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To identify risk genes whose expression are regulated by the reported risk variants and to explore the potential regulatory mechanism in schizophrenia (SCZ).
We systematically integrated three independent brain expression quantitative traits (eQTLs) (CommonMind, GTEx, and BrainSeq Phase 2, a total of 1039 individuals) and GWAS data (56 418 cases and 78 818 controls), with the use of transcriptome-wide association study (TWAS). Diffusion magnetic resonance imaging was utilized to quantify the integrity of white matter bundles and determine whether polygenic risk of novel genes linked to brain structure was present in patients with first-episode antipsychotic SCZ.
TWAS showed that eight risk genes (CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, PCDHA8, THOC7, and TYW5) reached transcriptome-wide significance (TWS) level. These findings were confirmed by an independent integrative approach (i.e. Sherlock). We further conducted conditional analyses and identified the potential risk genes that driven the TWAS association signal in each locus. Gene expression analysis showed that several TWS genes (including CORO7, DDAH2, DDHD2, ELAC2, GLT8D1, THOC7 and TYW5) were dysregulated in the dorsolateral prefrontal cortex of SCZ cases compared with controls. TWS genes were mainly expressed on the surface of glutamatergic neurons, GABAergic neurons, and microglia. Finally, SCZ cases had a substantially greater TWS genes-based polygenic risk (PRS) compared to controls, and we showed that fractional anisotropy of the cingulum-hippocampus mediates the influence of TWS genes PRS on SCZ.
Our findings identified novel SCZ risk genes and highlighted the importance of the TWS genes in frontal-limbic dysfunctions in SCZ, indicating possible therapeutic targets.
Mental disorders, including depression, obsessive compulsive disorder (OCD), and schizophrenia, share a common neuropathy of disturbed large-scale coordinated brain maturation. However, high-interindividual heterogeneity hinders the identification of shared and distinct patterns of brain network abnormalities across mental disorders. This study aimed to identify shared and distinct patterns of altered structural covariance across mental disorders.
Subject-level structural covariance aberrance in patients with mental disorders was investigated using individualized differential structural covariance network. This method inferred structural covariance aberrance at the individual level by measuring the degree of structural covariance in patients deviating from matched healthy controls (HCs). T1-weighted anatomical images of 513 participants (105, 98, 190 participants with depression, OCD and schizophrenia, respectively, and 130 age- and sex-matched HCs) were acquired and analyzed.
Patients with mental disorders exhibited notable heterogeneity in terms of altered edges, which were otherwise obscured by group-level analysis. The three disorders shared high difference variability in edges attached to the frontal network and the subcortical-cerebellum network, and they also exhibited disease-specific variability distributions. Despite notable variability, patients with the same disorder shared disease-specific groups of altered edges. Specifically, depression was characterized by altered edges attached to the subcortical-cerebellum network; OCD, by altered edges linking the subcortical-cerebellum and motor networks; and schizophrenia, by altered edges related to the frontal network.
These results have potential implications for understanding heterogeneity and facilitating personalized diagnosis and interventions for mental disorders.
To examine the thematic features of dignity therapy generativity documents of advanced cancer patients receiving chemotherapy in mainland China from the perspective of meaning-making during dignity therapy.
This is a qualitative descriptive study. Content analysis was used to analyze 24 dignity therapy generativity documents derived from a quasi-experimental trial of dignity therapy for advanced cancer patients receiving chemotherapy in a daycare center at a cancer hospital in northern China.
Among the 24 advanced cancer patients whose generativity documents were analyzed, 14 were male and ranged in age from 26 to 78 years (average = 50.3). Two dimensions emerged from the data: (1) the sources of meaning in life, which consisted of social relationships, things and circumstances providing meaning in life, and (2) the ultimate meaning in life, referring to finding one’s real self and realizing the purpose in life, including personal life goals, dignity and autonomy, and morality of patients.
Significance of results
The multidimensional constructs of meaning in life with distinctive traditional Chinese cultural characteristics could provide insights into dignity-conserving care for advanced cancer patients with Chinese culture and provide evidence for refining the implementation protocol of DT through intentionally addressing the ultimate meaning of patients in the therapeutic session.
