OBJECTIVETo study the methylation of CpG islands in the promoter region, expression of caveolin 1 (Cav-1) gene and their clinical significance in non-small cell lung cancers (NSCLC).

METHODSImmunohistochemistry and quanta Qd600 staining were used to detect the expression of Cav-1 in tissues from benign lung lesions (n = 17) and NSCLC (n = 123). DNA was treated with sodium bisulfite and the Cav-1 promoter region was screened using methylation-specific polymerase chain reaction for the possible methylation sites.

RESULTSCav-1 protein was highly expressed in cytoplasm and cell membrane of normal bronchial epithelium, alveolar epithelium, endothelial cells, fibroblasts and smooth muscle cells. The expression rates of Cav-1 protein were 100% (17/17) in the control group and 43.1% (53/123) in the NSCLC group (P = 0.001). Amongst the NSCLC group, there was no statistically significant difference in Cav-1 protein expression in different histologic types (P = 0.552) and tumor grades (P = 0.160). On the other hand, Cav-1 protein immunoreactivity was remarkably higher in advanced tumor stage: 72.7% in stage III A + III B, compared with 9.4% in stage I A + I B and 38.3% in stage II A + II B (P = 0.001). The expression rate of Cav-1 protein in the NSCLC cases with lymph node metastasis was 53.6%, compared with 20.5% in those without nodal involvement (P = 0.001). DNA from 40 NSCLC cases with negative Cav-1 protein expression and 12 cases of peritumoral lung tissues were extracted. Methylation in the promoter region of Cav-1 gene was not detected in lung cancer or peritumoral tissues.

CONCLUSIONSHigh expression of Cav-1 protein is respected of the aggressive clinical behavior and advanced tumor stage. Loss of Cav-1 protein expression seems not correlated to the methylation status in the promoter region of Cav-1 gene.

Aged ; Carcinoma, Non-Small-Cell Lung ; genetics ; pathology ; Caveolin 1 ; genetics ; metabolism ; DNA Methylation ; Female ; Gene Regulatory Networks ; genetics ; Humans ; Immunohistochemistry ; Lung Neoplasms ; classification ; genetics ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; methods ; Somatoform Disorders

BACKGROUNDThe high incidence of neuropsychologic deficits after cardiac surgery, including cognitive dysfunction and mood status, has significantly influenced the prognosis, outcome of treatment and long-term quality of life of patients. With a circadian secretion pattern, melatonin and cortisol are capable of modulating the human physiological processes and neuropsychological status, whereas disorder of their secretion pattern may lead to many diseases. However, it is unclear whether neuroendocrine variations are related to the neuropsychologic status in patients undergoing coronary artery bypass grafting (CABG).

METHODSForty male patients scheduled for CABG with hypothermic cardiopulmonary bypass (CPB) (n = 20) or off-pump coronary artery bypass (OPCAB) (n = 20) were studied. Blood samples were taken intraoperatively at specific time-points and every 3 hours within the first postoperative 24 hours to determine plasma concentrations of melatonin and cortisol. A neuropsychologic test battery including depression and anxiety was administered preoperatively and 7 to 10 days postoperatively. Statistical methods included the nonparametric analysis, multiple linear regression and cosinor analysis.

RESULTSThe patients in the CPB group exhibited more severe neuropsychologic deficits and more anxious than those in the OPCAB group after surgery. In both groups, patients were more depressed postoperatively than preoperatively and recovered 3 months after surgery. Depression and anxiety were correlated with some factors of cognitive dysfunctions. In the postoperative 24 hours, 2 patients in the CPB group, and 6 patients in the OPCAB group showed a circadian rhythm of melatonin secretion. As for cortisol secretion, there were 3 patients in the CPB group and 7 in the OPCAB group respectively. Parameters of circadian rhythm of melatonin in the CPB group and those of secretion rhythm of cortisol in both groups were correlated with depression and some neuropsychologic tests.

