The transmission network and spatial-temporal distributions of COVID-19: A case study in Lanzhou, China.

Public emergencies exert substantial adverse effects on the socioeconomic development of cities. Investigating the transmission characteristics of COVID-19 can lead to evidence-based strategies for future pandemic intervention and prevention. Drawing upon primary COVID-19 data collected at both the street level and from individuals with confirmed cases in Lanzhou, China, our study examined the spatial-temporal distribution of the pandemic at a detailed level. First, we constructed transmission networks based on social relationships and spatial behavior to elucidate the actual natural transmission chain of COVID-19. We then analyze key information regarding pandemic spread, such as superspreaders, superspreading places, and peak hours. Furthermore, we constructed a space-time path model to deduce the spatial transmission trajectory of the pandemic while validating it with real activity trajectory data from confirmed cases. Finally, we investigate the impacts of pandemic prevention and control policies. The progression of the pandemic exhibits distinct stages and spatial clustering characteristics. People with complex social relationships and daily life trajectories and places with high pedestrian flow and commercial activity venues are prone to becoming superspreaders and superspreading places. The transmission path of the pandemic showed a pattern of short-distance and adjacent transmission, with most areas not affected. Early-stage control measures effectively disrupt transmission hotspots and impede the spatiotemporal trajectory of pandemic propagation, thereby enhancing the efficacy of prevention and control efforts. These findings elucidate the characteristics and transmission processes underlying pandemics, facilitating targeted and adaptable policy formulation to shape sustainable and resilient cities.

Hypersensitivity of lung vagal C fibers induced by acute intermittent hypoxia in rats: role of reactive oxygen species and TRPA1.

Obstructive sleep apnea, manifested by intermittent hypoxia and excess production of reactive oxygen species (ROS) in airways, is associated with hyperreactive airway diseases, but the mechanism remains unclear. Sensitization of lung vagal C fibers (LVCFs) contributes to the airway hypersensitivity. We investigated the mechanisms underlying the sensitization of LVCFs with acute intermittent hypoxia (AIH), by 10 episodes of exposure to 30 s of hypoxic air (0%, 5%, or 10% O(2)) followed by 30 s of room air in anesthetized, open-chest, and artificially ventilated rats. Reflex apneic response to intravenous capsaicin (an LVCF stimulant), as measured by phrenic nerve activity, was concentration dependently augmented by AIH. Similarly, reflex apneic response to intravenous α,ß-methylene-ATP (another LVCF stimulant) was augmented by AIH (0% O(2)). The reflex apnea evoked by these two stimulants was abolished by bilateral vagotomy, which suggests the involvement of lung vagal afferents. The AIH-augmented apneic response to these two stimulants was prevented by pretreatment with dimethylthiourea (a hydroxyl radical scavenger), N-acetyl-l-cysteine (an antioxidant) and HC-030031 [a transient receptor potential ankyrin 1 (TRPA1) receptor antagonist]. Consistently, electrophysiological study revealed the afferent responses of LVCFs to capsaicin or α,ß-methylene-ATP were augmented by AIH, and this sensitization of LVCFs was prevented by dimethylthiourea, N-acetyl-l-cysteine, and HC-030031. In contrast, AIH did not alter the afferent response of LVCFs to mechanical stimulation by lung hyperinflation. We concluded that AIH sensitizes LVCFs in rats, thus resulting in exaggerated airway reflexogenic responses to chemical stimulants, possibly by ROS action and activation of TRPA1 receptors.

PSMA7 inhibits the tumorigenicity of A549 human lung adenocarcinoma cells.

The gene for proteasome subunit alpha type-7 (PSMA7) is located in chromosomal 20q13.33, a region frequently amplified in tumor. In this study, we employed A549 human lung adenocarcinoma cells and showed that PSMA7 inhibits the proliferation, tumorigenicity and invasion of A549 cells in vitro. Moreover, both gain and loss of function studies demonstrated that PSMA7 modulates the tumorigenicity of A549 cells in a xenograft nude mice model. In conclusion, these results identify inhibitory effects associated with PSMA7 that affect the tumorigenicity of A549 cells, suggesting PSMA7 as a potential tumor biomarker.

