Search

An ageing population coupled with an increase in morbidity places a considerable burden on health and social care systems. The aim of our study was to estimate the trends in functional dependency and project future care needs for older people in China.We analysed data from the China Health and Retirement Longitudinal Study, a nationally representative survey of a cohort of Chinese people (aged ≥45 years) from 150 counties or districts and 450 villages or urban communities across 28 provinces, who were selected by use of multistage stratified probability-proportionate-to-size sampling. The baseline survey was conducted in 2011 and follow-up surveys were conducted in 2013, 2015, 2018, and 2020. We excluded people younger than 60 years or people who had missing variables on dependency in the five follow-up interviews. Three dependency levels were determined on the basis of activities of daily living (ADLs) and instrumental activities of daily living (IADLs): any ADL items (level 1 dependency); any ADL items or difficulty cooking, shopping, or taking medications (level 2 dependency); and difficulty in any ADL or IADL items (level 3 dependency). The dependency rates were extrapolated to derive the number of people older than 60 years with dependency in China from 2011 to 2020. We used a regression model to project future changes and forecast the size of the older population with dependency between 2021 and 2030.A total of 89 031 individuals across five waves completed the surveys, of whom 46 619 were eligible for inclusion. The prevalence of level 1 dependency among older Chinese adults declined from 11·7% (95% CI 10·6-12·8) in 2011 to 8·1% (7·5-8·7) in 2020. Level 2 and level 3 dependency also declined. The total number of older people requiring care in 2020 was 20·61 million (95% CI 19·01-22·20) with level 1 dependency, 36·33 million (34·27-38·40) with level 2 dependency, and 45·30 million (43·02-47·59) with level 3 dependency. Improved education, housing, and access to health care was associated with 41·84% of the decline in level 3 dependency prevalence between 2011 and 2020. By 2030, the projected dependency rates could decline to 8·04% for level 1 dependency, 13·28% for level 2 dependency, and 16·05% for level 3 dependency. Nonetheless, the cohort size will grow, resulting in more older Chinese people who need care (29·71 million [27·07-32·36] in level 1, 49·07 million [45·98-52·16] in level 2, and 59·32 million [55·94-62·70] in level 3) in 2030. By 2030, we estimate that 14·02 million more older Chinese people will need care than in 2020.Rapid ageing of the population could offset the decline in dependency and result in a substantial increase in the population with complex care needs. Promoting healthy ageing and investing in an age-friendly environment are important in reducing care burdens in China.National Institute on Aging, Natural Science Foundation of China, China Medical Board.For the Chinese translation of the abstract see Supplementary Materials section.

Background:Nuezhenide (NZD), an iridoid glycoside isolated from Ilex pubescens Hook. & Arn. var. kwangsiensis Hand.-Mazz., used as a traditional Chinese medicine for clearing Hook. & Arn. var. kwangsiensis Hand.-Mazz., used as a traditional Chinese medicine for clearing away heat and toxic materials, displays a variety of biological activities such as anti-tumor, antioxidant, and other life-protecting activities. However, a few studies involving anti-inflammatory activity and the mechanism of NZD have also been reported. In the present study, the anti-inflammatory and antioxidative effects of NZD are illustrated.Objective:This study aims to test the hypothesis that NZD suppresses LPS-induced inflammation by targeting the NF-κB pathway in RAW264.7 cells.Methods:LPS-stimulated RAW264.7 cells were employed to detect the effect of NZD on the release of cytokines by ELISA. Protein expression levels of related molecular markers were quantitated by western blot analysis. The levels of ROS, NO, and Ca2+were detected by flow cytometry. The changes in mitochondrial reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were observed and verified by fluorescence microscopy. Using immunofluorescence assay, the translocation of NF-κB/p65 from the cytoplasm into the nucleus was determined by confocal microscopy.Results:NZD exhibited anti-inflammatory activity and reduced the release of inflammatory cytokines such as nitrite, TNF-α, and IL-6. NZD suppressed the expression of the phosphorylated proteins like IKKα/β, IκBα, and p65. Besides, the flow cytometry results indicated that NZD inhibited the levels of ROS, NO, and Ca2+in LPS-stimulated RAW264.7 cells. JC-1 assay data showed that NZD reversed LPS-induced MMP loss. Furthermore, NZD suppressed LPS-induced NF-B/p65 translocation from the cytoplasm into the nucleus.Conclusions:NZD exhibits anti-inflammatory effects through the NF-κB pathway on RAW264.7 cells.

Mycoplasma pneumoniae, an obligate parasitic pathogen without cell wall, can cause severe upper and lower respiratory tract symptoms. It is the pathogen of human bronchitis and walking pneumonia, and named community-acquired pneumonia. In addition to severe respiratory symptoms, there are clinical extrapulmonary manifestations in the skin, brain, kidney, musculoskeletal, digestive system, and even blood system after M. pneumoniae infection. Hereby, we comprehensively summarized and reviewed the intrapulmonary and extrapulmonary pathogenesis of M. pneumoniae infection. The pathogenesis of related respiratory symptoms caused by M. pneumoniae is mainly adhesion damage, direct damage including nutrient predation, invasion and toxin, cytokine induced inflammation damage and immune evasion effect. The pathogenesis of extrapulmonary manifestations includes direct damage mediated by invasion and inflammatory factors, indirect damage caused by host immune response, and vascular occlusion. The intrapulmonary and extrapulmonary pathogenic mechanisms of M. pneumoniae infection are independent and interrelated, and have certain commonalities. In fact, the pathogenic mechanisms of M. pneumoniae are complicated, and the specific content is still not completely clear, further researches are necessary for determining the detailed pathogenesis of M. pneumoniae. This review can provide certain guidance for the effective prevention and treatment of M. pneumoniae infection.

Physicochemical details at the interphase of protein aggregation have been less explored especially in live cells. Herein, we reported a crystallization induced emission fluorophore to quantitatively interrogate the polarity of aggregated proteins. This solvatochromic probe, namely "AggRetina" probe, inherently binds to aggregated proteins and exhibits both polarity-dependent fluorescence emission wavelength shift and viscosity-dependent fluorescence intensity increase. Regulation of its polarity sensitivity was achieved by extending the conjugation length. Empowered by this probe, we observed that different proteins bear diverse polarity upon aggregation, leading to different resistance to proteolysis. We further showed that polarity primarily decreases during protein misfolding but viscosity mainly increases upon the formation of insoluble aggregates. Finally, we quantified the polarity of aggregated protein-of-interest in live cells via HaloTag bioorthogonal labeling, revealing polarity heterogeneity within cellular aggregates. This work highlights the enriched micro-environment details inside misfolded and aggregated proteins that may correlate to their bio-chemical properties and pathogenicity.

