Summary Background Human infections with different avian influenza viruses—eg, H5N1, H9N2, and H7N9—have raised concerns about pandemic potential worldwide. We report the first human infection with a ...novel reassortant avian influenza A H10N8 virus. Methods We obtained and analysed clinical, epidemiological, and virological data from a patient from Nanchang City, China. Tracheal aspirate specimens were tested for influenza virus and other possible pathogens by RT-PCR, viral culture, and sequence analyses. A maximum likelihood phylogenetic tree was constructed. Findings A woman aged 73 years presented with fever and was admitted to hospital on Nov 30, 2013. She developed multiple organ failure and died 9 days after illness onset. A novel reassortant avian influenza A H10N8 virus was isolated from the tracheal aspirate specimen obtained from the patient 7 days after onset of illness. Sequence analyses revealed that all the genes of the virus were of avian origin, with six internal genes from avian influenza A H9N2 viruses. The aminoacid motif GlnSerGly at residues 226–228 of the haemagglutinin protein indicated avian-like receptor binding preference. A mixture of glutamic acid and lysine at residue 627 in PB2 protein—which is associated with mammalian adaptation—was detected in the original tracheal aspirate samples. The virus was sensitive to neuraminidase inhibitors. Sputum and blood cultures and deep sequencing analysis indicated no co-infection with bacteria or fungi. Epidemiological investigation established that the patient had visited a live poultry market 4 days before illness onset. Interpretation The novel reassortant H10N8 virus obtained is distinct from previously reported H10N8 viruses. The virus caused human infection and could have been associated with the death of a patient. Funding Emergency Research Project on human infection with avian influenza H7N9 virus, the National Basic Research Program of China, and the National Mega-projects for Infectious Diseases.
Background Abelmoschus manihot , a single medicament of traditional Chinese medicine, has been widely used to treat kidney disease. This is the first randomized controlled clinical trial to assess ...its efficacy and safety in patients with primary glomerular disease. Study Design Prospective, open-label, multicenter, randomized, controlled, clinical trial. Setting & Participants From May 2010 to October 2011, a total of 417 patients with biopsy-proven primary glomerular disease from 26 hospitals participated in the study. Interventions A manihot in the form of a huangkui capsule, 2.5 g, 3 times per day; losartan potassium, 50 mg/d; or combined treatment, a huangkui capsule at 2.5 g 3 times per day, was combined with losartan potassium, 50 mg/d. The duration of intervention was 24 weeks. Outcomes & Measurements The primary outcome was change in 24-hour proteinuria from baseline after treatment. Change in estimated glomerular filtration rate (eGFR) from baseline after treatment was a secondary outcome. The 24-hour proteinuria was measured every 4 weeks and eGFR was measured at 0, 4, 12, and 24 weeks. Results Mean baseline urine protein excretion was 1,045, 1,084, and 1,073 mg/d in the A manihot , losartan, and combined groups, respectively, and mean eGFR was 108, 106, and 106 mL/min/1.73 m2 , respectively. After 24 weeks of treatment, mean changes in proteinuria were protein excretion of −508, −376, and −545 mg/d, respectively ( P = 0.003 for A manihot vs losartan and P < 0.001 for the combined treatment vs losartan). Mean eGFR did not change significantly. The incidence of adverse reactions was not different among the 3 groups ( P > 0.05), and there were no severe adverse events in any group. Limitations Results cannot be generalized to those with nephrotic syndrome or reduced eGFR. Conclusions A manihot is a promising therapy for patients with primary kidney disease (chronic kidney disease stages 1-2) with moderate proteinuria.
