Search

The most suitable analytic method to systematically analyze numerous trials with contradictory results is unclear. Multiple trials assessing the use of N-acetylcysteine (NAC) for prevention of contrast-induced acute kidney injury (CI-AKI) have had contradictory results with recent trials confirming a lack of benefit.To systematically review the literature on NAC for the prevention of CI-AKI, and to explore the heterogeneity, publication bias, and small-study effect to determine the most suitable analytic method in a setting where the literature is contradictory.Medline, Embase, and Cochrane Central Register of Controlled Trials databases were used to find randomized clinical trials (RCTs) comparing NAC with any other prophylactic agent or placebo in adults.The search included studies published in English from database inception to January 2020. Two independent reviewers screened the studies, extracted data, and performed the risk of bias assessment.A meta-analysis was conducted about the effect of NAC on CI-AKI, the need for dialysis, and mortality. Fixed and random effects analyses were also performed. Funnel plots and the trim and fill method were used for assessment of publication bias. Metaregression was performed to explore the heterogeneity and subgroup analysis to examine the association between NAC and CI-AKI when studies were categorized according to sample size and number of events.A total of 101 trials were included in this meta-analysis. The median sample size was 112 (range, 20 to 4993). Twenty-nine trials had a sample size of 200 or more, and only 3 trials had a sample size of 500 or more. Forty-five trials reported the need for kidney replacement therapy, and 41 trials reported mortality as an outcome. NAC seemed to show a benefit, with a pooled OR of 0.72 (95% CI, 0.63-0.82) using random effects model and a pooled OR of 0.82 (95% CI 0.76-0.90) using a fixed effects model. However, there was significant heterogeneity (I2 = 37.6; P .001) and significant publication bias, which was reduced only when restricting to large RCTs (N ≥ 500). The clinical outcomes (ie, the need for kidney replacement therapy and mortality) revealed little heterogeneity and no publication bias, and each provided a robust neutral summary result.In this meta-analysis, NAC was associated with a benefit in the prevention of CI-AKI. However, because of substantial publication bias and other biases, standard meta-analytic techniques resulted in significant heterogeneity and a spurious, or factitious, association, even when using a random effects model. When the analysis was restricted to RCTs with a large sample size to account for publication bias or restricted to trials with clinical outcomes, this issue was reduced and resulted in more robust and neutral effect sizes.

Smoking carcinogen N-nitrosamines such as 4-methylnitrosamino-l-3-pyridyl-butanone (NNK) require metabolic activation to exert their genotoxicity. The first activation step is mainly catalyzed by cytochrome P450 (CYP) family. Estrogen receptor α (ERα) plays a role in lung pathology. The association between them is unknown. In this study, we explored the relationship and function of CYP1B1 and ERα in NNK-induced lung tumorigenesis. CYP1B1 and ERα expression was analyzed in human lung cancer tissues and NNK-induced lung tumor of A/J mice. Cell lines NCI-H23 and NCI-H460 were employed to further study the responsible mechanisms using various cellular and molecular approaches. Our in vivo experiments demonstrated that CYP1B1 and ERα were over-expressed at the early stage of NNK-induced lung tumorigenesis. Microarray analysis found that ERα was involved in the extracellular-signal-regulated kinase (ERK)/MAPK pathway. NNK activated RAS/ERK/AP1 as it remarkably increased the levels of p-ERK, c-Fos, and c-Jun but inhibited multiple negative regulators of Ras/ERK/AP1, Pdcd4, Spry1, Spry2, and Btg2 through up-regulating miR-21. Both CYP1B1 siRNA and ERK-specific inhibitor U0126 suppressed NNK-mediated ERα up-regulation, suggesting that ERα was downstream of CYP1B1 and ERK. ERK inactivation led to the accumulation of CYP1B1, indicating that CYP1B1 was upstream of ERK activation. Inhibition of ERK or ERα decreased NNK-induced cell proliferation. Blockage of CYP1B1 or ERα induced apoptosis of lung cancer cells. Collectively, NNK-mediated ERα induction is via CYP1B1 and ERK and contributes to the lung carcinogenesis. The inhibition of CYP1B1, ERK, or ERα may arrest the lung cancer cell growth, implicating a pivotal strategy for the treatment of lung cancer.Smoking carcinogen NNK requires metabolic activation to exert their genotoxicity. CYP1B1 is the enzyme to catalyze NNK. NNK activates CYP1B1 and ERK to induce ERα. Inhibition of CYP1B1, ERK, or ERα arrests the lung cancer cell growth.

