Objective To investigate the expression of paired amino acid cleaving enzyme 4 (PACE4) protein in non-small-cell lung cancer (NSCLC), analyze the correlation of its clinicopathologic characteristics, and investigate its significance in the process of occurrence, development, and metastasis of NSCLC.Methods Between January 2006 and May 2009, the First Affiliated Hospital of Guangzhou Medical College, 172 patients with NSCLC and 15 patients with non-neoplastic tissues were chosen.Immunohistochemistry was used to detect the expression of PACE4, and clinicopathologic characteristics of NSCLC were analyzed.Results (1)The positive expression rate of PACE4 protein in NSCLC was significantly higher than that in non-tumor tissues (P ＜ 0.05).PACE4 expression was observed in 111 of 172 (64.5％) NSCLC.PACE4 had cytoplasmic expression.(2)Clinicopathologically, PACE4 expression was significantly associated with lymph node metastasis (N stage) (P =0.007), and clinical stage (P =0.024).Conclusions High expression of PACE4 indicates that PACE4 may be involved in the processes of occurrence,development, and metastasis of NSCLC.

Objective To investigate the relationship between high sensitive C reactive protein(hsCRP) and monocyte chemotactic protein-1 (MCP-1) in patients with metabolic syndrome(MS).Methods Sixty-two patients with MS and 52 normal healthy individuals (NS) were recruited in the study.And the levels of hs-CRP and MCP-1 were detected by ELISA.The severity of Insulin resistance was calculated by homeostasismodel assessment of insulin resistance(HOMA-IR).The monocytes in blood were isolated,cultured and stimulated by different concentrations of CRP.MCP-lexpression of monocytes was measured by real-time PCR.Results Patients with MS displayed significantly higher serum levels of hs-CRP and MCP-1 compared with healthy control group [(80.26 ±35.52) nmol/L vs (3.12 ±2.55) nmol/L for hs-CRP,P ＜0.01 ; (15.35 ± 10.12) nmol/L vs (9.76 ± 6.15) nmol/L for MCP-1,P ＜ 0.05].There was significantly positive correlation between hs-CRP and MCP-1.Serum hs-CRP,MCP-1and insulin resistance index were positively correlated,respectively.In vitro experiments indicated that CRP could up-regulate MCP-1 expression of monocytes in a concentration-dependent way.When the concentration of CRP was 176nmol/L,the expression of MCP-1 could reach 105％ compared with non-stimulated group.Conclusion With the severity of the inflammatory response and enhanced insulin resistance,elevated serum CRP level may result in MCP-1 expression in patients with metabolic syndrome.

Objective To determine whether store-operated Ca2+ entry (SOCE) is involved in chronic hypoxia-induced alteration of intracellular Ca2 + concentration ([Ca2+] i) and proliferation in pulmonary arterial smooth muscle cells (PASMC).Methods Rat PASMCs were cultured and treated in normoxia (21％O2) or hypoxia (4％ O2) condition.The proliferation of PASMC was detected by cell counting kit-8 (CCK-8) assay.[Ca2 +] i,SOCE and the effects of store-operated Ca2 + channel (SOCC) inhibitors,SKF96365 and NiCl2,on SOCE in hypoxic PASMCs were tested by InCyte [Ca2 +] i measurement system.Results Hypoxia for 24-60 h augmented PASMC proliferation (1.12 ± 0.09 vs 0.71 ± 0.05,P ＜ 0.05) and [Ca2 +] i [(214.8 ± 20.4) nmol/L vs (115.2 ± 13.2) nmol/L,P ＜ 0.05] in a time-dependent manner with the maximum effect at 60 h.Perfusion of Ca2+-free Krebs solution containing nifedipine (5 μ mol/L),cyclopiazonic acid (CPA,10 μmol/L) in PASMCs caused a small transient increase of [Ca2+]i with peak [Ca2+]i (113.3 ± 49.3) nmol/L.Chronic hypoxia (4％ O2,60 h) enhanced [Ca2+]i level with peak value of (193.2 ± 22.7) nmol/L (P ＜ 0.05) in PASMC.After restoration of extracellular Ca2+,CPA caused marked increase of [Ca2+]i with peak value of (328.0 ± 56.7) nmol/L.Chronic hypoxia strengthened CPA-induced increase of [Ca2 +] i with peak value of (526.0 ± 33.7) nmol/L (P ＜ 0.05) in PASMCs.Either SKF96365 50 μmol/L or NiCl2 500 μmol/L distinctly attenuated CPA-induced enhancement of [Ca2 +] i,the peak value of which dropped from (526.0 ± 33.7) nmol/L to (170.4 ± 26.4) nmol/L (P＜0.05) or (177.4±45.9) nmol/L (P＜0.05) respectively.Conclusion Chronic hypoxia boosts the release of Ca2+ from sarcoplasmic reticulum and promotes the activity of SOCC and SOCE,leading to [Ca2 +] i elevation and proliferation of rat PASMCs.

