Neoadjuvant anti-PD-1 therapy has shown encouraging efficacy in patients with deficient DNA mismatch repair (dMMR)/microsatellite instability-high (MSI-H) locally advanced rectal cancer (LARC), which ...suggests its potential as a curative-intent therapy and a promising treatment option for organ preservation. We aimed to investigate the long-term outcomes of patients with dMMR/MSI-H LARC who experienced clinical complete response (cCR) after anti-PD-1 therapy.
We retrospectively analyzed patients with dMMR/MSI-H LARC who achieved cCR and received nonoperative management following neoadjuvant anti-PD-1-based treatment from 4 Chinese medical centers. Patients were followed up for at least 1 year after they achieved cCR, their clinical data were collected, and survival outcomes were analyzed using the Kaplan-Meier method.
A total of 24 patients who achieved cCR and received nonoperative management from March 2018 to May 2022 were included, with a median age of 51.0 years (range, 19.0-77.0 years). The median treatment course to reach cCR was 6.0 (range, 1.0-12.0). Fifteen patients (62.5%) continued their treatments after experiencing cCR, and the median treatment course was 17.0 (range, 3.0-36.0). No local regrowth or distant metastasis was observed in a median follow-up time of 29.1 months (range, 12.6-48.5 months) after cCR. The 3-year disease-free and overall survivals were both 100%.
Patients with dMMR/MSI-H locally advanced or low-lying rectal cancer who achieved cCR following anti-PD-1-based therapy had promising long-term outcomes. A prospective clinical trial with a larger sample size is required to further validate these findings.
Rheumatoid arthritis (RA) patients have increased risk of cardiovascular disease (CVD) death. Elevated asymmetric dimethylarginine (ADMA) levels have been reported to be an independent predictor of ...CVD morbidity and mortality, however, the role of ADMA in RA remains undetermined. To derive a more accurate estimation on circulating ADMA levels in RA patients, a meta-analysis was performed. Embase, PubMed, and The Cochrane Library database (up to October 7 2018) were used to acquire published literatures. Heterogeneity test was performed by the
Q
statistic and quantified using
I
2
. Publication bias was evaluated using a funnel plot and Egger’s linear regression test. A total of 174 articles were identified, 16 studies with 1365 subjects (666 RA patients and 699 healthy individuals) were ultimately included. Plasma/serum ADMA levels appeared to be higher in RA patients than healthy controls (SMD = 0.84, 95% CI 0.32, 1.35). By assessing the BMI, age, disease duration and disease activity as subgroups, BMI ≥ 24 and BMI < 24 groups both showed elevated ADMA levels than controls, disease duration ≥ 8, age < 50 and disease activity ≥ 3.2 and < 5.1 group had a higher ADMA level than control groups. However, disease duration < 8, disease activity ≥ 5.1 and age ≥ 50 groups showed no difference between two groups. Circulating ADMA levels are higher in RA patients compared with healthy controls. In addition, ADMA levels are influenced by age, disease duration and disease activity.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Backgrounds/Aims: It has been reported that myocardial infarction (MI) is a risk factor for vascular dementia. However, the molecular mechanism remains largely unknown. Methods: MI mice were ...generated by ligation of the left coronary artery (LCA) for 4 weeks. Passive and active avoidance tests were performed to evaluate the cognitive ability of MI mice. A theta-burst stimulation (TBS) protocol was applied to elicit long-term potentiation (LTP) of the perforant pathway-dentate gyrus synapse (PP-DG). Western blot analysis was employed to assess protein levels. Results: In this study, we demonstrated that after 4 weeks of MI, C57BL/6 mice had significantly impaired memory. Compared with the sham group, in vivo physiological recording in the MI group revealed significantly decreased amplitude of population spikes (PS) with no effect on the latency and duration of the stimulus-response curve. The amplitude of LTP was markedly decreased in the MI group compared with the sham group. Further examination showed that the expression of the TBS-LTP-related proteins BDNF, GluA1 and phosphorylated GluA1 were all decreased in the MI group compared with those in the sham group. Strikingly, all these changes were prevented by hippocampal stereotaxic injection of an anti-miR-1 oligonucleotide fragment carried by a lentivirus vector (lenti-pre-AMO-1). Conclusion: MI induced cognitive decline and TBS-LTP impairment, and decreased BDNF and GluA1 phosphorylation levels from overexpression of miR-1ated were involved in this process.
