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Abstract Background Previous studies have found that the temporal duration required for males to perceive visual motion direction is significantly shorter than that for females. However, the neural correlates of such shortened duration perception remain yet unclear. Given that motion perception is primarily associated with the neural activity of the middle temporal visual complex (MT+), we here test the novel hypothesis that the neural mechanism of these behavioral sex differences is mainly related to the MT+ region. Methods We utilized ultra-high field (UHF) MRI to investigate sex differences in the MT+ brain region. A total of 95 subjects (48 females) participated in two separate studies. Cohort 1, consisting of 33 subjects (16 females), completed task-fMRI (drafting grating stimuli) experiment. Cohort 2, comprising 62 subjects (32 females), engaged in a psychophysical experiment measuring motion perception along different temporal thresholds as well as conducting structural and functional MRI scanning of MT+. Results Our findings show pronounced sex differences in major brain parameters within the left MT+ (but not the right MT+, i.e., laterality). In particular, males demonstrate (i) larger gray matter volume (GMV) and higher brain’s spontaneous activity at the fastest infra-slow frequency band in the left MT+; and (ii) stronger functional connectivity between the left MT+ and the left centromedial amygdala (CM). Meanwhile, both female and male participants exhibited comparable correlations between motion perception ability and the multimodal imaging indexes of the MT+ region, i.e., larger GMV, higher brain’s spontaneous activity, and faster motion discrimination. Conclusions Our findings reveal sex differences of imaging indicators of structure and function in the MT+ region, which also relate to the temporal threshold of motion discrimination. Overall, these results show how behavioral sex differences in visual motion perception are generated, and advocate considering sex as a crucial biological variable in both human brain and behavioral research.

Based on previous research and combined with the S-O-R theoretical model, this study examines the characteristics of anchors on Dong Yuhui’s “With Hui” Live-stream account as independent variables. The characteristics, measured by professionalism, high interactivity, fame, and attractiveness, are analyzed to determine their impact on consumer purchase intention. Perceived trust is set as a mediating variable, anticipated regret as a moderating variable, and purchase intention as the dependent variable to construct a model for reference by anchors on Dong Yuhui’s “With Hui” Live-stream account. Results show that anchor characteristics significantly and positively influence purchase intention; professionalism, high interactivity, fame, and attractiveness all have a notable positive impact on purchase intention. And anchor characteristics significantly and positively impact perceived trust, with professionalism, high interactivity, fame, and attractiveness positively influencing perceived trust. Perceived trust positively affects purchase intention and perceived trust partially mediates the relationship between anchor characteristics and purchase intention, with partial mediation observed between professionalism, high interactivity, fame, and attractiveness on purchase intention. Anticipated regret moderates the relationship between perceived trust and purchase intention, with upward anticipated regret showing a negative moderating effect, while downward anticipated regret shows a positive moderating effect on the perceived trust-purchase intention relationship.

Background Kangaroo mother care (KMC) is a care of preterm and low birthweight infants carried skin-to-skin contact with the mother’s chest and breastfeeding when possible. KMC has been proven to reduce mortality and morbidity in these infants. However, research on KMC has been limited by significant variability and inconsistency in reported outcomes across studies. These discrepancies hinder the inclusion of KMC clinical research in systematic reviews or meta-analyses, reducing its research value, leading to resource wastage and raising concerns about selective reporting biases. A core outcome set (COS), which defines a list of critical outcomes, can help harmonise the outcomes reported across studies in the same healthcare field. Further, how these outcomes should be measured and/or reported is defined in a core measurement set (CMS). This study aims to develop both a COS and a CMS for KMC to standardise outcome reporting, improve the quality assessments in clinical trials and facilitate data integration. This protocol outlines the methodology for developing a COS and CMS for KMC.Methods and analysis The development of the COS and CMS for KMC will follow six phases: (1) a systematic review, (2) semistructured interviews, (3) merging outcomes, (4) two/three rounds of international Delphi survey, (5) a consensus meeting and (6) development of the CMS. In phases 1 and 2, we will conduct a systematic review and semistructured interviews to identify potential core outcomes and measurements, which will form an initial outcome pool. In phase 3, these outcomes will be categorised into domains based on the core outcome measures for effectiveness (COMET) classification, creating a long list of outcomes for the Delphi survey. In phase 4, the Delphi survey will involve two/three rounds with key stakeholders, including neonatal clinical experts (including doctors and nurses), users of COS (including editors, public health experts, experts in evidence-based medicine and researchers), parents of neonates and policymakers, to refine the candidate core outcomes and measurements. In phase 5, an online consensus meeting with representatives of all stakeholders will finalise the COS. In phase 6, the CMS will be following Consensus-based Standards for the selection of health Measurement Instruments guidelines, which involve conceptual considerations, finding existing outcome measurement instruments, assessing their quality and selecting appropriate instruments for the COS. Parents of neonates will participate in phases 2, 4 and 5.Ethics and dissemination Ethical approval of this study has been granted by the Medical Ethics Committee of West China Second University Hospital (Medical Research 2024 ethics approval no. 167). The finalised COS and CMS will be disseminated through publication in peer-reviewed journals.Trial registration number We have registered the COS in the COMET database (http://www.comet-initiative.org/Studies/Details/2940).

Abstract Schizophrenia (SZ) is a severe psychiatric disorder characterized by perceptual, emotional, and behavioral abnormalities, with cognitive impairment being a prominent feature of the disorder. Recent studies demonstrate irregularity in SZ with increased variability on the neural level. Is there also irregularity on the psychophysics level like in visual perception? Here, we introduce a methodology to analyze the irregularity in a trial-by-trial way to compare the SZ and healthy control (HC) subjects. In addition, we use an unsupervised clustering algorithm K-means + + to identify SZ subgroups in the sample, followed by validation of the subgroups based on intraindividual visual perception variability and clinical symptomatology. The K-means + + method divided SZ patients into two subgroups by measuring durations across trials in the motion discrimination task, i.e., high, and low irregularity of SZ patients (HSZ, LSZ). We found that HSZ and LSZ subgroups are associated with more negative and positive symptoms respectively. Applying a mediation model in the HSZ subgroup, the enhanced irregularity mediates the relationship between visual perception and negative symptoms. Together, we demonstrate increased irregularity in visual perception of a HSZ subgroup, including its association with negative symptoms. This may serve as a promising marker for identifying and distinguishing SZ subgroups.

Abstract Background Effective treatments for the alveolar bone defect remain a major concern in dental therapy. The objectives of this study were to develop a fibrin and konjac glucomannan (KGM) composite hydrogel as scaffolds for the osteogenesis of nasal mucosa-derived ectodermal mesenchymal stem cells (EMSCs) for the regeneration of alveolar bone defect, and to investigate the osteogenesis-accelerating effects of black phosphorus nanoparticles (BPNs) embedded in the hydrogels. Methods Primary EMSCs were isolated from rat nasal mucosa and used for the alveolar bone recovery. Fibrin and KGM were prepared in different ratios for osteomimetic hydrogel scaffolds, and the optimal ratio was determined by mechanical properties and biocompatibility analysis. Then, the optimal hydrogels were integrated with BPNs to obtain BPNs/fibrin-KGM hydrogels, and the effects on osteogenic EMSCs in vitro were evaluated. To explore the osteogenesis-enhancing effects of hydrogels in vivo, the BPNs/fibrin-KGM scaffolds combined with EMSCs were implanted to a rat model of alveolar bone defect. Micro-computed tomography (CT), histological examination, real-time quantitative polymerase chain reaction (RT-qPCR) and western blot were conducted to evaluate the bone morphology and expression of osteogenesis-related genes of the bone regeneration. Results The addition of KGM improved the mechanical properties and biodegradation characteristics of the fibrin hydrogels. In vitro, the BPNs-containing compound hydrogel was proved to be biocompatible and capable of enhancing the osteogenesis of EMSCs by upregulating the mineralization and the activity of alkaline phosphatase. In vivo, the micro-CT analysis and histological evaluation demonstrated that rats implanted EMSCs-BPNs/fibrin-KGM hydrogels exhibited the best bone reconstruction. And compared to the model group, the expression of osteogenesis genes including osteopontin (Opn, p