Summary Background Icotinib, an oral EGFR tyrosine kinase inhibitor, had shown antitumour activity and favourable toxicity in early-phase clinical trials. We aimed to investigate whether icotinib is ...non-inferior to gefitinib in patients with non-small-cell lung cancer. Methods In this randomised, double-blind, phase 3 non-inferiority trial we enrolled patients with advanced non-small-cell lung cancer from 27 sites in China. Eligible patients were those aged 18–75 years who had not responded to one or more platinum-based chemotherapy regimen. Patients were randomly assigned (1:1), using minimisation methods, to receive icotinib (125 mg, three times per day) or gefitinib (250 mg, once per day) until disease progression or unacceptable toxicity. The primary endpoint was progression-free survival, analysed in the full analysis set. We analysed EGFR status if tissue samples were available. All investigators, clinicians, and participants were masked to patient distribution. The non-inferiority margin was 1·14; non-inferiority would be established if the upper limit of the 95% CI for the hazard ratio (HR) of gefitinib versus icotinib was less than this margin. This study is registered with ClinicalTrials.gov , number NCT01040780 , and the Chinese Clinical Trial Registry, number ChiCTR-TRC-09000506. Findings 400 eligible patients were enrolled between Feb 26, 2009, and Nov 13, 2009; one patient was enrolled by mistake and removed from the study, 200 were assigned to icotinib and 199 to gefitinib. 395 patients were included in the full analysis set (icotinib, n=199; gefitinib, n=196). Icotinib was non-inferior to gefitinib in terms of progression-free survival (HR 0·84, 95% CI 0·67–1·05; median progression-free survival 4·6 months 95% CI 3·5–6·3 vs 3·4 months 2·3–3·8; p=0·13). The most common adverse events were rash (81 41% of 200 patients in the icotinib group vs 98 49% of 199 patients in the gefitinib group) and diarrhoea (43 22% vs 58 29%). Patients given icotinib had less drug-related adverse events than did those given gefitinib (121 61% vs 140 70%; p=0·046), especially drug-related diarrhoea (37 19% vs 55 28%; p=0·033). Interpretation Icotinib could be a new treatment option for pretreated patients with advanced non-small-cell lung cancer. Funding Zhejiang Beta Pharma (China), the Chinese National Key Special Program for Innovative Drugs, the 863 Project, and Zhejiang Provincial Key Special Program.
We report a measurement of electron antineutrino oscillation from the Daya Bay Reactor Neutrino Experiment with nearly 4 million reactor νover ¯_{e} inverse β decay candidates observed over 1958 days ...of data collection. The installation of a flash analog-to-digital converter readout system and a special calibration campaign using different source enclosures reduce uncertainties in the absolute energy calibration to less than 0.5% for visible energies larger than 2 MeV. The uncertainty in the cosmogenic ^{9}Li and ^{8}He background is reduced from 45% to 30% in the near detectors. A detailed investigation of the spent nuclear fuel history improves its uncertainty from 100% to 30%. Analysis of the relative νover ¯_{e} rates and energy spectra among detectors yields sin^{2}2θ_{13}=0.0856±0.0029 and Δm_{32}^{2}=(2.471_{-0.070}^{+0.068})×10^{-3} eV^{2} assuming the normal hierarchy, and Δm_{32}^{2}=-(2.575_{-0.070}^{+0.068})×10^{-3} eV^{2} assuming the inverted hierarchy.
Tea is the world's most popular non-alcoholic beverage. China and India are known to be the largest tea producing countries and recognized as the centers for the domestication of the tea plant ...(Camellia sinensis (L.) O. Kuntze). However, molecular studies on the origin, domestication and relationships of the main teas, China type, Assam type and Cambod type are lacking.
Twenty-three nuclear microsatellite markers were used to investigate the genetic diversity, relatedness, and domestication history of cultivated tea in both China and India. Based on a total of 392 samples, high levels of genetic diversity were observed for all tea types in both countries. The cultivars clustered into three distinct genetic groups (i.e. China tea, Chinese Assam tea and Indian Assam tea) based on STRUCTURE, PCoA and UPGMA analyses with significant pairwise genetic differentiation, corresponding well with their geographical distribution. A high proportion (30%) of the studied tea samples were shown to possess genetic admixtures of different tea types suggesting a hybrid origin for these samples, including the Cambod type.
