The role of upfront primary tumor resection in asymptomatic patients with unresectable stage IV colorectal cancer: A systematic review and meta-analysis

BackgroundControversy exists over the role of upfront primary tumor resection (PTR) in asymptomatic patients with unresectable stage IV colorectal cancer (CRC). The purpose of this study was to evaluate the effect of upfront PTR on survival outcomes and adverse outcomes.MethodsSearches were conducted on PubMed, EMBASE, Web of Science, and Cochrane Library from inception to August 2021. Studies comparing survival outcomes with or without adverse outcomes between PTR and non-PTR treatments were included. Review Manager 5.3 was applied for meta-analyses with a random-effects model whenever possible.ResultsOverall, 20 studies with 3,088 patients were finally included in this systematic review. Compared with non-PTR, upfront PTR was associated with better 3-year (HR: 0.69, 95% CI, 0.57–0.83, P = 0.0001) and 5-year overall survival (OS) (HR: 0.77, 95% CI, 0.62–0.95, P = 0.01), while subgroup analysis indicated that there was no significant difference between upfront PTR and upfront chemotherapy (CT) group. In addition, grade 3 or higher adverse effects due to CT were more frequent in the PTR group with marginal significance (OR: 1.74, 95% CI, 0.99–3.06, P = 0.05), and other adverse outcomes were comparable.ConclusionsPTR might be related to improved OS for asymptomatic patients with unresectable stage IV CRC, whereas receiving upfront CT is a rational alternative without detrimental influence on survival or adverse outcomes compared with upfront PTR.Systematic Review Registrationhttps://www.crd.york.ac.uk/prospero/display_record.php?RecordID=27267

Successful transplantation of guinea pig gut microbiota in mice and its effect on pneumonic plague sensitivity

Microbiota-driven variations in the inflammatory response are predicted to regulate host responses to infection. Increasing evidence indicates that the gastrointestinal and respiratory tracts have an intimate relationship with each other. Gut microbiota can influence lung immunity whereby gut-derived injurious factors can reach the lungs and systemic circulation via the intestinal lymphatics. The intestinal microbiota’s ability to resist colonization can be extended to systemic infections or to pathogens infecting distant sites such as the lungs. Unlike the situation with large mammals, the microtus Yersinia pestis 201 strain exhibits strong virulence in mice, but nearly no virulence to large mammals (such as guinea pigs). Hence, to assess whether the intestinal microbiota from guinea pigs was able to affect the sensitivity of mice to challenge infection with the Y. pestis 201 strain, we fed mice with guinea pig diets for two months, after which they were administered 0.5 ml of guinea pig fecal suspension for 30 days by oral gavage. The stools from each mouse were collected on days 0, 15, and 30, DNA was extracted from them, and 16S rRNA sequencing was performed to assess the diversity and composition of the gut microbiota. We found that the intestinal microbiota transplants from the guinea pigs were able to colonize the mouse intestines. The mice were then infected with Yersinia pestis 201 by lung invasion, but no statistical difference was found in the survival rates of the mice that were colonized with the guinea pig’s gut microbiota and the control mice. This indicates that the intestinal microbiota transplantation from the guinea pigs did not affect the sensitivity of the mice to pneumonic plague

Elevated first-trimester hepcidin level is associated with reduced risk of iron deficiency anemia in late pregnancy: a prospective cohort study

BackgroundIron deficiency (ID) and iron deficiency anemia (IDA) during pregnancy are highly prevalent worldwide. Hepcidin is considered an important biomarker of iron status. Currently, few longitudinal cohort studies have assessed the potential causal relationship between hepcidin and ID/IDA. Therefore, we aimed to investigate the association of first-trimester maternal serum hepcidin with third-trimester ID/IDA risk in a prospective cohort.MethodsTotal of 353 non-ID/IDA pregnant women at 11–13 weeks’ gestation were enrolled in Southern China and followed up to 38 weeks of gestation. Data on demography and anthropometry were obtained from a structured questionnaire at enrollment. Iron biomarkers including hepcidin were measured at enrollment and follow-up. Regression models were used to evaluate the association of first-trimester hepcidin with third-trimester ID/IDA risk.ResultsSerum hepcidin levels substantially decreased from 19.39 ng/mL in the first trimester to 1.32 ng/mL in the third trimester. Incidences of third-trimester ID and IDA were 46.2 and 11.4%, respectively. Moreover, moderate and high levels of first-trimester hepcidin were positively related to third-trimester hepcidin (log-transformed β = 0.51; 95% CI = 0.01, 1.00 and log-transformed β = 0.66; 95% CI = 0.15, 1.17). Importantly, elevated first-trimester hepcidin was significantly associated with reduced risk of third-trimester IDA (OR = 0.38; 95% CI = 0.15, 0.99), but not with ID after adjustment with potential confounders.ConclusionFirst-trimester hepcidin was negatively associated with IDA risk in late pregnancy, indicating higher first-trimester hepcidin level may predict reduced risk for developing IDA. Nonetheless, given the limited sample size, larger studies are still needed

Clinical and radiological characteristics of pediatric COVID-19 before and after the Omicron outbreak: a multi-center study

IntroductionThe emergence of the Omicron variant has seen changes in the clinical and radiological presentations of COVID-19 in pediatric patients. We sought to compare these features between patients infected in the early phase of the pandemic and those during the Omicron outbreak.MethodsA retrospective study was conducted on 68 pediatric COVID-19 patients, of which 31 were infected with the original SARS-CoV-2 strain (original group) and 37 with the Omicron variant (Omicron group). Clinical symptoms and chest CT scans were examined to assess clinical characteristics, and the extent and severity of lung involvement.ResultsPediatric COVID-19 patients predominantly had normal or mild chest CT findings. The Omicron group demonstrated a significantly reduced CT severity score than the original group. Ground-glass opacities were the prevalent radiological findings in both sets. The Omicron group presented with fewer symptoms, had milder clinical manifestations, and recovered faster than the original group.DiscussionThe clinical and radiological characteristics of pediatric COVID-19 patients have evolved with the advent of the Omicron variant. For children displaying severe symptoms warranting CT examinations, it is crucial to weigh the implications of ionizing radiation and employ customized scanning protocols and protective measures. This research offers insights into the shifting disease spectrum, aiding in the effective diagnosis and treatment of pediatric COVID-19 patients

Crowd-sourced machine learning prediction of long COVID using data from the National COVID Cohort Collaborative.

