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

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

A Performance Analysis Framework of Time-Triggered Ethernet Using Real-Time Calculus

With increasing demands of deterministic and real-time communication, network performance analysis is becoming an increasingly important research topic in safety-critical areas, such as aerospace, automotive electronics and so on. Time-triggered Ethernet (TTEthernet) is a novel hybrid network protocol based on the Ethernet standard; it is deterministic, synchronized and congestion-free. TTEthernet with a time-triggered mechanism meets the real-time and reliability requirements of safety-critical applications. Time-triggered (TT) messages perform strict periodic scheduling following the offline schedule tables. Different scheduling strategies have an effect on the performance of TTEthernet. In this paper, a performance analysis framework is designed to analyze the end-to-end delay, backlog bounds and resource utilization of network by real-time calculus. This method can be used as a base for the performance evaluation of TTEthernet scheduling. In addition, this study discusses the impacts of clock synchronization and traffic integration strategies on TT traffic in the network. Finally, a case study is presented to prove the feasibility of the performance analysis framework

A Hybrid Excitation Model Based Lightweight Siamese Network for Underwater Vehicle Object Tracking Missions

Performing object tracking tasks and efficiently perceiving the underwater environment in real time for underwater vehicles is a challenging task due to the complex nature of the underwater environment. A hybrid excitation model based lightweight Siamese network is proposed to solve the mismatch between underwater objects with limited characteristics and complex deep learning models. The lightweight neural network is applied to the residual network in the Siamese network to reduce the computational complexity and cost of the model while constructing a deeper network. In addition, to deal with the changeable complex underwater environment and consider the timing of video tracking, the global excitation model (HE module) is introduced. The model adopts the excitation methods of space, channel, and motion to improve the accuracy of the algorithm. Based on the designed underwater vehicle, the underwater target tracking and target grabbing experiments are carried out, and the experimental results show that the proposed tracking algorithm has a high tracking success rate

Ferroelectric Polarization Enhanced Photodetector Based on Layered NbOCl2

NbOCl2 is an emerging ferroelectric layered material with unique optoelectronic properties, in which the built‐in electric field caused by spontaneous polarization can independently drive the separation and transport of photoexcited electrons and holes. However, the optoelectronic performance of NbOCl2 and its device application have remained elusive. Here, few‐layer NbOCl2 is prepared by the liquid exfoliation method and used to construct photoelectrochemical (PEC)‐type photodetectors. The photodetectors are self‐powered with broadband photoresponse and long‐term cycle stability. Due to the built‐in electric field generated by the spontaneous polarization, the whole system exhibits an open circuit potential of approximately 0.205 V. Interestingly, the open circuit potential can be significantly increased to 0.446 V after poling treatment. The responsivity without external bias is increased by about 2.5 times after 1 V poling and by about 4 times after a poling time of 500 s. Moreover, the tunable ferroelectric polarization shows memory effect and retains about 25% enhancement in photocurrent density even after 60 min. The tuneability of the built‐in electric field in PEC systems based on NbOCl2 offers numerous possibilities for the development of photodetectors and nonvolatile memory devices

Tanshinone I and Tanshinone IIA/B attenuate LPS-induced mastitis via regulating the NF-κB

Background: Mastitis is a common disease occurs in breast-feeding mothers, but published data are poor. This study aimed to study the effects of Tanshinones on treating mastitis. Methods: Clinical trials performed in 58 breast-feeding mothers were carried out. B-ultrasound and blood test were used to measure the size of breast mass and the change of blood cell counts. BALB/c mice were injected with LPS and then treated by Tanshinone I or Tanshinone IIA/B. Myeloperoxidase (MPO) activity and the release of inflammatory cytokines were tested by MPO kit, RT-qPCR and ELISA. Mouse mammary epithelial cells (mMECs) were isolated and the effects of Tanshinones were measured by conducting CCK-8 assay, flow cytometry, RT-qPCR and ELISA. Results: Patients treated by Cefprozil combined with Tanshinone got better outcomes than patients treated by Cefprozil alone. In animal trials, Tanshinone I and Tanshinone IIA/B significantly reduced MPO activity, and the levels of TNF-α, IL-1β and IL-6 in serum and mammary gland tissues. In mMECs, Tanshinone I and Tanshinone IIA/B attenuated LPS-induced viability loss and apoptosis. And they effectively inhibited the release of TNF-α, IL-1β and IL-6. Also, Tanshinone I and Tanshinone IIA/B significantly attenuated LPS-evoked NF-κB activation. Conclusion: Tanshinone I and Tanshinone IIA/B have potentials in treating mastitis. The beneficial effects might be through regulating NF-κB activation