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Objective: To evaluate the possible mediation effect of smoking and healthy diet score on the association between educational level and the risk of lung cancer incidence. Methods: After excluding individuals with missing educational levels and cancer information at baseline, 446â 772 participants in the UK Biobank (UKB) prospective cohort study were included. Cox regression models were used to investigate the associations of educational level and smoking and healthy diet score with the incidence of lung cancer. Mediating effect analysis was conducted to analyze the mediating effect of smoking and healthy diet score on the correlation between educational level and lung cancer. Results: During a median follow-up of 7.13 years, 1â 994 new- onset lung cancer cases were observed. Per 1 standard deviation (5 years) increase in educational level was associated with a 12% lower risk of lung cancer (HR=0.88, 95%CI: 0.84-0.92). The corresponding level 1-5 in the International Standard Classification for Education (ISCED) were mapped to UKB self-report highest qualification to estimate the educational level. A higher rank means a higher educational level. Compared with level ISCED-1, the HR(95%CI) of level ISCED-2, ISCED-3, ISCED-4 and ISCED-5 were respectively 0.83 (0.72-0.94), 0.67 (0.53-0.85), 0.76 (0.65-0.89) and 0.72 (0.64-0.80) for lung cancer. Education years were negatively correlated with smoking, with ß coefficients (95%CI) being -0.079 (-0.081- -0.077), but positively correlated with healthy diet score (ß=0.042, 95%CI: 0.039-0.045). Analysis of mediating effect indicated that the association of educational level with lung cancer risk was mediated by smoking and healthy diet score, the proportions of mediating effect were 38.952% (95%CI: 31.802%-51.659%) and 1.784% (95%CI: 0.405%-3.713%), respectively. Conclusion: Smoking and healthy diet score might mediate the effect of educational level on the incidence of lung cancer, indicating that improving the level of education can reduce the risk of lung cancer by changing lifestyles such as smoking and diet.
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Neoplasias Pulmonares , Fumar , Humanos , Fumar/efeitos adversos , Fumar/epidemiologia , Fatores de Risco , Dieta Saudável , Estudos Prospectivos , Incidência , Neoplasias Pulmonares/epidemiologia , Dieta , EscolaridadeRESUMO
Our goal is an office-based, handheld ultrasound system to target, detach, break, and/or expel stones and stone fragments from the urinary collecting system to facilitate natural clearance. Repositioning of stones in humans (maximum 2.5 MPa, and 3-second bursts) and breaking of stones in a porcine model (maximum 50 cycles, 20 Hz repetition, 30 minutes, and 7 MPa peak negative pressure) have been demonstrated using the same 350-kHz probe. Repositioning in humans was conducted during surgery with a ureteroscope in the kidney to film stone movement. Independent video review confirmed stone movements (≥ 3 mm) in 15 of 16 kidneys (94%). No serious or unanticipated adverse events were reported. Experiments of burst wave lithotripsy (BWL) effectiveness on breaking human stones implanted in the porcine bladder and kidney demonstrated fragmentation of 8 of 8 stones on post mortem dissection. A 1-week survival study with the BWL exposures and 10 specific-pathogen-free pigs, showed all findings were within normal limits on clinical pathology, hematology, and urinalysis. These results demonstrate that repositioning of stones with ultrasonic propulsion and breaking of stones with BWL are safe and effective.
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Burst wave lithotripsy (BWL) is a new non-invasive method for stone comminution using bursts of sub-megahertz ultrasound. A porcine model of urolithiasis and techniques to implement BWL treatment has been developed to evaluate its effectiveness and acute safety. Six human calcium oxalate monohydrate stones (6-7 mm) were hydrated, weighed, and surgically implanted into the kidneys of three pigs. Transcutaneous stone treatments were performed with a BWL transducer coupled to the skin via an external water bath. Stone targeting and treatment monitoring were performed with a co-aligned ultrasound imaging probe. Treatment exposures were applied in three 10-minute intervals for each stone. If sustained cavitation in the parenchyma was observed by ultrasound imaging feedback, treatment was paused and the pressure amplitude was decreased for the remaining time. Peak negative focal pressures between 6.5 and 7 MPa were applied for all treatments. After treatment, stone fragments were removed from the kidneys. At least 50% of each stone was reduced to <2 mm fragments. 100% of four stones were reduced to <4 mm fragments. Magnetic resonance imaging showed minimal injury to the functional renal volume. This study demonstrated that BWL could be used to effectively fragment kidney stones with minimal injury.
