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The FNDC5 gene encodes the fibronectin type III domain-containing protein 5 that is a membrane protein mainly expressed in skeletal muscle and the FNDC5 rs3480 polymorphism may be associated with liver disease severity in nonalcoholic fatty liver disease (NAFLD). We investigated the influence of the FNDC5 rs3480 polymorphism on the relationship between sarcopenia and the histological severity of NAFLD.
370 adult individuals with biopsy-proven NAFLD were studied. Appendicular skeletal muscle mass was measured by bioelectrical impedance. The association between the key exposure sarcopenia, and the outcome liver histological severity, was investigated by binary logistic regression. Stratified analyses were undertaken to examine the impact of FNDC5 rs3480 polymorphism on the association between sarcopenia and the severity of NAFLD histology.
Patients with sarcopenia had more severe histological grades of steatosis and a higher prevalence of significant fibrosis and definite NASH than those without sarcopenia. There was a significant association between sarcopenia and significant fibrosis (adjusted odds ratio 2.79, 95%CI 1.31-5.95, p=0.008), independent of established risk factors and potential confounders. Among patients with sarcopenia, significant fibrosis occurred more frequently in the rs3480 AA genotype carriers than in those carrying the FNDC5 rs3480 G genotype (43.8% vs. 17.2%, p=0.031). In the association between sarcopenia and liver fibrosis, there was a significant interaction between the FNDC5 genotype and sarcopenia status (p-value for interaction=0.006).
Sarcopenia is independently associated with significant liver fibrosis, and the FNDC5 rs3480 G variant influences the association between sarcopenia and liver fibrosis in patients with biopsy-proven NAFLD.
Understanding the patterns of treatment response is critical for the treatment of patients with schizophrenia; one way to achieve this is through using a longitudinal dynamic process study design.
This study aims to explore the response trajectory of antipsychotics and compare the treatment responses of seven different antipsychotics over 6 weeks in patients with schizoprenia (trial registration: Chinese Clinical Trials Registry Identifier: ChiCTR-TRC-10000934).
Data were collected from a multicentre, randomised open-label clinical trial. Patients were evaluated with the Positive and Negative Syndrome Scale (PANSS) at baseline and follow-up at weeks 2, 4 and 6. Trajectory groups were classified by the method of k-means cluster modelling for longitudinal data. Trajectory analyses were also employed for the seven antipsychotic groups.
The early treatment response trajectories were classified into a high-trajectory group of better responders and a low-trajectory group of worse responders. The results of trajectory analysis showed differences compared with the classification method characterised by a 50% reduction in PANSS scores at week 6. A total of 349 patients were inconsistently grouped by the two methods, with a significant difference in the composition ratio of treatment response groups using these two methods (χ2 = 43.37, P < 0.001). There was no differential contribution of high- and low trajectories to different drugs (χ2 = 12.52, P = 0.051); olanzapine and risperidone, which had a larger proportion in the >50% reduction at week 6, performed better than aripiprazole, quetiapine, ziprasidone and perphenazine.
The trajectory analysis of treatment response to schizophrenia revealed two distinct trajectories. Comparing the treatment responses to different antipsychotics through longitudinal analysis may offer a new perspective for evaluating antipsychotics.
Toxoplasma gondii is an obligate intracellular protozoan parasite, which can infect almost all warm-blooded animals, including humans, leading to toxoplasmosis. Currently, the effective treatment for human toxoplasmosis is the combination of sulphadiazine and pyrimethamine. However, both drugs have serious side-effects and toxicity in the host. Therefore, there is an urgent need for the discovery of new anti-T. gondii drugs with high potency and less or no side-effects. Our findings suggest that lumefantrine exerts activity against T. gondii by inhibiting its proliferation in Vero cells in vitro without being toxic to Vero cells (P ≤ 0.01). Lumefantrine prolonged mice infected with T. gondii from death for 3 days at the concentration of 50 μg L−1 than negative control (phosphate-buffered saline treated only), and reduced the parasite burden in mouse tissues in vivo (P ≤ 0.01; P ≤ 0.05). In addition, a significant increase in interferon gamma (IFN-γ) production was observed in high-dose lumefantrine-treated mice (P ≤ 0.01), whereas interleukin 10 (IL-10) and IL-4 levels increased in low-dose lumefantrine-treated mice (P ≤ 0.01). The results demonstrated that lumefantrine may be a promising agent to treat toxoplasmosis, and more experiments on the protective mechanism of lumefantrine should be undertaken in further studies.
Little is known about the trend and predictors of 21-year mortality and suicide patterns in persons with schizophrenia.
To explore the trend and predictors of 21-year mortality and suicide in persons with schizophrenia in rural China.
This longitudinal follow-up study included 510 persons with schizophrenia who were identified in a mental health survey of individuals (≥15 years old) in 1994 in six townships of Xinjin County, Chengdu, China, and followed up in three waves until 2015. Kaplan–Meier survival analysis and Cox hazard regressions were conducted.