We demonstrate that Chinese Assam tea is a distinct genetic lineage from Indian Assam tea, and that China tea sampled from India was likely introduced from China directly. Our results further indicate that China type tea, Chinese Assam type tea and Indian Assam type tea are likely the result of three independent domestication events from three separate regions across China and India. Our findings have important implications for the conservation of genetic stocks, as well as future breeding programs.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Objectives This study sought to evaluate the safety and efficacy of rosuvastatin in preventing contrast-induced acute kidney injury (CI-AKI) in patients with diabetes mellitus (DM) and chronic kidney ...disease (CKD). Background CI-AKI is an important complication after contrast medium injection. While small studies have shown positive results with statin therapy, the role of statin therapy in prevention of CI-AKI remains unknown. Methods We randomized 2,998 patients with type 2 DM and concomitant CKD who were undergoing coronary/peripheral arterial angiography with or without percutaneous intervention to receive rosuvastatin, 10 mg/day (n = 1,498), for 5 days (2 days before, and 3 days after procedure) or standard-of-care (n = 1,500). Patients' renal function was assessed at baseline, 48 h, and 72 h after exposure to contrast medium. The primary endpoint of the study was the development of CI-AKI, which was defined as an increase in serum creatinine concentration ≥0.5 mg/dl (44.2 μmol/l) or 0.25% above baseline at 72 h after exposure to contrast medium. Results Patients randomized to the rosuvastatin group had a significantly lower incidence of CI-AKI than controls (2.3% vs. 3.9%, respectively; p = 0.01). During 30 days' follow-up, the rate of worsening heart failure was significantly lower in the patients treated with rosuvastatin than that in the control group (2.6% vs. 4.3%, respectively; p = 0.02). Conclusions Rosuvastatin significantly reduced the risk of CI-AKI in patients with DM and CKD undergoing arterial contrast medium injection. (Rosuvastatin Prevent Contrast Induced Acute Kidney Injury in Patients With Diabetes TRACK-D; NCT00786136 )
We report the first results of a light weakly interacting massive particles (WIMPs) search from the CDEX-10 experiment with a 10 kg germanium detector array immersed in liquid nitrogen at the China ...Jinping Underground Laboratory with a physics data size of 102.8 kg day. At an analysis threshold of 160 eVee, improved limits of 8×10^{-42} and 3×10^{-36} cm^{2} at a 90% confidence level on spin-independent and spin-dependent WIMP-nucleon cross sections, respectively, at a WIMP mass (m_{χ}) of 5 GeV/c^{2} are achieved. The lower reach of m_{χ} is extended to 2 GeV/c^{2}.
Summary Background Systemic lupus erythematosus is a heterogeneous autoimmune disease that is associated with B-cell hyperactivity, autoantibodies, and increased concentrations of B-lymphocyte ...stimulator (BLyS). The efficacy and safety of the fully human monoclonal antibody belimumab (BLyS-specific inhibitor) was assessed in patients with active systemic lupus erythematosus. Methods Patients (aged ≥18 years) who were seropositive with scores of at least 6 on the Safety of Estrogens in Lupus Erythematosus National Assessment–Systemic Lupus Erythematosus Disease Activity Index (SELENA-SLEDAI) were enrolled in a multicentre phase 3 study, which was done in Latin America, Asia-Pacific, and eastern Europe. Patients were randomly assigned by use of a central interactive voice response system in a 1:1:1 ratio to belimumab 1 mg/kg or 10 mg/kg, or placebo by intravenous infusion in 1 h on days 0, 14, and 28, and then every 28 days until 48 weeks, with standard of care. Patients, investigators, study coordinators, and sponsors were masked to treatment assignment. Primary efficacy endpoint was improvement in the Systemic Lupus Erythematosus Responder Index (SRI) at week 52 (reduction ≥4 points in SELENA-SLEDAI score; no new British Isles Lupus Assessment Group BILAG A organ domain score and no more than 1 new B organ domain score; and no worsening <0·3 increase in Physician's Global Assessment PGA score) versus baseline. Method of analysis was by modified intention to treat. This trial is registered with ClinicalTrials.gov , number NCT00424476. Findings 867 patients were randomly assigned to belimumab 1 mg/kg (n=289) or 10 mg/kg (n=290), or placebo (n=288). 865 were treated and analysed in the belimumab (1 mg/kg, n=288; 10 mg/kg, n=290) and placebo groups (n=287). Significantly higher SRI rates were noted with belimumab 1 mg/kg (148 51%, odds ratio 1·55 95% CI 1·10–2·19; p=0·0129) and 10 mg/kg (167 58%, 1·83 1·30–2·59; p=0·0006) than with placebo (125 44%) at week 52. More patients had their SELENA-SLEDAI score reduced by at least 4 points during 52 weeks with belimumab 1 mg/kg (153 53%, 1·51 1·07–2·14; p=0·0189) and 10 mg/kg (169 58%, 1·71 1·21–2·41; p=0·0024) than with placebo (132 46%). More patients given belimumab 1 mg/kg (226 78%, 1·38 0·93–2·04; p=0·1064) and 10 mg/kg (236 81%, 1·62 1·09–2·42; p=0·0181) had no new BILAG A or no more than 1 new B flare than did those in the placebo group (210 73%). No worsening in PGA score was noted in more patients with belimumab 1 mg/kg (227 79%, 1·68 1·15–2·47; p=0·0078) and 10 mg/kg (231 80%, 1·74 1·18–2·55; p=0·0048) than with placebo (199 69%). Rates of adverse events were similar in the groups given belimumab 1 mg/kg and 10 mg/kg, and placebo: serious infection was reported in 22 (8%), 13 (4%), and 17 (6%) patients, respectively, and severe or serious hypersensitivity reactions on an infusion day were reported in two (<1%), two (<1%), and no patients, respectively. No malignant diseases were reported. Interpretation Belimumab has the potential to be the first targeted biological treatment that is approved specifically for systemic lupus erythematosus, providing a new option for the management of this important prototypic autoimmune disease. Funding Human Genome Sciences and GlaxoSmithKline.