[Association of the C3 gene polymorphisms with susceptibility to adult asthma].

OBJECTIVE: To investigate the association between single nucleotide polymorphisms (SNPs) of the complement component 3 gene (C3) and adult asthma of Hans in southern China. METHODS: A case-control study was performed. Four hundred and eighty-four adult asthma patients diagnosed in Nanfang Hospital and Affiliated Hospital of Guangdong Medical College, and 553 healthy subjects were collected from 2006 to 2010 for the study. MassARRAY-IPLEX and matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF-MS) techniques was used to determine the genotypes of the rs10402876 and rs366510 loci of C3 gene. RESULTS: Genotypes GG, GT and TT in the rs366510 locus, and genotypes GG, GT and TT in the rs10402876 locus were detected. A total of 98.94 percent of samples were genotyped. There were no significant differences in genotype frequencies (chi-square =0.346,P=0.841) and allele frequencies (chi-square =0.101,P=0.751) of rs10402876 between the two groups. However, genotype and allele frequencies of the rs366510 locus were significantly different (chi-square =9.759, P=0.008, Bonferroni correction, P=0.016; chi-square =5.294,P=0.021, Bonferroni correction, P=0.042, respectively). Compared with genotypes GG+GT, genotype TT of rs366510 significantly increased the risk of asthma, with the odds ratio of 1.471 (95% confidence interval 1.125-1.923). CONCLUSION: These results suggest that C3 gene could be associated with adult asthma of Han population in southern China.

[Association of single nucleotide polymorphisms of MD-1 gene with asthma in adults of Han Nationality in Southern China].

OBJECTIVE: To investigate the correlation between MD-1 gene single nucleotide polymorphism (SNP) and bronchial asthma in adults of the Han nationality in Southern China as well as their lung functions. METHODS: From 2006 to 2010, 332 adult asthmatic patients of the Han nationality diagnosed in Nanfang Hospital, Southern Medical University, and 276 healthy volunteers were recruited for the study. The SNPs of MD-1 gene loci rs2233128 and rs7740529 were genotyped by using MassARRAY-IPLEX technology and matrix-assisted laser desorption ionization time of flight mass spectrometry platform (MALDI-TOF-MS). In addition, the lung function of 105 cases initially diagnosed with asthma was measured. RESULTS: There was no significant difference in sex (χ(2) = 0.50, P = 0.824) and age (t = 0.930, P = 0.357) between the asthma and the healthy groups. Genotypes AG and GG were detected in MD-1 gene at rs2233128 locus and genotypes CC, CT and TT at rs7740529 locus in this Han population at Southern China. Genotyping success rate was 94.74%. The rs2233128 genotype distribution (χ(2) = 0.030, P = 0.863) and allele (χ(2) = 0.029, P = 0.865) showed no significant difference between the asthma and the control groups. However, the rs7740529 genotype distribution (χ(2) = 8.681, P = 0.013) and allele (χ(2) = 8.005, P = 0.005) were significantly different in the asthma group as compared to the control group. Compared with the TT genotype, the rs7740529 of the CC and CC + CT genotypes could dramatically increase the risk of asthma, the odds ratio (95% confidence interval) being 2.451 (1.299 - 4.9626) and 2.172 (1.173 - 4.020), respectively. In the 105 patients initially diagnosed with asthma, FVC% and FEV(1)% were significantly different among the 3 different genotypes (CC, CT and TT) of the rs7740529 locus (F = 18.405, P = 0.000 and F = 25.700, P = 0.000). The percentages of predicted value of FVC and FEV(1) were decreased [(65 ± 12)%, (64 ± 11)%] in the CC genotype as compared to the TT genotypes [(86 ± 9)%, (88 ± 8)%], P < 0.05. There was no significant difference of genotype distribution of rs7740529 in different grades of severity of newly diagnosed asthma (χ(2) = 5.017, P = 0.081). CONCLUSIONS: MD-1 may be a susceptible gene for adult asthma in a Southern Han population in China. Genotype distribution of rs7740529 locus in newly diagnosed patients with asthma may be related to their lung function changes.

