PCSK9 inhibitor added to high-intensity statin therapy to prevent cardiovascular events in patients with acute coronary syndrome after percutaneous coronary intervention: a randomized, double- blind, placebo-controlled, multicenter SHAWN study.

BACKGROUND: It is currently uncertain whether the combination of a proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor and high-intensity statin treatment can effectively reduce cardiovascular events in patients with acute coronary syndrome (ACS) who have undergone percutaneous coronary intervention (PCI) for culprit lesions. METHODS: This study protocol describes a double-blind, randomized, placebo-controlled, multicenter study aiming to investigate the efficacy and safety of combining a PCSK9 inhibitor with high-intensity statin therapy in patients with ACS following PCI. A total of 1,212 patients with ACS and multiple lesions will be enrolled and randomly assigned to receive either PCSK9 inhibitor plus high-intensity statin therapy or high-intensity statin monotherapy. The randomization process will be stratified by sites, diabetes, initial presentation and use of stable (≥4 weeks) statin treatment at presentation. PCSK 9 inhibitor or its placebo is injected within 4 hours after PCI for the culprit lesion. The primary endpoint is the composite of cardiovascular death, myocardial infarction, stroke, re-hospitalization due to ACS or heart failure, or any ischemia-driven coronary revascularization at 1-year follow-up between 2 groups. Safety endpoints mean PCSK 9 inhibitor and statin intolerance. CONCLUSION: The SHAWN study has been specifically designed to evaluate the effectiveness and safety of adding a PCSK9 inhibitor to high-intensity statin therapy in patients who have experienced ACS following PCI. The primary objective of this study is to generate new evidence regarding the potential benefits of combining a PCSK9 inhibitor with high-intensity statin treatment in reducing cardiovascular events among these patients.

Zinc as a countermeasure for cadmium toxicity.

Cadmium (Cd) is an important environmental pollutant and long-term Cd exposure is closely related to autoimmune diseases, cancer, cardiovascular diseases (CVD), and hepatic dysfunction. Zinc (Zn) is an essential metal that plays key roles in protein structure, catalysis, and regulation of their function. Numerous studies have shown that Zn can reduce Cd toxicity; however, the underlying mechanisms have not been extensively explored. Preclinical studies have revealed direct competition for sarcolemmal uptake between these two metals. Multiple sarcolemmal transporters participate in Cd uptake, including Zn transporters, calcium channels, and DMT1 (divalent metal transporter 1). Zn also induces several protective mechanisms, including MT (metallothionein) induction and favorable redox homeostasis. This review summarizes current knowledge related to the role of Zn and metal transporters in reducing Cd toxicity and discusses potential future directions of related research.

Zinc protects against cadmium-induced toxicity in neonatal murine engineered cardiac tissues via metallothionein-dependent and independent mechanisms.

Cadmium (Cd) is a nonessential heavy metal and a prevalent environmental toxin that has been shown to induce significant cardiomyocyte apoptosis in neonatal murine engineered cardiac tissues (ECTs). In contrast, zinc (Zn) is a potent metallothionein (MT) inducer, which plays an important role in protection against Cd toxicity. In this study, we investigated the protective effects of Zn against Cd toxicity in ECTs and explore the underlying mechanisms. ECTs were constructed from neonatal ventricular cells of wild-type (WT) mice and mice with global MT gene deletion (MT-KO). In WT-ECTs, Cd (5-20 µM) caused a dose-dependent toxicity that was detected within 8 h evidenced by suppressed beating, apoptosis, and LDH release; Zn (50-200 µM) dose-dependently induced MT expression in ECTs without causing ECT toxicity; co-treatment of ECT with Zn (50 µM) prevented Cd-induced toxicity. In MT-KO ECTs, Cd toxicity was enhanced; but unexpectedly, cotreatment with Zn provided partial protection against Cd toxicity. Furthermore, Cd, but not Zn, significantly activated Nrf2 and its downstream targets, including HO-1; inhibition of HO-1 by a specific HO-1 inhibitor, ZnPP (10 µM), significantly increased Cd-induced toxicity, but did not inhibit Zn protection against Cd injury, suggesting that Nrf2-mediated HO-1 activation was not required for Zn protective effect. Finally, the ability of Zn to reduce Cd uptake provided an additional MT-independent mechanism for reducing Cd toxicity. Thus, Zn exerts protective effects against Cd toxicity for murine ECTs that are partially MT-mediated. Further studies are required to translate these findings towards clinical trials.

miR-125a inhibits porcine preadipocytes differentiation by targeting ERRα.