Abstract Heart failure (HF) is a significant global public health concern with a high readmission rate, posing a serious threat to the health of the elderly population. While several studies have used machine learning (ML) to develop all-cause readmission risk prediction models for elderly patients with HF, few have integrated ML-selected features with those chosen by human experts to assess HF patients readmission. A retrospective analysis of 8396 elderly HF patients hospitalized at the Affiliated Hospital of North Sichuan Medical College from January 1, 2018 to December 31, 2021 was conducted. Variables selected by XGBoost, LASSO regression, and random forest constituted the machine group, while the human expert group comprised variables chosen by two experienced cardiovascular professors. The variables selected by both groups were combined to form a human–machine collaboration group. Model performance was evaluated using the area under the receiver operating characteristic curve (AUC). The SHapley Additive exPlanations (SHAP) method was used to elucidate the importance of each predictive feature, explain the impact of individual features on the model, and provide visual representation. A total of 73 features were included for model development. The human–machine collaboration model, utilizing CatBoost, achieved an AUC of 0.83617, an F1-score of 0.73521, and a Brier score of 0.16536 on the validation set. This model demonstrated superior predictive performance compared to those created solely by human experts or machine. The SHAP plot was then used to visually display the feature analysis of the human–machine collaboration model, revealing HGB, NT-proBNP, smoking history, NYHA classification, and LVEF as the 5 most important features. This study indicate that the human–machine collaboration model outperforms those relying solely on human expert selection or machine algorithm at predicting all-cause readmission in elderly HF patients. The application of the SHAP method enhanced the interpretability of the model outcomes, aiding clinicians in accurately pinpointing risk factors associated with HF readmission. This advancement enables the formulation of tailored treatment strategies, offering a more personalized approach to patient care.

The gut microbiota has been shown to be associated with a range of illnesses and disorders, including hypertension, which is recognized as the primary factor contributing to the development of serious cardiovascular diseases. In this review, we conducted a comprehensive analysis of the progression of the research domain pertaining to gut microbiota and hypertension. Our primary emphasis was on the interplay between gut microbiota and blood pressure that are mediated by host and gut microbiota-derived metabolites. Additionally, we elaborate the reciprocal communication between gut microbiota and antihypertensive drugs, and its influence on the blood pressure of the host. The field of computer science has seen rapid progress with its great potential in the application in biomedical sciences, we prompt an exploration of the use of microbiome databases and artificial intelligence in the realm of high blood pressure prediction and prevention. We propose the use of gut microbiota as potential biomarkers in the context of hypertension prevention and therapy.

The prevailing opinion emphasizes fronto-parietal network (FPN) is key in mediating general fluid intelligence (gF). Meanwhile, recent studies show that human MT complex (hMT+), located at the occipito-temporal border and involved in 3D perception processing, also plays a key role in gF. However, the underlying mechanism is not clear, yet. To investigate this issue, our study targets visuo-spatial intelligence, which is considered to have high loading on gF. We use ultra-high field magnetic resonance spectroscopy (MRS) to measure GABA/Glu concentrations in hMT+ combining resting-state fMRI functional connectivity (FC), behavioral examinations including hMT+ perception suppression test and gF subtest in visuo-spatial component. Our findings show that both GABA in hMT+ and frontal-hMT+ functional connectivity significantly correlate with the performance of visuo-spatial intelligence. Further, serial mediation model demonstrates that the effect of hMT+ GABA on visuo-spatial gF is fully mediated by the hMT+ frontal FC. Together our findings highlight the importance in integrating sensory and frontal cortices in mediating the visuo-spatial component of general fluid intelligence.

Background The model for end-stage liver disease (MELD) score is widely used for the prognostication in end-stage liver disease but has limited performance in acute-on-chronic liver failure (ACLF). In this study, we identified additional predictive parameters and reformed the MELD score to predict ACLF more accurately.Methods A meta-analysis was performed on relevant studies to identify the predictive factors of 28-day/90-day outcomes of ACLF, which were validated in two large prospective cohorts. A prognostic score was developed by incorporating predictive parameters into the MELD score. The model was evaluated with a focus on discrimination and calibration.Results The meta-analysis incorporated 32 cohort studies with a total of 13 939 patients, of which 13 risk factors were identified, and 3 risk factors (age, neutrophil count and hepatic encephalopathy (HE) grade) besides MELD score were validated in 751 patients with ACLF derived from two prospective cohorts. A new model (Chinese Acute-on-Chronic Liver Failure Consortium (CATCH-LIFE)-MELD score) was developed as follows: 0.028×age+0.3×HE grade+0.039×neutrophil count+0.079×MELD score. CATCH-LIFE-MELD score achieved a concordance index of 0.791/0.788 for 28-day/90-day outcomes, which is superior to other traditional scores. Other discrimination indices, including net reclassification improvement, integrated discrimination improvement and probability density function, and calibration including Nagelkerke’s R2 and Brier scores confirmed its superiority. Moreover, the accuracy of CATCH-LIFE-MELD score remained stable. It was highest in patients with or without hepatitis B virus infection, cirrhosis, liver failure or under the Chinese Group on the Study of Severe Hepatitis B (COSSH) criteria or European Association for the Study of the Liver (EASL) criteria. All results were substantiated by an evaluation using an external cohort.Conclusions CATCH-LIFE-MELD score, a modified MELD score exhibited improved accuracy in predicting the short-term prognosis of ACLF than other traditional scores.

Abstract Major depressive disorder (MDD) is characterized by psychomotor retardation whose underlying neural source remains unclear. Psychomotor retardation may either be related to a motor source like the motor cortex or, alternatively, to a psychomotor source with neural changes outside motor regions, like input regions such as visual cortex. These two alternative hypotheses in main (n = 41) and replication (n = 18) MDD samples using 7 Tesla MRI are investigated. Analyzing both global and local connectivity in primary motor cortex (BA4), motor network and middle temporal visual cortex complex (MT+), the main findings in MDD are: 1) Reduced local and global synchronization and increased local‐to‐global output in motor regions, which do not correlate with psychomotor retardation, though. 2) Reduced local‐to‐local BA4 – MT+ functional connectivity (FC) which correlates with psychomotor retardation. 3) Reduced global synchronization and increased local‐to‐global output in MT+ which relate to psychomotor retardation. 4) Reduced variability in the psychophysical measures of MT+ based motion perception which relates to psychomotor retardation. Together, it is shown that visual cortex MT+ and its relation to motor cortex play a key role in mediating psychomotor retardation. This supports psychomotor over motor hypothesis about the neural source of psychomotor retardation in MDD.

Abstract To investigate the factors that influence readmissions in patients with acute non-ST elevation myocardial infarction (NSTEMI) after percutaneous coronary intervention (PCI) by using multiple machine learning (ML) methods to establish a predictive model. In this study, 1576 NSTEMI patients who were hospitalized at the Affiliated Hospital of North Sichuan Medical College were selected as the research subjects. They were divided into two groups: the readmitted group and the non-readmitted group. The division was based on whether the patients experienced complications or another incident of myocardial infarction within one year after undergoing PCI. Common variables selected by univariate and multivariate logistic regression, LASSO regression, and random forest were used as independent influencing factors for NSTEMI patients’ readmissions after PCI. Six different ML models were constructed using these common variables. The area under the ROC curve, accuracy, sensitivity, and specificity were used to evaluate the performance of the six ML models. Finally, the optimal model was selected, and a nomogram was created to visually represent its clinical effectiveness. Three different methods were used to select seven representative common variables. These variables were then utilized to construct six different ML models, which were subsequently compared. The findings indicated that the LR model exhibited the most optimal performance in terms of AUC, accuracy, sensitivity, and specificity. The outcome, admission mode (walking and non-walking), communication ability, CRP, TC, HDL, and LDL were identified as independent predicators of readmissions in NSTEMI patients after PCI. The prediction model constructed by the LR algorithm was the best. The established column graph model established proved to be effective in identifying high-risk groups with high accuracy and differentiation. It holds a specific predictive value for the occurrence of readmissions after direct PCI in NSTEMI patients.