Purpose To investigate the expression and significance of epiderma1 growth factor receptor( EGFR)mutation-specific anti-bodies in 1ung adenocarcinoma. Methods Immunohistochemica1( IHC)technique was used to detect the expression of EGFR muta-tion-specific antibodies(EGFR-19,EGFR-21)and EGFR tota1 protein antibody(EGFR-P)in 171 cases of 1ung adenocarcinoma with resected specimens,and EGFR gene mutation was a1so performed by amp1ification refractory mutation aystem-PCR( ARMS-PCR). The expression of EGFR-19,EGFR-21 and EGFR-P mutant proteins was compared with EGFR gene mutation and their re1ationship with histo1ogica1 c1assification and c1inica1 characteristics were ana1yzed. Results The expression of EGFR mutant protein was corre1ated with the poor differentiation group inc1uding micropapi11ary and so1id predominant types( P=0. 021 ). EGFR-21 high expression was re1ated to p1eura1 invasion(P=0. 005). The coherence of IHC(with EGFR-19/21 antibodies)and ARMS-PCR was existed(Kappa>0. 4 ). Taking ARMS-PCR as a standard,the sensitivity and specificity of EGFR-19 and EGFR-21 were 65. 0% and 89. 4%, 70. 0% and 97. 6%,respective1y. Conclusions Expression of EGFR mutation-specific antibodies is associated with poor differentia-tion and p1eura1 invasion. It suggests a worse prognosis indicator in 1ung adenocarcinoma. Because of the coherence with ARMS-PCR, using IHC with mutation-specific antibodies to detect the mutant proteins of EGFR-19/21 may act as a pre1iminary screening method of EGFR gene mutation.

Objective To explore the predictive value of serum N-terminal pro-brain natriuretic peptide (NT-proBNP) level in anthracycline-based chemotherapy-related cardiotoxicity of breast cancers.Methods A total of 135 breast cancer patients was analyzed if NT-proBNP was associated with chemotherapy-related cardiotoxicity.The level of NT-proBNP in the diagnosis of cardiotoxicity was assessed.Results A total of 22 patients (16.29％) had subsequent claims for cardiotoxicity events.NT-proBNP in cardiotoxicity group was significantly higher than that non-cardiotoxicity group (P ＜ 0.05).According to receiver operating characteristic (ROC) curve, the cut-off value of NT-proBNP was set at 350 pg/ml, specificity and sensitivity were 70.32％ and 82.58％ , respectively.Positive and negative predictive values were 78.12％ and 65.45％, respectively.Conclusions The present study is to confirm excellent clinical value of NTproBNP on cardiotoxicity.The level of NT-proBNP for early detection of cardiotoxicity has good prospects for high risk patients.

Administration, Sublingual ; Bacterial Vaccines ; administration & dosage ; immunology ; Child ; Child, Preschool ; Double-Blind Method ; Female ; Humans ; Immunoglobulin A ; blood ; Immunoglobulin A, Secretory ; analysis ; Male ; Pseudomonas Vaccines ; Recurrence ; Respiratory Tract Infections ; immunology ; prevention & control ; Treatment Outcome

OBJECTIVETo study the treatment effects of cultured Cordyceps sinensis combined with glucocorticosteroid on experimental pulmonary fibrosis in rats induced by bleomycin.

METHODFifty rats were randomly divided into five groups, including control group, model group, cultured C. sinensis groups, prednisone group, cultured C. sinensis combined with prednisone group. On experimental day 0, the rats were respectively intratracheally instilled with bleomycin, and rats in the control group and model group with the same volume of normal saline. One day after the injection, cultured C. sinensis and glucocorticosteroid was respectively given to rats daily by gastric gavage, while the same volume of normal saline was given to those in the control group and model group. On 28th d, bronchoalveolar lavage fluid (BALF) and lung tissue were collected. Histological changes of the lungs were evaluated by HE stain, Masson's trichrome stain. Collagen content of the lung tissue was assessed by hydroxyprolin concentration. Lung expression of CTGF protein was assessed by immunohistochemistry. The level of TGF-beta1 protein was measured by ELISA.

RESULTCompared to model group, pulmonary fibrosis were alleviated in cultured C. sinensis and prednisone group, and CTGF expression, Hydroxyproline concentrations and protein TGF-beta1 were decreased. The combination effect of C. sinensis and prednisone group is augmented compared with using C. sinensis or prednisone group alone.

CONCLUSIONThe cultured C. sinensis and prednisone alleviates pulmonary fibrosis, and the combination use of both drugs has synergia effects in anti-fibrous degeneration.