ISO-1, a macrophage migration inhibitory factor antagonist, inhibits airway remodeling in a murine model of chronic asthma.

Airway remodeling is the process of airway structural change that occurs in patients with asthma in response to persistent inflammation and leads to increasing disease severity. Drugs that decrease this persistent inflammation play a crucial role in managing asthma episodes. Mice sensitized (by intraperitoneal administration) and then challenged (by inhalation) with ovalbumin (OVA) develop an extensive eosinophilic inflammatory response, goblet cell hyperplasia, collagen deposition, airway smooth muscle thickening, and airway wall area increase, similar to pathologies observed in human asthma. We used OVA-sensitized/challenged mice as a murine model of chronic allergic airway inflammation with subepithelial fibrosis (i.e., asthma). In this OVA mouse model, mRNA and protein of macrophage migration inhibitory factor (MIF) are upregulated, a response similar to what has been observed in the pathogenesis of acute inflammation in human asthma. We hypothesized that MIF induces transforming growth factor-ß1 (TGF-ß1) synthesis, which has been shown to play an important role in asthma and airway remodeling. To explore the role of MIF in the development of airway remodeling, we evaluated the effects of an MIF small-molecule antagonist, (S,R)3-(4-hy-droxyphenyl)-4,5-dihydro-5-isoxazole acetic acid methyl ester (ISO-1), on pathologies associated with the airway-remodeling process in the OVA mouse model. We found that administration of ISO-1 significantly mitigated all symptoms caused by OVA treatment. In addition, the treatment of OVA-sensitized mice with the MIF antagonist ISO-1 significantly reduced TGF-ß1 mRNA levels in pulmonary tissue and its protein level in bronchial alveolar lavage fluid supernatants. We believe the repression of MIF in the ISO-1 treatment group led to the significant suppression observed in the inflammatory responses associated with the allergen-induced lung inflammation and fibrosis in our murine asthma (OVA) model. Our results implicate a possible function of MIF in the pathogenesis of chronic asthma and suggest that MIF might be an important therapeutic target for airway remodeling.

3,3'-Dibromo-1,1'-[(propane-1,3-diyl-dioxy)-bis(nitrilo-methyl-idyne)]dibenzene.

The mol-ecule of the title compound, C(17)H(16)Br(2)N(2)O(2), lies on a twofold axis that passes through the middle atom of the three-atom trimethyl-ene unit. The two aromatic rings are aligned at an angle of 76.02 (4)°.

3,3'-Dibromo-1,1'-[ethyl-enedioxy-bis(nitrilo-methyl-idyne)]dibenzene.

In the centrosymmetric title compound, C(16)H(14)Br(2)N(2)O(2), the intra-molecular interplanar distance between the parallel benzene rings is 1.305 (3) Å, while the inter-molecular interplanar distance (between neighbouring mol-ecules) is 3.463 (3) Å, exhibiting obvious strong inter-molecular π-π stacking inter-actions.

[Association of polymorphism of Met764Thr locus allele in ADAM33 gene with bronchial asthma and lung function of asthmatic subjects].