The coronavirus disease 2019 (COVID-19) has adversely influenced human physical and mental health, including emotional disorders and addictions. This study examined substance and Internet use behavior and their associations with anxiety and depression during the COVID-19 pandemic. An online self-report questionnaire was administered to 2196 Chinese adults between February 17 and 29, 2020. The questionnaire contained the seven-item Generalized Anxiety Disorder Scale (GAD-7) and Patient Health Questionnaire (PHQ-9), questions on demographic information, and items about substance and Internet use characteristics. Our results revealed that males consumed less alcohol (p p = 0.012) during the pandemic than before the pandemic. Age, gender, education status, and occupation significantly differed among increased substance users, regular substance users, and nonsubstance users. Time spent on the Internet was significantly longer during the pandemic (p p p p p p = 0.017), nonstudents (OR = 1.946–3.030, p = 0.001), and increased substance use (OR = 4.291, p

Myeloid-derived suppressor cells (MDSCs) are key players under various pathologic conditions, such as cancer. Epigenetic modifications such as DNA methylation, RNA-mediated processes, and histone modification can alter gene transcription, and thus regulating pathological process. Studies have shown that epigenetic modification contributes to the accumulation and function of MDSCs. This review summarizes the crosstalk between the epigenetic alterations and MDSCs functions, and briefly introduces how the accumulation and function of MDSCs caused by epigenetic modification impact on the disease development, which represents as a promising therapeutic strategy for the related disorders.

Berberine (BBR), an alkaloid produced by a traditional Chinese plant, was recently attributed multiple effects on lipometabolism, inflammation, and fibrosis. Thyroid-associated ophthalmopathy (TAO) is highly associated with these pathologic changes. Thus, we aimed to examine the potential therapeutic effect of BBR in an in vitro model of TAO.Orbital fibroblasts (OFs) obtained from control donors (n = 6) or patients with TAO (n = 6) were cultured. The CCK-8 assay was conducted for assessing the optimal concentration range. Oil Red O staining, Western blotting, and quantitative RT-PCR (qRT-PCR) were conducted to assess adipogenesis in OFs. RNA sequencing (RNA-seq) was used to screen the key pathways of the antiadipogenic effect mediated by BBR. Along with incremental concentrations of BBR, IL-1β-induced expression of proinflammatory molecules was determined by ELISA and qRT-PCR. In addition, TGF-β-induced hyaluronan (HA) production and fibrosis were evaluated by ELISA, qRT-PCR, and Western blotting.TAO-OFs, but not control fibroblasts (CON-OFs), were readily differentiated into adipocytes with the commercial medium. Intracellular lipid accumulation was dose-dependently decreased by BBR, and adipogenic markers were also downregulated. Moreover, the PPARγ and AMPK pathways were screened out by RNA-seq and their downstream effectors were suppressed by BBR. Besides, BBR attenuated IL-1β-induced expression of proinflammatory molecules in both TAO-OFs and CON-OFs by blocking nuclear factor-κB signaling. BBR's inhibitory effect on TGF-β-mediated tissue remodeling was also confirmed in OFs.These findings demonstrate BBR has outstanding capabilities of controlling adipogenesis, inflammation, HA production, and fibrosis in OFs, highlighting its potential therapeutic role in TAO management.

Thyroid-associated ophthalmopathy is a typical autoimmune disease of orbital tissues. Alternative splicing significantly influences many diseases progression, including cancer, age-related macular degeneration, and multiple sclerosis, by modulating the expression of transcripts. However, its role in thyroid-associated ophthalmopathy is still unclear. In this study, differential expression transcripts and differential alternative splicing genes in orbital adipose/connective tissues of thyroid-associated ophthalmopathy patients were detected using RNA sequencing, Cuffdiff, and replicate multivariate analysis of transcript splicing. Three thousand ninety six differential expression transcripts and 2355 differential alternative splicing genes were screened out, while functional enrichment analysis indicated that differential expression transcript and differential alternative splicing genes were associated with immune modulation, extracellular matrix remodeling, and adipogenesis. The expression of the SORBS1, SEPT2, COL12A1, and VCAN gene transcripts was verified by qRT-PCR. In conclusion, prevalent alternative splicing is involved in the disease development in thyroid-associated ophthalmopathy. More attention should be paid to the mechanism of alternative splicing to explore more potential therapeutic targets in thyroid-associated ophthalmopathy.

Interleukin (IL)-17 and its related cytokines have been shown to be involved in myocardial fibrosis and irreversible ventricular remodelling, which have predictive values in the development of left ventricular diastolic dysfunction (LVDD). This study aimed to assess the correlation between IL-17 and LVDD, and investigate the prognostic value of IL-17 among patients with normal left ventricular ejection fraction (LVEF).A total of 120 patients with normal LVEF underwent left ventricular (LV) catheterisation for LV end-diastolic pressure (LVEDP) measurement and routine echocardiography. The follow-up period was 30 (18, 35) months.The levels of IL-17 and IL-6 from the systemic blood were significantly increased in non-heart failure (HF) patients with LVDD (p0.001). Receiver operating characteristic (ROC) revealed that the combination of IL-17 and IL-6 showed the highest diagnostic accuracy in predicting LVDD (AUC, 0.890; 95% CI, 0.835-0.945; p0.001), and the cut-off value was 41.5 pg/mL. On logistic regression analysis, the increment of the combination of IL-17 and IL-6 was an independent predictor for the prognosis of LVDD (odds ratio, 1.25; 95% CI, 1.01-1.12; p0.05). According to the cut-off value of the combination of IL-17 and IL-6, the patients with lower levels of IL-17 and IL-6 (41.5 pg/mL group) had a better prognosis. The increased levels of IL17 and IL-6 were significantly correlated with the levels of fibrotic parameters.Assessment of LVDD by measuring the combination of IL-17 and IL-6 might provide valuable prognostic significance for non-HF patients with LVDD.

Cardiovascular diseases (CVDs) and cancer, which are the leading causes of mortality globally, have been viewed as two distinct diseases. However, the fact that cancer and CVDs may coincide has been noted by cardiologists when taking care of patients with CVDs caused by cancer chemotherapy; this entity is designated cardio-oncology. More recently, patients with CVDs have also been found to have increased risk of cancers, termed reverse cardio-oncology. Although reverse cardio-oncology has been highlighted as an important disease state in recent studies, how the diseased heart affects cancer and the potential mediators of the crosstalk between CVDs and cancer are largely unknown. Here, we focus on the roles of cardiac-specific microRNA-208a (miR-208a) in cardiac and cancer biology and explore its essential roles in reverse cardio-oncology. Accumulating evidence has shown that within the heart, increased miR-208a promotes myocardial injury, arrhythmia, cardiac remodeling, and dysfunction and that secreted miR-208a in the circulation may have novel roles in promoting tumor proliferation and invasion. This review, therefore, provides insights into the novel roles of miR-208a in reverse cardio-oncology and strategies to prevent secondary carcinogenesis in patients with early- or late-stage heart failure.

Long non‑coding RNAs play a role in a variety of malignancies, such as thyroid cancer (TC). However, the effects and function of lincRNA HOTAIRM1 (LINC HOTAIRM1) in TC remains obscure. In the present study, the expression of HOTAIRM1 was evaluated in TC tissues and cells by RT‑qPCR and the association between the lncRNA and disease progression was assessed. In vitro, the biological function of HOTAIRM1 was assessed in TC. Moreover, changes in the expression of Wnt10b were measured by western blot analysis. In addition, MTT assay, bioinformatics analysis and luciferase assays were performed to determine the target binding effect between LINC HOTAIRM1 and miR‑148a, as well as that between Wnt10b and miR‑148a. The changes in the metastatic ability of TPC‑1 and BCPAP cells were evaluated by Transwell assay. The pronounced upregulated expression of HOTAIRM1 was evident in TC cells and tissues, and was associated with TNM stage and lymph node metastasis. When HOTAIRM1 was knocked down, this inhibited the proliferative and invasive abilities of TPC‑1 and BCPAP cells in vitro. The knockdown of this lncRNA also increased the expression of microRNA‑148a (miR‑148a) and decreased Wnt10b expression in these cells, whereas transfection with miR‑148a inhibitor was sufficient to overcome this Wnt10b downregulation. In line with these results, the overexpression of miR‑148a markedly suppressed Wnt10b expression, whereas miR‑148a inhibition resulted in the opposite effects. The overexpression of Wnt10b was also sufficient to overcome the effects of miR‑148a mimics on TPC‑1 and BCPAP cells. Taken together, these results suggest that miR‑148a and Wnt10b are downstream effectors of the HOTAIRM1 signaling pathway in TC. This HOTAIRM1/miR‑148a/Wnt10 axis may thus be amenable to therapeutic targeting in order to improve disease outcomes in patients with TC.