Animals ; Bleomycin ; toxicity ; Connective Tissue Growth Factor ; analysis ; Cordyceps ; Drug Therapy, Combination ; Lung ; chemistry ; pathology ; Male ; Phytotherapy ; Prednisone ; administration & dosage ; Pulmonary Fibrosis ; chemically induced ; drug therapy ; pathology ; Rats ; Rats, Sprague-Dawley

Objective To develop a new type of blast injury simulator to establish a mouse model of brain blast injury and study its damage mechanism. Methods Thirty healthy Kunming mice were randomly(random number) divided into the normal control group and brain blast injury model (TBI) group. A mouse model of traumatic brain injury was prepared by a self-developed explosive injury simulator. Morris water maze, Evans blue experiment and HE staining were used to observe the effects of shockwave exposure on spatial memory, blood-brain barrier, and pathological changes of brain tissues. T test was used for statistical analysis. Western blot method was used for detecting expression of brain injury markers Tau, S100β, Choline, inflammatory factors IL-1β, IL-4, IL-6, IL-10, NF-κB, apoptosis factors Bcl-2, Bax, Caspase3, and oxide protein stress-related factors IREα, MDA5, COX2 SOD1, and SOD2. Results Compared with the normal control group, (11.2±2.1) s, the time of searching platform in the TBI group was (54.6±8.4) s, was significantly longer (t=-19.330, P<0.05), and the EB exudation in the TBI group was 3.22 times (t=-13.903, P<0.05). Pathological staining revealed neuronal damage in the hippocampus, and TBI induced brain injury markers Tau(0.26±0.03 vs 0.46±0.04,t=-9.788, P<0.05), S100β(0.54±0.03 vs 0.74±0.02,t=-12.433, P<0.05) and Choline(0.54±0.05 vs 0.80±0.04, t=-7.970, P<0.05), inflammatory cytokines IL-1β(0.22±0.04 vs 0.31±0.05,t=-3.431, P<0.05), IL-4(0.65±0.02 vs 0.97±0.03, t=-18.927, P<0.05), IL-6(0.88±0.05 vs 1.07±0.08, t=-9.488, P<0.05) and NF-κB(0.80±0.06 vs 1.03±0.07,t=-4.507, P<0.05), and pro-apoptotic cytokines Bax(0.66±0.04 vs 0.78±0.04, t=-13.007, P<0.05) and Caspase3(0.44±0.03 vs 0.60±0.05, t=-4.472, P<0.05), oxidative stress-related factor pro IREα(0.72±0.06 vs 1.07±0.04, t=-9.665, P<0.05), MDA5(0.47±0.02 vs 0.77±0.02, t=-23.678, P<0.05) and expression of COX2(0.70±0.07 vs 0.86±0.02, t=-6.421, P<0.05), inhibition of inflammation inhibitory factor IL-10(1.14±0.06 vs 0.74±0.07, t=13.729, P<0.05), inhibition of apoptosis factors Bcl-2(0.72±0.05 vs 0.46±0.02, t=11.491, P<0.05) and inhibition of oxidative stress factors SOD1(1.17±0.05 vs 0.99±0.01, t=7.731, P<0.05) and SOD2(0.81±0.05 vs 0.61±0.04, t=10.257, P<0.05) expression. Conclusions The brain injury induced by blast exposure can induce spatial learning and memory loss, blood brain barrier disruption, neuronal damage hippocampus in mice, and promote the expression of brain injury markers, induce inflammation, oxidative stress and apoptosis. The self-developed explosive shock simulator successfully establishes a mouse brain blast injury model.

ObjectiveTo investigate the effects of repetitive transcranial magnetic stimulation （rTMS） on the efficacy and cognitive function of adolescents with depression. MethodsA total of sixty adolescent depression patients who met the diagnostic criteria of the International Classification of Diseases， tenth edition （ICD-10） and were admitted to the psychological outpatient clinic of the Affiliated Hospital of North China University of Technology from September 2021 to March 2022 were selected for the study， and the random number table method was used to divide the study group （escitalopram oxalate combined with rTMS treatment） and a control group （escitalopram oxalate combined with rTMS pseudo-stimulation treatment） of 30 cases each， and both groups were treated for 4 weeks. Before treatment and at 1， 2， 3 and 4 weeks of treatment， patients' depressive symptoms were assessed using the scores and subtraction rates of the Hamilton Depression Scale-24 item （HAMD-24）， and before treatment and after 4 weeks of treatment， cognitive function was assessed using the Motion Screening Task （MOT）， Rule Switch Task （RST） and Delayed Matching-to-Sample （DMS） task of the Zhiyun Neuropsychological Automated Test System assessment. Adverse effects during treatment were recorded in both groups. ResultsRepeated measures ANOVA results showed statistically significant time main effects， group main effects， and the interaction between the two groups for HAMD-24 scores before treatment and after 1， 2， 3 and 4 weeks of treatment in patients （F=522.021， 39.905， 26.412， P<0.05）. Individual effect analysis showed statistically significant differences in HAMD-24 scores between the two groups after 2， 3 and 4 weeks of treatment （t=-12.784~-2.776， P<0.01）. After 4 weeks of treatment， the total effective rate of treatment in the study group was higher than that in the control group （93.33% vs. 73.33%， χ²=4.320， P<0.05）， and the differences in each indicator of RST and DMS between the two groups were statistically significant compared with those before treatment （t=-5.616~9.135， P<0.05 or 0.01）， and the differences between the two groups were statistically significant （t=-4.823~5.518， P<0.05 or 0.01）. ConclusionrTMS may help improve depressive symptoms as well as cognitive function in adolescents with depression.