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Herein, we define the role of ferroptosis in the pathogenesis of diabetic cardiomyopathy (DCM) by examining the expression of key regulators of ferroptosis in mice with DCM and a new ex vivo DCM model. Advanced glycation end-products (AGEs), an important pathogenic factor of DCM, were found to induce ferroptosis in engineered cardiac tissues (ECTs), as reflected through increased levels of Ptgs2 and lipid peroxides and decreased ferritin and SLC7A11 levels. Typical morphological changes of ferroptosis in cardiomyocytes were observed using transmission electron microscopy. Inhibition of ferroptosis with ferrostatin-1 and deferoxamine prevented AGE-induced ECT remodeling and dysfunction. Ferroptosis was also evidenced in the heart of type 2 diabetic mice with DCM. Inhibition of ferroptosis by liproxstatin-1 prevented the development of diastolic dysfunction at 3 months after the onset of diabetes. NRF2 activated by sulforaphane inhibited cardiac cell ferroptosis in both AGE-treated ECTs and hearts of DCM mice by upregulating ferritin and SLC7A11 levels. The protective effect of sulforaphane on ferroptosis was AMP-activated protein kinase (AMPK)-dependent. These findings suggest that ferroptosis plays an essential role in the pathogenesis of DCM; sulforaphane prevents ferroptosis and associated pathogenesis via AMPK-mediated nuclear factor erythroid 2-related factor 2 (NRF2) activation. This suggests a feasible therapeutic approach with sulforaphane to clinically prevent ferroptosis and DCM.

Pneumonia, such as acute lung injury (ALI), has been a type of lethal disease that is generally caused by uncontrolled inflammatory response and excessive generation of reactive oxygen species (ROS). Herein, we report Fe-curcumin-based nanoparticles (Fe-Cur NPs) with nanozyme functionalities in guiding the intracellular ROS scavenging and meanwhile exhibiting anti-inflammation efficacy for curing ALI. The nanoparticles are noncytotoxic when directing these biological activities. Mechanism studies for the anti-inflammation aspects of Fe-Cur NPs were systematically carried out, in which the infected cells and tissues were alleviated through downregulating levels of several important inflammatory cytokines (such as TNF-α, IL-1β, and IL-6), decreasing the intracellular Ca2+ release, inhibiting NLRP3 inflammasomes, and suppressing NF-κB signaling pathways. In addition, we performed both the intratracheal and intravenous injection of Fe-Cur NPs in mice experiencing ALI and, importantly, found that the accumulation of such nanozymes was enhanced in lung tissue (better than free curcumin drugs), demonstrating its promising therapeutic efficiency in two different administration methods. We showed that the inflammation reduction of Fe-Cur NPs was effective in animal experiments and that ROS scavenging was also effectively achieved in lung tissue. Finally, we revealed that Fe-Cur NPs can decrease the level of macrophage cells (CD11bloF4/80hi) and CD3+CD45+ T cells in mice, which could help suppress the inflammation cytokine storm caused by ALI. Overall, this work has developed the strategy of using Fe-Cur NPs as nanozymes to scavenge intracellular ROS and as an anti-inflammation nanodrugs to synergistically cure ALI, which may serve as a promising therapeutic agent in the clinical treatment of this deadly disease. Fe-Cur NP nanozymes were designed to attenuate ALI by clearing intracellular ROS and alleviating inflammation synergistically. Relevant cytokines, inflammasomes, and signaling pathways were studied., Fe-Cur NP nanozymes were designed to attenuate ALI by clearing intracellular ROS and alleviating inflammation synergistically. Relevant cytokines, inflammasomes, and signaling pathways were studied.

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.

Rodent diabetic models, used to understand the pathophysiology of diabetic cardiomyopathy (DCM), remain several limitations. Engineered cardiac tissues (ECTs) have emerged as robust 3D in vitro models to investigate structure–function relationships as well as cardiac injury and repair. Advanced glycation end-products (AGEs), produced through glycation of proteins or lipids in response to hyperglycemia, are important pathogenic factor for the development of DCM. In the current study, we developed a murine-based ECT model to investigate cardiac injury produced by AGEs. We treated ECTs composed of neonatal murine cardiac cells with AGEs and observed AGE-related functional, cellular, and molecular alterations: (1) AGEs (150 µg/mL) did not cause acute cytotoxicity, which displayed as necrosis detected by medium LDH release or apoptosis detected by cleaved caspase 3 and TUNEL staining, but negatively impacted ECT function on treatment day 9; (2) AGEs treatment significantly increased the markers of fibrosis (TGF-β, α-SMA, Ctgf, Collagen I-α1, Collagen III-α1, and Fn1) and hypertrophy (Nppa and Myh7); (3) AGEs treatment significantly increased ECT oxidative stress markers (3-NT, 4-HNE, HO-1, CAT, and SOD2) and inflammation response markers (PAI-1, TNF-α, NF-κB, and ICAM-1); and (4) AGE-induced pathogenic responses were all attenuated by pre-application of AGE receptor antagonist FPS-ZM1 (20 µM) or the antioxidant glutathione precursor N-acetylcysteine (5 mM). Therefore, AGEs-treated murine ECTs recapitulate the key features of DCM’s functional, cellular and molecular pathogenesis, and may serve as a robust in vitro model to investigate cellular structure-function relationships, signaling pathways relevant to DCM and pharmaceutical intervention strategies.

