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For individual cultures, findings on regulating embryo density by changing the microdrop volume are contradictory. The aim of this study was to investigate the relationship between embryo density and the developmental outcome of day 3 embryos after adjusting covariates. In total, 1196 embryos from 206 couples who had undergone in vitro fertilization treatment were analyzed retrospectively. Three embryo densities were used routinely, i.e. one embryo in a drop (30 μl/embryo), two embryos in a drop (15 μl/embryo) and three embryos in a drop (10 μl/embryo). Embryo quality on day 3 was evaluated, both the cell number of day 3 embryos and the proportion of successful implantations served as endpoints. Maternal age, paternal age, antral follicles and level of anti-Müllerian hormone, type of infertility, controlled ovarian stimulation protocol, length of stimulation, number of retrieved oocytes, number of zygotes (two pronuclei) and insemination type were covariates and adjusted. After adjusting fully for all covariates, the cell number of day 3 embryos was significantly increased by 0.40 (95% CI 0.00, 0.79; P = 0.048) and 0.78 (95% CI 0.02, 1.54; P = 0.044) in the 15 μl/embryo and 10 μl/embryo group separately, compared with the 30 μl/embryo group. The proportions of implanted embryos were 42.1%, 48.7% and 0.0% in the 30 μl/embryo, 15 μl/embryo and 10 μl/embryo groups respectively. There was no statistical significance (P = 0.22) between the 30 μl/embryo group and the 15 μl/embryo group. After adjusting for confounders that were significant in univariate analysis, embryo density was still not associated with day 3 embryo implantation potential (P > 0.05). In a 30-μl microdrop, culturing embryos with an embryo density of both 15 and 10 μl/embryo increased the cell number of day 3 embryos, which did not benefit embryo implanting potential, compared with individual culture of 30 μl/embryo.
Previous analyses of grey and white matter volumes have reported that schizophrenia is associated with structural changes. Deep learning is a data-driven approach that can capture highly compact hierarchical non-linear relationships among high-dimensional features, and therefore can facilitate the development of clinical tools for making a more accurate and earlier diagnosis of schizophrenia.
To identify consistent grey matter abnormalities in patients with schizophrenia, 662 people with schizophrenia and 613 healthy controls were recruited from eight centres across China, and the data from these independent sites were used to validate deep-learning classifiers.
We used a prospective image-based meta-analysis of whole-brain voxel-based morphometry. We also automatically differentiated patients with schizophrenia from healthy controls using combined grey matter, white matter and cerebrospinal fluid volumetric features, incorporated a deep neural network approach on an individual basis, and tested the generalisability of the classification models using independent validation sites.
We found that statistically reliable schizophrenia-related grey matter abnormalities primarily occurred in regions that included the superior temporal gyrus extending to the temporal pole, insular cortex, orbital and middle frontal cortices, middle cingulum and thalamus. Evaluated using leave-one-site-out cross-validation, the performance of the classification of schizophrenia achieved by our findings from eight independent research sites were: accuracy, 77.19–85.74%; sensitivity, 75.31–89.29% and area under the receiver operating characteristic curve, 0.797–0.909.
These results suggest that, by using deep-learning techniques, multidimensional neuroanatomical changes in schizophrenia are capable of robustly discriminating patients with schizophrenia from healthy controls, findings which could facilitate clinical diagnosis and treatment in schizophrenia.
Neuroinflammation and brain structural abnormalities are found in bipolar disorder (BD). Elevated levels of cytokines and chemokines have been detected in the serum and cerebrospinal fluid of patients with BD. This study investigated the association between peripheral inflammatory markers and brain subregion volumes in BD patients.
Euthymic patients with bipolar I disorder (BD-I) aged 20–45 years underwent whole-brain magnetic resonance imaging. Plasma levels of monocyte chemoattractant protein-1 (MCP-1), chitinase-3-like protein 1 (also known as YKL-40), fractalkine (FKN), soluble tumour necrosis factor receptor-1 (sTNF-R1), interleukin-1β, and transforming growth factor-β1 were measured on the day of neuroimaging. Clinical data were obtained from medical records and interviewing patients and reliable others.