MicroRNAs are a family of small, non-coding RNAs that regulate gene expression in a sequence-specific manner. Estrogen-related receptor α (ERRα) is an orphan nuclear receptor which plays an important role in adipocyte differentiation. Our previous Solexa sequencing results indicated a high expression of miR-125a in adult pig backfat. In this study, we predicated and experimentally validated ERRα as a target of miR-125a. To explore the role of miR-125a in porcine preadipocytes differentiation, miRNA agomir and antagomir were used to perform miR-125a overexpression or knockdown, respectively. Our results showed that overexpression of miR-125a could dramatically reduce the mRNA expression of adipogenic markers PPARγ, LPL, and aP2, as well as its target gene ERRα. Western blotting showed the protein level of aP2 and ERRα was also significantly down-regulated. The overexpression of miR-125a also led to a notable reduction in lipid accumulation which was detected by Oil Red O staining. In contrast, we observed promoted differentiation of porcine preadipocytes upon miR-125a inhibition. In conclusion, we verified miR-125a inhibits porcine preadipocytes differentiation through targeting ERRα for the first time, which may provide new insights in pork quality improvement and obesity control.

Efficacy of a combined contraceptive regimen consisting of condoms and emergency contraception pills.

BACKGROUND: To evaluate and compare the effectiveness of the combined regimen (consisting of condoms and emergency contraception pills (ECP)) and using condoms only for the purpose of preventing pregnancy. METHODS: One-thousand-five-hundred-and-sixty-two (1,562) couples as volunteers enrolled at nine centers in Shanghai. Eight-hundred-and-twelve (812) were randomized to use male condoms and ECP (i.e., Levonorgestrel) as a back-up to condoms (the intervention group) and 750 to use male condoms only(the control group), according to their working unit. Participants were visited at admission and at the end of 1, 3, 6, 9, and 12 months. The cumulative life table rates were calculated for pregnancy and other reasons for discontinuation. RESULT: The gross cumulative life table rates showed that the cumulative discontinuation rates for all reasons during the year of follow-up in the condoms plus emergency contraception group and the condoms only group were 7.76 ± 0.94 and 6.61 ± 0.91, respectively, per 100 women (χ2 = 0.41, p = 0.5227). The cumulative gross pregnancy rate of the condoms plus emergency contraception group and the condoms only group were 2.17 ± 0.52 and 1.25 ± 0.41, respectively, per 100 women (χ2 = 1.93, p = 0.1645). The Pearl Index in the condoms plus emergency contraception group and the condoms only group were 2.21% and 1.26%, respectively. CONCLUSION: Male condoms remain a highly effective contraceptive method for a period of one year while consistently and correctly used. In addition, the lowest pregnancy rate followed from perfect use condom.

MicroRNA-199a-5p affects porcine preadipocyte proliferation and differentiation.

MicroRNAs (miRNAs), a class of small non-coding RNAs, have emerged as novel and potent regulators of adipogenesis. However, few miRNAs have been fully investigated in porcine adipogenesis, given the fact that pig is not only an apropos model of human obesity research, but also a staple meat source of human diet. In this study, we showed that miRNA-199a-5p is highly expressed in porcine subcutaneous fat deposits compared to several other tissue types and organs measured alongside. Overexpression of miR-199a-5p in porcine preadipocytes significantly promoted cell proliferation while attenuating the lipid deposition in porcine adipocytes. By target gene prediction and experimental validation, we demonstrated that caveolin-1 (Cav-1) may be a bona fide target of miR-199a-5p in porcine adipocytes, accounting for some of miR-199a-5p's functions. Taken together, our data established a role of miR-199a-5p in porcine preadipocyte proliferation and differentiation, which is at least partially played by downregulating Cav-1.

Unmarried male migrants and sexual risk behavior: a cross-sectional study in Shanghai, China.