Graves’ disease (GD) is characterized by dysregulation of the immune system with aberrant immune cell function. However, there have been few previous studies on the role of monocytes in the pathology of GD. The object of this study was to investigate whether and how monocytes participate in GD pathology. CD14+ monocytes were isolated from untreated initial GD patients and healthy controls. Then, RNA-seq was performed to investigate changes in global mRNA expression in monocytes and found that type I interferon (IFN) signalling was among the top upregulated signalling pathways in GD monocytes. Type I IFN-induced sialic acid-binding immunoglobulin-like lectin1 (SIGLEC1) expression was significantly upregulated in untreated GD patients and correlated with thyroid parameters. Patient serum SIGLEC1 concentrations were reduced after anti-thyroid drug treatment. Inhibiting SIGLEC1 expression could inhibit proinflammatory cytokine (IL-1β, IL-6, IL-8, IL-10 and M-CSF) expression in monocytes. In conclusion, our study suggested that type I IFN-mediated monocyte activation could have a deleterious effect on the pathogenesis of GD. These observations indicated that the inhibition of type I IFN-activated monocytes/macrophages could have a therapeutic effect on GD remission.

Despite the growing research interest in gaming disorder, risk screening tools developed specifically for the Chinese population are still lacking. This study aimed to construct a screening tool to evaluate the risk of gaming disorder (GD) development, by assessing the severity of GD symptoms among Chinese gamers, based on clinical expert interviews, structured interviews with GD patients, a background literature review, and IGD/GD criteria proposed by the DSM-5 and ICD-11. It introduced the Gaming Hazard Assessment Scale—a multidimensional GD risk screening tool—and evaluated the dimension structure, reliability, and validity of the scale among 959 Chinese gamers. A three-level structure, consisting of 18 items scored from 0 to 54, ultimately indicated satisfactory reliability, good validity, and acceptable model fit. The scale will help large-scale initial screening and early identification of patients with a high risk of GD. Further evaluation of the Gaming Hazard Assessment Scale in clinical settings is highly recommended.

Background and objectives The clinical and pathological impact factors for renal function recovery in acute kidney injury (AKI) on the progression of renal function in primary membranous nephropathy (PMN) with AKI patients have not yet been reported, we sought to investigate the factors that may influence renal function recovery and develop a nomogram model for predicting renal function recovery in PMN with AKI patients. Methods Two PMN with AKI cohorts from the Nephrology Department, the First Affiliated Hospital of Wenzhou Medical University during 2012–2018 and 2019–2020 were included, i.e., a derivation cohort during 2012–2018 and a validation cohort during 2019–2020. Clinical characteristics and renal pathological features were obtained. The outcome measurement was the recovery of renal function within 12 months. Lasso regression was used for clinical and pathological features selection. Prediction model was built and nomogram was plotted. Model evaluations including calibration curves were performed. Result Renal function recovery was found in 72 of 124 (58.1%) patients and 41 of 72 (56.9%) patients in the derivation and validation cohorts, respectively. The prognostic nomogram model included determinants of sex, age, the comorbidity of hypertensive nephropathy, the stage of glomerular basement membrane and diuretic treatment with a reasonable concordance index of 0.773 (95%CI,0.716–0.830) in the derivation cohort and 0.773 (95%CI, 0.693–0.853) in the validation cohort. Diuretic use was a significant impact factor with decrease of renal function recovery in PMN with AKI patients. Conclusion The predictive nomogram model provides useful prognostic tool for renal function recovery in PMN patients with AKI.

Objective Maintaining a low-protein diet (LPD) is important for patients with chronic kidney disease (CKD) to delay renal degradation and alleviate clinical symptoms. For most patients with CKD, it is difficult to maintain the necessary low level of dietary protein intake (DPI). To improve the current dietary management of CKD, we conducted an intervention study by administering low-protein staple foods (LPSF). Design and methods We conducted a prospective case-crossover study among 25 patients with stage 3–4 CKD. During the initial 12 weeks of the study, we instructed the patients regarding a standard LPD according to the recommendations of a renal dietitian. In the second stage of the study, we requested the patients taking low-protein rice or low-protein flour (250 g/d) as an LPSF diet instead of regular staple food daily, and followed these patients up for 12 weeks. We compared the DPI, dietary energy intake (DEI), normalized protein equivalent of total nitrogen appearance (nPNA), serum creatinine levels, and nutritional index between baseline and the end of the study. Results We found no change in dietary variables among the patients during the first 12 weeks of the LPD. After subjecting them to an LPSF diet, the corresponding variables showed a pronounced change. The patients’ DPI decreased from 0.88 ± 0.20 to 0.68 ± 0.14 g/kg/d (P P P Conclusion Our prospective case-crossover study demonstrated that an LPSF diet can help patients with stage 3–4 CKD reduce DPI and nPNA values, improve the proportion of highly bioavailable proteins, ensure adequate calorie intake, and avoid malnutrition. An LPSF diet is an effective and simple therapy for patients with stage 3–4 CKD.

Summary Background & aims Previous studies on the association between skipping breakfast and risk of cardiovascular disease and all cause mortality have drawn controversial conclusions. Therefore, we carried out a meta-analysis to illuminate this association. Methods Studies about the association between skipping breakfast and risk of cardiovascular disease and all cause mortality were identified by searching Pubmed, Embase, Cochrane, and Web of Science databases until June 2019. Then we screened articles for eligibility, extracted data, and pooled the results using a random-effects model. Results Seven cohort studies concerning a total of 221,732 participants were included in this meta-analysis. Skipping breakfast was associated with elevated risk of cardiovascular disease (relative risk 1.22 95% confidence interval 1.10–1.35) and all cause mortality (relative risk 1.25 95% confidence interval 1.11–1.40) compared with eating breakfast regularly. Conclusion Skipping breakfast increases the risk of cardiovascular disease and all cause mortality. Eating breakfast regularly may promote cardiovascular health and decrease all cause mortality.

