First-generation epithelial growth factor receptor tyrosine kinase inhibitor in the first-line treatment of advanced non-small cell lung cancer: 166 cases analysis of progression-free survival / 中国实用内科杂志

OBJECTIVE: Explore the clinical benefit factors of progression-free survival(PFS) in sensitive epithelial growth factor receptor(EGFR) gene mutated advanced non-small cell lung cancer patients treated with first-generation of EGFR tyrosine kinase inhibitor(TKI).METHODS: The clinical data of 166 patients who received first-line treatment with first-generation EGFR-TKI were retrospectively collected in 2016-2017 from Xiangya Hospital, Central South University. The patients were divided into three groups: PFS≤3 m,3 m

Systemic disseminated Mycobacterium fortuitum infection:one case report and literature review / 中国感染控制杂志

Objective To explore the clinical characteristics of systemic disseminated infection caused by Mycobacterium fortuitum (M.fortuitum), and improve the diagnostic rate and understanding of the disease.Methods One case of systemic disseminated M.fortuituminfection was reported, and analyzed in combination with relevant literatures.Results Patient was with multiple systemic involvement (including lung, lymph node, skin, joint), lymph node tissue culture was positive for M.fortuitum, patient was given clarithromycin+levofloxacin+linezolid for treatment, disease was remitted.Conclusion Systemic disseminated M.fortuituminfection is rare, and patient with GATA2 deletion and IFN-γautoantibody may be a potential mechanism, diagnosis is mainly based on pathological morphology and microbiological detection, but positive rate is low, diagnosis is difficult.

Severe pneumonia associated with sepsis-induced myopathy: one case report and literature review / 中国感染控制杂志

Clinical data of one patient with sepsis-induced myopathy (SIM) who was successfully treated were reviewed retrospectively, analysis was conducted combined with the relevant literatures. Patient was a middle-aged woman without underlying disease, she was admitted to hospital because of fever, cough, chest tightness and shortness of breath, during the treatment period, type II respiratory failure occurred repeatedly, and it was difficult in withdrawing respirator, patient was finally diagnosed with SIM. After anti-infective treatment and rehabilitation training, she was successfully withdrawn respirator, muscle strength was recovered. This case suggests that SIM can be completely cured through early identification, neuromuscular nutrition therapy, graded rehabilitation training and lung rehabilitation therapy.

Effects of Glucocorticoid-Induced Transcript 1 Gene Deficiency on Glucocorticoid Activation in Asthmatic Mice / 中华医学杂志(英文版)

Background@#Glucocorticoid (GC) is the first-line therapy for asthma, but some asthmatics are insensitive to it. Glucocorticoid-induced transcript 1 gene (GLCCI1) is reported to be associated with GCs efficiency in asthmatics, while its exact mechanism remains unknown.@*Methods@#A total of 30 asthmatic patients received fluticasone propionate for 12 weeks. Forced expiratory volume in 1 s (FEV) and GLCCI1 expression were detected. Asthma model was constructed in wild-type and GLCCI1 knockout (GLCCI1) mice. Glucocorticoid receptor (GR) and mitogen-activated protein kinase phosphatase 1 (MKP-1) expression were detected by polymerase chain reaction and Western blotting (WB). The phosphorylation of p38 mitogen-activated protein kinase (MAPK) was also detected by WB.@*Results@#In asthmatic patients, the change of FEV was well positively correlated with change of GLCCI1 expression (r = 0.430, P = 0.022). In animal experiment, GR and MKP-1 mRNA levels were significantly decreased in asthmatic mice than in control mice (wild-type: GR: 0.769 vs. 1.000, P = 0.022; MKP-1: 0.493 vs. 1.000, P < 0.001. GLCCI1: GR: 0.629 vs. 1.645, P < 0.001; MKP-1: 0.377 vs. 2.146, P < 0.001). Hydroprednisone treatment significantly increased GR and MKP-1 mRNA expression levels than in asthmatic groups; however, GLCCI1 asthmatic mice had less improvement (wild-type: GR: 1.517 vs. 0.769, P = 0.023; MKP-1: 1.036 vs. 0.493, P = 0.003. GLCCI1: GR: 0.846 vs. 0.629, P = 0.116; MKP-1: 0.475 vs. 0.377, P = 0.388). GLCCI1 asthmatic mice had more obvious phosphorylation of p38 MAPK than wild-type asthmatic mice (9.060 vs. 3.484, P < 0.001). It was still higher even though after hydroprednisone treatment (6.440 vs. 2.630, P < 0.001).@*Conclusions@#GLCCI1 deficiency in asthmatic mice inhibits the activation of GR and MKP-1 and leads to more obvious phosphorylation of p38 MAPK, leading to a decremental sensitivity to GCs.@*Trial Registration@#ChiCTR.org.cn, ChiCTR-RCC-13003634; http://www.chictr.org.cn/showproj.aspx?proj=5926.