As a promising 2D nanocarrier, the biggest challenge of bare black phosphorus nanosheets (BP NSs) lies in the inherent instability, while it can be improved by surface modification strategies to a ...great extent. Considering the existing infirm BP NSs surface modification strategies, A mussels‐inspired strong adhesive biomimetic peptide with azide groups for surface modification to increase the stability of BP NSs is synthesized. The azide groups on the peptide can quickly and precisely bind to the targeting ligand through click chemistry, solving the problem of nonspecificity of secondary modification of other mussel‐mimicking materials. Besides, a catechol‐Gd3+ coordination network is further constructed for magnetic resonance imaging (MRI) and inducing intracellular endo/lysosome escape. The fabricated BP‐DOX@Gd/(DOPA)4‐PEG‐TL nanoplatform exhibits enhanced antitumor abilities through synergetic chemo/photothermal effects both in vitro and in vivo.
A mussels‐inspired strong adhesive biomimetic peptide with azide groups for surface modification to increase the stability of black phosphorus nanosheets (BP NSs) is developed. With the quick and precise clicking binding and coordination, targeting ligand (TL) and Gd3+ are introduced for tumor targeting, MRI and endo/lysosome escape. The fabricated BP‐DOX@Gd/(DOPA)4‐PEG‐TL nanoplatform exhibits enhanced antitumor abilities through synergetic chemo/photothermal effects both in vitro and in vivo.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SAZU, SBCE, SBMB, UL, UM, UPUK
Abstract
Most published newborn growth references are based on conventional monitoring data that usually included both low- and high-risk pregnancies. We sought to develop a set of neonatal growth ...standards constructed from only a large sample of low-risk pregnancies. A total of 24,375 naturally conceived singleton live births with gestational ages of 24–42 weeks were collected in 69 hospitals in thirteen Chinese cities between 2015 and 2018. Unhealthy infants or those with high-risk mother were excluded. Smoothed percentile curves of six anthropometric indicators were established using the Generalized Additive Model for Location, Scale and Shape. The 3rd, 10th, 25th, 50th, 75th, 90th, and 97th percentile references for birth weight, length, head circumference, weight/length, body mass index, and ponderal index were calculated for neonates with gestational ages of 24–42 weeks. This set of neonatal growth standards with six anthropometric indicators can provide more tools for growth and nutrition assessment and body proportionality in neonatal clinical practice. These standards might also help to show the differences between growth curves based on low-risk and mixed low- and high-risk pregnancies.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Staphylococcus aureus is known to be a predominant pathogen causing bloodstream infection (BSI) from burn units. Our study aimed to perform the clinical epidemiological analysis and virulence ...features of S. aureus strains isolated from the burn patients with BSI from a burn center in southeastern China during 2012-2016. A collection of 112 S. aureus isolates causing BSI from burn center of a tertiary care hospital in China was carried out. Antimicrobial susceptibility testing was conducted in accordance with the Clinical and Laboratory Standards Institute (CLSI) guidelines. Toxin gene profiles, multilocus sequence typing, staphylococcal protein A (spa) typing, accessory gene regulator (agr) locus typing, staphylococcal cassette chromosome mec (SCCmec) typing, and dendrographic analysis were used to characterize and analyze these isolates. Of 112 S. aureus isolates, 52 (46.4%) were methicillin-resistant S. aureus (MRSA) and 60 (53.6%) were methicillin-susceptible S. aureus (MSSA). ST239-SCCmec III-t030-agr I was the major prevalent clone (26 from MRSA and 6 from MSSA), which was followed by ST239-SCCmec III-t037-agr I (12, 10.0%) and ST5-SCCmec II-t002-agr I (11, 9.2%). The genotyping results showed high genetic diversity in molecular characterization and toxin gene profiles of the strains. Carriage of tsst-1 was mainly associated with ST239-SCCmec III-t030-agr I and ST30-SCCmec IV-t062-agr III, whereas lukS/F-PV was distributed in different clones. In conclusion, ST239-SCCmec III-t030-agr I is the commonest clone causing BSI among burn patients in eastern regions of China. In contrast to MRSA, polyclonality was statistically significantly higher among MSSA isolated from burn patients with BSI.