Tobacco smoking can cause a number of cancers. The role of thromboxane synthase (TxAS) in smoking-related cancers is largely unknown. In this study, 37 pairs of tumor and non-tumor lung tissues of non-small-cell lung cancer, 5 lung cancer cell lines, and a mouse tumor model were used to study TxAS and its related molecules. A mouse model of smoking carcinogen 4-methylnitrosamino-1-3-pyridyl-1-butanone (NNK)-induced lung tumor showed an increase in TxAS. Thromboxane A2 receptor (TP) was aberrant in lung cancer tissues of smokers. TxAS and TP were increased in lung tissues of NNK-treated mice. The in vitro studies showed that TPα rather than TPβ promoted tumor growth, and NNK increased TPα. NNK-induced TxAS, which depended on activation of cyclooxygenase-2 (COX-2), ERK and NF-κB, could be inhibited by miR-34b/c. TPα played a positive role in NNK-induced COX-2/ERK/NF-κB activation, leading to the upregulation of TxAS expression and thromboxane A2 (TxA2) synthesis. The newly synthesized TxA2 could further activate TPα, forming an autoregulatory feedback loop for TPα activation. Collectively, NNK promotes lung tumor growth via inducing TxAS and TPα, which constitutes an auto-positive feedback loop to exaggerate the growth. This study suggests that TPα and TxAS are the ideal targets against smoking-related lung cancer.

Aim: To investigate the impact of the Pharmacy Outreach Service (POS) on blood pressure (BP) and disease knowledge among community-dwelling elderly patients with hypertension, and to evaluate the sustainability of such impact of POS. Methods: A prospective open-labeled study of elderly adults (aged ≥65 years) with hypertension (BP ≥140/90 mmHg for non-diabetics and ≥130/80 mmHg for diabetics) was carried out at seven elderly community centers from July 2008 to March 2010. Pharmacists provided BP monitoring, medication review and disease knowledge assessment. The target BP was

The depletion potential between two colloid particles immersed in a hard-core Yukawa fluid was investigated by density functional theory for the depletion potential proposed by Roth, Evans, and Dietrich. An attempt was made to study the effects of several factors concerning the colloid particles and the solvent molecules on the depletion potential, which are the size ratio of the colloid particle to the solvent, the interaction between solvent molecules, the packing fraction of the solvent, and the interaction between the colloid particle and the solvent. By means of the depletion potential presented under various conditions, it is shown that the effects of these factors on the depletion potential are significant and this can provide some useful clues on regulating the interaction between colloid particles in related experiments.

The Glauber model is modified with the Fermi-motion effect in the calculation of elastic differential cross-sections and momentum distributions of a fragment from mother nucleus. Different reaction systems at low energies are calculated with the modified Glauber model. It is found that calculations including the Fermi-motion provide a better prescription relating the model to a proper nuclear density distribution by comparing with the experimental data. On the basis of the studies, the influence of the correction on the extracted nuclear radius is quantified. The results further confirm the importance of the Fermi-motion in the nucleus–nucleus collision reactions at low energies.

To investigate the impact of the Pharmacy Outreach Service (POS) on blood pressure (BP) and disease knowledge among community-dwelling elderly patients with hypertension, and to evaluate the sustainability of such impact of POS.A prospective open-labeled study of elderly adults (aged ≥65 years) with hypertension (BP ≥140/90 mmHg for non-diabetics and ≥130/80 mmHg for diabetics) was carried out at seven elderly community centers from July 2008 to March 2010. Pharmacists provided BP monitoring, medication review and disease knowledge assessment. The target BP was140/90 mmHg for non-diabetics and130/80 mmHg for diabetics. The primary outcome was BP change, whereas the secondary outcome was the change of disease knowledge of hypertension. All outcomes were compared between baseline and the last visit. For POS 2008/09 participants, BP was compared between values obtained during POS 2008/09 and 2009/10.A total of 97 participants were recruited. Systolic BP reduced significantly from 152.38±18.80 mmHg to 147.04±20.72 mmHg (P=0.021), and diastolic BP reduced from 73.84±11.36 mmHg to 71.03±10.97 mmHg (P=0.010). Cumulative reductions in mean systolic BP and diastolic BP throughout the 2-year study period were 21.39±24.72 mmHg and 9.88±13.48 mmHg, respectively (P0.001). A 12% increase in the at-goal rate was observed in new participants recruited in 2009 (P=0.039). Disease knowledge of hypertension improved significantly (P0.005), particularly in areas that included the definition of hypertension, diet and lifestyle modification.The POS might improve blood pressure control, hypertension and diabetes knowledge in elderly adults with hypertension in Hong Kong. The effect on blood pressure improvement was sustainable.