ObjectiveTo analyze the impact of different methods of Vitamin D administration on the prognosis of COVID-19 patients.MethodsA comprehensive literature search was conducted across four databases: PubMed, Embase, Web of Science, and Cochrane, up to January 5, 2024. Eligible studies included randomized controlled trials and cohort studies that compared Vitamin D supplementation with control groups in COVID-19 patients. Outcomes of interest were mortality rate, ICU (Intensive Care Unit) admission rate, length of hospital stay, and endotracheal intubation rate. Subgroup analyses were performed based on the dosing regimen (single-dose vs. continuous-dose), total Vitamin D intake within 14 days (≥100,000 IU vs.

Thrombocytopenia, anasarca, fever, reticulin fibrosis on bone marrow biopsy/renal dysfunction, and organomegaly (TAFRO) syndrome are infrequent conditions with diverse clinical and pathological characteristics related to multi-organ damage. There are few reports of TAFRO syndrome accompanied by liver damage with hyperbilirubinemia. We describe the case of a 61-year-old male who presented with sudden onset abdominal pain accompanied by liver damage with hyperbilirubinemia. His symptoms worsened, leading to fever, hepatic insufficiency, serous cavity effusions, thrombocytopenia, and acute renal failure. Fever and anasarca relapsed after steroid discontinuation. The patient was ultimately diagnosed with TAFRO syndrome by biopsies taken from the axillary lymph nodes. He was then administered steroids, which resolved his symptoms almost completely. Our case was notable for its atypical signs and total remission of TAFRO syndrome.

ObjectivePrevious studies have found that patients with Major Depressive Disorder (MDD) exhibit impaired visual motion perception capabilities, and multi-level abnormalities in the human middle temporal complex (MT+), a key brain area for processing visual motion information. However, the brain activity pattern of MDD patients during the perception of visual motion information is currently unclear. In order to study the effect of depression on the activity and functional connectivity (FC) of MT+ during the perception of visual motion information, we conducted a study combining task-state fMRI and psychophysical paradigm to compare MDD patients and healthy control (HC).MethodsDuration threshold was examined through a visual motion perception psychophysical experiment. In addition, a classic block-design grating motion task was utilized for fMRI scanning of 24 MDD patients and 25 HC. The grating moved randomly in one of eight directions. We examined the neural activation under visual stimulation conditions compared to the baseline and FC.ResultsCompared to HC group, MDD patients exhibited increased duration threshold. During the task, MDD patients showed decreased beta value and percent signal change in left and right MT+. In the sample comprising MDD and HC, there was a significant negative correlation between beta value in right MT+ and duration threshold. And in MDD group, activation in MT+ were significantly correlated with retardation score. Notably, no such differences in activation were observed in primary visual cortex (V1). Furthermore, when left MT+ served as the seed region, compared to the HC, MDD group showed increased FC with right calcarine fissure and surrounding cortex and decreased FC with left precuneus.ConclusionOverall, the findings of this study highlight that the visual motion perception function impairment in MDD patients relates to abnormal activation patterns in MT+, and task-related activity are significantly connected to the retardation symptoms of the disease. This not only provides insights into the potential neurobiological mechanisms behind visual motion perception disorder in MDD patients from the aspect of task-related brain activity, but also supports the importance of MT+ as a candidate biomarker region for MDD.

Background and AimsBlood metabolite abnormalities have revealed an association with cholestatic liver diseases (CLDs), while the underlying metabolic mechanisms have remained sluggish yet. Accordingly, the present evaluation aims to investigate the causal relationship between blood metabolites and the risk of two major CLDs, including primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC).MethodsUnivariable and multivariable Mendelian randomization (MR) approaches were employed to uncover potential causal associations between blood metabolites and 2 CLDs, including PBS and PSC, through extracting instrumental variables (IVs) for metabolites from genome-wide association studies (GWAS) conducted on European individuals. The GWAS summary data of PBC or PSC were sourced from two distinct datasets. The initial analysis employed inverse variance weighted (IVW) and an array of sensitivity analyses, followed by replication and meta-analysis utilizing FinnGen consortium data. Finally, a multivariable MR analysis was carried out to ascertain the independent effects of each metabolite. Furthermore, the web-based tool MetaboAnalyst 5.0 was used to perform metabolic pathway examination.ResultsA genetic causality between 15 metabolites and CLDs was recognized after preliminary analysis and false discovery rate (FDR) correction. Subsequently, 9 metabolites consistently represented an association through replication and meta-analysis. Additionally, the independent causal effects of 7 metabolites were corroborated by multivariable MR analysis. Specifically, the metabolites isovalerylcarnitine (odds ratio [OR] = 3.146, 95% confidence intervals [CI]: 1.471–6.726, p = 0.003), valine (OR = 192.44, 95%CI: 4.949–7483.27, p = 0.005), and mannose (OR = 0.184, 95%CI: 0.068–0.499, p

Introduction and Objectives: The increasing incidence of ischemic heart disease is a serious threat to human health. Increased CASC15, a long non-coding RNA, has been shown to adversely affect cardiac muscle. The objective of this paper was to explore the effect of CASC15 on a cell model of myocardial infarction and its possible mechanism. Methods: H9c2 cells were selected to establish the myocardial infarction model through hypoxia/reoxygenation (H/R) treatment. The expression of CASC15 was attenuated by cell transfection in vitro. The level of CASC15 was detected by RT-qPCR. Cell viability was detected by CCK-8 assay, and cell apoptosis was assessed by flow cytometry. The content of MDA and the activity of SOD and GSH-Px were measured by ELISA. Luciferase reporter gene assay was used to determine the relationship between CASC15 and miRNA. Results: CASC15 expression was increased in H/R-treated H9c2 cells. Overexpression of CASC15 adversely affected cell viability and promoted H/R-induced oxidative stress. Inhibition of CASC15 promoted cell viability and suppressed cell apoptosis and oxidative stress damage. Additionally, luciferase reporter gene assay confirmed the targeting relationship between CASC15 and miR-542-3p, and attenuating CASC15 expression enhanced the level of miR-542-3p. Reduction of miR-542-3p weakened the viability of the H/R cell model, increased apoptosis, and enhanced oxidative stress damage. Conclusion: This study suggests that overexpression of CASC15 may inhibit the viability of H9c2 cells, promote apoptosis and induce oxidative stress through targeted regulation of miR-542-3p expression. Resumo: Introdução e objetivos: O aumento da doença isquémica cardíaca representa uma séria ameaça à saúde humana. Um aumento no CASC15, um RNA não codificante longo, está associado à lesão do músculo cardíaco. O objetivo deste trabalho foi explorar o mecanismo celular através do qual a CASC15 contribui para o enfarte do miocárdio. Métodos: Células H9c2 expostas a hipóxia/reoxigenação (H/R) foram selecionadas como modelo para estudar os mecanismos envolvidos no enfarto do miocárdio. A expressão de CASC15 foi inibida pela transfecção com siRNA. Os níveis de CASC15 foram avaliados por RT-qPCR e a viabilidade celular e apoptose determinadas pelo ensaio CCK-8 e citometria de fluxo, respetivamente. Os teores de MDA, SOD e GSH-Px foram medidos por ELISA. O ensaio do gene repórter da luciferase foi utilizado para verificar a relação entre CASC15 e os níveis do miRNA miR-542-3p. Resultados: Células H9c2 sujeitas a H/R apresentam níveis aumentados de CASC15. A sobre-expressão de CASC15 afetou negativamente a função celular e promoveu a lesão induzida pelo stress associado H/R. Por outro lado, a inibição do CASC15 promoveu viabilidade celular e suprimiu apoptose celular e os danos oxidativos. Além disso, o ensaio do gene repórter da luciferase confirmou a relação alvo entre CASC15 e miR-542-3p, com uma diminuição da expressão de CASC15 a resultar num aumento do nível de miR-542-3p. Uma diminuição do miR-542-3p comprometeu a viabilidade do modelo de células H/R e aumentou a apoptose e o dano oxidativo. Conclusão: Este estudo sugere que um aumento da expressão de CASC15 durante a H/R pode contribuir para diminuir a viabilidade dos cardiomiócitos, promover apoptose e induzir stress oxidativo, através da regulação da expressão de miR-542-3p.