Due to the lack of research between the inner layers in the structure of colonic mucous and the metabolism of fatty acid in the constipation model, we aim to determine the changes in the mucous phenotype of the colonic glycocalyx and the microbial community structure following treatment with Rhubarb extract in our research. The constipation and treatment models are generated using adult male C57BL/6N mice. We perform light microscopy and transmission electron microscopy (TEM) to detect a Muc2-rich inner mucus layer attached to mice colon under different conditions. In addition, 16S rDNA sequencing is performed to examine the intestinal flora. According to TEM images, we demonstrate that Rhubarb can promote mucin secretion and find direct evidence of dendritic structure-linked mucus structures with its assembly into a lamellar network in a pore size distribution in the isolated colon section. Moreover, the diversity of intestinal flora has noticeable changes in constipated mice. The present study characterizes a dendritic structure and persistent cross-links have significant changes accompanied by the alteration of intestinal flora in feces in models of constipation and pretreatment with Rhubarb extract.
In this paper, effects of discharge parameters and modulation frequency on the signal of laser-induced fluorescence measurements of ion velocity distribution functions are investigated in the LIF Test Source. A maximum modulation frequency is found for each given set of parameters, beyond which the signal gradually declines. Meanwhile, this maximum modulation frequency occurred consistently at ~1/10 of the theoretical frequency limit and photon counts received by a photomultiplier tube, which indicates that as modulation frequency and the associated per-pulse-excitation-event count decrease, the transition from the macroscopic statistical signal to the microscopic probabilistic signal is a gradual process.
No relevant studies have yet been conducted to explore which measurement can best predict the survival time of patients with cancer cachexia. This study aimed to identify an anthropometric measurement that could predict the 1-year survival of patients with cancer cachexia. We conducted a nested case–control study using data from a multicentre clinical investigation of cancer from 2013 to 2020. Cachexia was defined using the Fearon criteria. A total of 262 patients who survived less than 1 year and 262 patients who survived more than 1 year were included in this study. Six candidate variables were selected based on clinical experience and previous studies. Five variables, BMI, mid-arm circumference, mid-arm muscle circumference, calf circumference and triceps skin fold (TSF), were selected for inclusion in the multivariable model. In the conditional logistic regression analysis, TSF (P = 0·014) was identified as a significant independent protective factor. A similar result was observed in all patients with cancer cachexia (n 3084). In addition, a significantly stronger positive association between TSF and the 1-year survival of patients with cancer cachexia was observed in participants aged > 65 years (OR: 0·94; 95 % CI 0·89, 0·99) than in those aged ≤ 65 years (OR: 0·96; 95 % CI 0·93, 0·99; Pinteraction = 0·013) and in participants with no chronic disease (OR: 0·92; 95 % CI 0·87, 0·97) than in those with chronic disease (OR: 0·97; 95 % CI 0·94, 1·00; Pinteraction = 0·049). According to this study, TSF might be a good anthropometric measurement for predicting 1-year survival in patients with cancer cachexia.
The present study evaluated whether fat mass assessment using the triceps skinfold (TSF) thickness provides additional prognostic value to the Global Leadership Initiative on Malnutrition (GLIM) framework in patients with lung cancer (LC). We performed an observational cohort study including 2672 LC patients in China. Comprehensive demographic, disease and nutritional characteristics were collected. Malnutrition was retrospectively defined using the GLIM criteria, and optimal stratification was used to determine the best thresholds for the TSF. The associations of malnutrition and TSF categories with survival were estimated independently and jointly by calculating multivariable-adjusted hazard ratios (HR). Malnutrition was identified in 808 (30·2 %) patients, and the best TSF thresholds were 9·5 mm in men and 12 mm in women. Accordingly, 496 (18·6 %) patients were identified as having a low TSF. Patients with concurrent malnutrition and a low TSF had a 54 % (HR = 1·54, 95 % CI = 1·25, 1·88) greater death hazard compared with well-nourished individuals, which was also greater compared with malnourished patients with a normal TSF (HR = 1·23, 95 % CI = 1·06, 1·43) or malnourished patients without TSF assessment (HR = 1·31, 95 % CI = 1·14, 1·50). These associations were concentrated among those patients with adequate muscle mass (as indicated by the calf circumference). Additional fat mass assessment using the TSF enhances the prognostic value of the GLIM criteria. Using the population-derived thresholds for the TSF may provide significant prognostic value when used in combination with the GLIM criteria to guide strategies to optimise the long-term outcomes in patients with LC.
