•Higher rate of increase in GDS was associated with faster cognitive decline and higher risk of progression to MCI or AD.•The rate of change in GDS was associated with Aβ accumulation and cerebral ...glucose metabolism.•The influences of the rate of change in GDS on cognition and clinical progression were partially mediated by Aβ accumulation and cerebral glucose metabolism.
Background: Depression is considered a psychological risk factor for Alzheimer's disease (AD). We sought to examine the differential associations of depression severity with cognitive decline, clinical progression to mild cognitive impairment (MCI) or AD, and neuroimaging markers of AD in cognitively normal older adults.
Methods: A total of 522 cognitively normal (CN) participants who underwent assessments for depression (longitudinal geriatric depression scale GDS ) and cognitive assessments were included from the Alzheimer Disease Neuroimaging Initiative (ADNI) cohort. The cross-sectional and longitudinal associations of the rate of change in GDS with amyloid-β (Aβ)-positron emission tomography (PET), tau-PET, and 18F-fluorodeoxyglucose (FDG)-PET were explored. Kaplan-Meier survival curves of clinical progression and Aβ accumulation were plotted based on mean annual changes in GDS. Mediation analyses were utilized to explore the mediation effects of AD markers.
Results: Higher rate of increase in GDS was associated with faster cognitive decline and higher risk of progression to MCI or AD. Moreover, the rate of change in GDS was significantly associated with Aβ accumulation and cerebral glucose metabolism. The influences of the rate of change in GDS on cognition and clinical progression were partially mediated by Aβ accumulation and cerebral glucose metabolism.
Limitations: GDS is a self-reported questionnaire and not the same as a clinical diagnosis of depression.
Conclusions: The cognitive and clinical consequences of changes in depressive symptoms partly stem from Aβ accumulation and cerebral glucose metabolism, which increases our understanding of how depressive symptoms may increase vulnerability to dementia.
Summary Background The prevalence of chronic kidney disease is high in developing countries. However, no national survey of chronic kidney disease has been done incorporating both estimated ...glomerular filtration rate (eGFR) and albuminuria in a developing country with the economic diversity of China. We aimed to measure the prevalence of chronic kidney disease in China with such a survey. Methods We did a cross-sectional survey of a nationally representative sample of Chinese adults. Chronic kidney disease was defined as eGFR less than 60 mL/min per 1·73 m2 or the presence of albuminuria. Participants completed a lifestyle and medical history questionnaire and had their blood pressure measured, and blood and urine samples taken. Serum creatinine was measured and used to estimate glomerular filtration rate. Urinary albumin and creatinine were tested to assess albuminuria. The crude and adjusted prevalence of indicators of kidney damage were calculated and factors associated with the presence of chronic kidney disease analysed by logistic regression. Findings 50 550 people were invited to participate, of whom 47 204 agreed. The adjusted prevalence of eGFR less than 60 mL/min per 1·73 m2 was 1·7% (95% CI 1·5–1·9) and of albuminuria was 9·4% (8·9–10·0). The overall prevalence of chronic kidney disease was 10·8% (10·2–11·3); therefore the number of patients with chronic kidney disease in China is estimated to be about 119·5 million (112·9–125·0 million). In rural areas, economic development was independently associated with the presence of albuminuria. The prevalence of chronic kidney disease was high in north (16·9% 15·1–18·7) and southwest (18·3% 16·4–20·4) regions compared with other regions. Other factors independently associated with kidney damage were age, sex, hypertension, diabetes, history of cardiovascular disease, hyperuricaemia, area of residence, and economic status. Interpretation Chronic kidney disease has become an important public health problem in China. Special attention should be paid to residents in economically improving rural areas and specific geographical regions in China. Funding The Ministry of Science and Technology (China); the Science and Technology Commission of Shanghai; the National Natural Science Foundation of China; the Department of Health, Jiangsu Province; the Sichuan Science and Technology Department; the Ministry of Education (China); the International Society of Nephrology Research Committee; and the China Health and Medical Development Foundation.
The 2015 Lancet Commission on Health and Climate Change has been formed to map out the impacts of climate change, and the necessary policy responses, in order to ensure the highest attainable ...standards of health for populations worldwide. This Commission is multidisciplinary and international in nature, with strong collaboration between academic centres in Europe and China.
