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Pancreatic cancer is one of the most malignant tumours with a poor prognosis. In recent years, the incidence of pancreatic cancer is on the rise. Traditional chemotherapy and radiotherapy for pancreatic cancer have been improved, first-line and second-line palliative treatments have been developed, and adjuvant treatments have also been used in clinical. However, the 5-year survival rate is still less than 10% and new treatment methods such as targeted therapy and immunotherapy need to be investigated. In the past decades, many clinical trials of targeted therapies and immunotherapies for pancreatic cancer were launched and some of them showed an ideal prospect in a subgroup of pancreatic cancer patients. The experience of both success and failure of these clinical trials will be helpful to improve these therapies in the future. Therefore, the current research progress and challenges of selected targeted therapies and immunotherapies for pancreatic cancer are reviewed.
Microsporidia of the genus Ovipleistophora are generally parasites of fishes and aquatic crustaceans. In the current study, Ovipleistophora diplostomuri and O. ovariae were firstly reported from Culter alburnus and Xenocypris argentea and Parabramis pekinensis, respectively. Both of them exclusively infected fish ovary and were morphologically, ultrastructurally and genetically characterized. Sporogony occurred in direct contact with the host cell cytoplasm and sporophorous vesicles were not observed for the new isolates of these two Ovipleistophora species. Spores of O. ovariae were for the first time observed to be dimorphic. Genetic analysis indicated that the genetic variation in the ITS and LSU sequences was distinct among between-host O. diplostomuri isolates. High sequence variation in ITS sequence suggests that it can be a reliable molecular marker to explore the population genetics of O. diplostomuri. This is the first report of these two Ovipleistophora species in China which extends their host and geographical range.
Many financial time series have varying structures at different quantile levels, and also exhibit the phenomenon of conditional heteroskedasticity at the same time. However, there is presently no time series model that accommodates both of these features. This paper fills the gap by proposing a novel conditional heteroskedastic model called “quantile double autoregression”. The strict stationarity of the new model is derived, and self-weighted conditional quantile estimation is suggested. Two promising properties of the original double autoregressive model are shown to be preserved. Based on the quantile autocorrelation function and self-weighting concept, three portmanteau tests are constructed to check the adequacy of the fitted conditional quantiles. The finite sample performance of the proposed inferential tools is examined by simulation studies, and the need for use of the new model is further demonstrated by analyzing the S&P500 Index.
The present study aimed to investigate the association of early-life exposure to famine with abdominal fat accumulation and function and further evaluate the influence of first-degree family history of diabetes and physical activity on this association. The present work analysed parts of the REACTION study. A total of 3033 women were enrolled. Central obesity was defined as waist circumferences (W) ≥ 85 cm. Chinese visceral adiposity index (CVAI) was used to evaluate visceral adipose distribution and function. Partial correlation analysis showed BMI, W, glycated Hb and CVAI were associated with early-life exposure to famine (both P < 0·05). Logistic regression showed that the risks of overall overweight/obesity and central obesity in fetal, early-childhood, mid-childhood and late-childhood exposed subgroups were increased significantly (all P < 0·05). Compared with the non-exposed group, the BMI, W and CVAI of fetal, early- to late-childhood exposed subgroups were significantly increased both in those with or without first-degree family history of diabetes and in those classified as physically active or inactive, respectively (all P < 0·05). The associations of BMI, W and CVAI with early-life exposure to famine were independent of their associations with first-degree family history of diabetes (all P < 0·01) or physical activity status (all P < 0·001). Early-life exposure to famine contributed to abdominal fat accumulation and dysfunction, which was independent of the influence of genetic background and exercise habits. Physical activity could serve as a supplementary intervention for women with high risk of central obesity.
This study aimed to evaluate the effectiveness of hypertension management and analyse the factors associated with blood pressure reduction within China’s primary healthcare system.
Hypertension is one of the leading risk factors for global disease burden and is strongly associated with cardiovascular diseases. In China, hypertension is a serious public health problem, but few studies have evaluated the effectiveness of hypertension management in China’s primary healthcare system.
The study sites were 24 primary healthcare institutions, selected using multistage stratified random sampling method. In each institution, hypertension patients aged at least 35 years who agreed to participate and had no disabilities or mental health problems were enrolled for hypertension management. Participants received comprehensive interventions in the primary healthcare system via a team. After a one-year intervention, data from 6575 hypertension patients were analysed to check the effectiveness of hypertension management and examined factors associated with hypertension control.
There was an overall mean reduction of 4.5 mmHg in systolic blood pressure (SBP) and 1.9 mmHg in diastolic blood pressure (DBP). The blood pressure reduction after one year was greater in rural patients than in urban patients, 6.6 mmHg versus 3.4 mmHg for SBP and 2.6 mmHg versus 1.6 mmHg for DBP, respectively. The hypertension control rate also increased more in rural areas (22.1%) than in urban areas (10.6%) after the one-year intervention. Age, body mass index, region and being in an urban area had a significant negative association with the reduction of SBP (P < 0.05). Education level and baseline SBP showed a significant positive association (P < 0.05).
Community-based hypertension management by general practitioners was feasible and effective. The effectiveness of hypertension management in rural areas was greater than in urban areas. Intervention strategies should pay more attention to patients in rural areas and western China.