Platelet Distribution Width on Admission Predicts In-Stent Restenosis in Patients with Coronary Artery Disease and Type 2 Diabetes Mellitus Treated with Percutaneous Coronary Intervention / 中华医学杂志(英文版)

<p><b>Background</b>It is known that there is a definite association between platelet distribution width (PDW) and poor prognosis in patients with coronary artery disease (CAD) and type 2 diabetes mellitus (T2DM). However, there are no data available regarding the prognostic significance of PDW for in-stent restenosis (ISR) in patients with CAD and T2DM. We aimed to determine the value of PDW on admission that predicted ISR in patients with CAD and T2DM.</p><p><b>Methods</b>Between January 2012 and December 2013, a total of 5232 consecutive patients diagnosed with CAD and T2DM undergoing percutaneous coronary intervention were admitted. Three years of retrospective follow-up was undertaken. A total of 438 patients with second angiography operations were included. ISR was defined as ≥50% luminal stenosis of the stent or peri-stent segments. Continuous data were presented as the mean ± standard deviation or median (P, P) and were compared by one-way analysis of variance or Kruskal-Wallis H-test. Categorical variables were presented as percentages and were compared by Chi-square test or Fisher's exact test. The association between PDW and ISR was calculated by logistic regression analysis. A two-sided value of P < 0.05 was considered statistically significant. Statistical analyses were performed by SPSS version 22.0 for windows.</p><p><b>Results</b>Fifty-nine patients with ISR, accounting for 13.5% of the total, were included. ISR was significantly more frequent in patients with higher PDW quartiles compared with lower quartiles. We observed that PDW had a strong relationship with mean platelet volume (r = 0.647, 95% confidence interval [CI]: 0.535-0.750, P < 0.0001). The receiver-operating characteristic curves showed that the PDW cutoff value for predicting ISR rate was 13.65 fl with sensitivity of 59.3% and specificity of 72.4% (area under curve [AUC] = 0.701, 95% CI: 0.625-0.777, P < 0.001). Multivariate analysis showed that the risk of ISR increased approximately 30% when PDW increased one unit (odds ratio [OR]: 1.289, 95% CI: 1.110-1.498, P = 0.001). Patients with higher PDW, defined as more than 13.65 fl, had a 4-fold higher risk of ISR compared with lower PDW (OR: 4.241, 95% CI: 1.879-9.572, P = 0.001). Furthermore, when patients were divided by PDW quartiles values, PDW was able to predict ISR (Q2: OR = 0.762, 95% CI: 0.189-3.062, P = 0.762; Q3: OR = 2.782, 95% CI: 0.865-8.954, P = 0.086; and Q4: OR = 3.849, 95% CI: 1.225-12.097, P = 0.021, respectively; P for trend <0.0001).</p><p><b>Conclusion</b>PDW is an independent predictor of ISR in patients with CAD and T2DM.</p>

Human decorin regulates proliferation and migration of human lung cancer A549 cells / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Decorin is a small leucine-rich proteoglycan and it plays an important role in regulation of cell growth and migration in various tumor cell lines. Decorin was found down-regulated in non-small cell lung cancer tissue and may be involved in regulation of lung cancer development.</p><p><b>METHODS</b>In this study, lentivirus-mediated RNA interference and over expression were employed to change the expression levels of decorin in lung cancer A549 cells. We tested the cell cycle of A549 cells and the expression of transforming growth factor (TGF)-β, cyclin D1, epidermal growth factor receptor (EGFR), P53, and P21.</p><p><b>RESULTS</b>We found that up-regulation of decorin could inhibit proliferation, block cell cycle at G1 and decrease invasive activity of A549 cells. Moreover, we also show that up-regulation of decorin induced significant decreases of TGF-β1, cyclin D1 expression, phosphorylation of EGFR, and increases of P53 and P21 expression. Opposite results were observed in A549 cells with down-regulation of decorin.</p><p><b>CONCLUSION</b>Our results suggest that decorin is a key regulator involved in proliferation and migration of A549 cells.</p>

