Summary Background On March 30, a novel influenza A subtype H7N9 virus (A/H7N9) was detected in patients with severe respiratory disease in eastern China. Virological factors associated with a poor ...clinical outcome for this virus remain unclear. We quantified the viral load and analysed antiviral resistance mutations in specimens from patients with A/H7N9. Methods We studied 14 patients with A/H7N9 disease admitted to the Shanghai Public Health Clinical Centre (SPHCC), China, between April 4, and April 20, 2013, who were given antiviral treatment (oseltamivir or peramivir) for less than 2 days before admission. We investigated the viral load in throat, stool, serum, and urine specimens obtained sequentially from these patients. We also sequenced viral RNA from these specimens to study the mutations associated with resistance to neuraminidase inhibitors and their association with disease outcome. Findings All patients developed pneumonia, seven of them required mechanical ventilation, and three of them further deteriorated to become dependent on extracorporeal membrane oxygenation (ECMO), two of whom died. Antiviral treatment was associated with a reduction of viral load in throat swab specimens in 11 surviving patients. Three patients with persistently high viral load in the throat in spite of antiviral therapy became ECMO dependent. An Arg292Lys mutation in the virus neuraminidase (NA) gene known to confer resistance to both zanamivir and oseltamivir was identified in two of these patients, both also received corticosteroid treatment. In one of them, wild-type sequence Arg292 was noted 2 days after start of antiviral treatment, and the resistant mutant Lys292 dominated 9 days after start of treatment. Interpretation Reduction of viral load following antiviral treatment correlated with improved outcome. Emergence of NA Arg292Lys mutation in two patients who also received corticosteroid treatment led to treatment failure and a poor clinical outcome. The emergence of antiviral resistance in A/H7N9 viruses, especially in patients receiving corticosteroid therapy, is concerning, needs to be closely monitored, and considered in pandemic preparedness planning. Funding National Megaprojects of China for Infectious Diseases, Shanghai Municipal Health and Family Planning Commission, the National Key Basic Research Program of China, Ministry of Science and Technology, and National Natural Science Foundation of China.
Summary Background China has achieved Millennium Development Goal 4 to reduce under-5 mortality rate by two-thirds between 1990 and 2015. In this study, we estimated the national and subnational ...levels and causes of child mortality in China annually from 1996 to 2015 to draw implications for achievement of the SDGs for China and other low-income and middle-income countries. Methods In this systematic analysis, we adjusted empirical data on levels and causes of child mortality collected in the China Maternal and Child Health Surveillance System to generate representative estimates at the national and subnational levels. In adjusting the data, we considered the sampling design and probability, applied smoothing techniques to produce stable trends, fitted livebirth and age-specific death estimates to natvional estimates produced by the UN for international comparison, and partitioned national estimates of infrequent causes produced by independent sources to the subnational level. Findings Between 1996 and 2015, the under-5 mortality rate in China declined from 50·8 per 1000 livebirths to 10·7 per 1000 livebirths, at an average annual rate of reduction of 8·2%. However, 181 600 children still died before their fifth birthday, with 93 400 (51·5%) deaths occurring in neonates. Great inequity exists in child mortality across regions and in urban versus rural areas. The leading causes of under-5 mortality in 2015 were congenital abnormalities (35 700 deaths, 95% uncertainty range UR 28 400–45 200), preterm birth complications (30 900 deaths, 24 200–40 800), and injuries (26 600 deaths, 21 000–33 400). Pneumonia contributed to a higher proportion of deaths in the western region of China than in the eastern and central regions, and injury was a main cause of death in rural areas. Variations in cause-of-death composition by age were also examined. The contribution of preterm birth complications to mortality decreased after the neonatal period; congenital abnormalities remained an important cause of mortality throughout infancy, whereas the contribution of injuries to mortality increased after the first year of life. Interpretation China has achieved a rapid reduction in child mortality in 1996–2015. The decline has been widespread across regions, urban and rural areas, age groups, and cause-of-death categories, but great disparities remain. The western region and rural areas and especially western rural areas should receive most attention in improving child survival through enhanced policy and programmes in the Sustainable Development Goals era. Continued investment is crucial in primary and secondary prevention of deaths due to congenital abnormalities, preterm birth complications, and injuries nationally, and of deaths due to pneumonia in western rural areas. The study also has implications for improving child survival and civil registration and vital statistics in other low-income and middle-income countries. Funding Bill & Melinda Gates Foundation.