CONCLUSIONSThe incidence of neuropsychological deficits was higher in patients receiving CABG with CPB than in those without CPB. The status of mood may contribute to the perioperative cognitive dysfunctions. The disordered circadian rhythm of melatonin secretion in patients undergoing CABG with CPB and the disordered cortisol secretion may correlate directly or indirectly through mood with neuropsychological deficits.

Cardiopulmonary Bypass ; adverse effects ; Circadian Rhythm ; physiology ; Cognition Disorders ; etiology ; Coronary Artery Bypass ; adverse effects ; Humans ; Hydrocortisone ; blood ; secretion ; Male ; Melatonin ; blood ; secretion ; Middle Aged ; Neuropsychological Tests ; Postoperative Complications ; etiology

Objective To investigate the phenotypes and genotypes of a hereditary protein C(PC) deficiency pedigree.Methods Imrnunoassay(ELISA)was used for PC antigen and PS antigen; Immunoturbidimetry assay was used for measuring AT antigen;Chromogenic substrate assay was used for measuring the activity of PC,PS and AT in Sysmex 1500 automatic Blood Coagulation Analyzer.Polymerase chain reaction(PCR)for amplification of the fragment of each exon and side sequences of PC gene in 10 members of the 3 generations;Direct DNA sequencing was used to examine the mutation site.Results Among 10 members of the 3 generation pedigree,8 of them had a PC:Ag level of 1.06-1.92 mg/L(normal references 3.00-6.00 rag/L),the activity of PC was between 41% and 67%(normal references 70%- 140%),which was significantly lower than the normal references while the levels of PS:Ag,PS:A,AT:Ag and AT:A were all within normal range.DNA sequencing analysis showed that there was a G to T mutation in exon IX of the PC gene at 12 918 position in 8 members.This mutation resulted in the substitution of terminator TGA for TGG which encoding tryptophan at 372 amino acid.There was a polymorphism in 2 405C/ T,2 418A/G,2 583A/T in the promotor area.Conclusions This pedigree is a type I hereditary protein C deficiency.There is a G12 918T mutation in exon IX of PC gene.This mutation is reported for the first time and there is a polymorphism in 2 405C/T,2 418A/G,2 583A/T in the promotor area.

Purpose: Numerous studies have produced conflicting findings regarding the efficacy of statins in prostate cancer treatment. Our objective was to examine the correlation between statin usage and clinical outcomes in Taiwanese men with de novo metastatic prostate cancer. Materials and Methods: We identified patients diagnosed with de novo metastatic prostate cancer from the Chang Gung Research Database spanning the years 2007 to 2020. To minimize confounding bias, we employed the inverse probability of treatment weighting (IPTW) method. Clinical outcomes were assessed using IPTW-adjusted Kaplan-Meier curves. Multivariate Cox proportional hazard regression analysis was utilized to evaluate the association between mortality and clinical factors. Results: The study cohort comprised 1,716 statin users and 276 non-users. Patients who used statins exhibited a longer median overall survival (85.4 months compared to 58.2 months; p=0.001) and cancer-specific survival (112.6 months compared to 75.7 months; p<0.001) compared to non-users. The median time to the development of castration-resistant status was similar between statin users and non-users (p=0.069). Multivariable Cox proportional hazards regression analysis, after IPTW adjustment, demonstrated that statin use was associated with improved overall survival. Conclusions Our study indicates that the use of statins following a de novo metastatic prostate cancer diagnosis enhances survival outcomes. However, statins did not appear to delay the onset of castration-resistant status. Further large-scale and long-term studies are warranted to investigate the biological effects of statins in men with prostate cancer.

OBJECTIVETo evaluate the efficacy of hepatitis B viruse (HBV) vaccination and its influencing factors among children in rural area of Jiangsu province.

