OBJECTIVETo investigate the relationship between the gene polymorphism of metabolizing enzymes and the genetic susceptibility to lung cancer as well as to study the synergistic effects between smoking and the genes.

METHODSA case-control study (case = 217, control = 200) was carried out to compare the frequent distribution of CYP1A1, 2E1, 2D6 and GSTM1 genotypes between the lung cancer group and the control group with a polymerase chain reaction-restriction fragment polymorphism (PCR-RFLP) method and to analyze the relationship between these genes and smoking.

RESULTSGSTM1-null genotype frequency was 58.5% in the lung cancer group and 47.5% in the control group with significant difference (P = 0.02). The frequent distribution of CYP1A1, 2E1, 2D6 genotypes was not significantly different in the two groups (P > 0.05). Synergistic effects were found between smoking and GSTM1 but not between smoking and CYP1A1, 2E1, 2D6.

CONCLUSIONSmoking and GSTM1-null genotype seemed to be the risk factors of lung cancer. Those who carrying GSTM1-null genotype and smoking cigarettes were prone to suffer from lung cancer to become the high-risk population of the disease.

Cytochrome P-450 CYP1A1 ; genetics ; Cytochrome P-450 CYP2D6 ; genetics ; Genetic Predisposition to Disease ; genetics ; Glutathione Transferase ; biosynthesis ; genetics ; Homozygote ; Humans ; Lung Neoplasms ; genetics ; Male ; Polymorphism, Genetic

OBJECTIVETo evaluate the growth inhibitory effect of adriamycin (ADM) conjugated to an anti-lung cancer single-chain antibody (ScFv) 2A7-1 on lung adenocarcinoma cell line A2 in vitro.

METHODS2A7-1 cell culture medium was concentrated by ultra-filtration (with Amicon P10Z filter), and soluble ScFv was purified using RPAS purification kit. ADM was conjugated to 2A7-1 by glutaraldehyde. A(280) and A(490) of the conjugate 2A7-1-ADM were determined by spectrophotometry and the molar ratio of 2A7-1 to ADM was calculated. Immunoreactivity of the conjugate was detected by immunohistochemistry. Its growth inhibitory effect on lung adenocarcinoma cell line A2 was determined by colony formation assay in vitro.

RESULTSThe molar ratio of 2A7-1 to ADM was 1:3.2. The conjugate strongly reacted with A2 cell. Its growth inhibitory effect on A2 cells was 4 times as potent as ADM.

CONCLUSIONAdriamycin conjugated to anti-lung cancer single-chain antibody 2A7-1 has much higher cytotoxic activity than unconjugated adriamycin against human lung adenocarcinoma.

Adenocarcinoma ; immunology ; pathology ; Cell Line, Tumor ; Cell Proliferation ; drug effects ; Colony-Forming Units Assay ; Doxorubicin ; administration & dosage ; pharmacology ; Humans ; Immunoconjugates ; pharmacology ; Immunoglobulin Variable Region ; chemistry ; pharmacology ; Lung Neoplasms ; immunology ; pathology

OBJECTIVETo investigate the inhibition of COX-2 gene expression and its effects on malignant proliferation of human lung adenocarcinoma A549 cells after interfering at different target sites in vitro.

METHODSThe 3rd, 7th and 10th exon of COX-2 were selected as the targets and three COX-2 siRNA expression vectors with human U6 promoter were constructed. Three siRNA expression vectors and two vacant vectors were transfected into A549 cells expressing COX-2 with lipofectamine, respectively. The transfected cell strains were constructed and the change of COX-2 expression levels was examined by Western blot and RT-PCR. The effects on the proliferation of A549 cells after interfering at different target sites were studied by cell growth curve and colony formation assay in vitro.

RESULTSThe three siRNAs and U6 promoter were validated by PCR, restriction endonuclease digestion, DNA sequencing and BLAST alignment, and cloned into the pEGFP vector. The cell strains transfected were named as A549-3, A549-7, A549-10, A549-p and A549-pU6, respectively. A549-p cells showed expression of GFP and A549-3, A549-7, A549-10, A549-p and A549-pU6 cells did not show at 24, 48 and 72 hours after transfection. The results of RT-PCR and Western blot showed an inhibition of COX-2 expression after interfering at three target sites (3rd, 7th and 10th exons). In contrast to A549 cells, the levels of COX-2 mRNA of A549-3, A549-7 and A549-10 cells were reduced by 10.6%, 33.4% and 61.2%, respectively. The levels of COX-2 protein of A549-3, A549-7 and A549-10 cells were reduced by 26.7%, 44.7% and 56.2%, respectively. The results of cell growth curve and colony formation assay showed a slowing down of the growth of A549-10 cells and reduction of their colony formation rate. The other two targets had no apparent effect on the growth of A549 cells.