The procoagulant effect of microparticles (MPs) contributes to hypercoagulability-induced thrombosis. We provide preliminary findings of the MPs-Activated Clotting Time (MPs-ACT) assay to determine ...the procoagulant activity of MPs. MPs-rich plasma was obtained and recalcified. Changes in plasma viscoelasticity were evaluated and the time to the peak viscoelastic changes was defined as the MPs-ACT. MPs concentration was measured by flow cytometry. Coagulation products produced during plasma clotting were identified by fibrin and fibrinopeptide A. MPs were prepared in vitro and added to standard plasma to simulate pathological samples. In addition, reproducibility and sensitivity were evaluated. We confirmed the linear relationship between MPs-ACT and MP concentrations. Dynamic changes in fibrin production were depicted. We simulated the correlation between MPs-ACT and standard plasma containing MPs prepared in vitro. The reproducibility of high-value and low-value samples was 6.0% and 10.8%, respectively. MPs-ACT sensitively detected hypercoagulable samples from patients with pre-eclampsia, hip fractures, and lung tumors. MPs-ACT largely reflects the procoagulant effect of MPs. MPs-ACT sensitively and rapidly detects hypercoagulability with MPs-rich plasma. It may be promising for the diagnosis of hypercoagulable states induced by MPs.
Summary Background The 2013–15 Ebola virus disease epidemic in west Africa greatly accelerated the development of Ebola vaccine. We aimed to analyse the immune persistence induced by one shot of an ...adenovirus type-5 vector-based Ebola virus vaccine up to 6 months and the effect of boosting with a homologous vector in healthy adults in China. Methods In a randomised, double-blind, placebo-controlled, phase 1 clinical trial in one site in Jiangsu Province, China, 120 healthy adults aged 18–60 years received an initial dose of intramuscular adenovirus type-5 Ebola virus vaccine of 4·0 × 1010 viral particles, 1·6 × 1011 viral particles, or placebo, and were followed up to day 168. Participants were subsequently re-recruited to receive a booster dose of the same vaccine or placebo, in the same dose, at month 6. Women who were pregnant, breastfeeding, or planned to become pregnant during the next month were excluded. Randomisation was conducted by computer-generated block randomisation. Randomisation data were unmasked for interim analysis of the data obtained between days 0–28 but not disclosed to participants or site staff. Safety and immunogenicity analysis were done on the intention-to-treat population. We aimed to assess the safety profile of the experimental vaccine and the immunity responses to a single-dose immunisation or a homologous prime-boost regimen. Primary outcomes were Ebola glycoprotein-specific ELISA antibody responses 28 days post-boost and the occurrences of adverse reactions post-boost. The original trial and the extended booster study were registered with ClinicalTrials.gov , numbers NCT02326194 and NCT02533791 , respectively. Findings Between Dec 28, 2014, and Jan 9, 2015, we enrolled 210 volunteers. 90 participants were not randomised due to not meeting inclusion criteria (61), meeting exclusion criteria (4), or withdrawal of consent (25). 120 people were randomly assigned to receive intramuscular Ebola vaccine at 4·0 × 1010 viral particles (low dose, n=40), Ebola vaccine at 1·6 × 1011 viral particles (high dose, n=40), or placebo (n=40, in two groups of 20). After prime vaccination, the geometric mean titer (GMT) of ELISA EC90 peaked at 682·7 (95% CI 424·3–1098·5) in the low-dose vaccine group and 1305·7 (970·1–1757·2) in the high-dose vaccine group at day 28, and then fell gradually through the next a few months to 575·5 (394·8–838·8) in the high-dose vaccine group and 197·9 (107·9–362·7) in the low-dose vaccine group at day 168. No specific response was recorded in the placebo group with a GMT of 5·0. Of the 120 participants involved in the initial trial, ten participants declined to participate, and 110 were included in the boost immunisation: 38 received the low dose, 35 received the high dose, and 37 received the placebo. At day 28 after boost vaccination, the ELISA EC90 titres rapidly rose to 6110 (95% CI 4705–7935) in the low-dose group and to 11825 (8904–15705) in the high dose group. 78 of 110 participants reported at least one solicited adverse reaction within the first 7 days after booster administration. Both of the groups who received vaccine showed significantly higher incidence of mild or moderate solicited adverse reactions than did the placebo group. Interpretation The adenovirus 5-vectored Ebola vaccine of 1·6 × 1011 viral particles was highly immunogenic and safe. The lower dose of 4·0 × 1010 viral particles was also safe, but immunogenicity seemed to be more vulnerable to the pre-existing immunity of adenovirus 5. A homologous priming-boosting regimen with adenovirus type-5 Ebola vaccine at 6 months interval was able to elicit greater antibody responses with longer duration. These results support an immunisation strategy to implement a booster injection for a more durable protection against Ebola virus disease. Funding Chinese Ministry of Science and Technology and The National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.
