preoperative to (38.9 +/- 31.1) kPa L(-1) S(-1) postoperative. The arterial partial pressure of oxygen changed from (52. 3 +/- 6.7 ) mm Hg preoperative to (87.6 +/- 6.5) mm Hg postoperative. The arterial oxygen saturation changed from (88.9 +/- 4.5)% preoperative to (95.3 +/- 2.8 )% postoperative (P < 0.05). With the follow-up of (41.8 +/- 36.4) months, there were 4 patients died. According to NYHA, there were 28 patients for class I , 10 patients for class II and 2 patients for class III. According to Kaplan-Meier survival curve, the 3-year, 4-year, 5-year and 8-year survival rate were (97.1 +/- 2.8 )%, (94.0 +/- 4.1)%, (90.8 +/- 5.2)% and (85.0 +/- 7.3)% respectively. Linear rate of bleeding and thromboembolic related to anticoagulation were 0. 63% patient-years and 0. 62% patient-years respectively. CONCLUSIONS: The operational mortality of acute pulmonary embolism is significantly higher than CTEPH, and the mid-long term survival rate is agreeable and the complication rate related to anticoagulation is relatively low.

[Prognosis of patients with chronic thromboembolic pulmonary hypertension receiving conservative or operative treatments according to a new clinical classification scheme].

OBJECTIVE: To compare the efficacy of conservative or pulmonary thromboendarterectomy (PTE) therapy for chronic thromboembolic pulmonary hypertension (CTEPH) patients according to a new clinical classification scheme. METHODS: This retrospective study analyzed 63 cases of CTEPH admitted to our hospital from February 1995 to October 2007 and 45 cases were treated surgically (Group A) and 18 cases received conservative therapy (Group B). Results were analyzed using Fisher exact test and t test according to San Diego medical center quartering classification scheme and Anzhen Hospital modified bifurcate classification scheme. RESULTS: There were 6 operational deaths in Group A and 2 deaths during hospital stay in Group B. During follow-ups (mean 3.6 +/- 2.5 years), there were 4 deaths in Group A and 9 deaths in Group B. the totality survival rate is significantly higher in Group A than that in Group B (P < 0.05). For patients with San Diego Type I CTEPH, survival rate was significantly higher in Group A compared with Group B (P = 0.009) and was similar for patients with type II and III and IV CTEPH between the two groups (P = 0.338, 0.455, 0.800). Survival rate was significantly higher in Group A than that in Group B for patients with Anzhen central type CTEPH (P = 0.009), but was similar between the two groups for patients with Anzhen peripheral type CTEPH (P = 0.125). The Kaplan-Meier survival curve 5 years survival rate in the Group A was (91.7 +/- 8.0)% for Anzhen central type and (76.0 +/- 8.5)% for Anzhen peripheral type (P = 0.04), and the 5 years Kaplan-Meier survival rate in the Group B was (42.9 +/- 18.7)% for Anzhen central type and (56.2 +/- 10.8)% for Anzhen peripheral type (P = 0.851). CONCLUSION: Anzhen Hospital modified bifurcate classification scheme is a simple and effective classification to predict the prognosis and choose treatment method of CTEPH.

[Evaluation of the changes of alveolar bone around the upper incisors after retraction with mini implant anchorage using cone-beam CT].

PURPOSE: The aim of this clinical study was to evaluate the changes of alveolar bone morphology before and after upper incisors retraction with mini implant anchorage using cone-beam CT (CBCT). METHODS: Twenty-two young patients with dentoalveolar maxillary protrusion and extraction of 2 maxillary first premolars were evaluated with CBCT. CBCT scans were obtained before treatment and 3 months after retraction of the incisors. The movement patterns of the upper incisors were assessed with Mimics15.0. The labial and palatal alveolar plates at crest level, midroot level, and apical level for bone-thickness changes and labial and palatal vertical bone level during retraction of the maxillary anterior segments were assessed with Invivo5.0. Paired t tests were used to evaluate the changes. RESULTS: The edge of the maxillary incisor and the root apex appeared lingual movement horizontally, but the moving distance was larger than the root apex. The edge of the incisors was moved downward, and the root apex was moved upward obviously. The palatal thickness and total thickness of the alveolar bone showed significant decrease at the crest level and midroot level after retraction while the apical level showed significant increase(P＜0.05). The palatal vertical bone level also showed great loss (P＜0.05). CONCLUSIONS: After extensive retraction of the maxillary incisors, tilt movements are controlled with high traction hooks and microscrew implants. The decreases in palatal bone thickness are much more significant compared with the increases in labial bone thickness. Alveolar bone remodeling doesn't follow the movement of tooth, suggesting that the limitation of anterior teeth retraction should be taken into consideration.

[Treatment of chronic thromboembolic pulmonary hypertension through pulmonary thromboendarterectomy and the effect of deep hypothermia circulation arrest thereon].

OBJECTIVE: To evaluate the role of the pulmonary thromboendarterectomy (PTE) in the treatment of chronic thromboembolic pulmonary hypertension (CTEPH) and the effect of the deep hypothermia circulation arrest (DHCA) thereon. METHODS: The clinical data of 40 cases of CTEPH, 25 cases of central type and 15 cases of peripheral type, 29 males and 11 females, aged 46 +/- 12 (20 - 70), underwent PTH, 17 under deep hypothermia circulatory arrest (DHCA, Group A) and 23 not under DHCA (Group B), from February 1995 to October 2006. Follow-up was conducted for 41.8 +/- 36.4 months. RESULTS: In the peri-operative period, no patient died in Group A and there were 6 deaths in Group B. 9 suffered with residual pulmonary hypertension and 18 with severe pulmonary reflux injury. 72 h after the PTE, the pulmonary artery systolic pressure (PASP) was 58.3 +/- 30.7 mm Hg, significantly lower than that before PTS (91.4 +/- 38.4 mm Hg, P < 0.05), the pulmonary vascular resistance (PVR) was 357 +/- 278.7 dynes x sec(-1) x cm(-5), significantly lower than that before PTE (978 +/- 675.6 dynes x sec(-1) x cm(-5), P < 0.01); the partial pressure of oxygen in the arterial blood (PaO(2)) was 89.9 +/- 7 mm Hg, significantly higher than that before the PTE (54.5 +/- 7.7 mm Hg, P < 0.01),; and the arterial oxygen saturation (SaO(2)) was 96.5 +/- 1.8%, significantly higher than that before the PTE (90 +/- 4.3%, P < 0.05). During the follow-up there were 2 late deaths, and the cardiac function was graded as NYHA class I in 22 patients, as NYHA class II in 9 patients, and as NYHA class III in 1 patient. CONCLUSION: DHCA is a necessary and elementary condition for PTE, and it is a key factor in promoting the effect of PTE to treat the pulmonary reflux injury and residual pulmonary hypertension properly.