Functional vascularization is critical for the clinical regeneration of complex tissues such as kidney, liver, or bone. The immobilization or delivery of growth factors has been explored to improve ...vascularization capacity of tissue‐engineered constructs; however, the use of growth factors has inherent problems such as the loss of signaling capability and the risk of complications including immunological responses and cancer. Here, a new method of preparing water‐insoluble silk protein scaffolds with vascularization capacity using an all‐aqueous process is reported. Acid is added temporally to tune the self‐assembly of silk in the lyophilization process, resulting in water‐insoluble scaffold formation directly. These biomaterials are mainly noncrystalline, offering improved cell proliferation than previously reported silk materials. These systems also have an appropriate softer mechanical property that could provide physical cues to promote cell differentiation into endothelial cells, and enhance neovascularization and tissue ingrowth in vivo without the addition of growth factors. Therefore, silk‐based degradable scaffolds represent an exciting biomaterial option, with vascularization capacity for soft tissue engineering and regenerative medicine.
Engineering complex organs requires functional vasculatures that can provide oxygen and nutrients to sustain cell viability. Here, silk materials with softer mechanical properties are developed and show the cell differentiation into endothelial cells and neovascularization capacity in vitro and in vivo, without the addition of the growth factors. The study suggests a promising way to fabricate a silk matrix used in complex soft tissues.
Increased oxidative stress and inflammation has a role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Drugs with antioxidant and anti-inflammatory properties, such as ...N-acetylcysteine, might provide a useful therapeutic approach for COPD. We aimed to assess whether N-acetylcysteine could reduce the rate of exacerbations in patients with COPD.
In our prospective, randomised, double-blind, placebo-controlled, parallel-group study, we enrolled patients aged 40-80 years with moderate-to-severe COPD (post-bronchodilator forced expiratory volume in 1 s FEV1/forced vital capacity <0·7 and FEV1 of 30-70% of predicted) at 34 hospitals in China. We stratified patients according to use of inhaled corticosteroids (regular use or not) at baseline and randomly allocated them to receive N-acetylcysteine (one 600 mg tablet, twice daily) or matched placebo for 1 year. The primary endpoint was the annual exacerbation rate in patients who received at least one dose of study drug and had at least one assessment visit after randomisation. This study is registered with the Chinese Clinical Trials Registry, ChiCTR-TRC-09000460.
Between June 25, 2009, and Dec 29, 2010, we screened 1297 patients, of whom 1006 were eligible for randomisation (504 to N-acetylcysteine and 502 to placebo). After 1 year, we noted 497 acute exacerbations in 482 patients in the N-acetylcysteine group who received at least one dose and had at least one assessment visit (1·16 exacerbations per patient-year) and 641 acute exacerbations in 482 patients in the placebo group (1·49 exacerbations per patient-year; risk ratio 0·78, 95% CI 0·67-0·90; p=0·0011). N-acetylcysteine was well tolerated: 146 (29%) of 495 patients who received at least one dose of N-acetylcysteine had adverse events (48 serious), as did 130 (26%) of 495 patients who received at least one dose of placebo (46 serious). The most common serious adverse event was acute exacerbation of COPD, occurring in 32 (6%) of 495 patients in the N-acetylcysteine group and 36 (7%) of 495 patients in the placebo group.
Our findings show that in Chinese patients with moderate-to-severe COPD, long-term use of N-acetylcysteine 600 mg twice daily can prevent exacerbations, especially in disease of moderate severity. Future studies are needed to explore efficacy in patients with mild COPD (GOLD I).
Hainan Zambon Pharmaceutical.