CONCLUSIONThere is a significant inhibiting effect of RNA interference on the malignant proliferation of A549 cells in vitro, and the most striking effect can be seen when the 10th exon of COX-2 is taken as the interference target.

Adenocarcinoma ; metabolism ; pathology ; Cell Line, Tumor ; Cell Proliferation ; Cyclooxygenase 2 ; genetics ; metabolism ; physiology ; Exons ; Genetic Vectors ; Humans ; Lung Neoplasms ; metabolism ; pathology ; Promoter Regions, Genetic ; RNA Interference ; RNA, Messenger ; metabolism ; RNA, Small Interfering ; genetics ; Transfection

Adult ; Female ; Humans ; Kidney Neoplasms ; diagnostic imaging ; metabolism ; Neuroectodermal Tumors ; diagnostic imaging ; metabolism ; Radiography ; Young Adult

OBJECTIVETo study the effect of extraneous p53 gene with deletion of c-terminal 356 - 393 amino acids on inhibition of malignant phenotype of human lung cancer cell line.

METHODSRecombinant plasmid pEGFP-p53 (del) with codon deletion of c-terminal 37 amino acids from 393 to 356 region and pEGFP-p53 (wild type) were constructed. The human lung cancer cell line 801D served as a receipt cell had p53 deletion and mutation at 248 codon. 801D cells, having been transfected by pEGFP-p53 (wild type), pEGFP-p53 (del) or pEGFP, were selected by G418. Growing transfected cells were cloned respectively by method of dilution. Presence of extraneous gene was detected by PCR, their expression in cells was examined by fluorescence microscopy. Cloning efficiency was in vitro tested to examine the cellular proliferating ability. The xenograft in nude mice was performed and xenograft tumors were weighed one month later. Expression of GFP in tumor and transplanted cellular mass were detected by blot slices.

RESULTSpEGFP-p53 (del)-801D, pEGFP-p53-801D and pEGFP-801D were established. Extraneous p53 gene and expression of GFP were found in pEGFP-p53 (del)-801D and pEGFP-p53-801D. Inhibitory rate of colony was 99.6% for pEGFP-p53 (del)-801D and 81.0% for pEGFP-p53-801D. Inhibition of malignant proliferation of extraneous p53 (del) was higher than that of p53 (wild type) (P < 0.01). Even when inhibition of malignant proliferation extraneous pEGFP-p53 (del) was obvious, 0.2% colonies were formed, extraneous p53 and expression of GFP were observed. Animal test showed that tumor on the nude mice was positive (4/4, 4/4) in the control group (801D and pEGFP-801D), but negative (0/4, 0/4) in the experiment group [pEGFP-p53 (del) 801D and pEGFP-p53 (wild type) 801D]. Expression of GFP in the cells of cellular mass transplanted by pEGFP-p53 (del) 801D or pEGFP-p53 (wild type) 801D was observed.

CONCLUSIONIn vitro inhibitory effect of extraneous p53 gene with deletion of C-terminal 356 - 393 amino acids on malignant growth of lung cancer cell with p53 mutation or deletion at 248 codon is marked. Inhibitory action of p53 on malignant proliferation of cancer cells is heterogeneous.

Animals ; Cell Cycle ; Cell Line, Tumor ; Genes, p53 ; Humans ; Lung Neoplasms ; genetics ; pathology ; Mice ; Mutation ; Phenotype ; Structure-Activity Relationship ; Transfection ; Tumor Suppressor Protein p53 ; chemistry ; physiology