Abstract Background Parathyroid glands are important endocrine glands, and the identification of normal parathyroid glands is crucial for their protection. The aim of this study is to explore the sonographic characteristics of normal parathyroid glands and analyze the factors affecting their display. Methods Seven hundred three subjects who underwent physical examination at our hospital were included. The number, location, size, morphology, echogenicity and blood flow distribution of parathyroid glands were recorded. The ultrasound characteristics and display rate were also summarized. Meanwhile, shear wave elastography was performed in 50 cases to provide the stiffness measurements, and 26 cases received contrast-enhanced ultrasonography for the assessment of microcirculatory perfusion. Furthermore, we analyzed the factors affecting parathyroid display, including basic information of the subjects and ultrasound features of the thyroid. Results ① A total of 1038 parathyroid glands were detected, among which, 79.29% were hyperechoic, 20.71% were isoechoic, 88.15% were oval-shaped, and 86.71% had blood flow of grade 0-I. ② 81.79% of the subjects had at least one parathyroid gland detected. ③ The Emean, Emax, PI and AUC of the parathyroid glands were significantly lower than those of the adjacent thyroid tissue (P

This study aimed to investigate the impact of IL-35 on the prognosis of patients with HBV-ACLF. We recruited 69 patients with HBV-ACLF, 20 patients with chronic hepatitis B (CHB), 17 patients with liver cirrhosis (LC), and 20 healthy controls (HCs) from a regional infectious disease treatment center in China. Plasma levels of IL-35 at baseline were detected using ELISA. Plasma IL-35 levels in the HBV-ACLF group were the highest among all four groups. Furthermore, survivors exhibited significantly higher IL-35 levels than non-survivors (p < 0.001). IL-35 levels correlated with MELD (r = −0.678, p < 0.001), COSSH-ACLF IIs (r = −0.581, p < 0.001), alpha-fetoprotein (AFP) (r = 0.433, p < 0.001), creatinine (Cr) (r =−0.396, p = 0.001), and lactate (r =−0.38, p =0.001). The combination of plasma IL-35 and MELD score had the highest mortality prediction efficiency, with an area under the curve (AUC) of 0.895 (95% CI: 0.812–0.978, p < 0.001), a sensitivity of 80.6%, and a specificity of 93.9%. Additionally, the Kaplan–Meier analysis revealed that lower levels of IL-35 (≤191.5pg/mL) were associated with poorer survival rates in HBV-ACLF patients (p < 0.001). Our results demonstrated that IL-35 could be an effective predictive marker for the prognosis of HBV-ACLF and improve the predictive performance when combined with the MELD score.

IntroductionChronic schizophrenia has a course of 5 years or more and has a widespread abnormalities in brain functional connectivity. This study aimed to find characteristic functional and structural changes in a long illness duration chronic schizophrenia (10 years or more).MethodsThirty-six patients with a long illness duration chronic schizophrenia and 38 healthy controls were analyzed by independent component analysis of brain network functional connectivity. Correlation analysis with clinical duration was performed on six resting state networks: auditory network, default mode network, dorsal attention network, fronto-parietal network, somatomotor network, and visual network.ResultsThe differences in the resting state network between the two groups revealed that patients exhibited enhanced inter-network connections between default mode network and multiple brain networks, while the inter-network connections between somatomotor network, default mode network and visual network were reduced. In patients, functional connectivity of Cuneus_L was negatively correlated with illness duration. Furthermore, receiver operating characteristic curve of functional connectivity showed that changes in Thalamus_L, Rectus_L, Frontal_Mid_R, and Cerebelum_9_L may indicate a longer illness duration chronic schizophrenia.DiscussionIn our study, we also confirmed that the course of disease is significantly associated with specific brain regions, and the changes in specific brain regions may indicate that chronic schizophrenia has a course of 10 years or more.

AimStudy results on blood glucose and the risk of delirium in patients receiving cardiac surgery are inconsistent, and there is also a gap in how to manage blood glucose after coronary artery bypass grafting (CABG). This study focused on patients with diabetes mellitus (DM) undergoing CABG and explored the associations of different blood glucose-related indexes and blood glucose change trajectory with postoperative delirium (POD), with the aim of providing some information for the management of blood glucose in this population.MethodsData of patients with DM undergoing CABG were extracted from the Medical Information Mart for Intensive Care (MIMIC)-IV database in this retrospective cohort study. The blood glucose-related indexes included baseline blood glucose, mean blood glucose (MBG), mean absolute glucose (MAG), mean amplitude of glycemic excursions (MAGE), glycemic lability index (GLI), and largest amplitude of glycemic excursions (LAGE). The MBG trajectory was classified using the latent growth mixture modeling (LGMM) method. Univariate and multivariate logistic regression analyses were utilized to screen covariates and explore the associations of blood glucose-related indexes and MBG trajectory with POD. These relationships were also assessed in subgroups of age, gender, race, estimated glomerular filtration rate (eGFR), international normalized ratio (INR), sepsis, mechanical ventilation use, and vasopressor use. In addition, the potential interaction effect between blood glucose and hepatorenal function on POD was investigated. The evaluation indexes were odds ratios (ORs), relative excess risk due to interaction (RERI), attributable proportion of interaction (AP), and 95% confidence intervals (CIs).ResultsAmong the eligible 1,951 patients, 180 had POD. After adjusting for covariates, higher levels of MBG (OR = 3.703, 95% CI: 1.743–7.870), MAG >0.77 mmol/L/h (OR = 1.754, 95% CI: 1.235–2.490), and GLI >2.6 (mmol/L)2/h/per se (OR = 1.458, 95% CI: 1.033–2.058) were associated with higher odds of POD. The positive associations of MBG, MAG, and GLI with POD were observed in patients aged

Abstract Aim The study aimed to investigate the short‐term outcomes of hospitalized patients with chronic liver disease (CLDs) and assess the prognostic impact of predisposition and precipitants, which currently remains unclear. Methods The study included 3970 hospitalized patients with CLDs from two prospective longitudinal multicenter studies (NCT02457637 and NCT03641872) conducted in highly endemic hepatitis B virus (HBV) areas. Competing risk analysis was used to evaluate the effect of predispositions, including the etiology and severity of CLDs and precipitants; on sequential 28, 90, and 365‐day liver transplantation (LT)‐free mortality. Results Among all enrolled patients, 76.8% of adverse outcomes (including death and LT) within one year occurred within 90 days. Compared with alcoholic etiology, the association of HBV etiology with poorer outcomes was remarkably on the 28th day (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.07–3.06; p = 0.026); however, and diminished or became insignificant at 90 days and 365 days. Cirrhosis increased the adjusted risk for 365‐day (HR, 1.50; CI, 1.13–1.99; p = 0.004) LT‐free mortality when compared with noncirrhosis. In patients with cirrhosis, prior decompensation (PD) independently increased the adjusted risk of 365‐day LT‐free mortality by 1.25‐fold (p = 0.021); however, it did not increase the risk for 90‐day mortality. Neither the category nor the number of precipitants influenced the adjusted risk of 28 or 90‐day LT‐free mortality. Conclusions The 90‐day outcome should be considered a significant endpoint for evaluating the short‐term prognosis of hospitalized patients with CLD. Predisposing factors, other than etiology, mainly affected the delayed (365‐day) outcome. Timely effective therapy for CLD etiology, especially antiviral treatments for HBV, and post‐discharge long‐term surveillance monitoring in cirrhotic patients undergoing PD are suggested to enhance disease management and reduce mortality.