OBJECTIVE: To analyze the association of the polymorphism of Met764Thr with bronchial asthma and lung function of asthmatic subjects of Han nationality in Southern China. METHODS: In 164 unrelated patients with asthma and 112 unrelated healthy controls, polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing were used to determine polymorphism of Met764Thr locus allele in ADAM33 gene. The clinical indexes associated with lung function (FVC%, FEV(1)%) were compared among the three genotypes (Met764/Met764, Met764/Thr764, Thr764/Thr764) in asthmatic subjects. RESULTS: No significant difference was found in the allele (Met764, Thr 764) frequency among populations in UK, US, German, Korean, and Southern China (chi(2) = 6.77, P > 0.05). The frequencies of the genotypes (Met764/Met764, Met764/Thr764, Thr764/Thr764) were respectively 78.7% (129), 18.3% (30), 3.0% (5) in 164 asthmatic subjects and respectively 91.1% (102), 6.3% (7), 2.7% (3) in the 112 controls. There was a significant difference in the distributions of the genotypes (Met764/Met764, Met764/Thr764, Thr764/Thr764) between asthmatic subjects and controls (chi(2) = 8.46, P < 0.05). The frequencies of alleles (Thr764) were respectively 12.2% in the asthmatic subjects and 5.8% in the controls. Significant difference was observed in the allele (Met764, Thr 764) frequency between the two groups (chi(2) = 6.27, P < 0.05). The presence of Thr764 allele of ADAM33 gene was found to be a greater risk factor in asthmatic subjects than in controls. The odds ratio (OR) of Met764/Thr764 and Met764/Thr764 + Thr764/Thr764 were 3.389 (1.430 - 8.030), 2.767 (1.308 - 5.854), respectively. When compared with Met764/Met764 genotype, all P < 0.05. There was a significant decrease in the FVC% and FEV(1)% levels of Met764/Thr764, Thr764/Thr764 and Met764/Met764 genotype. CONCLUSIONS: These results suggest that Met764Thr locus genetic polymorphism is associated with susceptibility of asthma and clinical indexes of lung function of asthmatic subjects of Han nationality in Southern China.

[Effects of dexamethasone on the expression of muscarinic receptor mRNA in asthmatic guinea pig airway smooth muscle and eosinophil infiltration in bronchoalveolar lavage fluid].

OBJECTIVE: To investigate the effect of dexamethasone on the expression of muscarinic receptor (MR) mRNA in smooth muscle and infiltration of eosinophils (Eos) in the airway of asthmatic guinea pigs. METHODS: Thirty healthy guinea pigs were randomized into 3 equal groups, the control group, asthmatic group and dexamethasone therapy group. Asthma was induced in the latter 2 groups with the asthma-inducing agents and received treatments as indicated. Bronchial alveolar lavage fluid(BALF) were collected subsequently from the guinea pigs for examining the total cell number and cell classification, and histopathologic examination of the lung tissue was performed. Semi-quantitative analysis with reverse transcriptional- polymerase chain reaction (RT-PCR) was performed for M(2) and M(3) receptor mRNA in airway smooth muscle. RESULTS: Compared with the control and the asthmatic group, the number of Eos in the BALF of dexamethasone therapy group was significantly lower (P<0.01). In spite of the presence of hyperemia and edema in the lung tissues of the dexamethasone therapy group, Eos infiltration was less severe than that in the asthmatic group. As found by RT-PCR, the quantity of M(2) receptor mRNA in the airway smooth muscle of the dexamethasone therapy group was significantly higher than those in both the control and asthmatic groups (P<0.01), and the quantity of M(3) receptor mRNA in the airway smooth muscle of dexamethasone therapy group was significantly higher than that in the asthmatic group, but did not significantly differ from that in the control group. The quantities of M(2) and M(3) receptor mRNAs in the control group were both significantly higher than that in asthmatic group (P<0.01). CONCLUSION: The expression of M(2) receptor is increased in antigen- challenged guinea pigs, and that of M(3) receptor decreased. Dexamethasone can treat asthma by inhibiting inflammatory action involving Eos infiltration, regulating the expressions of M(2) and M(3) receptors and restoring the function of M(2) receptor.

[Diagnosis of simple endobronchial tuberculosis by fiberobronchoscopy].

OBJECTIVE: To assess the efficacy of fibrobronchoscopy in diagnosis of simple endobronchial tuberculosis. METHOD: Biopsy, brush biopsy and bronchoalvelar lavage fluid examination were performed in 92 patients with simple endobronchial tuberculosis using an electronic fibrobronchoscope. RESULTS: Simple endobronchial tuberculosis commonly occurred in young people (25-35 years of age), often developed in the superior lobe apicoposterior segment, middle lobe (ligule) and superior branch of the inferior lobe of the left lung. Under fibrobronchoscope, congested edema, caseous necrosis and ulcer granulation were observed in patients with simple endobronchial tuberculosis. The successful detection rates for biopsy, brush biopsy and bronchoalvelar lavage liquid examination were 81.5%, 30.4% and 20.7%, respectively. CONCLUSION: Fiberobronchoscopy is effective for diagnosis of simple endobronchial tuberculosis.

