Summary Background Current staging methods do not accurately predict the risk of disease recurrence and benefit of adjuvant chemotherapy for patients who have had surgery for stage II colon cancer. ...We postulated that expression patterns of multiple microRNAs (miRNAs) could, if combined into a single model, improve postoperative risk stratification and prediction of chemotherapy benefit for these patients. Method Using miRNA microarrays, we analysed 40 paired stage II colon cancer tumours and adjacent normal mucosa tissues, and identified 35 miRNAs that were differentially expressed between tumours and normal tissue. Using paraffin-embedded specimens from a further 138 patients with stage II colon cancer, we confirmed differential expression of these miRNAs using qRT-PCR. We then built a six-miRNA-based classifier using the LASSO Cox regression model, based on the association between the expression of every miRNA and the duration of individual patients' disease-free survival. We validated the prognostic and predictive accuracy of this classifier in both the internal testing group of 138 patients, and an external independent group of 460 patients. Findings Using the LASSO model, we built a classifier based on the six miRNAs: miR-21-5p, miR-20a-5p, miR-103a-3p, miR-106b-5p, miR-143-5p, and miR-215. Using this tool, we were able to classify patients between those at high risk of disease progression (high-risk group), and those at low risk of disease progression (low-risk group). Disease-free survival was significantly different between these groups in every set of patients. In the initial training group of patients, 5-year disease-free survival was 89% (95% CI 77·3–94·4) for the low-risk group, and 60% (46·3–71·0) for the high-risk group (hazard ratio HR 4·24, 95% CI 2·13–8·47; p<0·0001). In the internal testing set of patients, 5-year disease-free survival was 85% (95% CI 74·3–91·8) for the low-risk group, and 57% (42·8–68·5) for the high-risk group (HR 3·63, 1·86–7·01; p<0·0001), and in the independent validation set of patients, was 85% (79·6–89·0) for the low-risk group and 54% (46·4–61·1) for the high-risk group (HR 3·70, 2·56–5·35; p<0·0001). The six-miRNA-based classifier was an independent prognostic factor for, and had better prognostic value than, clinicopathological risk factors and mismatch repair status. In an ad-hoc analysis, the patients in the high-risk group were found to have a favourable response to adjuvant chemotherapy (HR 1·69, 1·17–2·45; p=0·0054). We developed two nomograms for clinical use that integrated the six-miRNA-based classifier and four clinicopathological risk factors to predict which patients might benefit from adjuvant chemotherapy after surgery for stage II colon cancer. Conclusion Our six-miRNA-based classifier is a reliable prognostic and predictive tool for disease recurrence in patients with stage II colon cancer, and might be able to predict which patients benefit from adjuvant chemotherapy. It might facilitate patient counselling and individualise management of patients with this disease. Funding Natural Science Foundation of China.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Pores in a solid can effectively reduce thermal conduction, but they are not favored in thermoelectric materials due to simultaneous deterioration of electrical conductivity. Conceivably, creating a ...porous structure may endow thermoelectric performance enhancement provided that overwhelming reduction of electrical conductivity can be suppressed. This work demonstrates such an example, in which a porous structure is formed leading to a significant enhancement in the thermoelectric figure of merit (zT). By a unique BiI3 sublimation technique, pore networks can be introduced into tetrahedrite Cu12Sb4S13‐based materials, accompanied by changes in their hierarchical structures. The addition of a small quantity of BiI3 (0.7 vol%) results in a ≈72% reduction in the lattice thermal conductivity, whereas the electrical conductivity is improved due to unexpected enhanced carrier mobility. As a result, an enhanced zT of 1.15 at 723 K in porous tetrahedrite and a high conversion efficiency of 6% at ΔT = 419 K in a fabricated segmented single‐leg based on this porous material are achieved. This work offers an effective way to concurrently modulate the electrical and thermal properties during the synthesis of high‐performance porous thermoelectric materials.
A porous network structure with excellent electrical properties can enhance the thermoelectric performance of solid materials. This work demonstrates that a porous structure can be introduced into tetrahedrite‐based synthetic minerals by a unique BiI3 sublimation technique. The multiscale architectures simultaneously disrupt phonon transport and trigger energy‐dependent scattering of holes, leading to a superior zT value of 1.15 at 723 K.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Since December 2019, an epidemic caused by novel coronavirus (2019-nCoV) infection has occurred unexpectedly in China. As of 8 pm, 31 January 2020, more than 20 pediatric cases have been reported in ...China. Of these cases, ten patients were identified in Zhejiang Province, with an age of onset ranging from 112 days to 17 years. Following the latest
National recommendations for diagnosis and treatment of pneumonia caused by 2019-nCoV
(the 4th edition) and current status of clinical practice in Zhejiang Province, recommendations for the diagnosis and treatment of respiratory infection caused by 2019-nCoV for children were drafted by the National Clinical Research Center for Child Health, the National Children’s Regional Medical Center, Children’s Hospital, Zhejiang University School of Medicine to further standardize the protocol for diagnosis and treatment of respiratory infection in children caused by 2019-nCoV.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OBVAL, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Background
Vonoprazan‐amoxicillin (VA) dual therapy has been shown to achieve acceptable cure rates for treatment of Helicobacter pylori(H. pylori) in Japan. Its effectiveness in other regions is ...unknown. We aimed to explore the efficacy of VA dual therapy as first‐line treatment for H. pyloriinfection in China.