We recruited 31 patients with a mean age of 29.5 years. In multivariate regression analysis, plasma level YKL-40, a chemokine, was the most common inflammatory marker among these measurements displaying significantly negative association with the volume of various brain subareas across the frontal, temporal, and parietal lobes. Higher YKL-40 and sTNF-R1 levels were both significantly associated with lower volumes of the left anterior cingulum, left frontal lobe, right superior temporal gyrus, and supramarginal gyrus. A greater number of total lifetime mood episodes were also associated with smaller volumes of the right caudate nucleus and bilateral frontal lobes.
The volume of brain regions known to be relevant to BD-I may be diminished in relation to higher plasma level of YKL-40, sTNF-R1, and more lifetime mood episodes. Macrophage and macrophage-like cells may be involved in brain volume reduction among BD-I patients.
Atherosclerosis can result in serious cardiovascular disease (CVD) and is associated with inflammation and psychopharmacological treatment in bipolar disorder. We attempt to investigate the effects of lithium and inflammation on the atherosclerotic development in older bipolar adults at high risk for cardiovascular disease.
The euthymic out-patients with bipolar I disorder aged over 45 years and concurrent endocrine or cardiovascular disease were recruited to measure their bilateral carotid intima media thickness (CIMT) and circulating levels of lithium, valproate, sTNF-R1, sIL-6R, and lipid profile. All clinical information were obtained by directly interviewing patients and reviewing all medical records.
Forty eight patients with mean 48.3 years old and mean 27.2 years of age at illness onset were recruited. After controlling for the body mass index, multivariate regression analyses showed that older age, lower lithium level, and higher plasma sTNF-R1 level were associated with higher CIMT and collectively accounting for 33.1% of the variance in CIMT. Blood level of low density lipid or valproate has none relationship with CIMT.
Lithium treatment may protect older bipolar patient, even those at high risk for CVD, from atherosclerotic development. Furthermore, persistent inflammatory activation, particularly macrophage activation, may be associated with the accelerating development of atherosclerosis.
Evidence on sex-specific incidence and comorbidity risk factors of suicide among patients with bipolar disorder is scarce. This study investigated the sex-specific risk profiles for suicide among the bipolar disorder population in terms of incidence, healthcare utilization and comorbidity.
Using data from the Taiwan National Health Insurance Research Database between 1 January 2000 and 31 December 2016, this nationwide cohort study included patients with bipolar disorder (N = 46 490) and individuals representative of the general population (N = 185 960) matched by age and sex at a 1:4 ratio. Mortality rate ratios (MRRs) of suicide were calculated between suicide rates of bipolar disorder cohort and general population. In addition, a nested case–control study (1428 cases died by suicide and 5710 living controls) was conducted in the bipolar disorder cohort to examine the sex-specific risk of healthcare utilization and comorbidities.
Suicide risk was considerably higher in the cohort (MRR = 21.9) than in the general population, especially among women (MRR = 35.6). Sex-stratified analyses revealed distinct healthcare utilization patterns and physical comorbidity risk profiles between the sexes. Although female patients who died by suicide had higher risks of nonhypertensive cardiovascular disease, pneumonia, chronic kidney disease, peptic ulcer, irritable bowel syndrome, and sepsis compared to their living counterparts, male patients who died by suicide had higher risks of chronic kidney disease and sepsis compared to the living controls.
Patients with bipolar disorder who died by suicide had sex-specific risk profiles in incidence and physical comorbidities. Identifying these modifiable risk factors may guide interventions for suicide risk reduction.
In present study, we explored the effects and the underlying mechanisms of phospholipase C (PLC) mediating glucose-induced changes in intestinal glucose transport and lipid metabolism by using U-73122 (a PLC inhibitor). We found that glucose incubation activated the PLC signal and U-73122 pre-incubation alleviated the glucose-induced increase in plcb2, plce1 and plcg1 mRNA expression. Meanwhile, U-73122 pre-treatment blunted the glucose-induced increase in sodium/glucose co-transporters 1/2 mRNA and protein expressions. U-73122 pre-treatment alleviated the glucose-induced increase in TAG content, BODIPY 493/503 fluorescence intensity, lipogenic enzymes (glucose 6-phospate dehydrogenase (G6PD), 6-phosphogluconate dehydrogenase (6PGD), malic enzyme and fatty acid synthase (FAS)) activity and the mRNA expressions of lipogenic genes and related transcription factors (6pgd, g6pd, fas, acca, srebp1 and carbohydrate response element-binding protein (chrebp)) in intestinal epithelial cells of yellow catfish. Further research found that U-73122 pre-incubation mitigated the glucose-induced increase in the ChREBP protein expression and the acetylation level of ChREBP in HEK293T cells. Taken together, these data demonstrated that the PLC played a major role in the glucose-induced changes of glucose transport and lipid metabolism and provide a new perspective for revealing the molecular mechanism of glucose-induced changes of intestinal glucose absorption, lipid deposition and metabolism.