BACKGROUND Nutrition therapies in children with congenital heart disease (CHD) after cardiopulmonary bypass (CPB) is crucial, but energy and protein requirements remain undefined. We assessed energy and protein requirements, with nitrogen kinetics and clinical outcomes, in infants with complex CHD following CPB. METHODS Infants were randomized to control (1.3 g/kg/d), moderate protein (MP, 2.5 g/kg/d), or high protein (HP, 4 g/kg/d) groups. Resting energy expenditure (REE) was measured 6 hours post-CPB and then at 24-hour intervals, using indirect calorimetry to formulate energy intakes. Enteral formula feeding was initiated 6 hours post-CPB and continued for 5 days. Nitrogen balance (NB); urea nitrogen waste and nitrogen retention; serum prealbumin level; and hepatic, renal, and cardiac function were measured daily. Mid-upper arm circumference and triceps skinfold were measured preoperatively and 5 days after CPB. Adverse outcomes (bacterial infection, reintubation, and cardiac intensive care unit (CICU) stay > 8 days) were recorded. RESULTS REE was not different across the 3 groups (P = .37). It declined from 62 ± 6 to 57 ± 7 kcal/kg/d over 5 days post-CPB (P = .02). NB and nitrogen retention became positive by day 3 in the HP group but remained negative in the other 2 groups (P = .045-.003), despite higher urea nitrogen waste in the HP group (P < .0001). The HP group had a greater increase in serum prealbumin level and anthropometric measures (P = .009-.03). Other measures were not significantly different across the 3 groups. CONCLUSIONS In infants with complex CHD in the first 5 days post-CPB, protein and energy intakes of ≈4 g/kg/d and 60 kcal/kg/d, respectively, led to improved nutrition outcomes without increased adverse events.

Necrosis with inflammation plays a crucial role in acute respiratory distress syndrome (ARDS). Receptor-interacting protein 3 (RIPK3) regulates a newly discovered programmed form of necrosis called necroptosis. However, the underlying mechanism of necroptosis in ARDS remains unknown. Thus, the purpose of this study was to examine the possible involvement of RIPK3 in ARDS-associated necroptosis. RIPK3 protein levels were found to be significantly elevated in the plasma and bronchoalveolar lavage fluid of ARDS patients. Next, we utilised a mouse model of severe ARDS induced with high-dose lipopolysaccharide and found that lung injury was mainly due to RIPK3-mixed lineage kinase domain-like pseudokinase (MLKL)-mediated necroptosis and endothelial dysfunction. The activation of RIPK3-MLKL by tumour necrosis factor receptor 1 (TNFR1) and TNFR1-associated death domain protein (TRADD) required catalytically active RIPK1 and the inhibition of Fas-associated protein with death domain (FADD)/caspase-8 catalytic activity. We further showed that the molecular chaperone heat shock protein 90 (Hsp90)/p23, as a novel RIPK3- and MLKL-interacting complex, played an important role in RIP-MLKL-mediated necroptosis, inflammation and endothelial dysfunction in the pulmonary vasculature, which resulted in ARDS. Collectively, the results of our study indicate that necroptosis is an important mechanism of cell death in ARDS and the inhibition of necroptosis may be a therapeutic intervention for ARDS. KEY MESSAGES: Lung injury in high-dose LPS-induced severe ARDS is mainly due to RIP3-MLKL-mediated necroptosis and endothelial dysfunction. Chaperone HSP90/p23 is a novel RIP3- and MLKL-interacting complex in HPAECs. HSP90/p23 is a novel RIP3- and MLKL-interacting complex in RIP-MLKL-mediated necroptosis, inflammation and endothelial dysfunction.

IgG4-related disease (IgG4-RD) affects multiple organs and is characterized by immune-mediated inflammation and fibrosis; IgG-RD affecting orbital tissue is known as IgG4-related ophthalmic disease (IgG4-ROD). This research is aimed at exploring whether symptom duration and common serologic factors, such as IgG, IgE, and eosinophils, are potential risk factors for IgG4-ROD patient relapse after surgery and identifying possible causes of the positive correlation between symptom duration and relapse. This retrospective cohort study included 40 IgG4-ROD patients after surgery. Auxiliary inspection results were obtained before surgery and during follow-up, and relapse risk factors were identified based on previous studies. We used the Spearman rank correlation test to reveal the relationship between symptom duration and relapse time and identified the optimal cutoff value for symptom duration by X-tile. Then, we divided the patients into the long-duration and short-duration groups. Kaplan–Meier survival analyses and log-rank tests were performed to identify the relationship between symptom duration and relapse using X-tile software. Finally, we studied the relationship between previously studied relapse risk factors and symptom duration. The survival curves of the long-duration and short-duration groups were obviously different, and the baseline serum IgG, IgE, and eosinophil levels and asthma concomitant rate were significantly different between the long-duration and short-duration groups. Furthermore, the baseline serum IgG ( r = 0.485 , P = 0.002 ), IgE ( r = 0.350 , P = 0.037 ), and eosinophil ( r = 0.6535 , P < 0.0001 ) levels were positively correlated with symptom duration. Our study shows that IgG4-ROD symptom duration is significantly positively correlated with relapse rate and negatively correlated with relapse time. Symptom duration was positively correlated with serum baseline IgG4, IgE, and eosinophil levels and asthma history, which were potential risk factors for disease relapse. We recommended that IgG4-ROD patients with symptom durations greater than 96 months continue to receive maintenance steroid therapy longer than 1 year postsurgery to reduce the relapse rate.

Severe pneumonia related to human adenoviruses (HAdVs) has a high lethality rate in children and its early diagnosis and treatment remain a major challenge. Circular RNAs (circRNAs) are novel long noncoding RNAs that play important roles in gene regulation and disease pathogenesis. To investigate the roles of circRNAs in HAdV pneumonia, we analyzed the circRNA profiles of healthy children and children with HAdV pneumonia, including both mild and severe cases, and identified 139 significantly upregulated circRNAs in children with HAdV pneumonia vs healthy controls and 18 significantly upregulated circRNAs in children with severe HAdV pneumonia vs mild HAdV pneumonia. In particular, hsa_circ_0002171 was differentially expressed in both groups and might thus be useful as a diagnostic biomarker of HAdV pneumonia and severe HAdV pneumonia. To identify the underlying mechanisms of circRNAs in HAdV pneumonia, we analyzed the transcriptome of children with HAdV pneumonia and established a circRNA-mRNA regulatory network. Enrichment analysis of differentially expressed target mRNAs demonstrated that the differentially expressed genes between healthy controls and HAdV pneumonia patients were mainly involved in RNA splicing while the differentially expressed genes between children with mild and severe HAdV pneumonia were mainly involved in regulating lymphocyte activation. Receiver operating characteristic (ROC) curve analysis suggested that hsa_circ_0002171 had a significant value in the diagnosis of HAdV pneumonia and of severe HAdV pneumonia. Taken together, the circRNA expression profile was altered in children with HAdV pneumonia. These results demonstrated that hsa_circ_0002171 is a potential diagnostic biomarker of HAdV pneumonia.

Background and aims Asian countries are deemed to be high prevalence areas for gaming disorder (GD). This meta-analysis is the first to synthesize the overall prevalence of GD in East Asia and investigate characteristics that influence prevalence estimates. Methods Systematic and independent searches were conducted across PubMed, Web of Science, Embase, PsycINFO, and the Cochrane Library since their inception to January 27, 2021. The Agency for Healthcare Research and Quality scale was used for quality assessment. A random effect model was used to calculate the overall GD prevalence and 95% confidence intervals (CIs). Results In total, 22 articles (26 studies) comprising 51,525 participants were included in this meta-analysis. The overall pooled prevalence of GD in East Asia was 12%, 95% CI (10%–15%); this figure was adjusted to 6%, 95% CI (3%–9%) for a representative sample. Higher prevalence was observed in males than in females (16% vs. 8%, respectively, P < 0.05). Subgroup and meta-regression analyses revealed that studies among gamers or those without random sampling reported significantly higher prevalence rates. There were no significant differences between countries/regions, sample size, quality score, proportion of males, and scale used. Discussion and conclusions The prevalence of GD in East Asia is higher than that in other world regions. Future studies should extend such epidemiological research to other regions to calculate the accurate prevalence of GD to benefit the local identification, prevention, policy formulation, and treatment efforts. Considering its negative effects, effective preventive and treatment measures for GD in East Asia need greater attention.