Of the 510 participants, 196 died (38.4% mortality) between 1994 and 2015; 13.8% of the deaths (n = 27) were due to suicide. Life expectancy was lower for men than for women (50.6 v. 58.5 years). Males consistently showed higher rates of mortality and suicide than females. Older participants had higher mortality (hazard ratio HR = 1.03, 95% CI 1.01–1.05) but lower suicide rates (HR = 0.95, 95% CI 0.93–0.98) than their younger counterparts. Poor family attitudes were associated with all-cause mortality and death due to other causes; no previous hospital admission and a history of suicide attempts independently predicted death by suicide.
Our findings suggest there is a high mortality and suicide rate in persons with schizophrenia in rural China, with different predictive factors for mortality and suicide. It is important to develop culture-specific, demographically tailored and community-based mental healthcare and to strengthen family intervention to improve the long-term outcome of persons with schizophrenia.
Potassium and cerium co-doped Bi4Ti2.86W0.14O12 ceramics with a formula of (K0.5Ce0.5)xBi4−xTi2.86W0.14O12 (abbreviated as KC100x-BITW, x = 0, 0.02, 0.04, 0.06, 0.08, 0.1) were prepared by a conventional solid-state reaction method. The effect of (K0.5Ce0.5) complex doping amount on the structure, dielectric, and piezoelectric properties of the KC100x-BITW ceramics was investigated. X-ray diffraction results indicated that the KC100x-BITW ceramics are Aurivillius-type phase with the bismuth layer structure. (K0.5Ce0.5) complex addition first increases and then decreases the grain size which can be observed by scanning electron microscopy. With the increase of (K0.5Ce0.5) complex doping amount, the Curie temperature (TC) was slightly decreased from 632 to 608 oC. The dielectric and piezoelectric properties were optimized in KC100x-BITW ceramics with x = 0.08 as follows: d33 = 24 pC/N, kp = 8.2%, Qm = 6766, εr = 135 (@100 kHz), tanδ = 0.28% (@100 kHz), Tc = 611 oC, and resistivity ρ = 2.9 × 106 Ω cm at 500 oC, indicating that the KC100x-BITW ceramics are suitable for high-temperature piezoelectric sensing applications.
The mortality of coronavirus disease 2019 (COVID-19) differs between countries and regions. This study aimed to clarify the clinical characteristics of imported and second-generation cases in Shaanxi. This study included 134 COVID-19 cases in Shaanxi outside Wuhan. Clinical data were compared between severe and non-severe cases. We further profiled the dynamic laboratory findings of some patients. In total, 34.3% of the 134 patients were severe cases, 11.2% had complications. As of 7 March 2020, 91.8% patients were discharged and one patient (0.7%) died. Age, lymphocyte count, C-reactive protein, erythrocyte sedimentation rate, direct bilirubin, lactate dehydrogenase and hydroxybutyrate dehydrogenase showed difference between severe and no-severe cases (all P < 0.05). Baseline lymphocyte count was higher in survived patients than in non-survivor case, and it increased as the condition improved, but declined sharply when death occurred. The interleukin-6 (IL-6) level displayed a downtrend in survivors, but rose very high in the death case. Pulmonary fibrosis was found on later chest computed tomography images in 51.5% of the pneumonia cases. Imported and second-generation cases outside Wuhan had a better prognosis than initial cases in Wuhan. Lymphocyte count and IL-6 level could be used for evaluating prognosis. Pulmonary fibrosis as the sequelae of COVID-19 should be taken into account.
The time dispersion effect affects the accuracy of solar time difference of arrival (TDOA) navigation. In this celestial autonomous navigation, Mars's moons are reflecting celestial bodies, and their shape affects the TDOA dispersion model. In the modelling process of traditional methods, the moons of Mars (Phobos and Deimos) are regarded as points, which causes the model to be inaccurate. In order to solve these problems, we simplified the Mars's moons into ellipsoids or solid diamonds, and then established a TDOA model with the nonspherical Mars's moons as reflecting celestial bodies through differential geometry and geometric optics. Finally, we analysed the time dispersion caused by the Mars's moons in theory. Theoretical analysis and experiments show that the point model error is 5·66 km, and the 3D model error is within 70 m. Thus, the 3D TDOA model established in this paper is meaningful. In addition, the Sun–Mars-moons–spacecraft angle, solar flare, three-axis length, and attitude of the Mars's moons have a great effect on the dispersion profile, while the Mars's moons-to-spacecraft distance has a small effect.