The associations between sugar-sweetened beverage (SSB) and artificially sweetened beverage (ASB) consumption and the risk of metabolic syndrome (MetS) remain controversial. A quantitative assessment of dose–response associations has not been reported. This study aims to assess the associations between the risk of MetS and SSB, ASB, and total sweetened beverage (TSB, the combination of SSB and ASB) consumption by reviewing population-based epidemiological studies.
We searched PubMed, Embase and Web of Science databases prior to 4 November 2019, for relevant studies investigating the SSB–MetS and ASB–MetS associations. A random effects model was used to estimate pooled relative risks (RR) and 95 % CI. Dose–response association was assessed using a restricted cubic splines model.
We identified seventeen articles (twenty-four studies, including 93 095 participants and 20 749 MetS patients).
The pooled RR for the risk of MetS were 1·51 (95 % CI 1·34, 1·69), 1·56 (1·32, 1·83) and 1·44 (1·19, 1·75) in high consumption group of TSB, SSB and ASB, respectively; and 1·20 (1·13, 1·28), 1·19 (1·11, 1·28) and 1·31 (1·05, 1·65) per 250 ml/d increase in TSB, SSB and ASB consumption, respectively. Additionally, we found evidence of non-linear, TSB–MetS and SSB–MetS dose–response associations and a linear ASB–MetS dose–response association.
TSB, SSB and ASB consumption was associated with the risk of MetS. The present findings provide evidence that supports reducing intake of these beverages to lower the TSB-, SSB- and ASB-related risk of MetS.
Honeycomb phononic crystal can obtain wider band gaps in the low frequency based on local resonance theory. Its band structure can be adjustable if we change the height of the cores, which means different kinds of honeycomb phononic crystal can be selected on the basis of different damping demands. Meanwhile, the point defects and line defects affect the localized modes of sound waves and propagation characteristics, the dispersion relations and the displacement fields of the eigenmodes are calculated in the defected systems, as well as the propagation behaviors in the frequency ranges of the band structure, which are also discussed in detail. We constructed the model based on the periodic boundary condition and calculated the band structure according to Bloch theory, and also performed a series of simulation through the COMSOL software, showing that honeycomb has excellent features in reducing noise and vibration, which has a far-reaching influence in designing the new type of acoustic wave devices.
We aimed to describe the clinical features in coronavirus disease 2019 (COVID-19) cases. We studied 134 critically ill COVID-19 cases from 30 December 2019 to 20 February 2020 in an intensive care unit (ICU) at Wuhan Jinyintan Hospital. Demographics, underlying diseases, therapy strategies and test results were collected and analysed from patients on admission, admission to the ICU and 48 h before death. The non-survivors were older (65.46 (s.d. 9.74) vs. 46.45 (s.d. 11.09)) and were more likely to have underlying diseases. The blood group distribution of the COVID-19 cases differed from that of the Han population in Wuhan, with type A being 43.85%; type B, 26.92%; type AB, 10% and type O, 19.23%. Non-survivors tend to develop more severe lymphopaenia, with higher C-reactive protein, interleukin-6, procalcitonin, D-dimer levels and gradually increased with time. The clinical manifestations were non-specific. Compared with survivors, non-survivors more likely to have organ function injury, and to receive mechanical ventilation, either invasively or noninvasively. Multiple organ failure and secondary bacterial infection in the later period is worthy of attention.