Interferon regulatory factor-1 mediates the release of high mobility group box-1 in endotoxemia in mice / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The extracellular release of the danger signal high mobility group box-1 (HMGB1) has been implicated in the pathogenesis and outcomes of sepsis. Understanding the mechanisms responsible for HMGB1 release can lead to the identification of targets that may inhibit this process. The transcription factor interferon regulatory factor-1 (IRF-1) is an important mediator of innate immune responses and has been shown to participate in mortality associated with endotoxemia; however, its role in mediating the release of HMGB1 in these settings is unknown.</p><p><b>METHODS</b>Male IRF-1 knockout (KO) and age matched C57BL/6 wild type (WT) mice were given intraperitoneal (IP) injections of lipopolysaccharide (LPS). In some experiments, 96 hours survival rates were observed. In other experiments, mice were sacrificed 12 hours after LPS administration and sera were harvested for future analysis. In in vitro study, RAW 264.7 murine monocyte/macrophage-like cells or primary peritoneal macrophage obtained from IRF-1 KO and WT mice were cultured for LPS mediated HMGB1 release analysis. And the mechanism for HMGB1 release was analyzed by immune-precipitation.</p><p><b>RESULTS</b>IRF-1 KO mice experienced less mortality, and released less systemic HMGB1 compared to their WT counterparts. Exogenous administration of recombinant HMGB1 to IRF-1 KO mice returned the mortality rate to that seen originally in IRF-1 WT mice. Using cultures of peritoneal macrophages or RAW264.7 cells, in vitro LPS stimulation induced the release of HMGB1 in an IRF-1 dependent manner. And the janus associated kinase (JAK)-IRF-1 signal pathway appeared to participate in the signaling mechanisms of LPS-induced HMGB1 release by mediating acetylation of HMGB1.</p><p><b>CONCLUSION</b>IRF-1 plays a role in LPS induced release of HMGB1 and therefore may serve as a novel target in sepsis.</p>

Treatment with EGCG in NSCLC leads to decreasing interstitial fluid pressure and hypoxia to improve chemotherapy efficacy through rebalance of Ang-1 and Ang-2 / 中国天然药物

AIM@#Microvasculature and microenvironment play important roles in proliferation, invasion, metastasis and prognosis in non-small cell lung cancer (NSCLC), which might be altered by many anti-angiogenic drugs. Epigallocatechin-3-gallate (EGCG), a natural anti-angiogenesis agent refined from green tea, was defined to have multiple effects on angiogenesis factors, such as endothelial growth factor (VEGF), platelet-derived growth factor (PDGF) and angiopoietins (ANGs). Hypothesizing that EGCG might regulate microvasculature and microenvironment in NSCLC, the effects of EGCG on microvessel density (MVD), expression of Ang-1 and Ang-2, interstitial fluid pressure (IFP), tumor hypoxia, and chemotherapy sensitivity were examined.@*METHODS AND RESULTS@#EGCG treatment of A549 cells in mice bearing xenografts in vivo led to a significant decrease of MVD detected by CD31, and of Ang-2 expression detected by quantum dots double-label immunofluorescence assessment, while Ang-1 decreased with no significance. Decreased IFP was measured by the Wink-in-needle method, while hypoxia was assessed by polarographic electrode and pimonidazole (PIMO) immunohistochemistry. Assuming that these changes would increase response to chemotherapy, tumor growth studies were p[erformed in nude mice with xenografts, which were then treated with EGCG and the chemotherapeutic agent cisplatin. EGCG therapy combined with cisplatin led to synergistic inhibition of tumor growth, compared with administration of each treatment separately (P < 0.001). According to linear regression analysis, IFP was positively correlated with PIMO staining (R(2) = 0.618, P = 0.002), Ang-2 was correlated with MVD (R(2) = 0.423, P = 0.022), IFP (R(2) = 0.663, P = 0.01) and PIMO staining (R(2) = 0.694, P = 0.01).@*CONCLUSION@#IFP and delivery of oxygen might be improved by rebalance of Ang-1/Ang-2 under the treatment of EGCG in NSCLC, which also acts as a sensitizer of chemotherapy. These studies established a new mechanism for using EGCG as an adjuvant chemotherapy agent through modifying microvasculature and microenvironment.