BackgroundSuicidal ideation is the first step and a strong predictor of suicide. College students are at a considerably high risk of suicidal ideation, and smartphones are commonly used in this group. However, the relationship between suicidal ideation and smartphone use among Chinese college students is unclear. The current study aimed to investigate the prevalence of suicidal ideation among Chinese college students and its association with smartphone use and addiction factors.MethodsA total of 439 college students participated the survey. We collected the demographic information, physical health, psychosocial factors (depressive symptoms, social support, sleep quality), characteristics of smartphone use, and mobile phone addiction (MPA). Suicidal ideation was measured with a single question, “did you feel that life was not worth living in the past 1 year?”ResultsThe prevalence of suicidal ideation (“Yes” response) in the past year among Chinese college students was 7.5%. In binary logistic regression analysis, suicidal ideation was significantly correlated with less subjective social support (OR: 2.49, p = 0.049), lower utilization of social support (OR: 13.28, p = 0.012), more depressive symptoms (OR:4.96, p = 0.005), and more than 5 h of daily smartphone use (OR: 2.60, p = 0.025).ConclusionConsidering the widely use of smartphones in Chinese colleges and the correlation with suicidal ideation, excessive phone use among college students should be given more attention by administrators and health workers. It is necessary to obtain more information about the intention of smartphone use, make full use of smartphones for health education, and monitor excessive use of smartphones, while improving social support and coping mechanisms for depression, to identify suicidal ideation and prevent suicidal behavior among Chinese college students.

IntroductionIn July 2021, Zhangjiajie City became the new epicenter of the COVID-19 outbreak. Aside from the physical manifestations of COVID-19, patients are also victims of severe social stigmatization. Stigma affects not only COVID-19 patients or survivors, but also individuals associated with them. This study aims to describe and assess the COVID-19-related stigma between patients, their relatives, and healthy local residents.MethodsThe study included 43 COVID-19 patients, 68 relatives, and 75 healthy residents from Zhangjiajie. Demographic data was collected, including gender, age, marital status, and educational level. Stigma attitudes toward COVID-19 were measured using the Stigma Scale and Social Distance Scale. Frequencies and percentages were described for each item of the scales, and differences among the three groups were examined using the chi-square test.ResultsWith regards to personal and perceived stigma, most participants agreed that patients with COVID-19 “could snap out of the problem” and that “they were dangerous.” For social distance, over 30% of participants from the three groups agreed with the item “unwillingness to marry into the family of someone with COVID-19.” In all groups, there were significant statistical differences in the belief that “the problem is not a real medical illness” and the desire to “spend the evening socializing.”ConclusionAlthough the outbreak was well-contained in Zhangjiajie, stigmatizing attitudes toward COVID-19 and desire for social distance to such patients were common among patients, their relatives and healthy local residents. Our study's results suggest that public education, anti-stigma interventions, and policies are necessary for people living in Zhangjiajie in order to effectively curtail the spread of COVID-19 and provide a useful strategy for a tourist city like Zhangjiajie to recover sooner from economic decline.

Background RNFL thickness measured by optical coherence tomography (OCT) and visual pathway measured by diffusion tensor imaging (DTI) can be used to predict visual field recovery, respectively. However, the relationship between RNFL thickness and visual pathway injury in patients with pituitary adenoma (PA) remains unclear. This study aims to evaluate the combining DTI and OCT methods in observing the microstructural change in the visual pathway in patients with PA. Methods Twenty-nine patients who were diagnosed with PA were included in the study group, and 29 healthy subjects were included as the control group. OCT detected the thickness of circumpapillary retinal nerve fiber layer (CP-RNFL) and ganglion cell layer (GCL). DTI measured the values of fractional anisotropy (FA) and apparent diffusion coefficient (ADC). Correlation between CP-RNFL and GCL thickness and FA and ADC values was analyzed in the study group. Results Compared with the control group, the FA values of the bilateral optic nerve, chiasma, bilateral optic tract, and left optic radiation in the study group were reduced, and the ADC values of the bilateral optic nerve and optic chiasma were increased. Correlation analysis showed that the FA value of the optic chiasma was positively correlated with the average thickness of RNFL, the CP-RNFL thickness in the nasal and temporal retinal quadrants in both eyes, as well as the thickness of macular ring GCL in the nasal, supra, and inferior quadrants. The FA values of the optic nerve, optic chiasma, optic tract, and optic radiation were positively correlated with CP-RNFL thickness in the nasal and temporal quadrants. Conclusion Combined DTI and OCT can provide a comprehensive understanding of the microscopic changes in the structure and function of the whole visual pathway in patients with PA.

Anomalous origin of a single coronary artery arising from the innominate artery associated with coronary artery fistula and truncus arteriosus is extremely rare. We found this anomaly in a 16-month-old infant-girl who received Rastelli procedure during the operation. The three defects described above are rarely found together; indeed, such a case as ours may be the first reported in the literature.

Family with sequence similarity 20C (Fam20C), the major protein kinase in the secretory pathway, generates the vast majority of the secreted phosphoproteome. However, the regulatory mechanisms of Fam20C transport, secretion, and function remain largely unexplored. Here, we show that Fam20C exists as a type II transmembrane protein within the secretory compartments, with its N-terminal signal peptide-like region serving as a membrane anchor for Golgi retention. The secretion and kinase activity of Fam20C are governed by site-1 protease (S1P), a key regulator of cholesterol homeostasis. We find that only mature Fam20C processed by S1P functions in osteoblast differentiation and mineralization. Together, our findings reveal a unique mechanism for Fam20C secretion and activation via proteolytic regulation, providing a molecular link between biomineralization and lipid metabolism.

Monocytes are important mediators of immune system and are reported to be altered in autoimmune disorders. Little is known about the pathological role of monocytes in Graves’ disease (GD). Thus, we investigated monocytes in periphery and thyroid tissue in GD. Untreated GD patients were enrolled and followed up until remission. Monocytes were significantly increased and positively correlated with anti-thyrotropin receptor antibody (TRAb) in untreated GD (rcounts = 0.269, P rpercentage = 0.338, P P r = 0.384 and P = 0.001). CD14++ CD16+ monocytes expressed higher level of BAFF in untreated GD (P P

Osteoarthritis (OA) is one of the most characterized joint diseases associated with chondrocyte apoptosis. Juglanin has been reported to have anti-inflammation activity. This study aimed to evaluate the protective anti-inflammatory effects of juglanin in human OA chondrocytes. Human OA chondrocytes were pretreated with juglanin (10, 20 and 40 μM) for 2 h and subsequently stimulated with IL-1β for 24 h. Nitric oxide (NO) production was determined using the Griess method and prostaglandin E2 (PGE2), matrix metalloproteinase-3, -9 and -13 (MMP-3, MMP-9 and MMP-13), TNF-α, and IL-6 were assessed using ELISA. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), a disintegrin and metalloproteinase with thrombospondin motifs-4 and -5 (ADAMTS-4 and ADAMTS-5) were detected by qRT-PCR and western blot analysis. NF-κB signalling molecules were detected by western blot analysis. The results showed that juglanin dose-dependently suppressed PGE2, NO, MMP-1, MMP3, MMP13, TNF-α and IL-6 production induced by IL-1β. The expression of COX-2, iNOS, ADAMTS-4 and ADAMTS-5 induced by IL-1β were also suppressed by juglanin pretreatment. Western blot analysis showed that juglanin suppressed IL-1β-induced NF-κB activation. Taken together, we found that juglanin inhibits IL-1β-induced inflammation through the regulation of NF-κB signalling. Juglanin might be used as a therapeutic agent for treating OA.