Methods
This was a single center, prospective, randomized clinical pilot study conducted in China. Treatment naive H. pyloriinfected patients were randomized to receive either low‐ or high‐dose amoxicillin‐vonoprazan consisting of amoxicillin 1 g either b.i.d. or t.i.d plus VPZ 20 mg b.i.d for 7 or 10 days. 13C‐urea breath tests were used to access the cure rate at least 4 weeks after treatment.
Results
Three hundred and twenty‐three patients were assessed, and 119 subjects were randomized. The eradication rates of b.i.d. amoxicillin for 7 and 10 days, t.i.d. amoxicillin for 7 and 10 days were 66.7% (16/24), 89.2% (33/37), 81.0% (17/21), and 81.1% (30/37) (p = .191) by intention‐to‐treat analysis, respectively, and 72.7% (16/22), 89.2% (33/37), 81.0% (17/21), and 81.1% (30/37) (p = .454) by per‐protocol analysis, respectively.
Conclusion
Neither 7‐ or 10‐day VA dual therapy with b.i.d. or t.i.d. amoxicillin provides satisfied efficacy as the first‐line treatment for H. pyloriinfection in China. Further optimization is needed.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
A large amount of training data is usually crucial for successful supervised learning. However, the task of providing training samples is often time-consuming, involving a considerable amount of ...tedious manual work. In addition, the amount of training data available is often limited. As an alternative, in this paper, we discuss how best to augment the available data for the application of automatic facial landmark detection. We propose the use of a 3D morphable face model to generate synthesized faces for a regression-based detector training. Benefiting from the large synthetic training data, the learned detector is shown to exhibit a better capability to detect the landmarks of a face with pose variations. Furthermore, the synthesized training data set provides accurate and consistent landmarks automatically as compared to the landmarks annotated manually, especially for occluded facial parts. The synthetic data and real data are from different domains; hence the detector trained using only synthesized faces does not generalize well to real faces. To deal with this problem, we propose a cascaded collaborative regression algorithm, which generates a cascaded shape updater that has the ability to overcome the difficulties caused by pose variations, as well as achieving better accuracy when applied to real faces. The training is based on a mix of synthetic and real image data with the mixing controlled by a dynamic mixture weighting schedule. Initially, the training uses heavily the synthetic data, as this can model the gross variations between the various poses. As the training proceeds, progressively more of the natural images are incorporated, as these can model finer detail. To improve the performance of the proposed algorithm further, we designed a dynamic multi-scale local feature extraction method, which captures more informative local features for detector training. An extensive evaluation on both controlled and uncontrolled face data sets demonstrates the merit of the proposed algorithm.
Coronavirus disease 2019 (Covid-19) has resulted in a global outbreak. Few existing targeted medications are available. Lianhuaqingwen (LH) capsule, a repurposed marketed Chinese herb product, has ...been proven effective for influenza.
To determine the safety and efficacy of LH capsule in patients with Covid-19.
We did a prospective multicenter open-label randomized controlled trial on LH capsule in confirmed cases with Covid-19. Patients were randomized to receive usual treatment alone or in combination with LH capsules (4 capsules, thrice daily) for 14 days. The primary endpoint was the rate of symptom (fever, fatigue, coughing) recovery.
We included 284 patients (142 each in treatment and control group) in the full-analysis set. The recovery rate was significantly higher in treatment group as compared with control group (91.5% vs. 82.4%, p = 0.022). The median time to symptom recovery was markedly shorter in treatment group (median: 7 vs. 10 days, p < 0.001). Time to recovery of fever (2 vs. 3 days), fatigue (3 vs. 6 days) and coughing (7 vs. 10 days) was also significantly shorter in treatment group (all p < 0.001). The rate of improvement in chest computed tomographic manifestations (83.8% vs. 64.1%, p < 0.001) and clinical cure (78.9% vs. 66.2%, p = 0.017) was also higher in treatment group. However, both groups did not differ in the rate of conversion to severe cases or viral assay findings (both p > 0.05). No serious adverse events were reported.