To establish optimal gestational weight gain (GWG) in Chinese pregnant women by Chinese-specific BMI categories and compare the new recommendations with the Institute of Medicine (IOM) 2009 guidelines.
Multicentre, prospective cohort study. Unconditional logistic regression analysis was used to evaluate the OR, 95 % CI and the predicted probabilities of adverse pregnancy outcomes. The optimal GWG range was defined as the range that did not exceed a 1 % increase from the lowest predicted probability in each pre-pregnancy BMI group.
From nine cities in mainland China.
A total of 3731 women with singleton pregnancy were recruited from April 2013 to December 2014.
The optimal GWG (ranges) by Chinese-specific BMI was 15·0 (12·8–17·1), 14·2 (12·1–16·4) and 12·6 (10·4–14·9) kg for underweight, normal weight and overweight pregnant women, respectively. Inappropriate GWG was associated with several adverse pregnancy outcomes. Compared with women gaining weight within our proposed recommendations, women with excessive GWG had higher risk for macrosomia, large for gestational age and caesarean section, whereas those with inadequate GWG had higher risk for low birth weight, small for gestational age and preterm delivery. The comparison between our proposed recommendations and IOM 2009 guidelines showed that our recommendations were comparable with the IOM 2009 guidelines and could well predict the risk of several adverse pregnancy outcomes.
Inappropriate GWG was associated with higher risk of several adverse pregnancy outcomes. Optimal GWG recommendations proposed in the present study could be applied to Chinese pregnant women.
The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) is highly contagious, and the coronavirus disease 2019 (COVID-19) pandemic caused by it has forced many countries to adopt ‘lockdown’ measures to prevent the spread of the epidemic through social isolation of citizens. Some countries proposed universal mask wearing as a protection measure of public health to strengthen national prevention efforts and to limit the wider spread of the epidemic. In order to reveal the epidemic prevention efficacy of masks, this paper systematically evaluates the experimental studies of various masks and filter materials, summarises the general characteristics of the filtration efficiency of isolation masks with particle size, and reveals the actual efficacy of masks by combining the volume distribution characteristics of human exhaled droplets with different particle sizes and the SARS-CoV-2 virus load of nasopharynx and throat swabs from patients. The existing measured data show that the filtration efficiency of all kinds of masks for large particles and extra-large droplets is close to 100%. From the perspective of filtering the total number of pathogens discharged in the environment and protecting vulnerable individuals from breathing live viruses, the mask has a higher protective effect. If considering the weighted average filtration efficiency with different particle sizes, the filtration efficiencies of the N95 mask and the ordinary mask are 99.4% and 98.5%, respectively. The mask can avoid releasing active viruses to the environment from the source of infection, thus maximising the protection of vulnerable individuals by reducing the probability of inhaling a virus. Therefore, if the whole society strictly implements the policy of publicly wearing masks, the risk of large-scale spread of the epidemic can be greatly reduced. Compared with the overall cost of social isolation, limited personal freedoms and forced suspension of economic activities, the inconvenience for citizens caused by wearing masks is perfectly acceptable.
We aim to determine the correlation between parental rearing, personality traits, and obsessive–compulsive disorder (OCD) in different quantiles. In particular, we created an intermediary effect model in which parental rearing affects OCD through personality traits. All predictors were measured at the time of the survey, comprising parental rearing (paternal rearing and maternal rearing), demographics (grade and gender), and personality traits (neuroticism, extroversion, and psychoticism). These results suggest that (a) paternal emotional warmth was negatively correlated with OCD at the 0.40–0.80 quantile, while maternal emotional warmth was positively correlated with the OCD at the 0.45–0.69 quantile. (b) The correlation between negative parental rearing and OCD ranged from the 0.67 to 0.95 quantile for paternal punishment, 0.14–0.82 quantile for paternal overprotection, 0.05–0.36 and >0.50 quantile for maternal over-intervention and overprotection, and 0.08–0.88 quantile for maternal rejection. (c) Extroversion, neuroticism, and psychoticism were not only associated with OCD in a particular quantile but also mediated between parental rearing (namely parental emotional warmth, paternal punishment, paternal overprotection, maternal rejection, maternal over-intervention, and overprotection) and OCD. These findings provide targets for early interventions of OCD to improve the form of family education and personality traits and warrant validation.