Sarcopenia, a newly recognized geriatric syndrome, is characterized by age-related decline of skeletal muscle plus low muscle strength and/or physical performance. Previous studies have confirmed the ...association of sarcopenia and adverse health outcomes, such as falls, disability, hospital admission, long term care placement, poorer quality of life, and mortality, which denotes the importance of sarcopenia in the health care for older people. Despite the clinical significance of sarcopenia, the operational definition of sarcopenia and standardized intervention programs are still lacking. It is generally agreed by the different working groups for sarcopenia in the world that sarcopenia should be defined through a combined approach of muscle mass and muscle quality, however, selecting appropriate diagnostic cutoff values for all the measurements in Asian populations is challenging. Asia is a rapidly aging region with a huge population, so the impact of sarcopenia to this region is estimated to be huge as well. Asian Working Group for Sarcopenia (AWGS) aimed to promote sarcopenia research in Asia, and we collected the best available evidences of sarcopenia researches from Asian countries to establish the consensus for sarcopenia diagnosis. AWGS has agreed with the previous reports that sarcopenia should be described as low muscle mass plus low muscle strength and/or low physical performance, and we also recommend outcome indicators for further researches, as well as the conditions that sarcopenia should be assessed. In addition to sarcopenia screening for community-dwelling older people, AWGS recommends sarcopenia assessment in certain clinical conditions and healthcare settings to facilitate implementing sarcopenia in clinical practice. Moreover, we also recommend cutoff values for muscle mass measurements (7.0 kg/m(2) for men and 5.4 kg/m(2) for women by using dual X-ray absorptiometry, and 7.0 kg/m(2) for men and 5.7 kg/m(2) for women by using bioimpedance analysis), handgrip strength (<26 kg for men and <18 kg for women), and usual gait speed (<0.8 m/s). However, a number of challenges remained to be solved in the future. Asia is made up of a great number of ethnicities. The majority of currently available studies have been published from eastern Asia, therefore, more studies of sarcopenia in south, southeastern, and western Asia should be promoted. On the other hand, most Asian studies have been conducted in a cross-sectional design and few longitudinal studies have not necessarily collected the commonly used outcome indicators as other reports from Western countries. Nevertheless, the AWGS consensus report is believed to promote more Asian sarcopenia research, and most important of all, to focus on sarcopenia intervention studies and the implementation of sarcopenia in clinical practice to improve health care outcomes of older people in the communities and the healthcare settings in Asia.
The Daya Bay experiment has observed correlations between reactor core fuel evolution and changes in the reactor antineutrino flux and energy spectrum. Four antineutrino detectors in two experimental ...halls were used to identify 2.2 million inverse beta decays (IBDs) over 1230 days spanning multiple fuel cycles for each of six 2.9 GW_{th} reactor cores at the Daya Bay and Ling Ao nuclear power plants. Using detector data spanning effective ^{239}Pu fission fractions F_{239} from 0.25 to 0.35, Daya Bay measures an average IBD yield σover ¯_{f} of (5.90±0.13)×10^{-43} cm^{2}/fission and a fuel-dependent variation in the IBD yield, dσ_{f}/dF_{239}, of (-1.86±0.18)×10^{-43} cm^{2}/fission. This observation rejects the hypothesis of a constant antineutrino flux as a function of the ^{239}Pu fission fraction at 10 standard deviations. The variation in IBD yield is found to be energy dependent, rejecting the hypothesis of a constant antineutrino energy spectrum at 5.1 standard deviations. While measurements of the evolution in the IBD spectrum show general agreement with predictions from recent reactor models, the measured evolution in total IBD yield disagrees with recent predictions at 3.1σ. This discrepancy indicates that an overall deficit in the measured flux with respect to predictions does not result from equal fractional deficits from the primary fission isotopes ^{235}U, ^{239}Pu, ^{238}U, and ^{241}Pu. Based on measured IBD yield variations, yields of (6.17±0.17) and (4.27±0.26)×10^{-43} cm^{2}/fission have been determined for the two dominant fission parent isotopes ^{235}U and ^{239}Pu. A 7.8% discrepancy between the observed and predicted ^{235}U yields suggests that this isotope may be the primary contributor to the reactor antineutrino anomaly.
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