Summary Background Utidelone, a genetically engineered epothilone analogue, has shown promise as a potential treatment for breast cancer in phase 1 and 2 trials. The aim of this phase 3 trial was to ...compare the efficacy and safety of utidelone plus capecitabine versus capecitabine alone in patients with metastatic breast cancer. Methods We did a multicentre, open-label, superiority, phase 3, randomised controlled trial in 26 hospitals in China. Eligible participants were female patients with metastatic breast cancer refractory to anthracycline and taxane chemotherapy regimens. We randomly assigned participants (2:1) using computer based randomisation and block sizes of 6 to a 21-day cycle of either utidelone (30 mg/m2 intravenously once per day on days 1–5) plus capecitabine (1000 mg/m2 orally twice per day on days 1–14), or capecitabine alone (1250 mg/m2 orally twice per day on days 1–14), until disease progression or unacceptable toxicity occurred. Patients, physicians, and assessors were not masked to treatment allocation; however, an independent radiology review committee used to additionally assess response was masked to allocation. The primary endpoint was centrally assessed (by an independent radiology review committee) progression-free survival, and analysed using the Kaplan-Meier product-limit method in the intention-to-treat population. Safety was assessed in all participants who received at least one dose of study drug. Follow-up is ongoing. This study is registered at ClinicalTrials.gov , number NCT02253459. Findings Between Aug 8, 2014, and Dec 14, 2015, we enrolled and randomly assigned 270 patients to treatment with utidelone plus capecitabine, and 135 to capecitabine alone. Median follow-up for progression-free survival was 6·77 months (IQR 3·81–10·32) for the utidelone plus capecitabine group and 4·55 months (2·55–9·39) for the capecitabine alone group. Median progression-free survival by central review in the utidelone plus capecitabine group was 8·44 months (95% CI 7·95–9·92) compared with 4·27 months (3·22–5·68) in the capecitabine alone group; hazard ratio 0·46, 95% CI 0·36–0·59; p<0·0001. Peripheral neuropathy was the most common grade 3 adverse event in the utidelone plus capecitabine group (58 22% of 267 patients vs 1 <1% of 130 patients in the capecitabine alone group). Palmar-plantar erythrodysaesthesia was the most prominent grade 3 adverse event in the capacitabine alone group (in 10 8% of 130 patients) and was the next most frequent grade 3 event in the utidelone plus capecitabine group (in 18 7% of 267 patients). 16 serious adverse events were reported in the combination therapy group (diarrhoea was the most common, in three 1% patients) and 14 serious adverse events were reported in the monotherapy group (the most common were diarrhoea, increased blood bilirubin, and anaemia, in two 2% patients for each event). 155 patients died (99 in the combination therapy arm, 56 in the monotherapy arm). All deaths were related to disease progression except for one in each group (attributed to pericardial effusion in the combination therapy group and dyspnoea in the monotherapy group) that were considered possibly or probably treatment-related. Interpretation Despite disease progression with previous chemotherapies, utidelone plus capecitabine was more efficacious compared with capecitabine alone for the outcome of progression-free survival, with mild toxicity except for peripheral sensory neuropathy, which was manageable. The findings from this study support the use of utidelone plus capecitabine as an effective option for patients with metastatic breast cancer. Funding Beijing Biostar Technologies, Beijing, China.
•We performed a GWAS of brain tau load as measured by AV1451-PET.•Novel association with higher tau was identified for rs56298435 within ZBTB20.•Rs150532 in the protein phosphorylation regulatory ...gene EYA4 also affects tau load.•Tau pathology mediated the effects of novel loci on clinical progression.•EYA4 or VNN2 expression was highly correlated with the tau-related gene MAPT.
The related genetic variants of tau deposition, a seminal pathological hallmark of Alzheimer's disease, remain poorly understood. We sought to perform a genome-wide association study of brain tau load as measured by AV1451 positron emission tomography (PET). Among 543 non-demented European individuals, novel associations with higher tau were identified for rs56298435 (p = 8.35 × 10−10, β=0.31) within ZBTB20, and for rs150532 (p = 1.90 × 10−8, β=0.26) in the protein phosphorylation regulatory gene EYA4. The APOE association additionally reached genome-wide significant when APOE ε4 was not adjusted. Minor allele carriers of rs56298435 or rs150532 showed higher levels of tau PET load. As expected, phosphorylated-tau analyses in both plasma and cerebrospinal fluid also revealed the same direction of effect. Functionally, the effects of novel loci on cognitive decline could be mediated by tau pathology. In addition, we observed that the expression of VNN2 as regulated by rs150532, together with EYA4, displayed significant correlations with the tau-related gene MAPT in numerous brain regions. Our novel finding lends additional credence to heritable underpinnings of tau deposition.