By 2050, almost 5 billion people globally are projected to have myopia, of whom 20% are likely to have high myopia with clinically significant risk of sight-threatening complications such as myopic ...macular degeneration. These are diagnoses that typically require specialist assessment or measurement with multiple unconnected pieces of equipment. Artificial intelligence (AI) approaches might be effective for risk stratification and to identify individuals at highest risk of visual loss. However, unresolved challenges for AI medical studies remain, including paucity of transparency, auditability, and traceability.
In this retrospective multicohort study, we developed and tested retinal photograph-based deep learning algorithms for detection of myopic macular degeneration and high myopia, using a total of 226 686 retinal images. First we trained and internally validated the algorithms on datasets from Singapore, and then externally tested them on datasets from China, Taiwan, India, Russia, and the UK. We also compared the performance of the deep learning algorithms against six human experts in the grading of a randomly selected dataset of 400 images from the external datasets. As proof of concept, we used a blockchain-based AI platform to demonstrate the real-world application of secure data transfer, model transfer, and model testing across three sites in Singapore and China.
The deep learning algorithms showed robust diagnostic performance with areas under the receiver operating characteristic curves AUC of 0·969 (95% CI 0·959–0·977) or higher for myopic macular degeneration and 0·913 (0·906–0·920) or higher for high myopia across the external testing datasets with available data. In the randomly selected dataset, the deep learning algorithms outperformed all six expert graders in detection of each condition (AUC of 0·978 0·957–0·994 for myopic macular degeneration and 0·973 0·941–0·995 for high myopia). We also successfully used blockchain technology for data transfer, model transfer, and model testing between sites and across two countries.
Deep learning algorithms can be effective tools for risk stratification and screening of myopic macular degeneration and high myopia among the large global population with myopia. The blockchain platform developed here could potentially serve as a trusted platform for performance testing of future AI models in medicine.
None.
Summary Since the beginning of the 1980s, 33 emerging tick-borne agents have been identified in mainland China, including eight species of spotted fever group rickettsiae, seven species in the family ...Anaplasmataceae, six genospecies in the complex Borrelia burgdorferi sensu lato, 11 species of Babesia , and the virus causing severe fever with thrombocytopenia syndrome. In this Review we have mapped the geographical distributions of human cases of infection. 15 of the 33 emerging tick-borne agents have been reported to cause human disease, and their clinical characteristics have been described. The non-specific clinical manifestations caused by tick-borne pathogens present a major diagnostic challenge and most physicians are unfamiliar with the many tick-borne diseases that present with non-specific symptoms in the early stages of the illness. Advances in and application of modern molecular techniques should help with identification of emerging tick-borne pathogens and improve laboratory diagnosis of human infections. We expect that more novel tick-borne infections in ticks and animals will be identified and additional emerging tick-borne diseases in human beings will be discovered.