Inhibition of nuclear factor-κB activity enhanced chemosensitivity to cisplatin in human lung adeno-carcinoma A549 cells under chemical hypoxia conditions / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Tumor hypoxia, one of the features of solid tumors, is associated with chemo-resistance. Recently, nuclear factor-κB (NF-κB) was found to be activated during hypoxia. However, the impact of NF-κB activation on chemo-resistance during hypoxia remains unknown.</p><p><b>METHODS</b>Human lung adenocarcinoma A549 cells were transfected with NF-κB p65siRNA and treated with cobalt chloride (CoCl2) to mimic hypoxia in the presence or absence of cisplatin. NF-κB expression was measured by Western blotting, immune-fluorescence and real-time PCR. Hypoxia-inducible factor-1α (HIF-1α) and Bcl-2 expression were determined by Western blotting. Cell apoptosis and survival with half-maximum inhibitory concentration (IC50) of cisplatin were determined by Annexin V-FITC/PI and 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT), respectively.</p><p><b>RESULTS</b>Exposure of A549 cells to CoCl2 increased nuclear HIF-1a protein expression, and enhanced NF-κB p65 protein nuclear accumulation (the mark of NF-κB activation) in a time and dose dependant manner. CoCl2 did not promote apoptosis in A549 cells; on the contrary, it reduced cisplatin-induced apoptosis and increased the IC50 of cisplatin. However, when we inhibited CoCl2-induced activation of NF-κB through NF-κB p65siRNA, cisplatin-induced apoptosis was increased and IC50 of cisplatin was reduced to levels similar to those in control cells. Meanwhile, CoCl2-induced Bcl-2 overexpression was down-regulated in the presence of cisplatin when NF-κB activity was inhibited.</p><p><b>CONCLUSION</b>Up-regulating Bcl-2 might be involved in NF-κB activation induced resistance to cisplatin in A549 cells under CoCl2-induced chemical hypoxia.</p>

Preliminary molecular epidemiology of the Staphylococcus aureus in lower respiratory tract infections: a multicenter study in China / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Staphylococcus aureus (S. aureus) remains as an important microbial pathogen resulting in community and nosocomial acquired infections with significant morbidity and mortality. Few reports for S. aureus in lower respiratory tract infections (LRTIs) have been documented. The aim of this study was to explore the molecular epidemiology of S. aureus in LRTIs in China.</p><p><b>METHODS</b>A multicenter study of the molecular epidemiology of S. aureus in LRTIs was conducted in 21 hospitals in Beijing, Shanghai and twelve other provinces from November 2007 to February 2009. All the collected S. aureus strains were classified as minimum inhibitory concentration (MIC), mecA gene, virulence genes Panton-Valentine Leukocidin (PVL) and γ-hemolysin (hlg), staphylococcal cassette chromosome mec (SCCmec) type, agr type, and Multilocus Sequence Typing (MLST).</p><p><b>RESULTS</b>Totally, nine methicillin-sensitive S. aureus (MSSA) and 29 methicillin-resistant S. aureus (MRSA) strains were isolated after culture from a total of 2829 sputums or bronchoalveolar lavages. The majority of MRSA strains (22/29) had a MIC value of ≥ 512 µg/ml for cefoxitin. The mecA gene acting as the conservative gene was carried by all MRSA strains. PVL genes were detected in only one S. aureus strain (2.63%, 1/38). The hlg gene was detected in almost the all S. aureus (100% in MSSA and 96.56% in MRSA strains). About 75.86% of MRSA strains carried SCCmec III. Agr type 1 was predominant (78.95%) among the identified three agr types (agr types 1, 2, and 3). Totally, ten sequence type (ST) of S. aureus strains were detected. A new sequence type (ST1445) was found besides confirming ST239 as the major sequence type (60.53%). A dendrogram generated from our own MLST database showed all the bootstrap values ≤ 50%.</p><p><b>CONCLUSION</b>Our preliminary epidemiology data show SCCmec III, ST239 and agr type 1 of S. aureus as the predominant strains in LRTIs in Mainland of China.</p>