[Effects of Huobahuagen tablet on the expression of interleukin-3 receptor mRNA in asthmatic guinea pig bronchoalveolar lavage fluid and eosinophil infiltration].

OBJECTIVE: To investigate the effects of Huobahuagen tablet on the expression of interleukin-3 (IL-3) receptor mRNA in bronchoalveolar lavage fluid (BALF) and infiltration of eosinophil (Eos) in the airway of asthmatic guinea pigs. METHODS: Thirty-two healthy guinea pigs were randomized into 4 equal groups, the control group, asthmatic group, dexamethasone therapy group and Huobahuagen tablet therapy group. Asthma was induced in the latter 3 groups which were challenged with the asthma-inducing agents and at the same time received treatments as indicated. BALF were collected subsequently from the guinea pigs for examining the total cell number and cell classification, and histopathologic examination of the lung tissue was performed. Semi-quantitative analysis with reverse transcriptional-polymerase chain reaction (RT-PCR) of IL-3 receptor mRNA in the BALF was performed. RESULTS: Compared with the control and the asthmatic group, the number of Eos in the BALF of Huobahuagen tablet therapy group was significantly lower (P<0.05 and P<0.01, respectively). In spite of the presence of hyperemia and edema in the lung tissues of the Huobahuagen tablet therapy group, Eos infiltration was less severe than that in the asthmatic group. As found by RT-PCR, the quantity of IL-3 receptor mRNA in the BALF of the Huobahuagen tablet therapy group did not significantly differ from that in the dexamethasone therapy group, but was significantly higher than that in both the control and asthmatic group (P<0.01). CONCLUSION: Huobahuagen tablet can significantly lower the number of Eos in the airway of asthmatic guinea pigs, a finding that may potentially serve as the elementary theoretical basis for clinical therapy of asthma.

[Isolation of rat tracheal smooth muscle cells and electrophysiological examination of the L- type calcium channel].

OBJECTIVE: To establish a method for acute enzymatic isolation of rat tracheal smooth muscle cells (TSMCs) and study the electrophysiological properties of the L-type calcium channel of the cells. METHODS: Single rat TSMC was isolated by means of pronase E, followed by recording the electric currents in the single calcium channel using patch-clamp technique with cell attached configuration. RESULTS: Large amount of viable TSMCs were isolated through this method, characterized by normal cell morphology and easy detection of the L-type calcium channel activity in the cells. CONCLUSION: This method is relatively simple for high-yield isolation of TSMCs with normal morphology.

Emergency management of respiratory failure by endotracheal intubation through the nose under the guidance of portable bedside fibrobronchoscope.

OBJECTIVE: To investigate the value of portable fibrobronchoscope in the management of respiratory failure by endotracheal intubation through the nose. METHODS: Fifty-eight patients with acute or chronic respiratory failure received mechanical ventilation by endotracheal intubation through the nose under the guidance of portable fibrobronchoscope. RESULTS: Intubation was successfully performed in all the patients in a single attempt (which took 30 min to 5 min) without interruption of autonomous breathing or incurring laryngospasm or cardiac arrest. After mechanical ventilation for 30 min, conspicuous improvement of respiratory failure was observed in all the cases. CONCLUSION: With convenient and easy manipulation, portable fibrobronchoscope provides quick and accurate guidance for endotracheal intubation through the nose in the emergency management of respiratory failure.

[Effect of dexamethasone on expressions of TWEAK and Fn14 in the lung of asthmatic mice].