In order to clarify fine structures of the hypothetical meridian conduits of Chinese traditional medicine (CTM) in the skin, the present study used light and transmission electron microscopy to examine fasciae in different vertebrate species. Collagen fiber bundles and layers were arranged in a crisscross pattern, which developed into a special tissue micro-channel (TMC) network, in a manner that was analogs to the proposed skin meridian conduits. It was further revealed that tissue fluid in lateral TMC branches drained into wide longitudinal channels, which were distinctly different from lymphatic capillary. Mast cells, macrophages, and extracellular vesicles such as ectosomes and exosomes were distributed around telocytes (TCs) and their long processes (Telopodes, Tps) within the TMC. Cell junctions between TCs developed, which could enable the communication between contiguous but distant Tps. On the other hand, winding free Tps without cell junctions were also uncovered inside the TMC. Tissue fluid, cell junctions of TCs, mast cells, macrophages, and extracellular vesicles within the TMC corresponded to the circulating “气血” (“Qi-Xue”, i.e., information, message, and energy) of meridian conduits at the cytological level. These results could provide morphological evidence for the hypothesis that “meridians are the conduit for Qi-Xue circulation” in CTM.
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 investigate the benefit of Bonebridge devices in patients with single-sided deafness.
Five patients with single-sided deafness who were implanted with Bonebridge devices were recruited in a single-centre study. Participants’ speech perception and horizontal sound localisation abilities were assessed at 6 and 12 months post-operatively. Speech intelligibility in noisy environments was measured in three different testing conditions (speech and noise presented from the front, speech and noise presented from the front and contralateral (normal ear) side separately, and speech presented from the ipsilateral (implanted Bonebridge) side and noise from the contralateral side). Sound localisation was evaluated in Bonebridge-aided and Bonebridge-unaided conditions at different stimuli levels (65, 70 and 75 dB SPL).
All participants showed a better capacity for speech intelligibility in quiet environments with the Bonebridge device. The speech recognition threshold with the Bonebridge device was significantly decreased at both short- and long-term follow up in the speech presented from the ipsilateral (implanted Bonebridge) side and noise from the contralateral side condition (p < 0.05). Additionally, participants maintained similar levels of sound localisation between the Bonebridge-aided and unaided conditions (p > 0.05). However, the accuracy of localisation showed some improvement at 70 dB SPL and 75 dB SPL post-operatively.
The Bonebridge device provides the benefit of improved speech perception performance in patients with single-sided deafness. Sound localisation abilities were neither improved nor worsened with Bonebridge implantation at the follow-up assessments.
The effects of flow velocity on the fitness-related behaviours of Mesocentrotus nudus remain largely unknown, greatly hampering the efficiency of stock enhancement. To explore the appropriate velocities for stock enhancement, we investigated dislodgement and immobilization velocities up to 90 cm s−1. The experimental results showed that M. nudus (test diameter of ~30 mm) were dislodged at 73.50 ± 7.7 cm s−1 and that M. nudus movement occurred only when the flow velocity was less than 33.40 ± 2.7 cm s−1. Three flow velocities less than 33.40 ± 2.7 cm s−1 (2, 10 and 20 cm s−1) were subsequently used to study the effects of flow velocities on covering behaviour and the righting response time of M. nudus. The downstream movement velocity of M. nudus was significantly larger than that upstream at 2 cm s−1 (P = 0.016) and 10 cm s−1 (P = 0.008), but not at 20 cm s−1 (P = 0.222). The righting response time of M. nudus was significantly longer at 20 cm s−1 than that at 2 cm s−1 (P = 0.015). The present study indicates that a flow velocity less than 20 cm s−1, preferably 2–10 cm s−1, is probably appropriate for the stock enhancement of M. nudus. Notably, the current study is a laboratory investigation without considering the hydrographic complexity in the field. Further studies should be carried out to investigate the long-term effects of water flow on feeding and growth of M. nudus both in the laboratory and the field.
Renal fibrosis is common especially in the elderly population. Recently, we found that vitamin D deficiency caused prostatic hyperplasia. This study aimed to investigate whether vitamin D deficiency promotes renal fibrosis and functional impairment. All mice except controls were fed with vitamin D-deficient (VDD) diets, beginning from their early life. The absolute and relative kidney weights on postnatal week 20 were decreased in VDD diet-fed male pups but not in female pups. A mild pathological damage was observed in VDD diet-fed male pups but not in females. Further analysis showed that VDD-induced pathological damage was aggravated, accompanied by renal dysfunction in 40-week-old male pups. An obvious collagen deposition was observed in VDD diet-fed 40-week-old male pups. Moreover, renal α-smooth muscle actin (α-SMA), a marker of epithelial–mesenchymal transition (EMT), and Tgf-β mRNA were up-regulated. The in vitro experiment showed that 1,25-dihydroxyvitamin D3 alleviated transforming growth factor-β1 (TGF-β1)-mediated down-regulation of E-cadherin and inhibited TGF-β1-evoked up-regulation of N-cadherin, vimentin and α-SMA in renal epithelial HK-2 cells. Moreover, 1,25-dihydroxyvitamin D3 suppressed TGF-β1-evoked Smad2/3 phosphorylation in HK-2 cells. These results provide experimental evidence that long-term vitamin D deficiency promotes renal fibrosis and functional impairment, at least partially, through aggravating TGF-β/Smad2/3-mediated EMT in middle-aged male mice.