A higher dietary intake or serum concentration of betaine has been associated with greater lean body mass in middle-aged and older adults. However, it remains unknown whether betaine intake is associated with age-related loss of skeletal muscle mass (SMM). We assessed the association between dietary betaine intake and relative changes in SMM after 3 years in middle-aged adults. A total of 1242 participants aged 41–60 years from the Guangzhou Nutrition and Health Study 2011–2013 and 2014–2017 with body composition measurements by dual-energy X-ray absorptiometry were included. A face-to-face questionnaire was used to collect general baseline information. After adjustment for potential confounders, multiple linear regression found that energy-adjusted dietary betaine intake was significantly and positively associated with relative changes (i.e. percentage loss or increase) in SMM of legs, limbs and appendicular skeletal mass index (ASMI) over 3 years of follow-up (β 0·322 (se 0·157), 0·309 (se 0·142) and 0·303 (se 0·145), respectively; P < 0·05). The ANCOVA models revealed that participants in the highest betaine tertile had significantly less loss in SMM of limbs and ASMI and more increase in SMM of legs over 3 years of follow-up, compared with those in the bottom betaine tertile (all Ptrend < 0·05). In conclusion, our findings suggest that elevated higher dietary betaine intake may be associated with less loss of SMM of legs, limbs and ASMI in middle-aged adults.
The European Society for Clinical Nutrition and Metabolism (ESPEN) guidelines recommend the Royal Free Hospital-Nutritional Prioritizing Tool (RFH-NPT) to identify malnutrition risk in patients with liver disease. However, little is known about the application of the RFH-NPT to screen for the risk of malnutrition in China, where patients primarily suffer from hepatitis virus-related cirrhosis. A total of 155 cirrhosis patients without liver cancer or uncontrolled co-morbid illness were enrolled in this prospective study. We administered the Nutritional Risk Screening 2002 (NRS-2002), RFH-NPT, Malnutrition Universal Screening Tool (MUST) and Liver Disease Undernutrition Screening Tool (LDUST) to the patients within 24 h after admission and performed follow-up observations for 1·5 years. The RFH-NPT and NRS-2002 had higher sensitivities (64·8 and 52·4 %) and specificities (60 and 70 %) than the other tools with regard to screening for malnutrition risk in cirrhotic patients. The prevalence of nutritional risk was higher under the use of the RFH-NPT against the NRS-2002 (63 v. 51 %). The RFH-NPT tended more easily to detect malnutrition risk in patients with advanced Child–Pugh classes (B and C) and lower Model for End-stage Liver Disease scores (<15) compared with NRS-2002. RFH-NPT score was an independent predictive factor for mortality. Patients identified as being at high malnutrition risk with the RFH-NPT had a higher mortality rate than those at low risk; the same result was not obtained with the NRS-2002. Therefore, we suggest that using the RFH-NPT improves the ability of clinicians to predict malnutrition risk in patients with cirrhosis primarily caused by hepatitis virus infection at an earlier stage.
Take-away milk tea (TAMT) is popular among young generation, and the numbers of retails of TAMT have increased dramatically in recent years in many cities in China. Non-dairy cream is one of the major ingredients of TAMT. Concerns have been raised whether trans-fat originated from non-dairy cream may have an influence on cardio-metabolic traits. We evaluated the associations between daily intake of TAMT with plasma lipid profiles among young Chinese adults, who are the major customers of TAMT retailers.
Materials and Methods
The study population was from the phase 1 sample (104 adults) of the Carbohydrate Alternatives and Metabolic Phenotypes study. Those lacking blood samples or with a body mass index less than 18.5 kg/m2 were excluded, therefore, a total of 88 subjects with an average age of 22.8 years were included in the analysis. A food frequency questionnaire with 27 items was used to collect the dietary intake. Generalized linear regression was used to evaluate the associations between TAMT intake and cholesterol levels.
The estimated mean (± SE) of TAMT intake was 14.4 ± 3.4 ml/day, with apparent differences between males (8.8 ± 2.7 ml/day) and females (17.7 ± 5.1 ml/day). The mean of total cholesterol of the participants was 4.1 ± 0.1 mmol/L. After adjusted for age, sex, education attainment, smoking status, alcohol drink habit, and physical activity level, daily TAMT intake was positively associated with total cholesterol (beta ± SE = 0.0053 ± 0.0020, P = 0.011). The association was not substantially changed with further adjustment of body fat percentage (beta ± SE = 0.0053 ± 0.0020, P = 0.010). Similar associations were observed for high/low density lipoprotein cholesterols. When analysis was performed by sex, the association was only observed among females (beta ± SE = 0.0049 ± 0.0022, P = 0.031), but not in males (beta ± SE = 0.0022 ± 0.0060, P = 0.703).
