The mutagenic forces shaping the genomic landscape of lung cancer in never smokers.

Lung cancer in never smokers (LCINS) accounts for up to 25% of all lung cancers and has been associated with exposure to secondhand tobacco smoke and air pollution in observational studies. Here, we evaluate the mutagenic exposures in LCINS by examining deep whole-genome sequencing data from a large international cohort of 871 treatment-naïve LCINS recruited from 28 geographical locations within the Sherlock-Lung study. KRAS mutations were 3.8-fold more common in adenocarcinomas of never smokers from North America and Europe, while a 1.6-fold higher prevalence of EGFR and TP53 mutations was observed in adenocarcinomas from East Asia. Signature SBS40a, with unknown cause, was found in most samples and accounted for the largest proportion of single base substitutions in adenocarcinomas, being enriched in EGFR-mutated cases. Conversely, the aristolochic acid signature SBS22a was almost exclusively observed in patients from Taipei. Even though LCINS exposed to secondhand smoke had an 8.3% higher mutational burden and 5.4% shorter telomeres, passive smoking was not associated with driver mutations in cancer driver genes or the activities of individual mutational signatures. In contrast, patients from regions with high levels of air pollution were more likely to have TP53 mutations while exhibiting shorter telomeres and an increase in most types of somatic mutations, including a 3.9-fold elevation of signature SBS4 (q-value=3.1 × 10-5), previously linked mainly to tobacco smoking, and a 76% increase of clock-like signature SBS5 (q-value=5.0 × 10-5). A positive dose-response effect was observed with air pollution levels, which correlated with both a decrease in telomere length and an elevation in somatic mutations, notably attributed to signatures SBS4 and SBS5. Our results elucidate the diversity of mutational processes shaping the genomic landscape of lung cancer in never smokers.

Retrohepatic vena cava deroofing in living donor liver transplantation for caudate hepatocellular carcinoma.

The removal of tumor together with the native liver in living donor liver transplantation for hepatocellular carcinoma is challenged by a very close resection margin if the tumor abuts the inferior vena cava. This is in contrast to typical deceased donor liver transplantation where the entire retrohepatic inferior vena cava is included in total hepatectomy. Here we report a case of deroofing the retrohepatic vena cava in living donor liver transplantation for caudate hepatocellular carcinoma. In order to ensure clear resection margins, the anterior portion of the inferior vena cava was included. The right liver graft was inset into a Dacron vascular graft on the back table and the composite graft was then implanted to the recipient inferior vena cava. Using this technique, we observed the no-touch technique in tumor removal, hence minimizing the chance of positive resection margin as well as the chance of shedding of tumor cells during manipulation in operation.

Thromboxane synthase suppression induces lung cancer cell apoptosis via inhibiting NF-κB.

Accumulating evidence shows that the inhibition of thromboxane synthase (TXS) induced apoptosis in cancer cells. TXS inhibitor 1-Benzylimidzole (1-BI) can trigger apoptosis in lung cancer cells but the mechanism is not fully defined. In this study, lung cancer cells were treated with 1-BI. In this study, the level of reactive oxygen species (ROS) was measured and NF-κB activity was determined in human lung cancer cells. The roles of ROS and NF-κB in 1-BI-mediated cell death were analyzed. The results showed that 1-BI induced ROS generation but decreased the activity of NF-κB by reducing phosphorylated IκBα (p-IκBα) and inhibiting the translocation of p65 into the nucleus. In contrast to 1-BI, antioxidant N-acetyl cysteine (NAC) stimulated cell proliferation and significantly protected the cells from 1-BI-mediated cell death by neutralizing ROS. Collectively, apoptosis induced by 1-BI is associated with the over-production of ROS and the reduction of NF-κB. Antioxidants can significantly block the inhibitory effect of 1-BI.

Patterns of Sedentary Behavior among Older Adults in Care Facilities: A Scoping Review.