The neonatal heart possesses the ability to proliferate and the capacity to regenerate after injury; however, the mechanisms underlying these processes are not fully understood. Melatonin has been ...shown to protect the heart against myocardial injury through mitigating oxidative stress, reducing apoptosis, inhibiting mitochondrial fission, etc. In this study, we investigated whether melatonin regulated cardiomyocyte proliferation and promoted cardiac repair in mice with myocardial infarction (MI), which was induced by ligation of the left anterior descending coronary artery. We showed that melatonin administration significantly improved the cardiac functions accompanied by markedly enhanced cardiomyocyte proliferation in MI mice. In neonatal mouse cardiomyocytes, treatment with melatonin (1 μM) greatly suppressed miR-143-3p levels. Silencing of miR-143-3p stimulated cardiomyocytes to re-enter the cell cycle. On the contrary, overexpression of miR-143-3p inhibited the mitosis of cardiomyocytes and abrogated cardiomyocyte mitosis induced by exposure to melatonin. Moreover, Yap and Ctnnd1 were identified as the target genes of miR-143-3p. In cardiomyocytes, inhibition of miR-143-3p increased the protein expression of Yap and Ctnnd1. Melatonin treatment also enhanced Yap and Ctnnd1 protein levels. Furthermore, Yap siRNA and Ctnnd1 siRNA attenuated melatonin-induced cell cycle re-entry of cardiomyocytes. We showed that the effect of melatonin on cardiomyocyte proliferation and cardiac regeneration was impeded by the melatonin receptor inhibitor luzindole. Silencing miR-143-3p abrogated the inhibition of luzindole on cardiomyocyte proliferation. In addition, both MT1 and MT2 siRNA could cancel the beneficial effects of melatonin on cardiomyocyte proliferation. Collectively, the results suggest that melatonin induces cardiomyocyte proliferation and heart regeneration after MI by regulating the miR-143-3p/Yap/Ctnnd1 signaling pathway, providing a new therapeutic strategy for cardiac regeneration.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Abstract
Background:
According to previous studies on professional English course teaching, the evaluation of course teaching was positive, but the vast majorities focus on medical English literature ...reading, professional English vocabulary, and professional English translation. As an alternative, the course design based on academic learning needs under the outcome-oriented education/model emphasizes the improvement of students’ comprehensive ability in oral expression, literature reading, writing, and academic communication.
Objectives:
The objective of this study was to analyze nursing postgraduates’ opinions on learning the outcome-oriented academic English course.
Methods:
This is a cross-sectional descriptive study. A total of 150 first-year nursing postgraduates enrolled in the “Academic Professional English for Nursing Postgraduates” course. After completing the course learning, students scanned QR codes generated by the online questionnaire and completed it anonymously within 48 h.
Results:
The students who participated in this course strongly believed that it “helped them strengthen their English speakability” (4.8 points), “made them more confident to participate in international academic conferences and exchanges in the future” (4.8 points), and “helped them apply English more in the nursing professional field in the future” (4.7 points).
Conclusions:
The implementation of outcome-oriented course teaching helps students to understand the research of foreign scholars and effectively express their own research content with English as a tool. It motivates them to continuously use English for professional and academic communication.
China accounts for 25% of the global greening. There are temporal and spatial differences of China's greening and intrinsic driving forces. Thus, it is crucial to determinize the contributions of ...human activities and climate change on greening at region scale. The Beijing-Tianjin-Hebei Region (BTHR) is one of the most active areas with human activities in China. It is necessary to explore negative or positive impacts of human activities on the regional greening or browning under climate change. A time series of annual vegetation coverage from satellite data was selected to quantify regional greening in the BTHR from 2000 to 2019 and their responses to climate change and human activities. Results showed generally widespread greening over the last 20 years at an average increased rate of 0.036 decade
in vegetation coverage (P < 0.01). Overall warmer and wetter climate across the BTHR were positively correlated with regional greening. The positive effects of human activities on greening accounted for 48.4% of the BTHR, especially the benefits of ecological restoration projects and the agricultural activities. Increases in vegetation coverage had resulted from the combined effects of climate change and human activities. Climate change had a stronger influence on vegetation coverage than human activities. Contributions of climate change to greening and browning was about 74.1% and < 20%, respectively. The decrease in vegetation coverage was mainly the results of the inhibition of human activities. More detailed socioeconomic and anthropogenic datasets are required for further analysis. Further research consideration would focus on the nonlinear responses of vegetation to climate change.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Purpose
Understanding the association of iris colour and myopia may provide further insights into the role of the wavelength of lights in the pathophysiology of myopia. We aim to assess the ...association of iris colour and myopia in a school‐based sample of Chinese students.
Methods
Two thousand three hundred and forty‐six Year 7 students from 10 middle schools (93.5% response rate) aged 13–14 years in Mojiang, a small county located in Southwestern China, participated in the study. We obtained standardised slit lamp photographs and developed a grading system assessing iris colour (higher grade denoting a darker iris). Refractive error was measured after cycloplegia using an autorefractor by optometrists or trained technicians. An IOLMaster (www.zeiss.com) was used to measure ocular biometric parameters including axial length (AL).
Results
Of all the study participants, 693 (29.5%) were affected by myopia with the prevalence estimates being higher in girls (36.8%; 95% confidence interval CI: 34.0, 39.6) than in boys (22.8%; 95% CI: 20.4, 25.1) (p < 0.001). After adjusting for gender, height, parental history of myopia, time spent on computer, time spent watching TV, time spent outdoors, and time spent reading and writing, participants with a darker iris colour tended to have a higher prevalence of myopia, a more myopic refraction and a longer AL. Dose‐response relationships were observed in all regression models (p for trend <0.05).
Conclusions
Darker iris colour was associated with more myopic refractive errors and longer ALs among Chinese school‐aged children and this association was independent of other known myopia‐related risk factors.
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DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
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