Background: Sepsis, a global health challenge, necessitates a nuanced understanding of modifiable factors for effective prevention and intervention. The role of trace micronutrients in sepsis pathogenesis remains unclear, and their potential connection, especially with genetic influences, warrants exploration.Methods: We employed Mendelian randomization (MR) analyses to assess the causal relationship between genetically predicted blood levels of nine micronutrients (calcium, β-carotene, iron, magnesium, phosphorus, vitamin C, vitamin B6, vitamin D, and zinc) and sepsis susceptibility, severity, and subtypes. The instrumental variables for circulating micronutrients were derived from nine published genome-wide association studies (GWAS). In the primary MR analysis, we utilized summary statistics for sepsis from two independent databases (UK Biobank and FinnGen consortium), for initial and replication analyses. Subsequently, a meta-analysis was conducted to merge the results. In secondary MR analyses, we assessed the causal effects of micronutrients on five sepsis-related outcomes (severe sepsis, sepsis-related death within 28 days, severe sepsis-related death within 28 days, streptococcal septicaemia, and puerperal sepsis), incorporating multiple sensitivity analyses and multivariable MR to address potential heterogeneity and pleiotropy.Results: The study revealed a significant causal link between genetically forecasted zinc levels and reduced risk of severe sepsis-related death within 28 days (odds ratio [OR] = 0.450; 95% confidence interval [CI]: 0.263, 0.770; p = 3.58 × 10−3). Additionally, suggestive associations were found for iron (increased risk of sepsis), β-carotene (reduced risk of sepsis death) and vitamin C (decreased risk of puerperal sepsis). No significant connections were observed for other micronutrients.Conclusion: Our study highlighted that zinc may emerges as a potential protective factor against severe sepsis-related death within 28 days, providing theoretical support for supplementing zinc in high-risk critically ill sepsis patients. In the future, larger-scale data are needed to validate our findings.

Identifying the parameters of solar photovoltaic (PV) cell models accurately and reliably is crucial for simulating, evaluating, and controlling PV systems. For this reason, we present an improved chimp optimization algorithm (IChOA) for the generation of precise and reliable solar PV cell models. As a new and improved version of the standard chimp optimization algorithm (ChOA), IChOA embeds two mutation rules in ChOA that include the elite opposition-based learning and visual search mechanism. The first rule is applied to strengthen global exploration capacity of ChOA, and the second one is utilized to enhance ChOA’s local exploitation ability (convergence accuracy). Based on the six benchmark test functions with different characteristics, the effectiveness of IChOA is evaluated by comparing to other five well-known optimization algorithms. The results suggest that IChOA offers superior performance over other competing algorithms. Finally, IChOA’s performance is confirmed through optimizing parameters for three widely employed mathematical models, specifically the single diode model, the double diode model, and the multi-cell PV modules. The findings prove the excellent performance of the suggested approach.

Abstract Acute pancreatitis (AP) is one of the life‐threatening diseases of the digestive system. MicroRNA has been asserted to be a regulator of AP. This paper explored the miR‐374a‐5p expression in AP patients and investigated the efficacy of AR42J cells. In this study, 60 healthy people, 58 MAP patients and 58 SAP patients were included, and the serum miR‐374a‐5p levels of the subjects were detected by RT‐qPCR technology. The pancreatitis cell model was structured by stimulating AR42J cells with cerulein. Next, cell viability and apoptosis were detected by CCK‐8 assay and flow cytometry. ELISA was used to measure the concentration of cytokines, such as TNF‐α, IL‐6, and IL‐1β. The data showed that miR‐374a‐5p was downregulated in samples from AP patients, while showing discriminative power for AP populations. Attenuated miR‐374a‐5p were negatively bound up with patients' Ranson score and APACHE II score. Besides, miR‐374a‐5p was declined in cerulein‐treated AR42J cells and forced elevation of miR‐374a‐5p was beneficial to increase cell viability, and inhibit cell apoptosis and inflammation. The present study found that miR‐374a‐5p was reduced in AP serum samples, and up‐regulated expression level of miR‐374a‐5p in cell models had a protective effect on cerulein‐induced inhibition of cell function and inflammatory response.

Abstract Radix Astragali is one of the most famous and frequently used health food supplements and herbal medicines. Among more than 227 components of Radix Astragali, Astragaloside IV (AG IV) is famous functional compound and is commonly used as a quality marker for Radix Astragali. However, the relatively low content of AG IV in Radix Astragali (

AbstractBackground Septic shock is the development of sepsis to refractory circulatory collapse and metabolic derangements, characterized by persistent hypotension and increased lactate levels. Anisodamine hydrobromide (Ani HBr) is a Chinese medicine used to improve blood flow in circulatory disorders. The purpose of this study was to determine the therapeutic efficacy of Ani HBr in the treatment of patients with septic shock.Methods This was a prospective, multicenter, randomized controlled trial focusing on patients with septic shock in 16 hospitals in China. Patients were randomly assigned in a 1:1 ratio to either the treatment group or the control group. The primary endpoint was 28-day mortality. The secondary outcomes included 7-day mortality, hospital mortality, hospital length of stay, vasopressor-free days within 7 days, etc. These indicators were measured and collected at 0, 6h, 24h, 48h, 72h and 7d after the diagnosis.Results Between September 2017 and March 2021, 404 subjects were enrolled. 203 subjects received Ani HBr and 201 subjects were assigned to the control group. The treated group showed lower 28-day mortality than the control group. Stratified analysis further showed significant differences in 28-day mortality between the two groups for patients with a high level of illness severity. We also observed significant differences in 7-day mortality, hospital mortality and some other clinical indicators between the two groups.Conclusion Ani HBr might be an important adjuvant to conventional treatment to reduce 28-day mortality in patients with septic shock. A large-scale prospective randomized multicenter trial is warranted to confirm our results.

BackgroundThe incidence of progressive multifocal leukoencephalopathy (PML) in people living with HIV (PLWH) is 2%-4%. Currently, there is no effective therapeutic strategy for the treatment of PML in PLWH, resulting in a mortality of up to 50%. This study aimed to identify risk factors of death and prognostic markers in people living with HIV with PML.MethodsA retrospective cohort study of AIDS-related PML individuals was conducted from January 1, 2015, to October 1, 2022, in Shanghai, China. PLWH who were diagnosed with PML for the first time were included. Kaplan-Meier curve and Cox regression were used to analyze the survival and its predictors. Levels of inflammatory markers and immune checkpoint inhibitors in blood and cerebrospinal fluid (CSF) were measured in the prestored samples using bead-based multiplex assay Indolamine 2,3-dioxygenase was determined using ELISA.ResultsTwenty of 71 subjects had initiated antiretroviral therapy (ART) before PML onset and no patients discontinued ART during this period. In total, 34 patients (47.9%) had opportunistic infections (OIs), the median CD4+ T cell count was 73.0 (33.0-149.0) cells/μL. The estimated probability of survival at six months was 78% (95% confidential intervals [CIs]:0.63-0.85). OIs, low CD4+ T cell count were associated with lower estimated six-month survival (hazard ratio 8.01, 95% CIs: 1.80-35.00, P=0.006 and 5.01, 95% CIs:1.57-16.03, p=0.007). Indolamine 2,3-dioxygenase activity in CSF of non-survivors group were higher than survivors group (p

Engineered gut microbiota represents a new frontier in medicine, in part serving as a vehicle for the delivery of therapeutic biologics to treat a range of host conditions. The gut microbiota plays a significant role in blood pressure regulation; thus, manipulation of gut microbiota is a promising avenue for hypertension treatment. In this study, we tested the potential of Lactobacillus paracasei, genetically engineered to produce and deliver human angiotensin converting enzyme 2 (Lacto-hACE2), to regulate blood pressure in a rat model of hypertension with genetic ablation of endogenous Ace2 (Ace2-/- and Ace2-/y). Our findings reveal a sex-specific reduction in blood pressure in female (Ace2-/-) but not male (Ace2-/y) rats following colonization with the Lacto-hACE2. This beneficial effect of lowering blood pressure was aligned with a specific reduction in colonic angiotensin II, but not renal angiotensin II, suggesting the importance of colonic Ace2 in the regulation of blood pressure. We conclude that this approach of targeting the colon with engineered bacteria for delivery of ACE2 represents a promising new paradigm in the development of antihypertensive therapeutics.