Understanding the sedentary patterns can guide the design of strategies to engage older adults in physical activity. This scoping review aimed to synthesize available evidence on sedentary behaviors in care facilities. We searched PubMed/MEDLINE and Web of Science for studies published from inception through October 2020. Eighteen studies were included and reviewed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Data obtained were analyzed based on levels of care provided. Overall, daily sedentary time was higher among residents in high level care facilities (e.g., nursing homes) (11.6 h/day) than intermediate/mixed level care facilities (e.g., assisted living) (9.5 h/day). In intermediate/mixed level care facilities, television (TV) viewing was the most common sedentary activity (2.5-2.9 h/day; 26% of daily sedentary time), while napping was the most favorite sedentary activity (4.7 h/day; 36% of waking hours) in high level care facilities. Sex differences in daily patterns of sedentary behavior (sedentary time, uninterrupted bouts, and bout durations) were commonly observed in intermediate/mixed level care facilities, as exemplified by men being more sedentary by 0.7-1.1 h/day. In summary, this study highlights distinctive sedentary patterns among older adults residing in different levels of care facilities, addressing a pressing need for customized interventions to engage care facility residents in physical activity.

Mind-Body Health Benefits of Traditional Chinese Qigong on Women: A Systematic Review of Randomized Controlled Trials.

Most women live with an inactive lifestyle, which suggests a need for preference-based choices to promote their participation in physical activity. This systematic review synthesized key findings on the health benefits of Qigong among women. We conducted a systematic search of randomized controlled trials (RCTs) of Qigong among women according to the PRISMA guidelines using the following databases from their inception through March 2021: PubMed/MEDLINE, Web of Science, Cochrane Library, and US National Library of Medicine. The risk of bias was examined using the Cochrane Collaboration's tool for assessing the risk of bias in randomized trials. Altogether, 18 RCTs were included for final review. Results showed that Qigong was a feasible exercise in improving health outcomes, particularly depressive symptoms (63% of trials), quality of life (43%), and fatigue (29%), among general women, intimate partner violence survivors, and women with chronic conditions (e.g., breast cancer patients or survivors). Almost 90% (7/8) of trials reported high adherence rates ranging from 73 to 95% for supervised group training and 63 to 80% for home self-practice. Thus far, there was no evidence of serious adverse effects from performing Qigong. For the risk of bias across trials, a lack of allocation concealment (72% of trials), no blinding of participants and personnel (67%), and incomplete outcome data (67%) were the major sources. In summary, Qigong is a safe, feasible, and beneficial exercise for general women, abused sufferers, and health-compromised women. However, given the potential risk of bias found in many studies, improved rigor of study design in future trials will be imperatively required.

Inhibition of thromboxane synthase induces lung cancer cell death via increasing the nuclear p27.

The role of thromboxane in lung carcinogenesis is not clearly known, though thromboxane B2 (TXB(2)) level is increased and antagonists of thromboxane receptors or TXA2 can induce apoptosis of lung cancer cells. p27, an atypical tumor suppressor, is normally sequestered in the nucleus. The increased nuclear p27 may result in apoptosis of tumor cells. We hypothesize that the inhibition of thromboxane synthase (TXS) induces the death of lung cancer cells and that such inhibition is associated with the nuclear p27 level. Our experiment showed that the inhibition of TXS significantly induced the death or apoptosis in lung cancer cells. The activity of TXS was increased in lung cancer. The nuclear p27 was remarkably reduced in lung cancer tissues. The inhibition of TXS caused the cell death and apoptosis of lung cancer cells, likely via the elevation of the nuclear p27 since the TXS inhibition promoted the nuclear p27 level and the inhibition of p27 by its siRNA recovered the cell death induced by TXS inhibition. Collectively, lung cancer cells produce high levels of TXB(2) but their nuclear p27 is markedly reduced. The inhibition of TXS results in the p27-related induction of cell death in lung cancer cells.