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BACKGROUND: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a common problem with unclear etiology. Some diet and lifestyle factors were thought to correlate with CP/CPPS, but studies comprehensively investigate this correlation are rarely available. The current study was conducted to determine the potential lifestyle-related risk factors of CP/CPPS and its pain severity in Chinese population. METHODS: Participants were recruited from seven hospitals in Shanghai from July 2012 to August 2013. Demographics, medical history, diet and lifestyle information, and CP/CPPS symptoms were obtained from each participant using a questionnaire. Univariate and multivariate logistic regression analyses were used to identify potential lifestyle-related risk factors for CP/CPPS and its pain severity. RESULTS: A total of 784 men with CP/CPPS and 785 controls were enrolled in this study. Multivariate regression model indicated that age, nightshift work, stress, smoking status, alcohol consumption, less water intake, imbalanced diet, frequent sexual activity, delaying ejaculation and holding urine were identified as potential risk factors for CP/CPPS, whereas sedentary lifestyle, caffeinated drinks and less water intake were associated with severe pain in CP/CPPS patients. CONCLUSIONS: Several diet and lifestyle factors associated with CP/CPPS and pain severity were determined in this study. These modifiable conditions are potential targets for treatment of CP/CPPS. However, further studies are necessary to determine their role in the pathogenesis of CP/CPPS.
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Dor Pélvica/epidemiologia , Neoplasias da Próstata/epidemiologia , Prostatite/epidemiologia , Adolescente , Adulto , Idoso , China , Dieta , Disfunção Erétil/epidemiologia , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , Dor Pélvica/patologia , Neoplasias da Próstata/patologia , Prostatite/patologia , Fatores de Risco , Inquéritos e QuestionáriosRESUMO
This study aimed to establish a reference range of penile length and circumference of adult males in China, and to compare the penile dimensions of different ethnical backgrounds. To do this, penile length and circumference measurements were obtained from 5196 healthy males attending the Urology Counseling Clinic. The mean value of penile dimensions was a flaccid length of 6.5 ± 0.7 cm, a stretched length of 12.9 ± 1.2 cm and a flaccid circumference of 8.0 ± 0.8 cm. In the subgroup of 311 males, the mean erectile length was 12.9 ± 1.3 cm and the mean erectile circumference was 10.5 ± 0.9 cm, the mean flaccid and erectile glans lengths were 2.7 ± 0.3 and 3.4 ± 0.4 cm, respectively, and the mean flaccid and erectile glans diameters were 2.6 ± 0.2 and 3.4 ± 0.4 cm, respectively. We found that flaccid penile length and circumference varied among different ethnicities. This study established a reference range for penile dimensions, which will help when counseling patients worried about their penile size or seeking penis enlargement surgery. We also found that penile dimensions are different in different ethnicities, but further investigations are needed to validate this.