Summary Background After a massive syphilis epidemic in the first half of the 20th century, China was able to eliminate this infection for 20 years (1960–80). However, substantial changes in Chinese ...society have been followed by a resurgent epidemic of sexually transmitted diseases. Sporadic reports have provided clues to the magnitude of the spread of syphilis, but a national surveillance effort is needed to provide data for planning and intervention. Methods We collected and assessed case report data from China's national sexually transmitted disease surveillance system and sentinel site network. Findings In 1993, the reported total rate of cases of syphilis in China was 0·2 cases per 100 000, whereas primary and secondary syphilis alone represented 5·7 cases per 100 000 persons in 2005. The rate of congenital syphilis increased greatly with an average yearly rise of 71·9%, from 0·01 cases per 100 000 livebirths in 1991 to 19·68 cases per 100 000 livebirths in 2005. Interpretation The results suggest that a range of unique biological and social forces are driving the spread of syphilis in China. A national campaign for detection and treatment of syphilis, and a credible prevention strategy, are urgently needed.
Abstract Background The role of local therapy for the management of oligometastatic prostate cancer at diagnosis still remains poorly defined. We did a systematic review and meta-analysis evaluating ...local therapy of the primary tumour for patients with oligometastatic prostate cancer at diagnosis as well as the patients who can benefit the most. Methods For this systematic review, we searched PubMed, EMBASE, Medline, and the Cochrane Library for studies from database inception until March, 2016, for local therapy of the primary tumour in patients with oligometastatic prostate cancer. No language restrictions were applied. We estimated the risk of bias for the individual research studies using the Newcastle-Ottawa Scale (NOS). We assessed the publication bias using both the Egger's linear regression approach and funnel plots. The baseline characteristics on trial, patient, and treatment level were extracted. The primary outcomes were overall survival and disease-specific survival. All statistical analyses were performed using Stata v.12.0 software (StataCorp, College Station, TX, USA). Findings Seven retrospective studies were selected for inclusion, including a total of 24 203 patients who were recruited from 1989 to 2010 form Sweden, USA, and Germany. For overall survival, the pooled hazard ratio (HR) in patients treated with local therapy compared with no local therapy was 0·53 (95% CI 0·40–0·71; p <0·01). Local therapy was also associated with a 49% improvement of disease-specific survival (HR 0·51, 95% CI 0·37–0·69, p<0·01). This significant increase in disease-specific survival was better pronounced in patients younger (HR 0·34, 0·23–0·52, p<0·01) than 65 years than in those 65 years or older (HR 0·44, 0·28–0·68, p <0·01). The tumour-specific factor was associated with the improved survival in patients with AJCC (American Joint Committee on Cancer) M1a stage (HR 0·29, 0·18–0·48, p<0·01) than in those with M1b (HR 0·40, 0·24–0·68, p<0·001) and M1c (HR 0·34; 0·24–0·50, p<0·01). Interpretation Local therapy for a primary tumour conferred a significantly better outcome in fit patients with oligometastatic prostate cancer at diagnosis. The evidence also suggests that radical prostatectomy is a preferable local therapy procedure for patients aged 65 years or younger or for those who have an AJCC stage M1a tumour. We believe that important local therapy factors should be systematically assessed to develop a personalised approach to improve patient survival Funding This study was supported by the Prostate Cancer Foundation Young Investigator Award 2013, the National Natural Science Foundation of China (81300627 and 81370855) and Programs from Science and Technology Department of Sichuan Province (2013SZ0006 and 2014JY0219).
The related genetic variants of tau deposition, a seminal pathological hallmark of Alzheimer's disease, remain poorly understood. We sought to perform a genome-wide association study of brain tau ...load as measured by AV1451 positron emission tomography (PET). Among 543 non-demented European individuals, novel associations with higher tau were identified for rs56298435 (p = 8.35 × 10
, β=0.31) within ZBTB20, and for rs150532 (p = 1.90 × 10
, β=0.26) in the protein phosphorylation regulatory gene EYA4. The APOE association additionally reached genome-wide significant when APOE ε4 was not adjusted. Minor allele carriers of rs56298435 or rs150532 showed higher levels of tau PET load. As expected, phosphorylated-tau analyses in both plasma and cerebrospinal fluid also revealed the same direction of effect. Functionally, the effects of novel loci on cognitive decline could be mediated by tau pathology. In addition, we observed that the expression of VNN2 as regulated by rs150532, together with EYA4, displayed significant correlations with the tau-related gene MAPT in numerous brain regions. Our novel finding lends additional credence to heritable underpinnings of tau deposition.
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