The mechanism responsible for the apoptotic effect induced by ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F) is not fully understood and its in vivo effect has not been tested. In this study, the effect and mechanism of 5F was investigated in cigarette smoking carcinogen 4-methylnitrosamino-1-3-pyridyl-butanone (NNK)-induced mouse lung tumor model and in cultured lung cancer cells NCI-H23 and CRL-2066. 5F were given to mice after they were treated with NNK for 18 weeks. The effect of 5F on the lung tumor formation was examined, and its side effect was monitored. Cell proliferation and apoptosis were determined through expression of PCNA, Bcl-2, Bax, and TUNEL assay in in vivo animal model. 5F significantly inhibited the NNK-induced lung tumors by inducing apoptosis and suppressing cell proliferation in vivo with minimal side effects. Cell culture experiments showed that 5F translocated Bax into the mitochondria, downregulated Bcl-2, activated caspase-9 and caspase-3, released cytochrome c into the cytosol, and translocated AIF from the mitochondria to the nucleus, which leading to G2-M cell cycle arrest and cell apoptosis. 5F also activated ERK1/2 and the inhibition of ERK1/2 suppressed 5F-mediated changes in apoptotic molecules. In addition to ERK1/2, 5F activated Akt. The inhibition of Akt further facilitated the apoptosis induced, suggesting that Akt activation was anti-apoptotic rather than pro-apoptotic. Collectively, 5F is effective against lung cancer in vivo with minimal side effects. It induces apoptosis in lung cancer through the mitochondrial-mediated pathway, in which the activation of ERK is critical.

Peroxisome proliferator-activated receptor (PPAR)-α and PPARγ participate in cell proliferation and apoptosis. Few studies have simultaneously investigated both PPARα and PPARγ in lung cancers in vivo. The roles of PPARα and -γ were investigated in the development of pulmonary tumors induced in the adult A/J mouse by treatment with 4-(methylnitrosamino)-l-(3-pyridyl)-lbutanone (NNK). Compared with the normal lung tissues, PPARγ expression was much higher in the NNK-induced lung tumor tissues. However, PPARγ transcriptional activity, and the levels of two major endogenous PPARγ ligands, 13-hydroxyoctadecadienoic acid and 15-hydroxyeicosatetraenoic acid, were significantly lower in the NNK-treated lung tissues. The ligand changes in mice were confirmed in human lung cancer tissues. Along with the alteration of PPARγ and its endogenous ligands, the level of PPARα and its activity were increased in the NNK-induced mouse lung tumors. Treatment of mice with the synthetic PPARγ ligand, pioglitazone, significantly inhibited the formation of mouse lung tumors induced by NNK. Our study demonstrated that the reduction of endogenous PPARγ ligands and increased PPARα occurred before the formation of lung tumors, indicating that the molecular changes play a role in lung carcinogenesis. The results suggest that the enhancement of PPARγ activity with its ligands, and the suppression of PPARα with its inhibitors, may prevent the formation of lung tumors, as well as accelerate the therapy of lung cancer. Our findings may also reveal the possibility of using the level of endogenous PPARγ ligands and the activities of PPARγ or PPARα as tumor markers for lung cancer.

A study on pulmonary hemodynamics, radionuclide right ventricular ejection fraction and blood gas analysis in 62 cases of COPD induced cor pulmonale at different stages showed the following results: 1. In early stage of cor pulmonale, stroke volume could not increase after exercise, it proved that cardiac reserve has been reduced; 2. With the progression of the disease, cardiac stroke volume reduced but cardiac output increased gradually, it could be considered as the evolutionary characteristic of cardiac function in chronic cor pulmonale; 3. The right ventricular stroke work was normal and could increase with the rise of after-load, reflecting the relatively effective functional compensation; 4. In acute exacerbation of cor pulmonale, the cardiac failure should be attributed to hyperdynamic type with hypervolemia; 5. Correlation analyses suggested that cardiac output decreased along with the increase of right ventricular afterload only in acute exacerbation of late cor pulmonale; PaO2 and PaCO2 have only slight influence on right ventricular function.

SUMMARY: Fourteen of the sixteen nucleotides present in extracts of Dictyostelium discoideum were identified by thin-layer chromatography. Data are presented describing the incorporation of radioactive bases into the guanine nucleotide pools and into RNA. Studies with labelled guanine suggested that a small fraction of the RNA undergoes rapid turnover at the pre-culmination stage of differentiation. Analytical methods are described for determining flux rates in vivo and the percentage turnover of endogenous pools.