C12H8N6O8, orthorhombic, Pbcn (no. 60), a = 11.9333(5) Å, b = 9.2524(4) Å, c = 12.8675(7) Å, V = 1420.72(12) Å3, Z = 8, Rgt(F) = 0.0468, wRref(F2) = 0.1159, T = 170 K.

Adenomatoid tumor is a kind of benign tumor, accounts for a low percentage of scrotal tumors. It usually locates in epididymis, less commonly, arises from the tunica albuginea, spermatic cord or tunica vaginalis of male's urogenital tract system. Here, we report a case of a 32-year-old male, which presented as a 6-month history of left scrotal swelling pain with a scrotal mass, and it had progressively enlarged over the last 1 month. The ultrasonography (US) described a giant well-defined hypoechoic mass in the left scrotum, a thick pedicle connected the mass and the left scrotal wall, and the pedicle had large blood vessels in it. Enhanced CT showed an irregular solid mass in the left scrotum, the left testicular artery was thickened to supply blood for the mass, and the radiologist mentioned it could not be excluded as a malignant lesion. The patient underwent left radical orchiectomy, the mass was diagnosed as an adenomatoid tumor of the tunica vaginalis by pathology. We review literature regarding adenomatoid tumors originating in the tunica vaginalis, summarize the ultrasonographic presentations, provide the idea of diagnosis and differential diagnosis to improve diagnostic accuracy and avoid unnecessary orchiectomy.

Deep learning has been widely used in various fields and showed promise in recent years. Therefore, deep learning is the future trend to realize seismic data’s intelligent and automatic interpretation. However, traditional deep learning only uses labeled data to train the model, and thus, does not utilize a large amount of unlabeled data. Self-supervised learning, widely used in Natural Language Processing (NLP) and computer vision, is an effective method of learning information from unlabeled data. Thus, a pretext task is designed with reference to Masked Autoencoders (MAE) to realize self-supervised pre-training of unlabeled seismic data. After pre-training, we fine-tune the model to the downstream task. Experiments show that the model can effectively extract information from unlabeled data through the pretext task, and the pre-trained model has better performance in downstream tasks.

Background: Acute kidney injury (AKI) is a frequent complication in patients with hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) and is associated with high rates of mortality. We aimed to estimate serum high mobility group protein 1 (HMGB1) levels in hepatitis B virus-related acute-on-chronic liver failure patients and analyze their clinical value in the development and outcomes of Acute kidney injury.Methods: A total of 251 consecutive patients with hepatitis B virus-related acute-on-chronic liver failure were enrolled in this retrospective study. Using the International Club of Ascites staging criteria of Acute kidney injury, 153 patients developed Acute kidney injury. The clinical data of patients were collected and serum levels of high mobility group protein 1 were measured by ELISA. All patients were followed up until death or for a minimum of 3 months. Early prediction and prognostic implications of high mobility group protein 1 in Hepatitis B Virus-Related Acute-on-Chronic Liver Failure Patients with Acute Kidney Injury were investigated in different cohorts, including a propensity score-matched ACLF cohort.Results: Among all individuals with hepatitis B virus-related acute-on-chronic liver failure, the incidence of Acute kidney injury was 61.0% (153/251). The patients who developed stage 2/3 Acute kidney injury showed the highest high mobility group protein 1 levels, followed by those who developed stage 1 Acute kidney injury, and those without Acute kidney injury showed the lowest high mobility group protein 1 levels. Moreover, high mobility group protein 1 levels were significantly higher in non-survivors than in survivors among hepatitis B virus-related acute-on-chronic liver failure patients with Acute kidney injury. Furthermore, analysis of the area under the receiver operating characteristic curve (AUROC) indicated that serum high mobility group protein 1 levels (pre-matching: AUC = 0.740; post-matching: AUC = 0.661) may be a potential predictive factor for Acute kidney injury development and that high mobility group protein 1 (AUC = 0.727) might be a reliable biomarker for prognosis in patients with Acute kidney injury.Conclusion: In patients with hepatitis B virus-related acute-on-chronic liver failure, Acute kidney injury is universal. Acute kidney injury and its stages negatively influence the 90-day transplant-free mortality rate. Serum high mobility group protein 1 levels can serve as a positive predictor of Acute kidney injury development, and high mobility group protein 1 might also be a prognostic biomarker for Acute kidney injury among hepatitis B virus-related acute-on-chronic liver failure patients.

The single largest contributor to human mortality is cardiovascular disease, the top risk factor for which is hypertension (HTN). The last two decades have placed much emphasis on the identification of genetic factors contributing to HTN. As a result, over 1,500 genetic alleles have been associated with human HTN. Mapping studies using genetic models of HTN have yielded hundreds of blood pressure (BP) loci but their individual effects on BP are minor, which limits opportunities to target them in the clinic. The value of collecting genome-wide association data is evident in ongoing research, which is beginning to utilize these data at individual-level genetic disparities combined with artificial intelligence (AI) strategies to develop a polygenic risk score (PRS) for the prediction of HTN. However, PRS alone may or may not be sufficient to account for the incidence and progression of HTN because genetics is responsible for

INTRODUCTION: The global economic development pattern is changing, international economic and trade rules are being questioned, the global economy is not optimistic in the post-epidemic era, and it is more difficult to find growth points. OBJECTIVES: How to achieve economic growth has become a more complex global issue. China, as the world's second largest economy and the world's second largest consumer market, is also a key issue to be addressed: how to promote a strong economic recovery and maintain a high level of public confidence in the state of our economy. The aviation industry chain plays a relatively good role in achieving supply stability as well as industry chain stability, and has a strong positive effect on the domestic and foreign double-cycle strategy. Shenzhen, as a window of China's opening up, has policies, resources and places to promote the development of aviation logistics industry. METHODS: Information is obtained through literature review and fieldwork. Through the history of the development of aviation industry, the history of aviation logistics development and the current situation of the construction of China's aviation logistics are deeply reviewed and sorted out. RESULTS: The specific path to be taken for the development of aviation industry, aviation logistics development and air express and related industries is explained. It also makes a long-term plan for the subsequent development of aviation industry, aviation logistics and air express development of Shenzhen airport, and analyzes the related objectives, and finally uses the relevant theoretical knowledge to make a relevant outlook on aviation industry, aviation logistics and aviation industry development, and summarizes the experience of aviation logistics company development. Combined with the construction of Shenzhen domestic airport, the relevant design concept is proposed. CONCLUSION: Through the analysis of different routes, we finally found that the air logistics business of Shenzhen airport should take the road of synergistic development. In this way, the air logistics of Shenzhen airport should be built around five implementation points and six guarantee points in order to achieve a high-quality development in line with the new era.