Background::Accurate prediction of ischemic stroke is required for deciding anticoagulation use in patients with atrial fibrillation (AF). Even though only 6% to 8% of AF patients die from stroke, about 90% are indicated for anticoagulants according to the current AF management guidelines. Therefore, we aimed to develop an accurate and easy-to-use new risk model for 1-year thromboembolic events (TEs) in Chinese AF patients.Methods::From the prospective China Atrial Fibrillation Registry cohort study, we identified 6601 AF patients who were not treated with anticoagulation or ablation at baseline. We selected the most important variables by the extreme gradient boosting (XGBoost) algorithm and developed a simplified risk model for predicting 1-year TEs. The novel risk score was internally validated using bootstrapping with 1000 replicates and compared with the CHA 2DS 2-VA score (excluding female sex from the CHA 2DS 2-VASc score). Results::Up to the follow-up of 1 year, 163 TEs (ischemic stroke or systemic embolism) occurred. Using the XGBoost algorithm, we selected the three most important variables (congestive heart failure or left ventricular dysfunction, age, and prior stroke, abbreviated as CAS model) to predict 1-year TE risk. We trained a multivariate Cox regression model and assigned point scores proportional to model coefficients. The CAS scheme classified 30.8% (2033/6601) of the patients as low risk for TE (CAS score = 0), with a corresponding 1-year TE risk of 0.81% (95% confidence interval [CI]: 0.41%-1.19%). In our cohort, the C-statistic of CAS model was 0.69 (95% CI: 0.65-0.73), higher than that of CHA 2DS 2-VA score (0.66, 95% CI: 0.62-0.70, Z = 2.01, P = 0.045). The overall net reclassification improvement from CHA 2DS 2-VA categories (low = 0/high ≥1) to CAS categories (low = 0/high ≥1) was 12.2% (95% CI: 8.7%-15.7%). Conclusion::In Chinese AF patients, a novel and simple CAS risk model better predicted 1-year TEs than the widely-used CHA 2DS 2- VA risk score and identified a large proportion of patients with low risk of TEs, which could potentially improve anticoagulation decision-making. Trial Registration::www.chictr.org.cn (Unique identifier No. ChiCTR-OCH-13003729).

OBJECTIVE: A study was conducted to systematically evaluate the clinical efficacy of inflammatory factors in patients with chronic kidney disease and periodontitis after non-surgical periodontal therapy. METHODS: We searched the databases of CNKI, Wanfang, CBM, PubMed, Embase, and Cochrane Library from inception to December 2019. Two reviewers independently collected all literature related to inflammatory factors in patients with chronic kidney disease and periodontitis after non-surgical periodontal therapy. These factors include C-reactive protein (CRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α). The literature was screened according to the inclusion and exclusion criteria. The quality of the studies was strictly evaluated, and the data were extracted. The literature of randomized controlled trials in accordance with the standards was Meta-analyzed with Revman 5.3 software. RESULTS: Six randomized controlled trials were included. Compared with the control groups, the results of meta-analysis showed that non-surgical periodontal therapy significantly reduced the levels of CRP [MD=-0.58, 95%CI (-1.13, -0.02), P=0.04] and IL-6 [MD=-2.76, 95%CI (-5.15, -0.37), P=0.02] in these patients but not that of TNF-α [MD=-3.87, 95%CI (-8.79, 1.05), P=0.12]. CONCLUSIONS Simultaneous regular renal treatment and non-surgical periodontal therapy can help relieve the periodontal damage on patients with chronic kidney disease and periodontitis. Moreover, it can improve the status of some inflammatory factors. This finding is conducive to the control and treatment of chronic kidney disease and periodontitis and needs to be a focus of research and in clinical operation.
C-Reactive Protein ; Chronic Periodontitis ; Humans ; Interleukin-6 ; Renal Insufficiency, Chronic/therapy* ; Tumor Necrosis Factor-alpha

Selective dorsal neurotomy (SDN) is a surgical treatment for primary premature ejaculation (PE), but there is still no standard surgical procedure for selecting the branches of the dorsal penile nerves to be removed. We performed this study to explore the value of intraoperative neurophysiological monitoring (IONM) of the penile sensory-evoked potential (PSEP) for standard surgical procedures in SDN. One hundred and twenty primary PE patients undergoing SDN were selected as the PE group and 120 non-PE patients were selected as the normal group. The PSEP was monitored and compared between the two groups under both natural and general anesthesia (GA) states. In addition, patients in the PE group were randomly divided into the IONM group and the non-IONM group. During SDN surgery, PSEP parameters of the IONM group were recorded and analyzed. The differences in PE-related outcome measurements between the perioperative period and 3 months' postoperation were compared for the PE patients, and the differences in effectiveness and complications between the IONM group and the non-IONM group were compared. The results showed that the average latency of the PSEP in the PE group was shorter than that in the normal group under both natural and GA states (P < 0.001). Three months after surgery, the significant effective rates in the IONM and non-IONM groups were 63.6% and 34.0%, respectively (P < 0.01), and the difference in complications between the two groups was significant (P < 0.05). IONM might be useful in improving the short-term therapeutic effectiveness and reducing the complications of SDN.
Male ; Humans ; Premature Ejaculation/surgery* ; Intraoperative Neurophysiological Monitoring/methods* ; Prospective Studies ; Neurosurgical Procedures/methods* ; Penis/surgery* ; Retrospective Studies