Long non-coding RNAs (LncRNAs) have been proven to be involved in the progression of osteosarcoma. LncRNA DLEU1 was found to act as an oncogene in various types of cancer. In this study, we aimed to explore the biological functions of DLEU1 in osteosarcoma and the specific mechanism. Our results showed that DLEU1 was highly expressed in osteosarcoma tissue specimens and cells. Downregulation of DLEU1 in osteosarcoma cells inhibited the cell proliferation, migration and invasion. Further mechanistic analysis and functional assays demonstrated that DLEU1 exerted its role by sponging microRNA (miR)-671-5p in osteosarcoma cells. Moreover, DEAD-box helicase 5 (DDX5) was confirmed as the target of miR-671-5p. Furthermore, rescue assays indicated that miR-671-5p inhibitor significantly reversed the effects of DLEU1 knockdown on osteosarcoma cell proliferation and invasion while restoration of DDX5 rescued the proliferation and invasion of osteosarcoma cells transfected with miR-671-5p mimics. In conclusion, DLEU1 acted as an oncogene in osteosarcoma by directly sponging miR-671-5p and regulating the expression of DDX5. These findings suggested that DLEU1 might be a novel therapeutic target in the treatment of osteosarcoma.

Objective:To compare and validate neurocognitive tests in the Harmonized Cognitive Assessment Protocol (HCAP) for the China Health and Retirement Longitudinal Study (CHARLS), and to identify appropriate tests to be administered in future waves of CHARLS.Methods:We recruited 825 individuals from the CHARLS sample and 766 subjects from hospitals in six provinces and cities in China. All participants were administered the HCAP-neurocognitive tests, and their informants were interviewed regarding the respondents’ functional status. Trained clinicians administered the Clinical Dementia Rating scale (CDR) to assess the respondents’ cognitive status independently.Results:The testing protocol took an average of 58 minutes to complete. Refusal rates for tests of general cognition, episodic memory, and language were less than 10%. All neurocognitive test scores significantly correlated with the CDR global score (correlation coefficients ranged from 0.139 to 0.641). The Mini-Mental State Examination (MMSE), the Health and Retirement Study (HRS) - telephone interview for cognitive status (TICS), community screening instrument for dementia (CSI-D) for respondent, episodic memory and language tests each accounted for more than 20% of the variance in global CDR score (p < 0.001) in bivariate tests. In the CHARLS subsample, age and education were associated with neuropsychological performance across most cognitive domains, and with functional status.Conclusion:A brief set of the CHARLS-HCAP neurocognitive tests are feasible and valid to be used in the CHARLS sample and hospital samples. It could be applied in the future waves of the CHARLS study, and it allows estimating the prevalence of dementia in China through the population-based CHARLS.

This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the authors and the Editor-in-Chief as the validity of the data cannot be guaranteed. The journal was initially contacted by the corresponding author to report that, when the authors verified post publication PTEN as their former target of miR-140-3p, they found that treatment with miR-140-3p or miR-155-5p antagomir increased PTEN protein levels in patient-derived chordoma cells without having a significant effect on the malignancy of the tumor cells. The journal further requested the author to provide more information about their post publication findings with regard to this article. However, the author was not able to fulfil this request.

Objective: Epidemiologic studies on the relationship between iodine and thyroid antibodies are inconsistent. Iodine nutrition, genetic, and environmental factors have been shown to modify the effects of iodine on thyroid autoimmunity. We investigated the relationship between urinary iodine concentration (UIC) and thyroglobulin antibodies (TgAbs) in individuals living in iodine-sufficient areas in this cross-sectional study. Methods: A total of 15,008 participants were recruited according to the age range of the population of China in our study. An oral questionnaire was administered to collect basic demographic information. Serum thyrotropin (TSH), thyroid peroxidase antibodies (TPOAbs), TgAbs, and UIC were measured, and thyroid ultrasonography was performed in all subjects. Participants were further divided according to the level of UIC and the status of TgAb, and logistic regression was applied to determine the relationship between UIC and TgAbs. Results: The median UIC of the study population was 205.23 (95% confidence interval lCI], 65.7 to 537.67) μg/L. A total of 17.6% of participants had UIC Conclusion: Low UIC is an independent risk factor for positive TgAb in individuals living in iodine-sufficient areas. Abbreviations: CI = confidence interval; CV = coefficient of variation; FT3 = free triiodothyronine; FT4 = free thyroxine; OR = odds ratio; TgAb = thyroglobulin antibody; TPOAb = thyroid peroxidase antibody; TSH = thyrotropin; UIC = urinary iodine concentration; USI = universal salt iodization

A growing number of studies have been conducted on the relationship between anger and hostility and the risk of stroke, and their conclusions are not consistent. Accordingly, we performed a meta-analysis to evaluate the relationship between anger and hostility and the risk of stroke. We searched the PubMed and Embase databases for cohort studies, focusing on the relationship between anger and hostility and risk of stroke. Then studies were selected according to the inclusion and exclusion criteria. Study results were pooled using a random effects model. Ten studies from seven articles involving 52,277 participants were included in this meta-analysis. No significant association was found between anger and hostility level and risk of stroke (hazard ratio 1.08; 95% confidence interval 0.79–1.47). However, a positive association was seen when people with high socioeconomic status were excluded (hazard ratio 1.30; 95% confidence interval 1.06–1.59). A higher level of anger and hostility is not associated with elevated risk of stroke. However, the association is positive among people with lower socioeconomic status.

The novel fluorescent agonists were discovered herein for α

Daytime napping is common in many regions around the world and has been an important part of people's daily life. Daytime napping has attracted increasing attention in recent years. Thus, we conducted a meta-analysis to evaluate the relationship between daytime napping and stroke, and help reduce the risk of stroke by improving living habits. The Embase, PubMed, Web of Science and PsycINFO databases were searched for cohort studies published before October 2020 and eight eligible studies with 524,408 participants and 5,875 stroke cases were included in the final analysis. The pooled relative risk (RR) of stroke was 1.47 (95% confidence interval [CI]: 1.24-1.74; p

Background This research aims to summarize the findings of the early single-stage revascularization of remnant pulmonary artery in unilateral absent intrapericardial pulmonary artery. Methods We retrospectively analyzed the medical records of 10 patients with unilateral absent pulmonary artery, in which 7 were right and 3 were left, the median age and mean weight at surgery was 4 months and 5.6 kg, respectively. The patients received operation from January 2009 to June 2020. Results Ten patients, 1 case associated with atrial septal defect, 2 cases with tetralogy of Fallot, and 1 case with aortopulmonary window. The mean diameter of the affected hilar pulmonary artery remnants was 3.14 ± 1.09 mm (1.6-5 mm), and the Z value was − 3.66 ± 1.86 (range, − 6.7 to − 1.75). All the patients received single-stage revascularization: tube graft interposition in 3 patients, autologous pericardial roll in 4, direct anastomosis in one, and main pulmonary artery flap angioplasty in the rest 3. No hospital deaths occurred. Mean follow-up in this cohort was 3.3 ± 1.9 years One case underwent percutaneous balloon dilatation due to new pulmonary artery stenosis. Nonetheless, the results were encouraging, symptoms have improved in all patients. The median Z value of the latest ipsilateral pulmonary artery diameter was − 1.88 (range, − 4.52 to − 1.35), a significantly improvement when compared to the preoperative value. The Z value of that in patients who using Gore-Tex tube increased relatively small. Conclusions Single-stage pulmonary artery revascularization is effective at restoring normal antegrade flow to the affected lung, resulting in improved diameter of the PA, regression of pulmonary hypertension, and patient’s symptoms. Revascularization by using the autologous tissue or autologous pericardium may obtain a preferred result. The new pulmonary artery stenosis certainly will need to be addressed in the long-term follow-up.