AIM: To investigate the effect of dexamethasone (Dex) on the expressions of TNF-like weak inducer of apoptosis (TWEAK) and fibroblast growth factor-inducible immediate-early response protein 14 (Fn14) in the lung of asthmatic mice. METHODS: Ovalbumin (OVA) was used to induce asthma in BALB/c mice. Thirty-six female mice were randomly divided into control group (n=12), asthmatic group (n=12) and Dex treated group (n=12). The airway inflammation was evaluated by HE staining. The expressions of TWEAK and Fn14 at mRNA and protein levels were detected by RT-PCR and immunohistochemistry, respectively. RESULTS: Both mRNA and protein levels of TWEAK and Fn14 in the asthmatic model group were significantly higher than those of control group (P<0.01), and both mRNA and protein levels of TWEAK and Fn14 in the Dex treated group were significantly lower than those of asthmatic group (P<0.01). CONCLUSION: Dex can reduce the airway inflammation through inhibiting the expressions of TWEAK and Fn14.

[Construction of recombinant eukaryotic expression vector pDsRed1-C3/XAPC7 and cellular localization of XAPC7 protein in different cell lines].

AIM: To construct the recombinant eukaryotic expression vector pDsRed1-C3/XAPC7 and to investigate the cellular localization of XAPC7 protein in 786-O and 293T and Chang liver cell lines. METHODS: The cDNA of XAPC7 was amplified from HBE135-E6E7 cell line by RT-PCR method. The aim gene fragment XAPC7 from pMD18-T/XAPC7 was subcloned into eukaryotic expression vector pDsRed1-C3. The recombinant plasmid pDsRed1-C3/XAPC7 was identificated by BamH I/Xho I double digestion and sequence analysis, and then transfected into786-O and 293T and Chang liver cell lines by lipofectamine 2000. The expression and cellular localization of XAPC7 protein were detected by fluorescence microscope. RESULTS: The construction of the recombinant plasmid pDsRed1-C3/XAPC7 was proved successfully by restriction enzyme digestion analysis and DNA sequencing. Red fluorescent protein pDsRed1-C3/XAPC7 was distributed granularly in transfected cell lines. Our researches showed that XAPC7 protein was mainly expressed in the cytoplasm of 786-O cell line, rare in its nucleus, evenly distributed in the cytoplasm and nucleus of 293T cell line, and mainly located in the cytoplasm of Chang liver cell line, few in its nucleus. CONCLUSION: The eukaryotic expression plasmid pDsRed1-C3/XAPC7 has been successfully constructed and expressed in the 786-O and 293T and Chang liver cell lines, but there was obvious difference in different cell lines. Our researches will help further studies on the function of human gene XAPC7.

[Alteration of PTEN gene expression affects the migration of human airway smooth muscle cells in vitro].

OBJECTIVE: To investigate the changes in human airway smooth muscle cell (HASMC) migration and related signaling pathway after interference with PTEN gene expression. METHOD: HASMCs were infected with an adenovirus vector and RNA interference vector of human PTEN gene to establish the cell model with PTEN gene over-expression (Ad-GFP-PTEN-HASMC) and one with PTEN gene silencing (Ad-shPTEN-HASMC), using Ad-GFP-infected and a blank cells as the negative controls and LY294002 as the positive control. Fluorescence microscopy and flow cytometric analysis were used to evaluate the transfection efficiency, and Western blotting was performed to examine the expression of PTEN and the activation of AKT and ERK1/2 signal pathway. Transwell assay and wound healing assay were used to assess the migration of HASMCs. RESULTS: The adenovirus over-expression vector and RNA interference vector significantly affected the expression of human PTEN gene. Up-regulation of PTEN gene resulted in a slow-down of the HASMC migration, an inhibition of PI3K/AKT signal pathway at the protein level but no changes in Ras-Raf-MEK1/2-ERK1/2 signal pathway. Down-regulated PTEN gene expression, however, was not associated with an enhancement of HASMC migration, but activated PI3K/AKT signal pathway and inhibited Ras-Raf-MEK1/2-ERK1/2 signal pathway. CONCLUSION: Upregulation of PTEN gene can effectively inhibit airway smooth muscle cell migration, the effect of which is probably mediated by the PI3K/AKT pathway.

[Change of IL-22R1 expression in human airway smooth muscle cells in response to different stimulating agents].

