Summary Background A recombinant adenovirus type-5 vector-based vaccine expressing the glycoprotein of Ebola Zaire Makona variant showed good safety and immunogenicity in a phase 1 trial of healthy ...Chinese adults. We aimed to assess the safety and immunogenicity of this vaccine in healthy adults in Sierra Leone and to determine the optimal dose. Methods We did a single-centre, randomised, double-blind, placebo-controlled, phase 2 clinical trial at Sierra Leone–China Friendship Hospital, Freetown, Sierra Leone. We recruited healthy adults aged 18–50 years who were HIV negative, had no history of Ebola virus infection, and had no previous immunisation with other Ebola vaccine candidates. Participants were sequentially enrolled and randomly assigned (2:1:1), by computer-generated block randomisation (block size of eight), to receive the high-dose vaccine (1·6 × 1011 viral particles), low-dose vaccine (8·0 × 1010 viral particles), or placebo (containing only vaccine excipients, with no viral particles). Participants, investigators, and study staff (except two study pharmacists) were masked from treatment allocation. The primary safety outcome was occurrence of solicited adverse reactions within 7 days of vaccination, analysed by intention to treat. The primary immunogenicity outcome was glycoprotein-specific antibody responses at days 14, 28, and 168 after vaccination, analysed in all vaccinated participants who had blood samples drawn for antibody tests. The trial is registered with the Pan African Clinical Trials Registry, number PACTR201509001259869, and is completed. Findings During Oct 10–28, 2015, 500 participants were enrolled and randomly assigned to receive the high-dose vaccine (n=250), low-dose vaccine (n=125), or placebo (n=125). 132 (53%) participants in the high-dose group, 60 (48%) in the low-dose group, and 54 (43%) in the placebo group reported at least one solicited adverse reaction within 7 days of vaccination. Most adverse reactions were mild and self-limiting. Solicited injection-site adverse reactions were significantly more frequent in vaccine recipients (65 26% in high-dose group and 31 25% in low-dose group) than in those receiving placebo (17 14%; p=0·0169). Glycoprotein-specific antibody responses were detected from day 14 onwards (geometric mean titre 1251·0 95% CI 976·6–1602·5 in low-dose group and 1728·4 1459·4–2047·0 in high-dose group) and peaked at day 28 (1471·8 1151·0–1881·8 and 2043·1 1762·4–2368·4), but declined quickly in the following months (223·3 148·2–336·4 and 254·2 185·0–349·5 at day 168). Geometric mean titres in the placebo group remained around 6·0–6·8 throughout the study period. Three serious adverse events (malaria, gastroenteritis, and one fatal asthma episode) were reported in the high-dose vaccine group, but none was deemed related to the vaccine. Interpretation The recombinant adenovirus type-5 vector-based Ebola vaccine was safe and highly immunogenic in healthy Sierra Leonean adults, and 8·0 × 1010 viral particles was the optimal dose. Funding Chinese Ministry of Science and Technology and the National Health and Family Planning Commission, Beijing Institute of Biotechnology, and Tianjin CanSino Biotechnology.
From 2003 to 2005, standardised 5-year cancer survival in China was much lower than in developed countries and varied substantially by geographical area. Monitoring population-level cancer survival ...is crucial to the understanding of the overall effectiveness of cancer care. We therefore aimed to investigate survival statistics for people with cancer in China between 2003 and 2015.
We used population-based data from 17 cancer registries in China. Data for the study population was submitted by the end of July 31, 2016, with follow-up data on vital status obtained on Dec 31, 2015. We used anonymised, individual cancer registration records of patients (aged 0–99 years) diagnosed with primary, invasive cancers from 2003 to 2013. Patients eligible for inclusion had data for demographic characteristics, date of diagnosis, anatomical site, morphology, behaviour code, vital status, and last date of contact. We analysed 5-year relative survival by sex, age, and geographical area, for all cancers combined and 26 different cancer types, between 2003 and 2015. We stratified survival estimates by calendar period (2003–05, 2006–08, 2009–11, and 2012–15).