In this paper, CuCr–Zr alloys prepared by vacuum melting with adding La and Ni elementswere heat-treated and aged, followed by plastic deformation using low-energy cyclic impact tests, to simultaneously improve their mechanical and electrical properties. Results showed that the grain size of the casted Cu–Cr–Zr alloys was significantly reduced after the solid-solution aging and plastic deformation process. There were a lot of dispersed Cr and Cu5Zr precipitates formed in the alloys, and the numbers of dislocations were significantly increased. Accordingly, the hardness was increased from 78 to 232 HV, and the tensile strength was increased from 225 to 691 MPa. Electrical conductivity has not been significantly affected after these processes. The enhancement of overall performance is mainly attributed to the combined effects of solid-solution hardening, fine grain hardening, and precipitation/dislocation strengthening.
Increased population movements and increased mobility made it possible for severe acute respiratory syndrome coronavirus 2, which is mainly spread by respiratory droplets, to spread faster and more easily. This study tracked and analysed the development of the coronavirus 2019 (COVID-19) outbreak in the top 100 cities that were destinations for people who left Wuhan before the city entered lockdown. Data were collected from the top 100 destination cities for people who travelled from Wuhan before the lockdown, the proportion of people travelling into each city, the intensity of intracity travel and the daily reports of COVID-19. The proportion of the population that travelled from Wuhan to each city from 10 January 2020 to 24 January 2020, was positively correlated with and had a significant linear relationship with the cumulative number of confirmed cases of COVID-19 in each city after 24 January (all P < 0.01). After the State Council launched a multidepartment joint prevention and control effort on 22 January 2020 and compared with data collected on 18 February, the average intracity travel intensity of the aforementioned 100 cities decreased by 60−70% (all P < 0.001). The average intensity of intracity travel on the nth day in these cities during the development of the outbreak was positively related to the growth rate of the number of confirmed COVID-19 cases on the n + 5th day in these cities and had a significant linear relationship (P < 0.01). Higher intensities of population movement were associated with a higher incidence of COVID-19 during the pandemic. Restrictions on population movement can effectively curb the development of an outbreak.
This study aimed to evaluate associations between toxoplasmosis and psychiatric disorders in Taiwan based on the National Health Insurance Research Database, Taiwan (1997–2013). Patients newly diagnosed with toxoplasmosis formed the case group (n = 259), and the control group included propensity-score matched patients without toxoplasmosis (n = 1036). The primary outcome was incidence of psychiatric disorders. Cox proportional hazards regression and stratified analyses were performed to examine risk of developing specific psychiatric disorders between patients with and without toxoplasmosis. Patients with toxoplasmosis had significantly higher incidence of psychiatric disorders than those without toxoplasmosis (P = 0.016). A significant difference was found in numbers of psychiatric disorders between the two groups during 14 years of follow-up (log-rank P < 0.001). Those with toxoplasmosis had significantly higher risk of bipolar disorder [adjusted hazard ratio (aHR = 3.60, 95% confidence interval (CI) = 2.07, 7.26), depression (aHR = 4.94, 95% CI = 2.15, 11.80) and anxiety (aHR = 5.36, 95% CI = 2.98, 25.88), but no significant between-group differences were found for schizophrenia and other psychiatric disorders. In conclusion, the present nationwide population-based analysis revealed that Toxoplasma gondii infection in Taiwan significantly increases the risk for developing bipolar disorder, depression and anxiety, but not for schizophrenia and other psychiatric disorders.
Trichosporon is a yeast-like basidiomycete, a conditional pathogenic fungus that is rare in the clinic but often causes fatal infections in immunocompromised individuals. Trichosporon asahii is the most common pathogenic fungus in this genus and the occurrence of infections has dramatically increased in recent years. Here, we report a systematic literature review detailing 140 cases of T. asahii infection reported during the past 23 years. Statistical analysis shows that T. asahii infections were most frequently reported within immunodeficient or immunocompromised patients commonly with blood diseases. Antibiotic use, invasive medical equipment and chemotherapy were the leading risk factors for acquiring infection. In vitro susceptibility, clinical information and prognosis analysis showed that voriconazole is the primary drug of choice in the treatment of T. asahii infection. Combination treatment with voriconazole and amphotericin B did not show superiority over either drug alone. Finally, we found that the types of infections prevalent in China are significantly different from those in other countries. These results provide detailed information and relevant clinical treatment strategies for the diagnosis and treatment of T. asahii infection.