BACKGROUND: In China, there is increasing concern because of the rapid increase in HIV infection recorded over recent years. Migrant workers are recognized as one of the groups most affected. In this study, HIV/AIDS-related knowledge, attitudes, and behavior among unmarried migrant workers in Shanghai are investigated, with the aim of providing critical information for policy makers and sex educators to reinforce sexual health services and sex health education targeting the behavior and sexual health of unmarried male migrants. METHODS: A cross-sectional survey was conducted among unmarried male migrant workers in Shanghai, China's largest city and housing the most migrants. A self-administered, anonymous questionnaire was used to collect information on knowledge, attitudes, and behavior associated with increased risk of HIV/AIDS. RESULTS: A total of 2254 subjects were questioned, with a response rate of 91.3%. Among those interviewed, 63.5% reported sexual activities. Misconceptions regarding HIV transmission, poor perception of HIV infection, and low use of condoms were not uncommon. Among those who had sexual intercourse, 73.7% had not used condoms in their last sexual intercourse, and 28.6% reported having engaged in sexual risk behavior (defined as having at least one non-regular partner). Multivariate logistic regression analyses identified several indicators of sexual risk behavior, including younger age at first sexual intercourse (OR: 0.67, 95% CI: 0.31-0.91 for older age at first sexual intercourse), more cities of migration (OR: 2.91, 95% CI: 2.17-3.81 for high level; OR: 1.15, 95% CI: 1.06-1.29 for medium level), poor perception of acquiring HIV/AIDS (OR: 1.52, 95% CI: 1.33-1.96 for unlikely; OR: 2.38, 95% CI: 1.61-3.70 for impossible), frequent exposure to pornography (OR: 0.33, 95% CI: 0.11-0.43 for never; OR: 0.69, 95% CI: 0.60-1.81 for less frequently), not knowing someone who had or had died of HIV/AIDS and related diseases (OR: 2.13, 95% CI: 1.70-2.53 for no), and having peers who engaged in sex with a non-regular sex partner (OR: 4.40, 95% CI: 3.37-5.56 for yes). CONCLUSIONS: Today, it is necessary to reinforce sex health education among unmarried migrants and sexual health services should target vulnerable migrant young people.

Exacerbation of diabetic cardiac hypertrophy in OVE26 mice by angiotensin II is associated with JNK/c-Jun/miR-221-mediated autophagy inhibition.

Both diabetes and angiotensin II (Ang II) excess trigger cardiac remodeling and dysfunction, and diabetic cardiomyopathy. We hypothesized that cardiac hypertrophy associated with the development of diabetic cardiomyopathy is worsened by increased Ang II. Male type 1 diabetic OVE26 and wild-type mice were given Ang II (sc., 1.15 mg/kg, twice a day) for 14 days. Diabetes-induced cardiac dysfunction and hypertrophy was exacerbated by Ang II treatment as determined by echocardiography, wheat germ agglutinin staining and atrial natriuretic peptide. Ang II treatment dramatically exacerbated diabetes-caused decreased LC3-II, a marker of autophagy, and increased p62, an indicator of cytosolic protein clearance. Ang II treatment also augmented diabetes-associated increased phosphorylated levels of c-Jun, JNK, mTOR, and miR-221, and decreased of p27 expression, a direct target of miR-221. Chromatin immunoprecipitation assay showed that Ang II elevated c-Jun binding to the promoter of miR-221 in diabetic mice. These results suggest that Ang II accelerates cardiac hypertrophy in the early stage of murine diabetes, probably through activation of the JKN/c-Jun/miR-221 axis and inhibition of downstream autophagy. Therefore, inhibition of Ang II or miR-221 in diabetic individuals may be a potential approach for delaying the onset and/or reducing the severity of diabetic cardiomyopathy.

Male rural-to-urban migrants and risky sexual behavior: a cross-sectional study in Shanghai, China.

This study examined the prevalence and the determinants of risky sexual behavior (defined as having multiple sex partners and paying for sex) among male rural-to-urban migrants in China. An anonymous questionnaire was used to collect information on socio-demographics, knowledge, attitudes, and behavior associated with increased risk of risky sexual behavior from 4,069 subjects. In total 1,132 (27.8%) participants reported two or more sex partners and 802 (19.7%) participants paid for sex. A considerable proportion (29.6%-41.5%) did not use a condom during risky sexual behavior. Logistic regression analysis revealed that unmarried status (OR: 0.62, CI: 0.42-0.85 for married), earlier age at first sexual experience (OR: 0.67, 95% CI: 0.31-0.91 for ≥ 22 years old), poor perception of risk of acquiring HIV/AIDS (OR: 1.51, 95% CI: 1.33-1.96 for unlikely; OR: 2.38, 95% CI: 1.61-3.70 for impossible), frequent exposure to pornography (OR: 0.67, 95% CI: 0.60-0.81 for sometimes; OR: 0.31, 95% CI: 0.11-0.43 for never), attitudes toward legalization of commercial sex (OR: 0.39, 95% CI: 0.21-0.59 for no), peer influence (OR: 0.51, 95% CI: 0.27-0.88 for no), and not knowing someone who had/had died from HIV/AIDS (OR: 0.35, 95% CI: 0.20-0.53 for yes) were all significantly associated with having multiple sex partners. Those who paid for sex showed similar findings.