There were 678 842 records of patients with invasive cancer who were diagnosed between 2003 and 2013. Of these records, 659 732 (97·2%) were eligible for inclusion in the final analyses. From 2003–05 to 2012–15, age-standardised 5-year relative survival increased substantially for all cancers combined, for both male and female patients, from 30·9% (95% CI 30·6–31·2) to 40·5% (40·3–40·7). Age-standardised 5-year relative survival also increased for most cancer types, including cancers of the uterus (average change per calendar period 5·5% 95% CI 2·5–8·5), thyroid (5·4% 3·2–7·6), cervix (4·5% 2·9–6·2), and bone (3·2% 2·1–4·4). In 2012–15, age-standardised 5-year survival for all patients with cancer was higher in urban areas (46·7%, 95% CI 46·5–47·0) than in rural areas (33·6%, 33·3–33·9), except for patients with oesophageal or cervical cancer; but improvements in survival were greater for patients residing in rural areas than in urban areas. Relative survival decreased with increasing age. The increasing trends in survival were consistent with the upward trends of medical expenditure of the country during the period studied.
There was a marked overall increase in cancer survival from 2003 to 2015 in the population covered by these cancer registries in China, possibly reflecting advances in the quality of cancer care in these areas. The survival gap between urban and rural areas narrowed over time, although geographical differences in cancer survival remained. Insight into these trends will help prioritise areas that need increased cancer care.
National Key R&D Program of China, PUMC Youth Fund and the Fundamental Research Funds for the Central Universities, and Major State Basic Innovation Program of the Chinese Academy of Medical Sciences.
•Ultrasound application can decrease freezing time and drip loss of red radish.•Ultrasound-assisted freezing (UAF) showed better retention on firmness and color.•UAF improved the retention of ...anthocyanins, vitamin C and phenolics content.•Microstructure of frozen radish was better preserved by UAF.•Red radish aromatic profile was deeply affected by the freezing/thawing process.
Power ultrasound, which can enhance nucleation rate and crystal growth rate, can also affect the physico-chemical properties of immersion frozen products. In this study, the influence of slow freezing (SF), immersion freezing (IF) and ultrasound-assisted freezing (UAF) on physico-chemical properties and volatile compounds of red radish was investigated. Results showed that ultrasound application significantly improved the freezing rate; the freezing time of ultrasound application at 0.26W/cm2 was shorten by 14% and 90%, compared to IF and SF, respectively. UAF products showed significant (p<0.05) reduction in drip loss and phytonutrients (anthocyanins, vitamin C and phenolics) loss. Compared to SF products, IF and UAF products showed better textural preservation and higher calcium content. The radish tissues exhibited better cellular structures under ultrasonic power intensities of 0.17 and 0.26W/cm2 with less cell separation and disruption. Volatile compound data revealed that radish aromatic profile was also affected in the freezing process.
To evaluate the effects of combining the assessment of circulating high-sensitivity C-reactive protein (hs-CRP) with that of Epstein-Barr virus DNA (EBV DNA) in the pretherapy prognostication of ...nasopharyngeal carcinoma (NPC).
Three independent cohorts of NPC patients (training set of n=3113, internal validation set of n=1556, and prospective validation set of n=1668) were studied. Determinants of disease-free survival, distant metastasis-free survival, and overall survival were assessed by multivariate analysis. Hazard ratios and survival probabilities of the patient groups, segregated by clinical stage (T1-2N0-1M0, T3-4N0-1M0, T1-2N2-3M0, and T3-4N2-3M0) and EBV DNA load (low or high) alone, and also according to hs-CRP level (low or high), were compared.
Elevated hs-CRP and EBV DNA levels were significantly correlated with poor disease-free survival, distant metastasis-free survival, and overall survival in both the training and validation sets. Associations were similar and remained significant after excluding patients with cardiovascular disease, diabetes, and chronic hepatitis B. Patients with advanced-stage disease were segregated by high EBV DNA levels and high hs-CRP level into a poorest-risk group, and participants with either high EBV DNA but low hs-CRP level or high hs-CRP but low EBV DNA values had poorer survival compared with the bottom values for both biomarkers. These findings demonstrate a significant improvement in the prognostic ability of conventional advanced NPC staging.
Baseline plasma EBV DNA and serum hs-CRP levels were significantly correlated with survival in NPC patients. The combined interpretation of EBV DNA with hs-CRP levels led to refinement of the risks for the patient subsets, with improved risk discrimination in patients with advanced-stage disease.