METHODSTwenty-five hundred and twenty-two children born after 1998 in rural area were selected as the study population using multistage cluster sampling method. HBsAg and anti-HBs were detected by enzyme linked immunoassay (ELISA) and radio-immunoassay (RIA), respectively. Anti-HBs negative children were boosted using different hepatitis B vaccines and the efficacy was compared. Factors causing HBV infection in HBsAg positive children were also investigated.

RESULTSHBsAg positive rates in 1-7 year olds were 0.28%-1.28%, and the anti-HBs positive rates decreased from 76.7% to 45.5%. The HBsAg positive rate in children not timely vaccinated was significantly higher than those with HBV vaccine injection within 24 hours after birth (1.4% vs. 0.5%, P = 0.031). More than 90% of the anti-HBs negative children had protective level of anti-HBs after boosted with HBV vaccine.

CONCLUSIONHBsAg positive rate in children born after 1998 in rural area of Jiangsu province decreased significantly, with an average of 0.8%. The reason for HBsAg carriage in children might be attributed to mother-to-infant transmission or not timely HBV vaccination.

Adult ; Child ; Child, Preschool ; China ; epidemiology ; Female ; Hepatitis B ; epidemiology ; immunology ; prevention & control ; transmission ; Hepatitis B Surface Antigens ; blood ; Hepatitis B Vaccines ; administration & dosage ; immunology ; Humans ; Infant ; Infectious Disease Transmission, Vertical ; Pregnancy ; Rural Population

OBJECTIVETo study the immune memory in vaccinees after the completion of a full schedule hepatitis B immunization.

METHODSOne thousand and two hundred one infants born in 1987 -1989 were immunized with 3 doses of plasma derived hepatitis B vaccine, while 2484 newborn babies during 1996-1999 were injected with 3 doses of the yeast recombinant hepatitis B vaccine. All of the infants under observation were tested for HBsAg, anti-HBs and anti-HBc, in 2005. Of 959 individuals negative for anti-HBs (< 10 mIU/ml), HBsAg and anti-HBc, 228 were immunized with plasma-derived vaccine and 731 with yeast recombinant vaccine after birth. All of them were detected for anti-HBs 15 days after a booster of 10 Ipg yeast recombinant vaccine. In addition, interleukin-2 (IL-2) was detected in 11 non-responders and 22 responders after boostering, using an enzyme-linked immunospot (ELISPOT). The anti-HBs levels of 190 individuals (91 with plasma derived vaccine and 99 with yeast recombinant vaccine) who had had quantitative data on their antibody status after the primary hepatitis B vaccination, were compared with that after the boostering.

RESULTSAmong the individuals who received plasma derived vaccine 16-18 years ago, 79.82% of them showed the signs of immune memory after one booster, with a geometric mean titer (GMT)of 325.69 mIU/ml. Of the individuals who received the yeast recombinant vaccine 6-9 years ago, 95.62% showed immune memory after one booster,with its GMT of 745.18 mIU/ml. Anti-HBs levels induced by the booster were associated with that after the primary immunization. The positive rate of IL-2 was 40.91% in subjects with good immune memory. However, IL-2 was not detected in non-responders after the booster (P < 0.01).

CONCLUSIONMost of the individuals who had received a completed schedule of primary hepatitis B vaccination and seroconverted from anti-HBs positive to negative,showed the signs of having immune memory after the booster. Only a small proportion of the vaccinees had lost their immune memory during the long term follow-up period, suggesting that these individuals should receive a booster of hepatitis B vaccine in the highly endemic areas of hepatitis B. Hepatitis B virus; Immune memory; Booster immunization

Antibody Formation ; Hepatitis B ; immunology ; prevention & control ; Hepatitis B Vaccines ; administration & dosage ; immunology ; Humans ; Immunization, Secondary ; Immunologic Memory ; Infant ; Infant, Newborn ; Interleukin-2 ; blood

BACKGROUNDUrsolic acid (UA) is a ubiquitous molecule in the plant kingdom with specific anticancer effects that have been shown in vitro and in vivo. Although UA can inhibit the proliferation of liver cancer cells and induce apoptosis of many types of tumor cells, the molecular mechanism of its anti-hepatoma activity is still not well defined. The objective of this study was to investigate the inhibitory effect and mechanisms of UA on the human hepatoma cell line SMMC-7721.