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Pênis/anatomia & histologia , Adolescente , Adulto , Fatores Etários , Povo Asiático , Índice de Massa Corporal , Peso Corporal , China , Etnicidade , Humanos , Masculino , Pessoa de Meia-Idade , Ereção Peniana , Estudos Prospectivos , Valores de Referência , Adulto JovemRESUMO
Mutated constituents of the DNA replication complex might contribute to the mutational load of the genome during tumor development by impairing DNA synthesis as well as cell cycle-related control of DNA replication. To prove or disprove this hypothesis, we looked for mutations in the cDNA sequences of the four subunits of DNA polymerase alpha-primase from both highly malignant Novikoff hepatoma cells and regenerating normal rat liver and compared physicochemical and catalytic properties of the DNA polymerase alpha-primase complexes purified from both sources. Sequence analysis showed two mutations in subunit B from Novikoff cells: one in nucleotide position 855 (CCG-->CCA) that did not result in an amino acid exchange and one in position 862 (GTG-->ATG) that caused a change of valine to methionine in codon 288. No mutation was found in the three other subunits. The wild-type and mutated sequences of subunit B were cloned and expressed in vitro. Sedimentation analysis of the expressed polypeptides revealed different sedimentation constants, indicating that the amino acid exchange affected the conformation of subunit B. The analysis of the purified DNA polymerase alpha-primase complexes showed a sedimentation value that was significantly higher for the enzyme complex from normal liver than for that from Novikoff cells. In addition, DNA polymerase alpha-primase complexes from Novikoff cells showed higher sensitivity to camptothecin, topotecan, and structurally related compounds (such as (R,S)-7-ethyl-10-hydroxy camptothecin, 9-aminocamptothecin, and 10-hydroxycamptothecin) than the enzyme from normal rat liver. Thus, the amino acid change found in subunit B appears to result in a conformational change of the DNA polymerase alpha-primase complex from Novikoff hepatoma cells. Whether this mutation influences genetic instability or tumor development needs to be explored.
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DNA Polimerase I/genética , DNA Polimerase I/metabolismo , DNA Primase/genética , DNA Primase/metabolismo , Mutação , Animais , Sequência de Bases , Catálise , DNA Polimerase I/isolamento & purificação , DNA Primase/isolamento & purificação , DNA Complementar/genética , DNA de Neoplasias/genética , Feminino , Fígado/enzimologia , Fígado/fisiologia , Neoplasias Hepáticas Experimentais/enzimologia , Neoplasias Hepáticas Experimentais/genética , Camundongos , Dados de Sequência Molecular , Biossíntese de Proteínas , Conformação Proteica , Ratos , Ratos Sprague-Dawley , Homologia de Sequência do Ácido Nucleico , Transcrição GênicaRESUMO
A hydrothermally synthesized mixed-ligand molecular solid composed of pillared bilayers has been formulated; it presents a new remarkable three-dimensional architecture sustained by the catenation of two-fold decked layers, and exhibits intense photoluminescence upon photoexcitation at 314 nm.
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To test the hypothesis whether DNA polymerases acquire mutator properties during tumor development (mutator hypothesis), we examined DNA polymerase delta mRNA in 6 colon cancer cell lines (DLD-1, HCT116, SW48, HT29, SW480 and SW620) and 7 sporadic human colorectal cancers. For analysis we used amplification of cDNA by polymerase chain reaction, single-strand conformation polymorphism and sequencing techniques. In 5 of the cell lines, 9 mutations leading to changes of the amino acid sequence of DNA polymerase delta were detected. Most mutations were found in the cell lines DLD-1, HCT116 and SW48 for which defects in mismatch repair genes had been identified previously. In the majority of cases, wild type and mutated sequences were present. In 2 cell lines (HCT116 and SW48), a single-nucleotide deletion occurred at the same position. This resulted in a premature termination codon by which the DNA interaction domain of the enzyme was eliminated. Furthermore, sequence deviations were found in the tumor tissues of 4 colon cancer patients. Wild-type and altered sequences were present simultaneously. The deviations included missense mutations (2 cases) and silent mutations (2 cases). The missense mutations and one of the silent mutations were found in normal mucosa as well. In addition, the mutation clustered region of a tumor suppressor gene, often found to be defective in colon cancer, the adenomatous polyposis coli (APC) gene, was investigated in surgical specimens and cell lines. One carcinoma and 2 cell lines exhibited amino acid changes in both the DNA polymerase delta gene and in the mutation clustered region of the APC gene. Since most of the mutations detected in the DNA polymerase delta mRNA are likely to alter the structure of the protein, the enzyme is expected to be functionally impaired. In particular, copying fidelity might be decreased, thus contributing to the high mutation rate observed in colorectal cancer.