Abstract Purpose Resistance to the antiemetic ondansetron is still a major problem resulting in discomfort and poor compliance with chemotherapy in acute myeloid leukemia (AML) patients. Based on our ...hypothesis that this clinical resistance to ondansetron is associated with ABCB1 genetic polymorphisms, we investigated whether ABCB1 gene variations affect the efficacy of ondansetron in chemotherapy-induced nausea and vomiting. Methods AML patients (n = 215) treated for 3 days with high-dose cytarabine were enrolled in this study. Thirty minutes before the beginning of chemotherapy, 8 mg ondansetron was administered intravenously, followed by 24 mg by continuous infusion and 8 mg intravenously, once per day, until 2 days after chemotherapy. Chemotherapy-induced nausea and vomiting occurrence in the acute and delayed phases was calculated. ABCB1 and CYP2D6 polymorphisms were analyzed by allele-specific matrix-assisted laser desorption. Basic clinical characteristics of the AML patients were collected from medical records. Findings No differences in genotype distribution frequencies of ABCB1 polymorphisms and haplotypes were observed in patients with different CYP2D6 -predicted phenotypes. During the acute phase, patients with the CG haplotype (C3435T and G2677T) were associated with a high risk of grade 3/4 nausea and vomiting ( P = 0.003 and P = 0.026, respectively). After adjustment for age, sex, smoking status, alcohol drinking status, body surface area, body mass index, and Eastern Cooperative Oncology Group−Performance Status, multivariate survival analysis implicated the CG haplotype as a predictive marker of the risk of grade 3/4 chemotherapy-induced nausea and vomiting in AML patients ( P = 0.003 and P = 0.039, respectively). In addition, a significant association between the 3435CC genotype and grade 3/4 vomiting in AML patients was observed ( P = 0.016). However, no association between these ABCB1 gene polymorphisms and ondansetron efficacy was found in the delayed phase. Implications These findings suggest that ABCB1 gene polymorphisms are associated with antiemetic efficacy of ondansetron in the acute phase after high-dose cytarabine chemotherapy in AML patients.
Health effects of air pollution on diabetes have been scarcely studied in developing countries. We aimed to explore the associations of long-term exposure to ambient particulate matter (PM) and ...gaseous pollutants with diabetes prevalence and glucose-homoeostasis markers in China.
Between April 1 and Dec 31, 2009, we recruited a total of 15 477 participants aged 18–74 years using a random number generator and a four-staged, stratified and cluster sampling strategy from a large cross-sectional study (the 33 Communities Chinese Health Study) from three cities in Liaoning province, northeastern China. Fasting and 2 h insulin and glucose concentrations and the homoeostasis model assessment of insulin resistance index and β-cell function were used as glucose-homoeostasis markers. Diabetes was defined according to the American Diabetes Association's recommendations. We calculated exposure to air pollutants using data from monitoring stations (PM with an aerodynamic diameter of 10 μm or less PM10, sulphur dioxide, nitrogen dioxide, and ozone) and a spatial statistical model (PM with an aerodynamic diameter of 1 μm or less PM1 and 2·5 μm or less PM2·5). We used two-level logistic regression and linear regression analyses to assess associations between exposure and outcomes, controlling for confounders.
All the studied pollutants were significantly associated with increased diabetes prevalence (eg, the adjusted odds ratios associated with an increase in IQR for PM1, PM2·5, and PM10 were 1·13, 95% CI 1·04–1·22; 1·14, 1·03–1·25; and 1·20, 1·12–1·28, respectively). These air pollutants were also associated with higher concentrations of fasting glucose (0·04–0·09 mmol/L), 2 h glucose (0·10–0·19 mmol/L), and 2 h insulin (0·70–2·74 μU/L). No association was observed for the remaining biomarkers. Stratified analyses indicated greater effects on the individuals who were younger (<50 years) or overweight or obese.
Long-term exposure to air pollution was associated with increased risk of diabetes in a Chinese population, particularly in individuals who were younger or overweight or obese.
The National Key Research and Development Program of China, the National Natural Science Foundation of China, the Fundamental Research Funds for the Central Universities, the Guangdong Province Natural Science Foundation, the Career Development Fellowship of Australian National Health and Medical Research Council, and the Early Career Fellowship of Australian National Health and Medical Research Council.