Relationship between multi-slice spiral CT pulmonary perfusion imaging and the expression of EphB4 and ephrinB2 in non-small cell lung cancer / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the role of the expression of ephrinB2 and EphB4 in non-small cell lung cancer (NSCLC), and their relationship with multi-slice spiral CT pulmonary perfusion imaging.</p><p><b>METHODS</b>Thirty-one nodules with pathologically proven NSCLC underwent CT perfusion scan. The perfusion parameters including blood flow (BF), blood volume (BV), peak enhancement image (PEI) were collected. The expression of ephrinB2 and EphB4 in tumor cells and interstitial vasculature were detected by immunohistochemistry. Correlation analysis and trend test were used to assess the relationship between ephrinB2/EphB4 expression and clinicopathological features, and between ephrinB2/EphB4 expression and perfusion parameters.</p><p><b>RESULTS</b>Positive expression of ephrinB2 and EphB4 in the NSCLC group was 83.9% and 71.0%, respectively, significantly higher than that in the internal control group (P < 0.01). The expression of ephrinB2 and EphB4 was consistently in tumor parenchyma but differently in tumor vessels. The expressions of ephrinB2 and EphB4 were positively correlated with lymphatic metastasis (P < 0.05). The expression of EphB4 was negatively correlated with blood flow (BF) and blood volume (BV), respectively (P < 0.05). There was a significant positive correlation between ephrinB2 expression and BF (r = 0.516, P = 0.003), and a positive correlation between ephrinB2 expression and BV (r = 0.448, P = 0.013). The expressions of ephrinB2 and EphB4 were not correlated with PEI (P > 0.05). The values of BF and BV in the high and moderate EphB4 expression groups were significantly decreased compared with that in the negative group (P < 0.01). The value of BF in the high ephrinB2 expression group was significantly increased compared with that in the moderately positive group and negative group (P < 0.01). The value of BV in the high ephrinB2 expression group was significantly increased compared with that in the negative group (P < 0.01).</p><p><b>CONCLUSION</b>The CT pulmonary perfusion imaging reflects the density difference of blood vessels with functional lumen, and such difference also depends on the quantity and quality of vasculature with functional lumen.</p>

Drug-resistant genes carried by Acinetobacter baumanii isolated from patients with lower respiratory tract infection / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Acinetobacter baumanii (A. baumanii ) remains an important microbial pathogen resulting in nosocomial acquired infections with significant morbidity and mortality. The mechanism by which nosocomial bacteria, like A. baumanii, attain multidrug resistance to antibiotics is of considerable interest. The aim in this study was to investigate the spread status of antibiotic resistance genes, such as multiple β-lactamase genes and aminoglycoside-modifying enzyme genes, from A. baumanii strains isolated from patients with lower respiratory tract infections (LRTIs).</p><p><b>METHODS</b>Two thousand six hundred and ninety-eight sputum or the bronchoalveolar lavage samples from inpatients with LRTIs were collected in 21 hospitals in the mainland of China from November 2007 to February 2009. All samples were routinely inoculated. The isolated bacterial strains and their susceptibility were analyzed via VITEK-2 expert system. Several kinds of antibiotic resistant genes were further differentiated via polymerase chain reaction and sequencing methods.</p><p><b>RESULTS</b>Totally, 39 A. baumanii strains were isolated from 2698 sputum or bronchoalveolar lavage samples. There was not only a high resistant rate of the isolated A. baumanii strains to ampicillin and first- and second-generation cephalosporins (94.87%, 100% and 97.44%, respectively), but also to the third-generation cephalosporins (ceftriaxone at 92.31%, ceftazidine at 51.28%) and imipenem (43.59%) as well. The lowest antibiotic resistance rate of 20.51% was found to amikacin. The OXA-23 gene was identified in 17 strains of A. baumanii, and the AmpC gene in 23 strains. The TEM-1 gene was carried in 15 strains. PER-1 and SHV-2 genes were detected in two different strains. Aminoglycoside-modifying enzyme gene aac-3-Ia was found in 23 strains, and the aac-6'-Ib gene in 19 strains. aac-3-Ia and aac-6'-Ib genes hibernated in three A. baumanii strains that showed no drug-resistant phenotype.</p><p><b>CONCLUSIONS</b>A. baumanii can carry multiple drug-resistant genes at the same time and result in multi-drug resistance. Aminoglycoside-modifying enzyme genes could be hibernating in aminoglycoside sensitive strains without expressing their phenotype.</p>