In young adult Chinese, we observed an association between TAMT intake with plasma cholesterol level, independent of body adiposity.
Existing data on folate status and hepatocellular carcinoma (HCC) prognosis are scarce. We prospectively examined whether serum folate concentrations at diagnosis were associated with liver cancer-specific survival (LCSS) and overall survival (OS) among 982 patients with newly diagnosed, previously untreated HCC, who were enrolled in the Guangdong Liver Cancer Cohort (GLCC) study between September 2013 and February 2017. Serum folate concentrations were measured using chemiluminescent microparticle immunoassay. Cox proportional hazards models were performed to estimate hazard ratios (HR) and 95 % CI by sex-specific quartile of serum folate. Compared with patients in the third quartile of serum folate, patients in the lowest quartile had significantly inferior LCSS (HR = 1·48; 95 % CI 1·05, 2·09) and OS (HR = 1·43; 95 % CI 1·03, 1·99) after adjustment for non-clinical and clinical prognostic factors. The associations were not significantly modified by sex, age at diagnosis, alcohol drinking status and Barcelona Clinic Liver Cancer (BCLC) stage. However, there were statistically significant interactions on both multiplicative and additive scale between serum folate and C-reactive protein (CRP) levels or smoking status and the associations of lower serum folate with worse LCSS and OS were only evident among patients with CRP > 3·0 mg/l or current smokers. An inverse association with LCSS were also observed among patients with liver damage score ≥3. These results suggest that lower serum folate concentrations at diagnosis are independently associated with worse HCC survival, most prominently among patients with systemic inflammation and current smokers. A future trial of folate supplementation seems to be promising in HCC patients with lower folate status.
Schizophrenia is a complex mental disorder with high heritability and polygenic inheritance. Multimodal neuroimaging studies have also indicated that abnormalities of brain structure and function are a plausible neurobiological characterisation of schizophrenia. However, the polygenic effects of schizophrenia on these imaging endophenotypes have not yet been fully elucidated.
To investigate the effects of polygenic risk for schizophrenia on the brain grey matter volume and functional connectivity, which are disrupted in schizophrenia.
Genomic and neuroimaging data from a large sample of Han Chinese patients with schizophrenia (N = 509) and healthy controls (N = 502) were included in this study. We examined grey matter volume and functional connectivity via structural and functional magnetic resonance imaging, respectively. Using the data from a recent meta-analysis of a genome-wide association study that comprised a large number of Chinese people, we calculated a polygenic risk score (PGRS) for each participant.
The imaging genetic analysis revealed that the individual PGRS showed a significantly negative correlation with the hippocampal grey matter volume and hippocampus–medial prefrontal cortex functional connectivity, both of which were lower in the people with schizophrenia than in the controls. We also found that the observed neuroimaging measures showed weak but similar changes in unaffected first-degree relatives of patients with schizophrenia.
These findings suggested that genetically influenced brain grey matter volume and functional connectivity may provide important clues for understanding the pathological mechanisms of schizophrenia and for the early diagnosis of schizophrenia.
The three-dimensional flow characteristics of the compressible vortex ring generated by under-expanded circular jets with two typical pressure ratios, i.e. $n=1.4$ (moderate) and 4.0 (high), are investigated numerically with the use of large-eddy simulations. Our results illustrate that these two pressure ratios correspond to different shock structures (shock cell and Mach disc, respectively) within the jet. These two typical types of flow structures and characteristics are discussed and validated with experiments, and the different generation mechanisms of the secondary vortex rings are compared. Moreover, detailed information about the evolution of the secondary vortex ring, primary vortex ring and turbulence transition features, including the radial and azimuthal modes, is investigated. The geometric features and mixing effects of the jets are also explored.
Research on the risk of stroke following the use of mood stabilisers specific to patients with bipolar disorder is limited.
In this study, we investigated the risk of stroke following the exposure to mood stabilisers in patients with bipolar disorder.