BACKGROUND: While many patients seem to recover from SARS-CoV-2 infections, many patients report experiencing SARS-CoV-2 symptoms for weeks or months after their acute COVID-19 ends, even developing new symptoms weeks after infection. These long-term effects are called post-acute sequelae of SARS-CoV-2 (PASC) or, more commonly, Long COVID. The overall prevalence of Long COVID is currently unknown, and tools are needed to help identify patients at risk for developing long COVID. METHODS: A working group of the Rapid Acceleration of Diagnostics-radical (RADx-rad) program, comprised of individuals from various NIH institutes and centers, in collaboration with REsearching COVID to Enhance Recovery (RECOVER) developed and organized the Long COVID Computational Challenge (L3C), a community challenge aimed at incentivizing the broader scientific community to develop interpretable and accurate methods for identifying patients at risk of developing Long COVID. From August 2022 to December 2022, participants developed Long COVID risk prediction algorithms using the National COVID Cohort Collaborative (N3C) data enclave, a harmonized data repository from over 75 healthcare institutions from across the United States (U.S.). FINDINGS: Over the course of the challenge, 74 teams designed and built 35 Long COVID prediction models using the N3C data enclave. The top 10 teams all scored above a 0.80 Area Under the Receiver Operator Curve (AUROC) with the highest scoring model achieving a mean AUROC of 0.895. Included in the top submission was a visualization dashboard that built timelines for each patient, updating the risk of a patient developing Long COVID in response to clinical events. INTERPRETATION: As a result of L3C, federal reviewers identified multiple machine learning models that can be used to identify patients at risk for developing Long COVID. Many of the teams used approaches in their submissions which can be applied to future clinical prediction questions. FUNDING: Research reported in this RADx® Rad publication was supported by the National Institutes of Health. Timothy Bergquist, Johanna Loomba, and Emily Pfaff were supported by Axle Subcontract: NCATS-STSS-P00438

SIRT1 Overexpression Antagonizes Cellular Senescence with Activated ERK/S6k1 Signaling in Human Diploid Fibroblasts

Sir2, a NAD-dependent deacetylase, modulates lifespan in yeasts, worms and flies. The SIRT1, mammalian homologue of Sir2, regulates signaling for favoring survival in stress. But whether SIRT1 has the function to influence cell viability and senescence under non-stressed conditions in human diploid fibroblasts is far from unknown. Our data showed that enforced SIRT1 expression promoted cell proliferation and antagonized cellular senescence with the characteristic features of delayed Senescence-Associated β-galactosidase (SA-β-gal) staining, reduced Senescence-Associated Heterochromatic Foci (SAHF) formation and G1 phase arrest, increased cell growth rate and extended cellular lifespan in human fibroblasts, while dominant-negative SIRT1 allele (H363Y) did not significantly affect cell growth and senescence but displayed a bit decreased lifespan.. Western blot results showed that SIRT1 reduced the expression of p16INK4A and promoted phosphorylation of Rb. Our data also exposed that overexpression of SIRT1 was accompanied by enhanced activation of ERK and S6K1 signaling. These effects were mimicked in both WI38 cells and 2BS cells by concentration-dependent resveratrol, a SIRT1 activator. It was noted that treatment of SIRT1-.transfected cells with Rapamycin, a mTOR inhibitor, reduced the phosphorylation of S6K1 and the expression of Id1, implying that SIRT1-induced phosphorylation of S6K1 may be partly for the decreased expression of p16INK4A and promoted phosphorylation of Rb in 2BS. It was also observed that the expression of SIRT1 and phosphorylation of ERK and S6K1 was declined in senescent 2BS. These findings suggested that SIRT1-promoted cell proliferation and antagonized cellular senescence in human diploid fibroblasts may be, in part, via the activation of ERK/ S6K1 signaling

Guidelines for burn rehabilitation in China

Abstract Quality of life and functional recovery after burn injury is the final goal of burn care, especially as most of burn patients survive the injury due to advanced medical science. However, dysfunction, disfigurement, contractures, psychological problems and other discomforts due to burns and the consequent scars are common, and physical therapy and occupational therapy provide alternative treatments for these problems of burn patients. This guideline, organized by the Chinese Burn Association and Chinese Association of Burn Surgeons aims to emphasize the importance of team work in burn care and provide a brief introduction of the outlines of physical and occupational therapies during burn treatment, which is suitable for the current medical circumstances of China. It can be used as the start of the tools for burn rehabilitation.</jats:p

Research progress in numerical simulation of Laval nozzle

Abstract The Laval nozzle is a very widely used device that has made great contributions due to its invention in aerospace, mechanical engineering, applied chemistry etc. The development of many modern technologies relies on the establishment of nozzles. In this paper, the current research advances on the numerical simulation methods of the nozzle flow and nozzle-related investigation or applications in different fields are reviewed. For example, the analytical and numerical simulation of nozzles in subsonic and supersonic modes are mentioned in this article. In summary, although the applications for various fields of nozzles are now very mature, the solution of the Navier-Stokes equation for nozzles is still a future direction where science and mathematics need to be strongly developed.</jats:p