METHODSAfter treatment with UA, the growth inhibition of SMMC-7721 cells was assessed by MTT assay. Cells were also evaluated by flow cytometric analysis, Wright-Giemasa staining, Hoechst 33258 staining and transmission electron microscope after they were induced by UA. DNA microarray technology was used to investigate the gene expression pattern of SMMC-7721 cells exposed to UA 40 micromol/L. The molecular mechanism of cells death was analyzed by real-time RT-PCR and Western blotting.

RESULTSThe proliferation of SMMC-7721 cells was significantly inhibited in a dose- and time-dependent manner after UA treatment. UA induced cell cycle arrest and apoptosis. The DNA microarray analysis indicated that 64 genes were found to be markedly up- or down-expressed, including GDF15, SOD2, ATF3, and fos. The result of Western blotting showed the apoptotic proteins p53 and Bax were up-regulated while the anti-apoptotic protein Bcl-2 was down-regulated. Real-time RT-PCR confirmed UA could up-regulate the mRNA expressions of GDF15, SOD2, ATF3 and down-regulate the mRAN expression of fos. Meanwhile these effects were partly blocked by pretreatment with the p53 inhibitor Pft-alpha.

CONCLUSIONActivation of the p53 pathway is involved in UA inhibition of SMMC-7721 human hepatocellular carcinoma cell growth and induction of apoptosis.

Apoptosis ; drug effects ; Blotting, Western ; Carcinoma, Hepatocellular ; drug therapy ; metabolism ; Cell Cycle ; drug effects ; Cell Line, Tumor ; Flow Cytometry ; Humans ; Liver Neoplasms ; drug therapy ; metabolism ; Microscopy, Electron, Transmission ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; drug effects ; Triterpenes ; therapeutic use ; Tumor Suppressor Protein p53 ; metabolism

This study was aimed to investigate the clinical features of multiple myeloma (MM) complicated by spinal infiltration (extramedullary plasmacytoma) so as to enhance the understanding of this kind of MM and reduce the missed diagnosis for these MM patients. 10 patients with MM complicated by spinal infiltration were enrolled in this study. Bone marrow, blood, hepatic and renal function, electrolyte, beta2 microglobulin, C-reactive protein and immunoglobulin (M-protein) were detected. The involved spinal sites were examined by using magnetic resonance imaging (MRI) or computerized tomography (CT). 10 patients were staged according to International Stage System (ISS) and Duric-Salmon stage system. The clinical data of patients were analyzed. The results showed that among 10 cases of MM complicated by spinal infiltration, involved pectoral cord was observed in 7 cases, involved lumbar cord in 2 cases and sacral cord in 1 case. The treatment with operation and protocol containing cisplatin, ifosfamide etoposide, prednisone, and bortezomib in combination with other drugs indicated that the total remission rate was 80% (8/10), no serious adverse responses was observed. In conclusion, the patients with MM complicated by spinal infiltration must be diagnosed and treated as early as possible. Once paraplegia happened in patients, the therapeutic efficacy and prognosis would be very poor.
Adult ; Aged ; Female ; Humans ; Male ; Middle Aged ; Multiple Myeloma ; pathology ; Neoplasm Invasiveness ; Spinal Canal ; pathology ; Spinal Neoplasms ; secondary

OBJECTIVETo investigate the effects of inhaled short-acting bronchodilators on diaphragm function and neural respiratory drive in patients with chronic obstructive pulmonary disease (COPD) during maximal isocapnic ventilation (MIV).