Data for this nationwide population-based study were derived from the Taiwan National Health Insurance Research Database. Among a retrospective cohort of patients with bipolar disorder (n = 19 433), 609 new-onset cases of stroke were identified from 1999 to 2012. A case–crossover study design utilising 14-day windows was applied to assess the acute exposure effect of individual mood stabilisers on the risk of ischaemic, haemorrhagic and other types of stroke in patients with bipolar disorder.
Mood stabilisers as a group were significantly associated with the increased risk of stroke in patients with bipolar disorder (adjusted risk ratio, 1.26; P = 0.041). Among individual mood stabilisers, acute exposure to carbamazepine had the highest risk of stroke (adjusted risk ratio, 1.68; P = 0.018), particularly the ischaemic type (adjusted risk ratio, 1.81; P = 0.037). In addition, acute exposure to valproic acid elevated the risk of haemorrhagic stroke (adjusted risk ratio, 1.76; P = 0.022). In contrast, acute exposure to lithium and lamotrigine did not significantly increase the risk of any type of stroke.
Use of carbamazepine and valproic acid, but not lithium and lamotrigine, is associated with increased risk of stroke in patients with bipolar disorder.
Manipulating the thermal conductivity of solids is important for practical applications. Due to the fact that phonons in thermoelectric materials have longer mean free paths (MFPs) than electrons, strengthening phonon scattering to reduce lattice thermal conductivity (κlat) becomes the most straightforward and effective approach to enhance the thermoelectric figure of merit, ZT, which determines the maximum device efficiency. Phonons have a wide range of MFPs in semiconductors, and different dimensions of lattice defects can be targeted to scatter particular phonons with distinct relaxation times. Designing hierarchical nano-microstructures, spanning from point defects to volume defects, would be beneficial to achieve low κlat via a full spectrum of phonon scattering. Herein, we review the formation and underlying mechanisms for lattice defects and highlight the role of all-scale hierarchical nano-microstructure on phonon engineering. Existing challenges in simulations are also discussed.
It is a challenging task to discover information from a large amount of data in an open domain.1 In this paper, an event network framework is proposed to address this challenge. It is in fact an empirical construct for exploring open information, composed of three steps: document event detection, event network construction and event network analysis. First, documents are clustered into document events for reducing the impact of noisy and heterogeneous resources. Secondly, linguistic units (e.g., named entities or entity relations) are extracted from each document event and combined into an event network, which enables content-oriented retrieval. Then, in the final step, techniques such as social network or complex network can be applied to analyze the event network for exploring open information. In the implementation section, we provide examples of exploring open information via event network.
Geochronological, elemental and isotopic data of the Dashizhuzi granites and lamprophyre dykes from the eastern Hebei – western Liaoning on the northern North China Craton (NCC) provide an insight into the nature of their magma sources and subcontinental lithospheric mantle. The Dashizhuzi granites have an emplacement age of 226 Ma. They have enriched lithospheric mantle type 1 (EM1-like) Sr–Nd isotopic compositions, and have distinctive features of high Na2O and Sr and low Y with high Sr/Y and (La/Yb)N ratios. These characteristics show that the Dashizhuzi granites originated directly from melting of mafic lower crust composed of pre-existing ancient crustal and enriched mantle-derived juvenile crustal materials at normal continental crustal depth of 33–40 km. The lamprophyre dykes are dated at 167 Ma, and can be divided into two groups. The Group 1 dykes have variable Sr–Nd isotopic compositions and mid-ocean-ridge basalt (MORB-) like Th/U, Ba/Th and Ce/Pb ratios, whereas the Group 2 dykes have enriched Sr–Nd isotopic compositions and notable high Co, Cr, MgO and low Al2O3 characteristics. These distinctive features suggest that the Group 1 dykes were derived from a relatively fertile lithospheric mantle source (garnet-facies amphibole-bearing lherzolite) which has experienced variable degrees of asthenospheric mantle-derived melt–peridotite interaction prior to melting. However, the Group 2 dykes were derived from an ancient garnet-facies phlogopite and/or amphibole-bearing lherzolite lithospheric mantle. Thinning of the Early Mesozoic lithospheric mantle beneath the northern NCC is dominantly through melt–peridotite interaction and thermo-mechanical erosion prior to Middle Jurassic time. The chemical compositions have been modified at the bottom of the lithospheric mantle through melt–peridotite interaction processes.