Objectives: Despite the development of various cancer treatment methods, chemotherapy remains the most common approach for treating cancer. The risk of tumors acquiring resistance to chemotherapy ...remains a significant hurdle to the successful treatment of various types of cancer. Therefore, overcoming or predicting multidrug resistance in clinical treatment is essential. The detection of circulating tumor cells (CTCs) is an important component of liquid biopsy and the diagnosis of cancer. This study aims to test the feasibility of single-cell bioanalyzer (SCB) and microfluidic chip technology in identifying patients with cancer resistant to chemotherapy and propose new methods to provide clinicians with new choices. Methods: In this study, we used rapidly isolated viable CTCs from the patient blood samples method combined with SCB technology and a novel microfluidic chip, to predict whether patients with cancer are resistant to chemotherapy. SCB and microfluidic chip were used to select single CTCs, and the accumulation of chemotherapy drug was fluorescently measured in real time on these cells in the absence and presence of permeability-glycoprotein inhibitors. Results: Initially, we successfully isolated viable CTCs from the blood samples of patients. Additionally, the present study accurately predicted the response of 4 lung cancer patients to chemotherapeutic drugs. In addition, the CTCs of 17 patients with breast cancer diagnosed at Zhuhai Hospital of Traditional Chinese and Western Medicine were assessed. The results indicated that 9 patients were sensitive to chemotherapeutic drugs, 8 patients were resistant to a certain degree, and only 1 was completely resistant to chemotherapy. Conclusion: The present study indicated that the SCB technology could be used as a prognostic assay to evaluate the CTCs response to available drugs and guide physicians to treatment options that are most likely to be effective.
Vanadium, an important pollutant produced from anthropogenic activities, has been suggested to be embryotoxic and fetotoxic in animal studies. However, little is known about its effects on humans. We ...aimed to assess the association of prenatal exposure to vanadium with the risk of adverse birth outcomes in babies born to women in China.
For this population-based cohort study, the Healthy Baby Cohort, women were recruited from three cities in Hubei Province, China. Women included in this analysis were recruited from Wuhan Women and Children Medical Care Center, Wuhan. We measured urinary concentrations of vanadium and other metals simultaneously using inductively coupled plasma mass spectrometry. We used multivariable logistic regressions, with adjustment for potential confounders, to estimate the associations of natural logarithm transformed creatinine-corrected urinary vanadium (Ln-vanadium) concentrations as continuous variables and categorised into quartiles (Q; Q1: ≤0·84 μg/g creatinine, Q2: 0·84–1·40 μg/g creatinine, Q3: 1·40–2·96 μg/g creatinine, Q4: >2·96 μg/g creatinine, with the lowest quartile set as reference) with preterm delivery, early-term delivery, low birthweight, and being small for gestational age. We applied restricted cubic spline models to evaluate the dose-response relationships.
Data from 7297 women recruited between Sept 22, 2012, and Oct 22, 2014, were included in this study. Urinary Ln-vanadium concentrations showed non-linear dose-response relationships with risk of preterm delivery (S-shaped, p<0·0001) and low birthweight (J-shaped, p=0·0001); the adjusted odds ratios (ORs) for increasing quartiles of urinary vanadium were 1·76 (95% CI 1·05–2·95) for Q2, 3·17 (1·96–5·14) for Q3, and 8·86 (5·66–13·86) for Q4 for preterm delivery, and 2·29 (95% CI 1·08–4·84) for Q2, 3·22 (1·58–6·58) for Q3, and 3·56 (1·79–7·10) for Q4 for low birthweight. Ln-vanadium concentrations were linearly associated with the risk of early-term delivery (linear, p<0·0001) and being small for gestational age (linear, p=0·0027), with adjusted ORs of 1·15 (95% CI 1·10–1·21) for early-term delivery and 1·12 (1·04–1·21) for being small for gestational age per unit increase in Ln-vanadium concentrations.
Our findings reveal a relationship between prenatal exposure to higher levels of vanadium and increased risk of adverse birth outcomes, suggesting that vanadium might be a potential toxic metal for human beings. Further studies are needed to replicate the observed associations and investigate the interaction effects of prenatal exposure to different metals on adverse birth outcomes.
National Key R&D Plan of China, National Natural Science Foundation of China, and Fundamental Research Funds for the Central Universities, Key Laboratory of Environment and Health.
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