In this study, the effect of ultrasound irradiation temperature and ultrasound intensity on the freezing and nucleation in strawberry samples was studied. The application of ultrasound irradiation at ...different temperatures was able to induce nucleation at lower degree of supercooling compared to the control samples. The achieved degree of supercooling in the ultrasound irradiated strawberries was linearly correlated to the ultrasound irradiation temperature. At the ultrasound irradiation temperature of −1.6 °C, the characteristic freezing time (CFT) was significantly shorter than that in the control sample (p < 0.05). The application of ultrasound at higher intensities was found to effectively shorten the CFT. The degree of supercooling in ultrasound irradiated samples was not linearly correlated to ultrasound intensity. In conclusion, the combination of ultrasound irradiation temperature and intensity can be effective in controlling nucleation and freezing processes of perishable fruits such as strawberry.
•Ultrasound irradiation applied at any temperature was able to induce nucleation at lower degree of supercooling.•The supercooling degrees in ultrasound irradiated samples were linearly related to the ultrasound irradiation temperatures.•Ultrasound irradiation at −1.6 °C significantly lowered the characteristic freezing time of strawberries.•Ultrasound intensity when applied at higher magnitude was very effective in shortening the characteristic freezing time.
Summary Background Prophylactic treatment of individuals with latent Mycobacterium tuberculosis infection is an essential component of tuberculosis control in some settings. In China, the prevalence ...of latent tuberculosis infection, and preventive interventions against this disease, have not been systematically studied. We aimed to assess the prevalence of latent tuberculosis and its associated risk factors in rural populations in China. Methods Between July 1, and Sept 30, 2013, we undertook a baseline survey of a population-based, multicentre, prospective cohort study of registered residents (≥5 years old) at four study sites in rural China. Eligible participants were identified by door-to-door survey with a household sampling design. We screened participants for active tuberculosis and history of tuberculosis then used a tuberculin skin test and an interferon-γ release assay (QuantiFERON QFT) to test for latent infection. We used odds ratios (ORs) and 95% CIs to assess variables associated with positivity of QFT and tuberculin skin tests. Findings 21 022 (90%) of 23 483 eligible participants completed a baseline survey. Age-standardised and sex-standardised rates of skin-test positivity (≥10 mm) ranged from 15% to 42%, and QFT positivity rates ranged from 13% to 20%. Rates of positivity for the tuberculin skin test and the QFT test were low in study participants younger than 20 years and gradually increased with age (p for trend <0·0001). Rates of latent tuberculosis infection were higher for men than women (p<0·0001). Overall agreement between the tuberculin skin test and the QFT test was moderate (81·06%; kappa coefficient 0·485), with skin-test-only positive results associated with the presence of BCG scar, male sex, and ages of 60 years and older, and QFT-only positive results associated with male sex and ages of 60 years and older. Interpretation On the basis of findings showing that the performance of the tuberculin skin test might be affected by various factors including BCG vaccination and age, our results suggest that the prevalence of latent tuberculosis in China might be overestimated by skin tests compared with interferon-γ release assays. Funding The National Science and Technology Major Project of China, the Program for Changjiang Scholars and Innovative Research Team in University of China.
The role of activation of the coagulation and fibrinolysis system in the pathogenesis and prognosis of cardiovascular diseases (CVDs) has drawn wide attention. Recently, the D-dimer to fibrinogen ...ratio (DFR) is considered as a useful biomarker for the diagnosis and prognosis of ischemic stroke and pulmonary embolism. However, few studies have explored the relationship between DFR and cardiovascular disease. In our study, patients were divided into 2 groups according to DFR value: the lower group (DFR < 0.52, n = 2123) and the higher group (DFR ≥ 0.52, n = 1073). The primary outcome was all-cause mortality (ACM) and cardiac mortality (CM). The average follow-up time was 37.59 ± 22.24 months. We found that there were significant differences between the 2 groups in term of ACM (2.4% vs 6.6%, P < 0.001) and CM (1.5% vs 4.0%, P < 0.001). Kaplan–Meier analyses showed that elevated DFR had higher incidences of ACM (log rank P < 0.001) and CM (log rank P < 0.001). Multivariate Cox regression analyses showed that DFR was an independent predictor of ACM (HR = 1.743, 95%CI: 1.187-2.559 P = 0.005) and CM (HR = 1.695, 95%CI: 1.033-2.781 P = 0.037). This study indicates that DFR is an independent and novel predictor of long-term ACM and CM in post-PCI patients with CAD.