OBJECTIVE: To explore the effects of serum of asthmatic patients, dexamethasone, interleukin-4 (IL-4), interferon-gamma (IFN-γ) and transforming growth factor-ß (TGF-ß) on the expression of interleukin-22 receptor 1 (IL-22R1) mRNA and protein in HASMCs in vitro. METHODS: IL-22R1 mRNA and protein expressions in HASMCs treated with different stimulating agents were measured by real-time PCR and Western blotting, respectively. RESULTS: IL-22R1 mRNA and protein expressions in HASMCs were significantly increased after stimulation by serum from asthmatic patients, but decreased after co-stimulation with dexamethasone. IL-22R1 mRNA and protein expressions in the cells both increased after stimulation by IL-4, IFN-γ and TGF-ß. CONCLUSION: IL-22R1 in HASMCs might be involved in the pathogenesis of asthma, and the therapeutic effect of dexamethasone on asthma is mediated, at least partially, by IL-22R1. The effects of IFN-γ, IL-4, and TGF-ß on asthma may also be attributed to their actions on HASMCs.

The generation of the endothelial specific cdc42-deficient mice and the effect of cdc42 deletion on the angiogenesis and embryonic development.

BACKGROUND: High microvascular permeability plays an essential role in pathological process of multiple diseases such as septic shock, acute lung injury and acute respiratory distress syndrome, and burns. Inhibiting hyperpermeability is significant for controlling these conditions. Cdc42, as a main member of the small Rho GTPase family, plays a critical role in controlling and regulating the endothelial junctional permeability. We aimed to generate and identify endothelial specific cdc42-deficient mice by the Cre/loxp recombination approach, for examination in an animal model of the contribution of the cdc42 gene in the microvascular barrier function. METHODS: We crossed cdc42(Flox/Flox) mice with mice expressing endothelial cell-specific Cre recombinase, and the offspring with the genotype cdc42(Flox/+)Tie2Cre(+/-) were back-crossed with the cdc42(Flox/Flox) mice. The cdc42(Flox/Flox)Tie2Cre(+/-) mice in the F2 generation were the target mice. If the cdc42 deficient mice did not survive, we would observe the cdc42 deficient mice embryos, and compare them with wild-type mice embryos. RESULTS: Cdc42(flox/+)Cre(+/-) mice were mated with the cdc42(Flox/Flox) mice and among the living offspring there were no cdc42(Flox/Flox)Cre(+/-) target mice. We found the endothelial special cdc42 deficient embryos at the E7.5-E16.5 stage. We observed that cdc42 deficient embryos were much smaller, had fewer vessels and were a little more swollen compared with the wild-type embryos. CONCLUSIONS: Endothelial specific knockout of cdc42 caused embryonic lethality and the mice did not survive to birth. The target embryos were much smaller, had fewer vessels and were a little more swollen compared with the wild-type embryos. These results demonstrated that the cdc42 plays an important role in development of embryos and in development of microvessels as well as microvascular permeability.

[Application of flexirigid thoracoscopy in the diagnosis of pleural disease with unknown etiology].

OBJECTIVE: To investigate the diagnostic accuracy of flexirigid thoracoscopy for pleural diseases and the patients' compliance. METHODS: Forty-seven patients with pleural effusion and thickening of unknown etiology underwent examinations with flexirigid thoracoscopy with subsequent pathological examination, and the diagnostic accuracy and the patients' compliance were observed. RESULTS: Thoracoscopy identified lesions in the pleural and/or diaphragm in 42 patients and no lesions in 5 patients. Malignancy was confirmed in 21 (44.7%), tuberculosis in 17 (36.2%), idiopathic hypereosinophilic syndrome in 1 (2.1%), nocardiasis in 1 (2.1%), constrictive pericarditis in 1 (2.1%), chronic empyema in 2 (4.3%), splenic artery embolization in 1 (2.1%), and negative result in 3 (6.4%) of the cases. The diagnostic accuracy rate of flexirigid thoracoscopy reached 93.6%, and no serious complications in relation to the examination was found. CONCLUSION: Flexirigid thoracoscopy is efficient and relatively safe for diagnosis of pleural diseases with or without hydrothorax.