Neural plasticity occurs in the adrenal medulla of asthmatic rats / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Airway symptoms in asthma are related to decrease of epinephrine secretion, which may be ascribed to elevated nerve growth factor (NGF) in the organism. The aim of this study was to monitor the neuroendocrine alteration in the adrenal medulla of asthmatic rats.</p><p><b>METHODS</b>Sixteen rats were randomly divided into two groups (n = 8), control group and asthma group, and the asthmatic rats were sensitized and challenged with ovalbumin (OVA). The levels of NGF, epinephrine and norepinephrine in serum were detected by enzyme linked immunosorbent assay (ELISA), the NGF expression in adrenal medulla was detected by immunohistochemistry, and the changes in the ultrastructure of the adrenal medulla was observed by electron microscopy.</p><p><b>RESULTS</b>The NGF expression was increased in asthmatic rats compared with control rats. Compared with control rats, the results indicated that the epinephrine level was decreased in asthmatic rats, but no significant difference was found in norepinephrine levels. We found more ganglion cells in the adrenal medulla of asthmatic rats than in control rats, with NGF immunostaining mainly located in these ganglion cells. Electron microscopic images showed the density of chromaffin granula decreased and there was shrunken nucleolemma in the adrenal medullary cells of asthmatic rats.</p><p><b>CONCLUSION</b>The innervation of the adrenal medulla is changed in asthmatic rats, and it may contribute to the epinephrine decrease in asthma.</p>

Significance and mechanism of MSCT perfusion scan on differentiation of NSCLC / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To determine the significance of MSCT perfusion scan on differentiation of NSCLC and to investigate its possible mechanisms.</p><p><b>METHODS</b>Forty four NSCLC patients underwent CT perfusion scan by MSCT. Among them, 22 cases were selected to detected the two-dimensional tumor microvascular architecture phenotype (2D-TMAP), the relationships between CT perfusion parameters (BF, BV, PEI, TIP), and the differentiation of NSCLC were analysed by using the correlation analysis and trend test. Spearman correlation analysis was used to study the relationships between CT perfusion parameters, differentiation, and 2D-TMAP.</p><p><b>RESULTS</b>The total BF, BV and PEI decreased with decreasing differentiation of NSCLC (P<0.05). The total PEI showed a positive correlation with the total MVD (P<0.05). There were negative correlations between the surrounding area BF, the total BF, BV, and PEI, the uncomplete lumen of the surrounding area MVD, and expression of PCNA, respectively (P<0.05). There were positive correlations between degree of differentiation and the uncomplete lumen of the surrounding area MVD (P<0.05). It was the same as degree of differentiation and expression of PCNA, VEGF, respectively. There were positive correlations between the uncomplete lumen of the surrounding area MVD and expression of VEGF, ephrinB2, EphB4, and PCNA, respectively (P<0.05).</p><p><b>CONCLUSION</b>Perfusion parameters reflect the difference of density of vassels with mature functional lumen. Careful evaluation of the differences of blood flow pattern in pulmonary space-occupying lesions by MSCT perfusion scan can be used to identify the degree of NSCLC differentiation.</p>

Establishment of a lung adenocarcinoma cell line stably expressing small interfering RNA targeting hepatoma-derived growth factor and detection of interference effect / 南方医科大学学报