Abstract Object We aimed to investigate the effect of coiling for small unruptured intracranial aneurysms(UIAs)﹤5mm) on progressive occlusion and recanalization, and the dubious factors related to ...progressive occlusion and recanalization among UIAs without complete occlusion. Methods A total of 264 patients with 287 small UIAs were coiled in our institute between June 2009 and December 2014. All UIAs enrolled were divided into small (3–5mm) and very small (＜3mm) groups, and UIAs without initial complete occlusion were divided into progressive, stable and recanalization groups. Baseline characteristics, procedure-related complications, angiographic follow-up results, and clinical outcomes were statistically analyzed. Results Among 287 aneurysms, 211 aneurysms (73.5%) were completely coiled, three (1.2%) intraoperative ruptures and 12 (4.2%) perioperative thromboembolic events occurred. Angiographic follow-up was available for 174 patients(65.9%), the incidence of recanalization was 5.7%. Among 56 aneurysms without complete occlusion, 43 (76.8%) had progressive occlusion and 6(10.7%) had recanalization. Anatomic results of initial and follow-up between small and very small groups were similar in both groups. On logistic regression analysis, smaller size (＜3mm) without complete occlusion related to recanalization(OR, 8.0, 95% CI, 1.3–50.0, P=0.026). Conclusions Our study suggested that coil embolization of small UIAs can achieve a high rate of progressive occlusion and low rate of recanalization during follow-up. Anatomic results of initial and follow-up between small (3–5mm) and very small (＜3mm) groups were similar in both groups. What’s more, smaller size (＜3mm) without complete occlusion may relate to recanalization.
BACKGROUNDMediastinal neoplasms are typical thoracic diseases with increasing incidence in the general global population and can lead to poor prognosis. In clinical practice, the mediastinum's ...complex anatomic structures and intertype confusion among different mediastinal neoplasm pathologies severely hinder accurate diagnosis. To solve these difficulties, we organised a multicentre national collaboration on the basis of privacy-secured federated learning and developed CAIMEN, an efficient chest CT-based artificial intelligence (AI) mediastinal neoplasm diagnosis system. METHODSIn this multicentre cohort study, 7825 mediastinal neoplasm cases and 796 normal controls were collected from 24 centres in China to develop CAIMEN. We further enhanced CAIMEN with several novel algorithms in a multiview, knowledge-transferred, multilevel decision-making pattern. CAIMEN was tested by internal (929 cases at 15 centres), external (1216 cases at five centres and a real-world cohort of 11 162 cases), and human-AI (60 positive cases from four centres and radiologists from 15 institutions) test sets to evaluate its detection, segmentation, and classification performance. FINDINGSIn the external test experiments, the area under the receiver operating characteristic curve for detecting mediastinal neoplasms of CAIMEN was 0·973 (95% CI 0·969-0·977). In the real-world cohort, CAIMEN detected 13 false-negative cases confirmed by radiologists. The dice score for segmenting mediastinal neoplasms of CAIMEN was 0·765 (0·738-0·792). The mediastinal neoplasm classification top-1 and top-3 accuracy of CAIMEN were 0·523 (0·497-0·554) and 0·799 (0·778-0·822), respectively. In the human-AI test experiments, CAIMEN outperformed clinicians with top-1 and top-3 accuracy of 0·500 (0·383-0·633) and 0·800 (0·700-0·900), respectively. Meanwhile, with assistance from the computer aided diagnosis software based on CAIMEN, the 46 clinicians improved their average top-1 accuracy by 19·1% (0·345-0·411) and top-3 accuracy by 13·0% (0·545-0·616). INTERPRETATIONFor mediastinal neoplasms, CAIMEN can produce high diagnostic accuracy and assist the diagnosis of human experts, showing its potential for clinical practice. FUNDINGNational Key R&D Program of China, National Natural Science Foundation of China, and Beijing Natural Science Foundation.
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