Bimetallic nanoparticles (NPs) have attracted a great deal of attention due to the synergistic interaction between metal components. In this work, the thermal process in which the reducing agent is not expensive or hazardous as those in traditional methods was employed to prepare alloy Ag–Cu NPs. The molar ratio between Ag and Cu was varied from 1:9 to 9:1. Nearly monodisperse NPs with alloy structure were characterized by X-ray diffraction and high-resolution transmission electron microscopy with energy dispersive spectroscopy In comparison with monometallic Ag and Cu NPs, the alloyed Ag–Cu NPs showed better monodispersity, especially when the ratio between Ag and Cu was 1:1. Moreover, the alloyed Ag–Cu NPs exhibited enhanced resistance to electromigration and oxidation, the respective problem of pure Ag and Cu. The alloyed Ag–Cu NPs also exhibited improved properties than a mixture of Ag–Cu NPs. This study should serve as the foundation for exploring high performance alloyed bimetallic NPs.
Research suggests people try to protect their social self-esteem from threats from the ingroup or the outgroup. However, how members react to a threat to social self-esteem from a third party remains unclear. Three studies were conducted to examine the influence of a threat to social self-esteem from an authoritative third party on ingroup favoritism. We explored the effect of negative (versus positive) evaluation from the testing system on explicit and implicit ingroup favoritism in Study 1 and Study 2 respectively. We compared the effect of negative evaluation posed by the testing system or the competitive outgroup on ingroup favoritism in Study 3. Results suggested that individuals experiencing a threat to social self-esteem from an authoritative third party manifested less ingroup favoritism than those experiencing no threat or outgroup threat. The theoretical implications of this research on social identity theory and the practical implications of reducing intergroup bias are discussed.
As important epigenetic regulators, microRNA regulate protein expression by triggering the degradation of target mRNA and/or by inhibiting their translation. Dysregulation of microRNA expression has been reported in several cancers, including colorectal cancer. In this study, microRNA-array differential analysis revealed strongly enhanced expression of miR-24-1-5p in the colon tissue of azoxymethane/dextran sulphate sodium-induced mice that were fed with black raspberry anthocyanins for 9 weeks. Overexpression of miR-24-1-5p in human colorectal cancer cells significantly repressed β-catenin expression, and simultaneously decreased cell proliferation, migration and survival. Furthermore, miR-24-1-5p could target β-catenin and trigger a negative regulatory loop for β-catenin and its downstream target genes. β-Catenin signalling is vital to the formation and progression of human colorectal cancer. The current findings therefore identified miR-24-1-5p as a potent regulator of β-catenin, and this may provide a novel chemopreventive and therapeutic strategy for β-catenin signalling-driven colorectal cancer.
Plasma levels of very-long-chain SFA (VLCSFA) are associated with the metabolic syndrome (MetS). However, the associations may vary by different biological activities of individual VLCSFA or population characteristics. We aimed to examine the associations of VLCSFA and MetS risk in Chinese adults. Totally, 2008 Chinese population aged 35–59 years were recruited and followed up from 2010 to 2012. Baseline MetS status and plasma fatty acids data were available for 1729 individuals without serious diseases. Among 899 initially metabolically healthy individuals, we identified 212 incident MetS during the follow-up. Logistic regression analysis was used to estimate OR and 95 % CI. Cross-sectionally, each VLCSFA was inversely associated with MetS risk; comparing with the lowest quartile, the multivariate-adjusted OR for the highest quartile were 0·18 (95 % CI 0·13, 0·25) for C20 : 0, 0·26 (95 % CI 0·18, 0·35) for C22 : 0, 0·19 (95 % CI 0·13, 0·26) for C24 : 0 and 0·16 (0·11, 0·22) for total VLCSFA (all Pfor trend<0·001). The associations remained significant after further adjusting for C16 : 0, C18 : 0, C18 : 3n-3, C22 : 6n-3, n-6 PUFA and MUFA, respectively. Based on follow-up data, C20 : 0 or C22 : 0 was also inversely associated with incident MetS risk. Among the five individual MetS components, higher levels of VLCSFA were most strongly inversely associated with elevated TAG (≥1·7 mmol/l). Plasma levels of VLCSFA were significantly and inversely associated with MetS risk and individual MetS components, especially TAG. Further studies are warranted to confirm the findings and explore underlying mechanisms.
Autophagy process in Toxoplasma gondii plays a vital role in regulating parasite survival or death. Thus, once having an understanding of certain effects of autophagy on the transformation of tachyzoite to bradyzoite this will allow us to elucidate the function of autophagy during parasite development. Herein, we used three TgAtg proteins involved in Atg8 conjugation system, TgAtg3, TgAtg7 and TgAtg8 to evaluate the autophagy level in tachyzoite and bradyzoite of Toxoplasma in vitro based on Pru TgAtg7-HA transgenic strains. We showed that both TgAtg3 and TgAtg8 were expressed at a significantly lower level in bradyzoites than in tachyzoites. Importantly, the number of parasites containing fluorescence-labelled TgAtg8 puncta was significantly reduced in bradyzoites than in tachyzoites, suggesting that autophagy is downregulated in Toxoplasma bradyzoite in vitro. Moreover, after treatment with drugs, bradyzoite-specific gene BAG1 levels decreased significantly in rapamycin-treated bradyzoites and increased significantly in 3-MA-treated bradyzoites in comparison with control bradyzoites, indicating that Toxoplasma autophagy is involved in the transformation of tachyzoite to bradyzoite in vitro. Together, it is suggested that autophagy may serve as a potential strategy to regulate the transformation.