BackgroundThe accurate prediction of the outcome of hepatitis B virus-related acute-on-chronic liver failure (HBV-ACLF) is impeded by population heterogeneity. The study aimed to assess the impact of underlying cirrhosis on the performance of clinical prediction models (CPMs).MethodsUsing data from two multicenter, prospective cohorts of patients with HBV-ACLF, the discrimination, calibration, and clinical benefit were assessed for CPMs predicting 28-day and 90-day outcomes in patients with cirrhosis and those without, respectively.ResultsA total of 919 patients with HBV-ACLF were identified by Chinese Group on the Study of Severe Hepatitis B (COSSH) criteria, including 675 with cirrhosis and 244 without. COSSH-ACLF IIs, COSSH-ACLFs, Chronic Liver Failure-Consortium Acute-on-Chronic Liver Failure score (CLIF-C ACLFs), Tongji Prognostic Predictor Model score (TPPMs), Model for End-Stage Liver Disease score (MELDs), and MELD-Sodium score (MELD-Nas) were all strong predictors of short-term mortality in patients with HBV-ACLF. In contrast to a high model discriminative capacity in ACLF without cirrhosis, each prognostic model represents a marked decline of C-index, net reclassification index (NRI), and integrated discrimination improvement (IDI) in predicting either 28-day or 90-day prognosis of patients with cirrhosis. The hazard analysis identified largely overlapping risk factors of poor outcomes in both subgroups, while serum bilirubin was specifically associated with short-term mortality in patients with cirrhosis and blood urea nitrogen in patients without cirrhosis. A subgroup analysis in patients with cirrhosis showed a decline of discrimination of CPMS in those with ascites or infections compared to that in those without.ConclusionPredicting the short-term outcome of HBV-ACLF by CPMs is optimal in patients without cirrhosis but limited in those with cirrhosis, at least partially due to the complicated ascites or infections.

Background The gut and gut microbiota, which were previously neglected in blood pressure regulation, are becoming increasingly recognized as factors contributing to hypertension. Diseases affecting the gut such as inflammatory bowel disease (IBD) present with aberrant energy metabolism of colonic epithelium and gut dysbiosis, both of which are also mechanisms contributing to hypertension. We reasoned that current measures to remedy deficits in colonic energy metabolism and dysbiosis in IBD could also ameliorate hypertension. Among them, 5‐aminosalicylic acid (5‐ASA; mesalamine) is a PPARγ (peroxisome proliferator‐activated receptor gamma) agonist. It attenuates IBD by a dual mechanism of selectively enhancing colonic epithelial cell energy metabolism and ameliorating gut dysbiosis. Methods and Results A total of 2 groups of 11‐ to 12‐week‐old male, hypertensive, Dahl salt‐sensitive (S) rats were gavaged with (n=10) or without (n=10) 5‐aminosalicylic acid (150 mg/kg) for 4 weeks. Rats receiving 5‐aminosalicylic acid treatment had a lower mean blood pressure than controls (145±3 mm Hg versus 153±4 mm Hg; P

Background & Aims: Pre-acute-on-chronic liver failure (ACLF) is a distinct intermediate stage between acute decompensation (AD) and ACLF. However, identifying patients with pre-ACLF and predicting progression from AD to ACLF is difficult. This study aimed to identify pre-ACLF within 28 days, and to develop and validate a prediction model for ACLF in patients with HBV-related decompensated cirrhosis. Methods: In total, 1,736 patients with HBV-related cirrhosis and AD were enrolled from 2 large-scale, multicenter, prospective cohorts. ACLF occurrence within 28 days, readmission, and 3-month and 1-year outcomes were collected. Results: Among 970 patients with AD without ACLF in the derivation cohort, the 94 (9.6%) patients with pre-ACLF had the highest 3-month and 1-year LT-free mortality (61.6% and 70.9%, respectively), which was comparable to those with ACLF at enrollment (57.1% and 67.1%); the 251 (25.9%) patients with unstable decompensated cirrhosis had mortality rates of 22.4% and 32.1%, respectively; while the 507 (57.9%) patients with stable decompensated cirrhosis had the best outcomes (1-year mortality rate of 2.6%). Through Cox proportional hazard regression, specific precipitants, including hepatitis B flare with HBV reactivation, spontaneous hepatitis B flare with high viral load, superimposed infection on HBV, and bacterial infection, were identified to be significantly associated with ACLF occurrence in the derivation cohort. A model that incorporated precipitants, indicators of systemic inflammation and organ injuries reached a high C-index of 0.90 and 0.86 in derivation and validation cohorts, respectively. The optimal cut-off value (0.22) differentiated high-risk and low-risk patients, with a negative predictive value of 0.95. Conclusions: Three distinct clinical courses of patients with AD are validated in the HBV-etiology population. The precipitants significantly impact on AD-ACLF transition. A model developed by the precipitant–systemic inflammation–organ injury framework could be a useful tool for predicting ACLF occurrence. Clinical trial number: NCT02457637 and NCT03641872. Lay summary: It was previously shown that patients with decompensated cirrhosis could be stratified into 3 groups based on their short-term clinical prognoses. Herein, we showed that this stratification applies to patients who develop cirrhosis as a result of hepatitis B virus infection. We also developed a precipitant-based model (i.e. a model that incorporated information about the exact cause of decompensation) that could predict the likelihood of these patients developing a very severe liver disease called acute-on-chronic liver failure (or ACLF).

AIM: To investigate the expression of high mobility group A1(HMGA1)protein in uveal melanoma(UM)tissues, and the effect of inhibiting the expression of HMGA1 on cell proliferation and invasion. METHODS: A total of 53 cases(53 eyes)of UM patients who underwent surgical treatment in our hospital from February 2014 to August 2019 were selected. In the same period, 34 cases(34 eyes)of normal uveal tissues removed from the eye due to trauma were selected. The expression of HMGA1 protein in tissues was detected by immunohistochemistry. The human UM cell line M23 was cultured and divided into HMGA1 downregulation group, negative control group and blank group, respectively, transfected with HMGA1 interference sequence, negative control sequence and without any treatment. The expression of HMGA1 was detected by real-time quantitative PCR. The cell proliferation ability was detected by CCK-8 method, and the cell migration and invasion abilities were detected by Transwell method.RESULTS: The positive expression rate of HMGA1 protein in UM tissue was 77%, which was higher than that in the normal uveal tissue, which was 29%(P

Objective Lactobacilli in rabbit intestine is rare and its function in rabbit gut health is not fully understood. The present study aimed to evaluate in vivo the probiotic potential of Lactobacillus casei for suckling rabbits. Methods Two healthy 5-day-old suckling rabbits with similar weights from each of 12 New Zealand White litters were selected and disturbed to control group and treatment group. All rabbits were artificially fed. The treatment group had been supplemented with live Lactobacillus casei in the milk from the beginning of the trial to 13 days of age. At 15 days of age, healthy paired rabbits were slaughtered to collect intestinal samples. Results i) Oral administration of Lactobacillus casei significantly increased the proportion of Lactobacilli in the total intestinal bacteria (p

ObjectivesPrevious studies of the associations between white matter hyperintensities (WMH) and chronic kidney disease (CKD) were still conflicting; therefore, our study aimed to conduct a systematic review of all of the available research on this topic and a meta-analysis of the association between WMH and CKD among observational studies.Setting and DesignSystematic review and meta-analysis.Outcome MeasuresSeverity of WMH.Methods and ParticipantsAll relevant studies in public databases were examined until 15 November 2020. Two independent reviewers assessed all the included studies using the Cross-Sectional/Prevalence Study Quality (CSSQ) scale, and then literature review and meta-analyses were undertaken.ResultsWe pooled the odds ratio (OR) for the presence of WMH, periventricular hyperintensities (PVH), and deep subcortical white matter hyperintensities (DWMH) of patients with CKD vs. non-CKD patients by subgroup analysis, and the results obtained were WMH OR 2.07, 95% CI [1.58, 2.70], PVH OR 2.41, 95% CI [1.90, 3.05], and DWMH OR 2.11, 95% CI [1.60, 2.80], respectively. The main outcome showed that patients with CKD were more likely to have WMH in the brain compared to the normal controls. Another meta-analysis showed a statistically significant decline in renal function in patients with moderate to severe WMH compared with those with no to mild WMH.ConclusionsThe findings indicated that patients with CKD were more likely to experience WMH than demographically matched controls. On the other hand, patients with moderate to severe WMH in the brain had poor renal function more frequently than those with no to mild WMH.

