AbstractBackgroundContact tracing is especially useful for identifying an infection with few cases in the population, such as HIV in China. Little such research is available in China.MethodsEvery newly diagnosed HIV case from 2008–2010 in Taizhou Prefecture, Zhejiang Province in China, was invited to participate as an “index case” in a contact tracing survey by providing contact information for up to eight sexual contacts who themselves were approached for voluntary HIV counseling and testing (VCT). Those who tested HIV-positive were then subjected to another contact tracing survey. This process was repeated until no more sexual contacts were reported or tested positive.ResultsA total of 463 HIV-infected individuals were newly identified during the study period, including 338 cases who were identified from routine surveillance programs and 125 cases who were identified from the present contact tracing survey. Among these 463 cases, 398 (86.0%) served as ‘index cases’ in the survey, including 290 (85.8%) out of the 338 cases identified from routine surveillance programs and 108 (86.4%) out of the 125 cases identified from the present survey. These 398 ‘index cases’ reported a total of 1,403 contactable sexual contacts, of whom 320 (22.8%) received HIV testing and 125 (39.1%) tested positive for HIV. Willingness to receive HIV testing was high among spouses and long term heterosexual or homosexual partners but extremely low among casual and commercial sex partners of ‘index cases’. Consistent condom use was rare for all participants. A total of 290 independent sexual network components were constructed, with high complexity.ConclusionContact tracing is useful for identifying new HIV infections from spouses or long term sexual partners of HIV-infected individuals. The complicated sexual networks existing between and beyond HIV-infected persons provide opportunities for rapid spread of HIV in such areas.

Early detection has the potential to reduce cancer mortality, but an effective screening test must demonstrate asymptomatic cancer detection years before conventional diagnosis in a longitudinal study. In the Taizhou Longitudinal Study (TZL), 123,115 healthy subjects provided plasma samples for long-term storage and were then monitored for cancer occurrence. Here we report the preliminary results of PanSeer, a noninvasive blood test based on circulating tumor DNA methylation, on TZL plasma samples from 605 asymptomatic individuals, 191 of whom were later diagnosed with stomach, esophageal, colorectal, lung or liver cancer within four years of blood draw. We also assay plasma samples from an additional 223 cancer patients, plus 200 primary tumor and normal tissues. We show that PanSeer detects five common types of cancer in 88% (95% CI: 80-93%) of post-diagnosis patients with a specificity of 96% (95% CI: 93-98%), We also demonstrate that PanSeer detects cancer in 95% (95% CI: 89-98%) of asymptomatic individuals who were later diagnosed, though future longitudinal studies are required to confirm this result. These results demonstrate that cancer can be non-invasively detected up to four years before current standard of care.

The common aldehyde dehydrogenase 2 (ALDH2) alcohol flushing variant known as ALDH2*2 affects ∼8% of the world's population. Even in heterozygous carriers, this missense variant leads to a severe loss of ALDH2 enzymatic activity and has been linked to an increased risk of coronary artery disease (CAD). Endothelial cell (EC) dysfunction plays a determining role in all stages of CAD pathogenesis, including early-onset CAD. However, the contribution of ALDH2*2 to EC dysfunction and its relation to CAD are not fully understood. In a large genome-wide association study (GWAS) from Biobank Japan, ALDH2*2 was found to be one of the strongest single-nucleotide polymorphisms associated with CAD. Clinical assessment of endothelial function showed that human participants carrying ALDH2*2 exhibited impaired vasodilation after light alcohol drinking. Using human induced pluripotent stem cell-derived ECs (iPSC-ECs) and CRISPR-Cas9-corrected ALDH2*2 iPSC-ECs, we modeled ALDH2*2-induced EC dysfunction in vitro, demonstrating an increase in oxidative stress and inflammatory markers and a decrease in nitric oxide (NO) production and tube formation capacity, which was further exacerbated by ethanol exposure. We subsequently found that sodium-glucose cotransporter 2 inhibitors (SGLT2i) such as empagliflozin mitigated ALDH2*2-associated EC dysfunction. Studies in ALDH2*2 knock-in mice further demonstrated that empagliflozin attenuated ALDH2*2-mediated vascular dysfunction in vivo. Mechanistically, empagliflozin inhibited Na⁺/H⁺-exchanger 1 (NHE-1) and activated AKT kinase and endothelial NO synthase (eNOS) pathways to ameliorate ALDH2*2-induced EC dysfunction. Together, our results suggest that ALDH2*2 induces EC dysfunction and that SGLT2i may potentially be used as a preventative measure against CAD for ALDH2*2 carriers.