In light of the safety and effectiveness profiles, LH capsules could be considered to ameliorate clinical symptoms of Covid-19.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Osteoarthritis (OA) is characterized as the degeneration and destruction of articular cartilage. In recent decades, leonurine (LN), the main active component in medical and edible dual purpose plant ...Herba Leonuri, has been shown associated with potent anti‐inflammatory effects in several diseases. In the current study, we examined the protective effects of LN in the inhibition of OA development as well as its underlying mechanism both in vitro and in vivo experiments. In vitro, interleukin‐1 beta (IL‐1β) induced over‐production of prostaglandin E2, nitric oxide, inducible nitric oxide synthase, cyclooxygenase‐2, interleukin‐6 and tumor necrosis factor alpha were all inhibited significantly by the pretreatment of LN at a dose‐dependent manner (5, 10, and 20 µM). Moreover, the expression of thrombospondin motifs 5 (ADAMTS5) and metalloproteinase 13 (MMP13) was downregulated by LN. All these changes led to the IL‐1β induced degradation of extracellular matrix. Mechanistically, the LN suppressed IL‐1β induced activation of the PI3K/Akt/NF‐κB signaling pathway cascades. Meanwhile, it was also demonstrated in our molecular docking studies that LN had strong binding abilities to PI3K. In addition, LN was observed exerting protective effects in a surgical induced model of OA. To sum up, this study indicated LN could be applied as a promising therapeutic agent in the treatment of OA.
Inhibition of PI3K/Akt/NF‐κB signaling with leonurine for ameliorating the progression of osteoarthritis: in vitro and in vivo studies
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Thermal properties strongly affect the applications of functional materials, such as thermal management, thermal barrier coatings, and thermoelectrics. Thermoelectric (TE) materials must have a low ...lattice thermal conductivity to maintain a temperature gradient to generate the voltage. Traditional strategies for minimizing the lattice thermal conductivity mainly rely on introduced multiscale defects to suppress the propagation of phonons. Here, the origin of the anomalously low lattice thermal conductivity is uncovered in Cd‐alloyed Mg3Sb2 Zintl compounds through complementary bonding analysis. First, the weakened chemical bonds and the lattice instability induced by the antibonding states of 5p‐4d levels between Sb and Cd triggered giant anharmonicity and consequently increased the phonon scattering. Moreover, the bond heterogeneity also augmented Umklapp phonon scatterings. Second, the weakened bonds and heavy element alloying softened the phonon mode and significantly decreased the group velocity. Thus, an ultralow lattice thermal conductivity of ≈0.33 W m−1 K−1 at 773 K is obtained, which is even lower than the predicated minimum value. Eventually, Na0.01Mg1.7Cd1.25Sb2 displays a high ZT of ≈0.76 at 773 K, competitive with most of the reported values. Based on the complementary bonding analysis, the work provides new means to control thermal transport properties through balancing the lattice stability and instability.
The traditional strategies for reducing the lattice thermal conductivity mainly rely on the introduced hierarchical architecture to impede the propagation of the phonons. Herein, the chemical alloying to balance the lattice stability and instability is subtly used, which lead to an ultralow lattice thermal conductivity that breaks the minimum limit of the Mg3Sb2 system estimated by the Cahill model.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The super antibiotic resistance genes (SARGs) demonstrate more severe threats than other antibiotic resistance genes while have not received enough attention in the environment. The study explored ...the prevalence and the antibiotic tolerance profiles of two typical SARGs, MCR-1 and NDM-1, and their hosting bacteria in the downstream of the Yangtze River and the nearby wastewater treatment plant (WWTP) and drinking water treatment plant (DWTP). Results indicated that MCR-1 and NDM-1 were prevalent in the influent and biological units of the WWTP. Their hosting bacteria were effectively removed, but 2.49 × 108 copies/L MCR-1 and 7.00 × 106 copies/L NDM-1 were still persistent in the effluent. In the Yangtze River, MCR-1 and NDM-1 were detected with higher abundance and antibiotic tolerance than the WWTP effluent and were significantly affected by nearby water contamination and human activities. In the DWTP, MCR-1 and NDM-1 were detected with average values 5.56 × 107 copies/L and 2.14 × 105 copies/L in the influent. Their hosting bacteria were undetectable in the effluent, but the two SARGs were still persistent with 1.39 × 107 copies/L and 6.29 × 104 copies/L, and were greatly enriched in the sludge. Molecular ecological networks demonstrated wide hosting relationships between MCR-1/NDM-1 and bacteria community in the DWTP. Redundancy analysis found that MCR-1 positively correlated with COD and NH3-N, while negatively correlated with turbidity. Additionally, MCR-1 hosting bacteria positively correlated with NO3−-N and negatively correlated with COD and NH3-N. NDM-1 positively correlated with turbidity and NDM-1 hosting bacteria positively correlated with COD and NO2−-N. The study demonstrated that the WWTP could not effectively remove SARGs with high amount of them being discharged into the Yangtze River. Then they were transported into the DWTP and the persistent SARGs in the effluent would probably be transferred into human, thus imposing great threats on public health.
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•MCR-1 and NDM-1 are prevalent in the WWTP, DWTP and the Yangtze River samples.•WWTP and DWTP treatment processes cannot effectively remove MCR-1 and NDM-1.•Drinking water is a direct source of SARGs pollution threating public health.•The two SARGs abundance and tolerance are affected greatly by human activities.•Hosting relationships drive the correlation between ARGs and influencing factors.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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