METHODSForty-seven patient with moderate to severe COPD were randomized into 4 groups: placebo group (n=12), salbutamol group (n=13), ipratropium group (n=10), and combined group (salbutamol and ipratropium, n=12). Each subject received an initial MIV for 3 min at baseline and inhaled placebo (400 µg), salbutamol (400 µg), ipratropium (80 µg), or both salbutamol and ipratropium, followed 30 min later by another 3 min of MIV. The parameters of diaphragm function and neural respiratory drive were monitored continuously and calculated during MIV.

RESULTSDuring the initial MIV, all the patients experienced a linear increase in root mean square (RMS) of diaphragm electromyogram with a gradual decrease in transdiaphragmatic pressure (Pdi), minute ventilation (VE), and VE/RMS, and these parameters all improved significantly after inhalation of the bronchodilators. Compared with the placebo group at the same time point, the 3 bronchodilator-treated groups showed significantly decreased RMS and Borg score and increased Pdi, VE and VE/RMS; VE/RMS was the highest in the combined treatment group (P<0.05). The Delta Borg was significantly correlated with Delta Pdi, Delta VE, Delta RMS, and Delta VE/RMS (P<0.05).

CONCLUSIONSIn COPD patients, inhaled short-acting bronchodilators can alleviate diaphragm fatigue during MIV, increase lung ventilation, reduce neural respiratory drive, and improve neuro-ventilatory coupling to relieve dyspnoea, and the combination of β-2 agonists and anti-muscarinic antagonists produces a stronger efficacy.

Administration, Inhalation ; Albuterol ; therapeutic use ; Bronchodilator Agents ; therapeutic use ; Diaphragm ; drug effects ; Humans ; Ipratropium ; therapeutic use ; Pulmonary Disease, Chronic Obstructive ; drug therapy ; Respiration

OBJECTIVETo investigate the relationship between the circadian rhythm of perioperative cortisol secretion and neuropsychological states in patients undergoing coronary artery bypass grafting surgery.

METHODSForty male patients scheduled for elective coronary artery bypass grafting (CABG) under hypothermic cardio-pulmonary bypass (CPB) or off-pump were enrolled in this study. They were allocated into CPB group or off-pump group with 20 patients in each group. Blood samples were withdrawn during surgery at specific time-points and every 3 h for 24 h in the immediate postoperative period. Plasma cortisol was measured by radioimmunoassay. All subjects were investigated preoperatively as well as 7 to 10 d and 3 months postoperatively with a comprehensive neuropsychologic assessment, while depression and anxiety were assessed by Self-Rating Depression Scale and the State-Trait Anxiety Inventory respectively.

RESULTSDuring postoperative 24 h, three patients in the CPB group and 7 patients in the off-pump group were demonstrating a circadian secretion pattern, while they were disturbed in the remaining patients in both groups. Postoperative depression scores of patients in both groups were significantly higher than preoperative values. Postoperative anxiety scores of patients in the CPB group were significantly higher than those in the off-pump group. The CABG with CPB patients showed a significant deficit in the Digit Span subtest of the WAIS-R and the Stroop colour word interference test. The disturbed cortisol circadian secretion in the CPB group correlated with depression and the Stroop colour word interference test, whereas in the off-pump group it correlated with depression, Digit Span subtest (forward), symbol digit modalities test and the Stroop colour word interference test. Degree of depression correlated with some items of cognitive dysfunctions.

CONCLUSIONPerioperative secretion rhythm of cortisol in patients undergoing CABG surgery with CPB or off-pump was disturbed. The disordered cortisol may correlate directly or indirectly through mood with neuropsychological deficits.

Cardiopulmonary Bypass ; Circadian Rhythm ; Coronary Artery Bypass ; adverse effects ; psychology ; Coronary Artery Bypass, Off-Pump ; psychology ; Extracorporeal Circulation ; Humans ; Hydrocortisone ; secretion ; Hypothermia, Induced ; Intraoperative Period ; Male ; Middle Aged ; Postoperative Period