Hypertrophic cardiomyopathy is an autosomal dominant hereditary disease characterised by left ventricular asymmetry hypertrophy. However, our knowledge of the genetic background in hypertrophic cardiomyopathy cases is limited. Here, we aimed to evaluate pathogenic gene mutations in a family with high-risk hypertrophic cardiomyopathy and analyse the genotype/phenotype relationships in this family.
The proband, her parents, and her niece underwent whole-exome sequencing, and the genotypes of family members were identified using Sanger sequencing. mRNA expression was detected using reverse transcription sequencing. Structural impairments were predicted by homologous modelling. A family survey was conducted for patients with positive results to obtain information on general clinical symptoms, electrocardiography, ambulatory electrocardiography, echocardiography, and 3.0T cardiac magnetic resonance findings. Regular follow-up was performed for up to 6 months.
Five family members, including the proband, carried a cleavage site mutation in the MYBPC3 gene (c.2737+1 (IVS26) G>T), causing exon 26 of the MYBPC3 gene transcript to be skipped and leading to truncation of cardiac myosin-binding protein C. Family survey showed that the earliest onset age was 13 years old, and three people had died suddenly at less than 40 years old. Three pathogenic gene carriers were diagnosed with hypertrophic cardiomyopathy, and all showed severe ventricular septal hypertrophy.
The c.2737+1 (IVS26) G>T mutation in the MYBPC3 gene led to exon 26 skipping, thereby affecting the structure and function of cardiac myosin-binding protein C and leading to severe ventricular hypertrophy and sudden death.
The microbiota–gut–brain axis, especially the microbial tryptophan (Trp) biosynthesis and metabolism pathway (MiTBamp), may play a critical role in the pathogenesis of major depressive disorder (MDD). However, studies on the MiTBamp in MDD are lacking. The aim of the present study was to analyze the gut microbiota composition and the MiTBamp in MDD patients.
We performed shotgun metagenomic sequencing of stool samples from 26 MDD patients and 29 healthy controls (HCs). In addition to the microbiota community and the MiTBamp analyses, we also built a classification based on the Random Forests (RF) and Boruta algorithm to identify the gut microbiota as biomarkers for MDD.
The Bacteroidetes abundance was strongly reduced whereas that of Actinobacteria was significantly increased in the MDD patients compared with the abundance in the HCs. Most noteworthy, the MDD patients had increased levels of Bifidobacterium, which is commonly used as a probiotic. Four Kyoto Encyclopedia of Genes and Genomes (KEGG) orthologies (KOs) (K01817, K11358, K01626, K01667) abundances in the MiTBamp were significantly lower in the MDD group. Furthermore, we found a negative correlation between the K01626 abundance and the HAMD scores in the MDD group. Finally, RF classification at the genus level can achieve an area under the receiver operating characteristic curve of 0.890.
The present findings enabled a better understanding of the changes in gut microbiota and the related Trp pathway in MDD. Alterations of the gut microbiota may have the potential as biomarkers for distinguishing MDD patients form HCs.
High inductive helical support provides a solution to controlling the alignment error of inner electrodes in magnetically insulated transmission lines (MITLs). Three-dimensional particle-in-cell simulations were performed to examine the current loss mechanism and the effects of structural parameters on electron flow in an MITL with a helical inductor. An empirical expression related to the ratio of electron current loss to anode current and the ratio of anode current to self-limited current was obtained. Electron current loss caused by helical inductor with different structures was displayed. The results indicate that the current loss in an MITL, near an inductive helical support, comprises both the inductor current and the electron current loss. The non-uniform structure and current of a helical inductor cause an abrupt change in the magnetic field near the helical support, which leads to anomalous behavior and current loss of electron flow. In addition, current loss in the inductive helical-supported MITL is negligible when the inductance of the support is sufficiently high. This work facilitates the estimation of electron current loss caused by the inductive helical support in MITLs.