<p><b>OBJECTIVE</b>To construct a small interfering RNA (siRNA) expression vector targeting hepatoma-derived growth factor (HDGF) and establish a lung adenocarcinoma cell line stably expressing siRNA-HDGF.</p><p><b>METHOD</b>RT-PCR was used to examine HDGF expression in lung adenocarcinoma samples and the matched adjacent lung tissues, and also in lung adenocarcinoma SPC-A-1 cell line. A recombinant lentivirus shRNA-HDGF vector was constructed and transfected into SPC-A-1 cells via Lipofectamine 2000, and the cells with stable expression of HDGF-siRNA was screened by blasticidin selection. The interference effect of siRNA-HDGF was assessed by real-time PCR.</p><p><b>RESULTS</b>Compared to the adjacent lung tissues, lung adenocarcinoma and SPC-A-1 cells showed increased expression of HDGF. The recombinant lentivirus shRNA-HDGF vector was successfully constructed and verified by sequence analysis. siRNA-HDGF recombinants markedly inhibited the expression of HDGF in SPC-A-1 cells.</p><p><b>CONCLUSION</b>HDGF expression increases in lung adenocarcinoma and SPC-A-1 cell lines. The recombinant siRNA-HDGF lentivirus vector can inhibit the expression of HDGF in SPC-A-1 cells.</p>

Mesh structure of two-dimensional tumor microvascular architecture phenotype heterogeneity in non-small cell lung cancer / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the structural characteristics and clinical significance of two-dimensional tumor microvascular architecture phenotype (2D-TMAP) in non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>Thirty surgical specimens of NSCLC were collected. The sections of the tumor tissues corresponding to the slice of CT perfusion imaging were selected to construct the 2D-TMAP expression. Spearman correlation analysis was used to examine the relation between the 2D-TMAP expression and the clinicopathological features of NSCLC.</p><p><b>RESULTS</b>A heterogeneity was noted in the 2D-TMAP expression of NSCLC. The microvascular density (MVD) in the area surrounding the tumor was higher than that in the central area, but the difference was not statistically significant. The density of the microvessels without intact lumen was significantly greater in the surrounding area than in the central area (P=0.030). The total MVD was not correlated to tumor differentiation (r=0.042, P=0.831). The density of the microvessels without intact lumen in the surrounding area was positively correlated to degree of tumor differentiation and lymph node metastasis (r=0.528 and 0.533, P=0.041 and 0.028, respectively), and also to the expressions of vascular endothelial growth factor (VEGF), ephrinB2, EphB4, and proliferating cell nuclear antigen (PCNA) (r=0.504, 0.549, 0.549, and 0.370; P=0.005, 0.002, 0.002, and 0.048, respectively). The degree of tumor differentiation was positively correlated to PCNA and VEGF expression (r=0.604 and 0.370, P=0.001 and 0.048, respectively), but inversely to the integrity of microvascular basement membrane (r=-0.531, P=0.033).</p><p><b>CONCLUSION</b>The 2D-TMAP suggests the overall state of the micro-environment for tumor growth. The 2D-TMAP of NSCLC regulates angiogenesis and tumor cell proliferation through a mesh-like structure, and better understanding of the characteristics and possible mechanism of 2D-TMAP expression can be of great clinical importance.</p>

A novel mutation of the SLC34A2 gene in a Chinese pedigree with pulmonary alveolar microlithiasis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify the mutation of solute carrier family 34 member 2 (SLC34A2) gene in a Chinese family with pulmonary alveolar microlithiasis (PAM).</p><p><b>METHODS</b>Genomic DNA was extracted from the family members. DNA sequencing was carried out to confirm the mutation detected by polymerase chain reaction-single strand conformation polymorphisms (PCR-SSCP). The fragments with variation were screened in 100 healthy controls by PCR-SSCP.</p><p><b>RESULTS</b>In both patients of the family, a homozygous mutation of the SLC34A2 gene was identified in exon 8 (c.A910T), resulting in a premature stop codon. In addition, a homozygous single nucleotide polymorphism (SNP) was found in intron 2 in both patients and the daughter of proband.</p><p><b>CONCLUSION</b>A novel homozygous mutation in SLC34A2 gene, leading to a premature stop codon therefore a truncated protein, was probably responsible for the PAM in this family. The SNP in intron 2 needs further study.</p>