To overcome the low accuracy, poor reliability, and delay in the current drought prediction models, we propose a new extreme learning machine (ELM) based on an improved variational mode decomposition (VMD). The model first redefines the output of the hidden layer of the ELM model with orthogonal triangular matrix decomposition (QR) to construct an orthogonal triangular ELM (QR-ELM), and then introduces an online sequence learning mechanism (OS) into the QR-ELM to construct an online sequence OR-ELM (OS-QR-ELM), which effectively improves the efficiency of the ELM model. The mutual information extension method was then used to extend both ends of the original signal to improve the VMD end effect. Finally, VMD and OS-QR-ELM were combined to construct a drought prediction method based on the VMD-OS-QR-ELM. The reliability and accuracy of the VMD-OS-QR-ELM model were improved by 86.19% and 93.20%, respectively, compared with those of the support vector regression model combined with empirical mode decomposition. Furthermore, the calculation efficiency of the OS-QR-ELM model was increased by 88.65% and 85.32% compared with that of the ELM and QR-ELM models, respectively.

The Caenorhabditis elegans spe-38 gene encodes a four-pass transmembrane molecule that is required in sperm for fertilization. In previous work, the localization of the SPE-38 protein was examined using polyclonal antibodies on spermatids and mature amoeboid spermatozoa. SPE-38 is localized to unfused membranous organelles (MOs) in nonmotile spermatids. Different fixation conditions revealed that SPE-38 either localized to fused MOs and the cell body plasma membrane or the pseudopod plasma membrane of mature sperm. To address this localization paradox in mature sperm, CRISPR/Cas9 genome editing was used to tag endogenous SPE-38 with fluorescent wrmScarlet-I. Homozygous male and hermaphrodite worms encoding SPE-38::wrmScarlet-I were fertile indicating the fluorescent tag does not interfere with SPE-38 function during sperm activation or fertilization. We found that SPE-38::wrmScarlet-I localized to MOs in spermatids consistent with previous antibody localization. In mature and motile spermatozoa we found SPE-38::wrmScarlet-I in fused MOs, the cell body plasma membrane, and the pseudopod plasma membrane. We conclude that the localization pattern observed with SPE-38::wrmScarlet-I represents the complete distribution of SPE-38 in mature spermatozoa and this localization pattern is consistent with a hypothesized role of SPE-38 directly in sperm-egg binding and/or fusion.

Acute-on-chronic liver failure (ACLF) is defined as a syndrome of acutely decompensated cirrhosis in patients with chronic liver disease (CLD). Here we report an ACLF case caused by a flare of occult hepatitis C infection. This patient was infected with hepatitis C virus (HCV) more than a decade ago and hospitalized due to alcohol-associated CLD. Upon admission, the HCV RNA in the serum was negative and the anti-HCV antibody was positive, whereas the viral RNA in the plasma dramatically increased during hospitalization, which suggests an occult hepatitis C infection. Overlapped fragments encompassing the nearly whole HCV viral genome were amplified, cloned, and sequenced. Phylogenetic analysis indicated an HCV genotype 3b strain. Sanger sequencing to 10-fold coverage of the 9.4-kb nearly whole genome reveals high diversity of viral quasispecies, an indicator of chronic infection. Inherent resistance-associated substitutions (RASs) in the NS3 and NS5A but not in the NS5B regions were identified. The patient developed liver failure and accepted liver transplantation, followed by direct-acting antiviral (DAA) treatment. The hepatitis C was cured by the DAA treatment despite the existence of RASs. Thus, care should be taken for occult hepatitis C in patients with alcoholic cirrhosis. The analysis of viral genetic diversity may help to identify an occult hepatitis C virus infection and predict the efficacy of anti-viral treatment.

Background and aims: Hepatitis B virus-associated acute-on-chronic liver failure (HBV-ACLF) is a complicated syndrome with extremely high short-term mortality. Whether plasma exchange (PE) improves HBV-ACLF outcomes remains controversial. Here, PE-based non-bioartificial liver support system (NB-ALSS) effects on short-term HBV-ACLF patient outcomes were investigated.Materials and methods: HBV-ACLF patients from Chinese Acute-on-chronic Liver Failure (CATCH-LIFE) cohort receiving standard medical therapy (SMT) alone or PE-based NB-ALSS in addition to SMT were allocated to SMT and SMT+PE groups, respectively; propensity score matching (PSM) was used to eliminate confounding bias. Short-term (28/90-day and 1-year) survival rates were calculated (Kaplan-Meier).Results: In total, 524 patients with HBV-ACLF were enrolled in this study; 358 received SMT alone (SMT group), and the remaining 166 received PE-based NB-ALSS in addition to SMT (SMT+PE group). PSM generated 166 pairs of cases. In the SMT+PE group, 28-day, 90-day, and 1-year survival rates were 11.90, 8.00, and 10.90%, respectively, higher than those in the SMT group. Subgroup analysis revealed that PE-based NB-ALSS had the best efficacy in patients with ACLF grade 2 or MELD scores of 30–40 (MELD grade 3). In MELD grade 3 patients who received SMT+PE, 28-day, 90-day, and 1-year survival rates were improved by 18.60, 14.20, and 20.10%, respectively. According to multivariate Cox regression analysis, PE-based NB-ALSS was the only independent protective factor for HBV-ACLF patient prognosis at 28 days, 90 days, and 1 year (28 days, HR = 0.516, p = 0.001; 90 days, HR = 0.663, p = 0.010; 1 year, HR = 0.610, p = 0.051). For those who received SMT+PE therapy, PE-based NB-ALSS therapy frequency was the only independent protective factor for short-term prognosis (28-day, HR = 0.597, p = 0.001; 90-day, HR = 0.772, p = 0.018).Conclusions: This multicenter prospective study showed that the addition of PE-based NB-ALSS to SMT improves short-term (28/90 days and 1-year) outcomes in patients with HBV-ACLF, especially in MELD grade 3 patients. Optimization of PE-based NB-ALSS may improve prognosis or even save lives among HBV-ACLF patients.

Background and Objective: An increase in the international normalized ratio (INR) is associated with increased mortality in patients with cirrhosis and other chronic liver diseases, while little is known about the quantitative relationship. This study aimed to investigate the quantitative relationship between the INR and short-term prognosis among patients hospitalized with cirrhosis or advanced fibrosis and to evaluate the role of the INR as a risk factor for short-term liver transplant (LT)-free mortality in these patients.Patients and Methods: This study prospectively analyzed multicenter cohorts established by the Chinese Acute-on-Chronic Liver Failure (CATCH-LIFE) study. Cox regression was used to describe the relationship between the INR and independent risk factors for short-term LT-free mortality. Forest plots were used in the subgroup analysis. Generalized additive models (GAMs) and splines were used to illustrate the quantitative curve relationship between the INR and the outcome and inflection point on the curve.Results: A total of 2,567 patients with cirrhosis and 924 patients with advanced fibrosis were included in the study. The 90-day LT-free mortality of patients with cirrhosis and advanced fibrosis was 16.7% (428/2,567) and 7.5% (69/924), respectively. In the multivariable Cox regression analysis, the increase in the INR was independently associated with the risk of 90-day LT-free mortality both in patients with cirrhosis (HR, 1.06; 95% CI, 1.04–1.07, p < 0.001) and in patients with advanced fibrosis (HR, 1.09; 95% CI, 1.06–1.12, p < 0.001). An INR of 1.6/1.7 was found to be the starting point of coagulation dysfunction with a rapid increase in mortality in patients with cirrhosis or in patients with advanced fibrosis, respectively. A 28-day LT-free mortality of 15% was associated with an INR value of 2.1 in both cirrhosis and advanced fibrosis patients.Conclusions: This study was the first to quantitatively describe the relationship between the INR and short-term LT-free mortality in patients with cirrhosis or advanced fibrosis. The starting points of INR indicating the rapid increase in mortality and the unified cutoff value of coagulation failure in cirrhosis and advanced fibrosis, will help clinicians accurately recognize early disease deterioration.