Echinococcus granulosus sensu stricto (s.s.), Echinococcus multilocularis and Echinococcus canadensis are the common causes of human echinococcosis in China. An accurate species identification tool for human echinococcosis is needed as the treatments and prognosis are different among species. The present work demonstrates a method for the simultaneous detection of these three Echinococcus species based on multiplex polymerase chain reaction (mPCR). Specific primers of this mPCR were designed based on the mitochondrial genes and determined by extensive tests. The method can successfully detect either separated or mixed target species, and generate expected amplicons of distinct size for each species. Sensitivity of the method was tested by serially diluted DNA, showing a detection threshold as less as 0.32 pg for both E. granulosus s.s. and E. canadensis, and 1.6 pg for E. multilocularis. Specificity assessed against 18 other parasites was found to be 100% except weakly cross-react with E. shiquicus. The assay was additionally applied to 69 echinococcosis patients and 38 healthy persons, confirming the high reliability of the method. Thus, the mPCR described here has high application potential for clinical identification purposes, and can further provide a useful tool for evaluation of serology and imaging method.
The output performances of a bidirectional ring amplifier with twin pulses are demonstrated. Compared to the extraction efficiency of 32% for single-pulse injection, the extraction efficiency of stored energy for twin-pulse injection with bidirectional propagation is increased to 60%. The maximum output energies of the twin pulses are 347 mJ and 351 mJ, and the output energy of a single pulse is only 373 mJ under the same amplifier operating conditions. The experimental results show that the bidirectional ring amplifier with twin pulses can achieve a higher extraction efficiency of stored energy at a lower operating fluence, and has potential applications in high-power and high-energy laser facilities.
The preparation of three-dimensional honeycomb nitrogen-doped carbon materials (3D-HNCMs) which can be used as electrode materials for supercapacitors is reported. The composites with the 3D honeycomb structure exhibited better electrochemical performance, and the structure and properties were proved by various means, such as SEM, TEM, IR, N2 sorption, XRD and XPS. Used as electrode materials for supercapacitors in the KOH electrolyte, 3D-HNCMs displayed a significantly high specific capacitance (409 F/g at a current of 0.5 A/g). Moreover, the 3D-HNCM electrode exhibited superior electrochemical performance, such as excellent cycling stability (98% capacitance retention after 10,000 cycles), a maximum energy density of 15.37 W h/kg, a maximum power density of 40.3 kW/kg, and low equivalent series resistance (2.1 Ω). Particularly, the electrochemical characteristic of 3D-HNCMs could be attributed to the synergistic effect of a high surface area, unique microporous and mesoporous structure, and nitrogen atom doping. These carbon materials with unique structure are promising electrode materials for future supercapacitor application.
A 15-year-old teenager presented with a 2-month history of headache. Neurological examination was normal except for papilledema. Further lumbar puncture indicated intracranial hypertension (330 mm H2O). Brain magnetic resonance imaging (MRI) was normal but phase contrast-magnetic resonance venography (PC-MRV) (Figure 1(A)) suggested possible left transverse-sigmoid sinus thrombosis; subsequent contrast-enhanced 3D fat-saturated T1 volumetric isotropic turbo spin echo acquisition (VISTA) MRI (Figure 1(B)) confirmed the pathology. Hyper-coagulable panel results (including six steroid sex hormones, antithrombin III, protein C, protein S, lupus anticoagulant, and anticardiolipin antibodies) were all within normal range. In further examination, computed tomography (CT) venography images (Figure 1(C) and (D)) showed that the left jugular vein was compressed by the styloid process, consistent with Eagle syndrome.1 The patient who refused the recommended surgical treatment, however, chose anticoagulant therapy consisting of low-molecular weight heparin subcutaneous injection in addition to new oral anticoagulant. At 18-month follow-up, the patient reported no symptoms remained.
Underground Nuclear Astrophysics in China (JUNA) will take the advantage of the ultra-low background in Jinping underground lab. High current accelerator with an ECR source and detectors were commissioned. JUNA plans to study directly a number of nuclear reactions important to hydrostatic stellar evolution at their relevant stellar energies. At the first period, JUNA aims at the direct measurements of 25Mg(p,γ)26 Al, 19F(p,α) 16 O, 13C(α, n) 16O and 12C(α,γ) 16O near the Gamow window. The current progress of JUNA will be given.