Background and objectives The impact of acute kidney injury (AKI) on the progression of renal function in idiopathic membranous nephropathy (iMN) with nephrotic syndrome (NS) patients have not yet been reported, we sought to investigate the incidence, clinical features and prognosis of AKI in iMN with NS patients and determine clinical predictors for progression from AKI to advanced chronic kidney disease (CKD) stage. Methods We analyzed clinical and pathological data of iMN with NS patients retrospectively collected from Jan 2012 to Dec 2018. The primary renal endpoint was defined as persistent eGFR

Objective To detect the expression of inducible co-stimulator and inducible co-stimulator ligand (ICOS/ICOSL) on peripheral lymphocytes in patients with Graves' disease (GD) and its clinical significance. Methods A total of 105 untreated GD patients and 67 healthy controls were enrolled in our study. 19 GD patients treated with anti-thyroid drugs were followed up in the outpatient department until TRAb were negative. The peripheral blood mononuclear cells (PBMCs) were separated and analyzed with PCR. ICOS expression on CD4

To evaluate the left ventricular end diastolic pressure (LVEDP) in patients with diastolic heart failure by echocardiography and explore the clinical value of echocardiography. From July 2017 to January 2018, 120 patients were prospectively selected from the affiliated hospital of Jiangsu university diagnosed as diastolic heart failure (York Heart Association class ≥II, LVEF ≥50%). The patients were divided into group with LVEDP ≤15 mm hg (1 mm hg = 0.133 kpa) (43 cases) and the group with LVEDP >15 mm hg (77 cases) according to the real-time measurement of LVEDP. Receiver operator characteristic curves of each parameter of echocardiography in diagnosis of LVEDP were compared between the 2 groups. Common ultrasonic parameters such as left ventricular inflow tract blood flow propagation velocity, mitral valve diastole e peak velocity/mitral valve diastole a peak velocity, e peak deceleration time, a peak duration, and early diastole interventricular septum bicuspid annulus velocity e’ (e'sep) were used to evaluate LVEDP elevation with low accuracy (AUC is only between 0.5 and 0.7). Other ultrasonic parameters such as left atrial volume index (LAVI), tricuspid regurgitation maximum flow rate (TRmax), early diastole left ventricular sidewall bicuspid annulus velocity e’ (e’lat), average e’, E/e'sep, E/e’lat, average E/e’ were used to evaluate LVEDP elevation with a certain improvement in accuracy (AUC between 0.7 and 0.9). Propagation velocity, mitral valve diastole e peak velocity/mitral valve diastole a peak velocity, e peak deceleration time, a peak duration, e'sep, average e’, E/e'sep have very low correlation with LVEDP (r = −0.283 to 0.281); LAVI, TRmax, e’lat, E/e’lat, average E/e’ and LVEDP are not highly correlated (r = 0.330–0.478). Through real-time left ventricular manometry, multiple regression analysis showed that TRmax, average e’, e’lat, LAVI were independently correlated with the actual measured LVEDP. Echocardiography can recognize the increase of LVEDP in patients with heart failure preserved by LVEF, and estimate the value of LVEDP roughly, which can reflect LVEDP to a certain extent, with high feasibility and accuracy.

Objective This study aimed to provide an insight into the impact of early outbreak of the novel coronavirus disease 2019 (COVID-19) on the care management for patients with congenital heart disease. Methods This study respectively enrolled a cohort of surgical patients (patients undergoing surgery in 2018 [group I], 2019[group II], and 2020 [group III]) and a cohort of follow-up patients (patients having follow-up in 2017 [group A], 2018 [group B] and 2019 [group C]) from 13 children hospitals. Results During the COVID-19 era, there was a significant decrease in total surgical volume and a change in case mix in terms of an increase in the proportion of emergency operations. Decrease in migration scale index was correlated to the decrease in both surgical volume (r=0.64, p=0.02) and outpatient visit volume (r=0.61, p=0.03). There was a significantly higher proportion of patients who had follow-up through the internet or phone in group C (26.4% vs. 9.6% in group B and 8.9% in group A; p< 0.0001). There was no statistical difference in death or rehospitalization among the 3 follow-up groups (p=0.49). There was higher parents’ anxiety score (p < 0.0001) and more utilization of telemedicine (p = 0.004) in group C comparing to group A and B. Conclusion The COVID-19 pandemic has resulted in a considerable decrease in total surgical volume and a change of case mix, which seems to be related to the strict traffic ban. Follow-up through the online medical service appears to be an effective alternative to the conventional method., Graphical abstract

OBJECTIVES The postoperative risk factors for electroencephalogram(EEG) abnormalities after paediatric cardiopulmonary bypass (CPB) remain to be identified. We investigated the characteristics of EEG abnormalities and risk factors in routine clinical management post-CPB. METHODS EEG and cerebral oxygen saturation (ScO2) were monitored in 96 patients (aged 3 days, 37 months, median 5 months) for 72 h post-CPB. Clinical measurements included 4-hourly arterial and central venous pressure, arterial blood gases, doses of inotropic and vasoactive drugs, daily C-reactive protein (CRP) and NT-proB-type Natriuretic Peptide (NT-proBNP). Demographics, STAT categories and outcomes (duration of mechanical ventilation,CICU stay) were recorded. Un RESULTS Seizures occurred in 20 patients (20.8%) beginning at 0–48 hand lasting 10 min–31 h; background abnormalities occurred in 67 (69.8%) beginning at 0–8 h and lasting 4–48 h. Patients with EEG abnormalities had worse outcomes. In univariable regression, seizures positively correlated with STAT categories, CPB time, temperature, blood pressure, central venous pressure, NT-proBNP, CRP, lactate and epinephrine, negatively with ScO2 and PaCO2 (P CONCLUSIONS Numerous perioperative risk factors are associated with EEG abnormalities post-CPB. The most significant and consistent risk factor is epinephrine.