Study on the relationship between the polymorphism of p53 gene intron 7 and non-small cell lung cancer (NSCLC) and p53 mutation in NSCLC tissues / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between p53 gene intron 7 polymorphism and non-small cell lung cancer (NSCLC).</p><p><b>METHODS</b>One hundred and five patients with NSCLC and 100 controls were selected with case-control analysis. Polymerase chain reaction (PCR), Apa I restriction enzyme digestion and agarose gel electrophoretic separation were used to identify genotypes of p53 intron 7 in peripheral blood. Then, NSCLC biopsy tissues (n=64) and NSCLC paraffin-embedded tissues (n=40) were selected for mutation analysis. PCR products of p53 exons 5-8 were sequenced on an automated sequencer following the identification of intron 7 genotypes as previously described.</p><p><b>RESULTS</b>In NSCLC patients, the homozygote positive for ApaI site in p53 intron 7 was 23.8%, the homozygote negative was 12.34%, and the heterozygote was 63.8%. Whereas in control group, the homozygote positive, the homozygote negative and the heterozygote were 44.0%, 11.0% and 45.0%, respectively (P<0.01). In the second part, mutation rate of p53 exons 5-8 was 20.0%, 50.0% and 52.9% in samples with ApaI positive, negative and heterozygotes, respectively (P<0.05).</p><p><b>CONCLUSION</b>p53 intron 7 ApaI polymorphism may be associated with human NSCLC.</p>

Medical thoracoscopy in the diagnosis of complicate pleural effusion / 中南大学学报(医学版)

OBJECTIVE@#To evaluate the role of medical thoracoscopy in the diagnosis of the pleural effusion of unknown etiology.@*METHODS@#The results of 36 patients with the pleural disease of unknown etiology diagnosed by medical thoracoscopy were retrospectively analyzed, including the pathologic results and the complications.@*RESULTS@#Among the 36 patients, 35 were determined with positive rate of 97.2%, and no serious complications was found.@*CONCLUSION@#Medical thoracoscopy is an important method of diagnosing complicate pleural effusion, and has high positive rate. It is a simple operation, with no serious complication, and fast recovery.

Effect of Th1/Th2 cytokine immune imbalance on the expression of nerve growth factors in asthma / 中南大学学报(医学版)

OBJECTIVE@#To explore the effect of Th1/Th2 cytokines on the expression of nerve growth factor(NGF)in splenic lymphocytes in asthmatic model.@*METHODS@#Four SD rats were sensitized and challenged with ovalbumin to establish an asthmatic model, and the rat splenic lymphocytes were isolated and cultured with ConA. The expressions of NGF mRNA were detected by reverse transcription-polymerase chain reaction (RT-PCR), and were observed after the lymphocytes were exogenously added with interferon-gamma(IFN-gamma) or interleukin-4 (IL-4).@*RESULTS@#The lymphocytes of the asthmatic model stimulated by ConA in vitro expressed NGF mRNA in a time-dependent manner. After the lymphocytes had been cultured with IL-4 for 12 h, 24 h, 36 h, and 48 h, 50 microg/L IL-4 upregulated the expressions of NGF mRNA in a time-dependent manner and all the NGF mRNA expressions were significantly higher than the basal values at the same time(all Ps<0.01). After 0, 10, 50, and 100 microg/L IL-4 had been added for 24 h, IL-4 upregulated the expressions of NGF mRNA in a dose-dependent manner and the NGF mRNA expressions were all significantly higher than the values of the lower dose IL-4(all Ps<0.05). After the lymphocytes had been cultured with 10 mug/L IFN-gamma for 0 h, 12 h, 24 h, 36 h, and 48 h, IFN-gamma downregulated the expressions of NGF mRNA in a time-dependent manner and all the NGF mRNA expressions were significantly lower than the basal values at the same time(all Ps<0.01). After 0, 1, 10, and 50 microg/L IFN-gamma have been added for 24 h, IFN-gamma downregulated the expressions of NGF mRNA in a dose-dependent manner and all the NGF mRNA expressions were significantly lower than the values of the lower IFN-gamma dose(all Ps<0.05).@*CONCLUSION@#In the splenic lymphocytes of asthmatic rats, IL-4, one of the Th2 cytokines, can upregulate the expressions of NGF; IFN-gamma, one of the Th1 cytokines, can downregulate the expressions of NGF both in a time-dependent manner and in a dose-dependent manner. Th1/Th2 cytokine immune imbalance may indirectly induce the airway neurogenic inflammation by regulating the NGF mRNA expression.