Background Xenogeneic organ transplantation has been proposed as a potential approach to fundamentally solve organ shortage problem. Xenogeneic immune responses across species is one of the major obstacles for clinic application of xeno-organ transplantation. The generation of glycoprotein galactosyltransferase α 1, 3 (GGTA1) knockout pigs has greatly contributed to the reduction of hyperacute xenograft rejection. However, severe xenograft rejection can still be induced by xenoimmune responses to the porcine major histocompatibility complex antigens swine leukocyte antigen class I and class II. Methods We simultaneously depleted GGTA1, β2-microglobulin (β2M), and major histocompatibility complex class II transactivator (CIITA) genes using clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins technology in Bamma pig fibroblast cells, which were further used to generate GGTA1β2MCIITA triple knockout (GBC-3KO) pigs by nuclear transfer. Results The genotype of GBC-3KO pigs was confirmed by polymerase chain reaction and Sanger sequencing, and the loss of expression of α-1,3-galactose, SLA-I, and SLA-II was demonstrated by flow cytometric analysis using fluorescent-conjugated lectin from bandeiraea simplicifolia, anti-β2-microglobulin, and swine leukocyte antigen class II DR antibodies. Furthermore, mixed lymphocyte reaction assay revealed that peripheral blood mononuclear cells from GBC-3KO pigs were significantly less effective than (WT) pig peripheral blood mononuclear cells in inducing human CD3CD4 and CD3CD8 T-cell activation and proliferation. In addition, GBC-3KO pig skin grafts showed a significantly prolonged survival in immunocompetent C57BL/6 mice, when compared with wild-type pig skin grafts. Conclusions Taken together, these results demonstrate that elimination of GGTA1, β2M, and CIITA genes in pigs can effectively alleviate xenogeneic immune responses and prolong pig organ survival in xenogenesis. We believe that this work will facilitate future research in xenotransplantation.

Extracellular matrix remodeling and orbital adipose/connective tissue expansion are two key features of thyroid-associated ophthalmopathy (TAO). Recent studies have indicated the critical role of long non-coding RNAs (lncRNAs) in the pathogenesis of ocular disorders. However, little is known about the roles of lncRNAs in orbital adipose/connective tissue of TAO. In this study, the profiles of lncRNAs and mRNAs in the orbital adipose/connective tissue of TAO were identified by RNA sequencing. A total of 809 differential lncRNAs and 607 differential mRNAs were identified, among which 52 genes were found to be significantly related to the extracellular matrix. Co-expression network analysis suggested that lncRNAs might regulate extracellular matrix remodeling in orbital adipose/connective tissue of TAO. Additionally, the target genes of lncRNAs involved in the lipid metabolism and cytokine-cytokine receptor interaction were also identified. These results may provide potential regulatory mechanisms of lncRNAs in the orbital adipose/connective tissue of TAO.

14-3-3γ is a small protein regulating its target proteins through binding to phosphorylated serine/threonine residues. Sequence analysis of large-conductance Ca(2+)-activated K(+) (BK) channels revealed a putative 14-3-3 binding site in the COOH-terminal region. Our previous data showed that 14-3-3γ is widely expressed in the mouse kidney. Therefore, we hypothesized that 14-3-3γ has a novel role in the regulation of BK channel activity and protein expression. We used electrophysiology, Western blot analysis, and coimmunoprecipitation to examine the effects of 14-3-3γ on BK channels both in vitro and in vivo. We demonstrated the interaction of 14-3-3γ with BK α-subunits (BKα) by coimmunoprecipitation. In human embryonic kidney-293 cells stably expressing BKα, overexpression of 14-3-3γ significantly decreased BK channel activity and channel open probability. 14-3-3γ inhibited both total and cell surface BKα protein expression while enhancing ERK1/2 phosphorylation in Cos-7 cells cotransfected with flag-14-3-3γ and myc-BK. Knockdown of 14-3-3γ by siRNA transfection markedly increased BKα expression. Blockade of the ERK1/2 pathway by incubation with the MEK-specific inhibitor U0126 partially abolished 14-3-3γ-mediated inhibition of BK protein expression. Similarly, pretreatment of the lysosomal inhibitor bafilomycin A1 reversed the inhibitory effects of 14-3-3γ on BK protein expression. Furthermore, overexpression of 14-3-3γ significantly increased BK protein ubiquitination in embryonic kidney-293 cells stably expressing BKα. Additionally, 3 days of dietary K(+) challenge reduced 14-3-3γ expression and ERK1/2 phosphorylation while enhancing renal BK protein expression and K(+) excretion. These data suggest that 14-3-3γ modulates BK channel activity and protein expression through an ERK1/2-mediated ubiquitin-lysosomal pathway.

We aimed to evaluate and compare the physical fitness of children with different severity of the cardiac defect with their healthy peers. We included 182 children after cooperation for congenital heart disease (CHD) and 129 healthy children as controls, 6–18 years old, who performed a complete cardiopulmonary exercise test (CPET) in a cross-sectional observational study. The CHD patients were further subdivided into three subgroups according to diagnostic characteristics and surgical methods: simple CHD group (SCHD), complex CHD group (CCHD)and total cavopulmonary connection group (TCPC). Physical fitness was compared between groups using generalized linear model and multiple linear regression analysis. In comparison with age and gender adjusted healthy controls, children in SCHD, CCHD, and TCPC subgroups had accordingly graded down values of peak oxygen consumption (VO2max: 44.86 ± 5.41 vs. 39.91 ± 5.59 vs. 36.95 ± 5.92 vs. 32.04 ± 5.38 mL/kg/min, P 80%predicted VO2max). However, TCPC group had much lower exercise capacity.

We aimed to derive and validate an effective risk score to identify high-risk patients of very late stent thrombosis (VLST), following percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). Stepwise multivariable Cox regression was used to build the risk model using data from 5,185 consecutive ACS patients treated with PCI (derivation cohort) and 2,058 patients from the external validation cohort. Eight variables were independently associated with the development of VLST: history of diabetes mellitus, previous PCI, acute myocardial infarction as admitting diagnosis, estimated glomerular filtration rate 2, three-vessel disease, number of stents per lesion, sirolimus-eluting stent, and no post-dilation. Based on the derived score, patients were classified into low- (≤7), intermediate- (8–9), and high- (≥10) risk categories. Observed VLST rates were 0.5%, 2.2%, and 8.7% and 0.45%, 2.3%, and 9.3% across the 3 risk categories in the derivation and validation cohorts, respectively. High discrimination (c-statistic = 0.80 and 0.82 in the derivation and validation cohorts, respectively) and excellent calibration were observed in both cohorts. VLST risk score, a readily useable and efficient tool to identify high-risk patients of VLST after PCI for ACS, may aid in risk-stratification and pre-emptive decision-making.

BACKGROUND Ischemia-reperfusion injury (IRI) frequently follows successful PCI for STEMI and is recognized by multiple modalities. Multilayer speckle tracking echocardiography (STE) has the potential of detecting myocardial dysfunction in different myocardial layers. Our objective was to describe the changes in layer-specific myocardial function over the 24 hours after successful PCI for ST-elevation myocardial infarction (STEMI). METHODS Patients (n = 120) with STEMI and no prior myocardial infarction underwent echocardiography prior to PCI, immediately after and at 3- and 24-hours post-PCI. Worsening focal dysfunction (WFD) was defined as an immediate reduction, compared to the pre-PCI value, in the amplitude of endo-myocardial longitudinal strain (endo-MLS) within the infarction territory. RESULTS Patients with WFD (52%) had further reductions in endo-MLS, mid-MLS, and epi-MLS in the infarction region immediately post-PCI; at 3 hours strain began to improve and continued to improve at 24 hours. Reductions of endo-MLS strain were more evident than those of global, mid-MLS, and epi-MLS. This same pattern was seen in each of the ischemic territories of the anterior descending, circumflex, and right coronary arteries. Immediate improvement in endo-MLS following PCI was seen in 48% of patients. The time from symptom onset to balloon time was markedly longer in those with WFD (P