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.

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.

Hypertrophic scar (HS) is a kind of serious pathological scar with no currently effective treatment. HS fibroblasts (HSFs) are the main effector cells for HS formation. Ellagic acid (EA) exerts regulatory effects in some diseases, but its role in HS remains unclear. This study aimed to evaluate the effect of EA on the fibrotic phenotypes of HSFs and to further investigate the downstream signaling mechanism. The cell counting kit-8 (CCK-8) assay was used to perform cytotoxicity and proliferation assays. HSFs migration was assessed using wound healing and transwell assays. HSFs contraction was measured by a collagen lattice contraction assay and detection of α-smooth muscle actin (α-SMA) expression. The levels of mRNA and protein were determined by qPCR and western blotting, respectively. The results showed that EA inhibited the proliferation, migration, and contraction of HSFs and collagen expression in HSFs in a dose-dependent manner. Furthermore, EA not only suppressed the Smad2/3 pathway but also reversed TGF-β1-induced activation of the Smad2/3 pathway and up-regulation of the fibrotic cellular phenotypes in HSFs. These findings demonstrate that EA exerts anti-fibrotic effects on HSFs by blocking the TGF-β1/Smad2/3 pathway, which indicates that EA is a potential therapeutic candidate for treatment of HS.

Background: Although the type and structure of substance abuse treatment have changed, the overall approaches of drug rehabilitation in China has remained largely unchanged. Evidence of effectiveness for compulsory drug rehabilitation centers (CRCs) and voluntary drug rehabilitation centers (VRCs) remains mixed. The main objective of our study is to reveal the outcomes of CRCs and VRCs and examine the factors associated with relapse in these two centers.Methods: In this cross-sectional study, we recruited a total of 1,299 drug abusers in Hunan Province, 709 from CRCs and 590 from VRC, respectively. We used Pearson chi-squared test and t-test to examine the differences in demographics and drug-related characteristics. Binary logic regression was used to examine the relationship between important factors and relapse in CRCs and VRC.Results: Patients from CRCs and VRC significantly differed in age, sex, types of drug used, medical illness, education, occupation, mental illness, and marital status. After drug rehabilitation, both groups both had improved in occupation, family support, and social function (p < 0.05). In addition, employment and family support were significantly associated with a decreased risk of relapse (p < 0.05).Conclusion: This study revealed that compulsory rehabilitation is as effective as voluntary rehabilitation in (1) getting jobs and increasing monthly income, (2) having a good relationship with family, and (3) becoming more satisfied with their spared time. The components of these two settings were very different and may imply the necessity of these two approaches in China. In addition, employment and family support may prevent relapse.

Background: Acute kidney injury (AKI) is a common and serious complication faced by children following ventricular septal defect (VSD) surgery with cardiopulmonary bypass (CPB). The objective of this study was to explore potential predictors inherent to AKI.Methods: VSD infants who were scheduled for elective cardiac surgery with CPB from 2017 to 2020 were enrolled in this study. Based on the Pediatric Risk, Injury, Failure, Loss, End-Stage Renal Disease (pRIFLE) criteria, patients were divided into AKI and non-AKI groups. Univariate and multivariate logistic regression analyses were carried out in order to evaluate potential risk factors for AKI. Receiver operating characteristic (ROC) curves were generated to evaluate the predictive probabilities of risk factors for AKI.Results: Of all the 338 enrolled VSD infants, 49 manifested AKI with an incidence of 14.5% (49/338). The ROC curve indicated that albumin-to-fibrinogen ratio (AFR) during CPB was a significant predictor of AKI [area under the curve (AUC), 0.711; p < 0.001]. Based on the univariate and multivariate logistic analyses, AFR during CPB [odds ratio (OR), 1.89; 95% confidence interval (CI), 1.22–2.76, p = 0.011] was the only independent risk factor for AKI.Conclusions: This study demonstrated that a low AFR (

Objective. We retrospectively analyzed the surgical results of pulmonary blood flow studies to guide ventricular septal defect (VSD) closure in the correction of pulmonary atresia and ventricular septal defect with major aortopulmonary collateral arteries (PA/VSD/MAPCAs). Methods. A total of 57 children who were diagnosed with PA/VSD/MAPCAs and who underwent intraoperative pulmonary blood flow studies at our hospital between August 2016 and June 2019 were included. Surgery and cardiopulmonary bypass records were collected. The receiver operating characteristic (ROC) curve was used to verify the accuracy of pulmonary blood flow studies to predict VSD closure. Results. Complete VSD closure was achieved in 39 of 57 children (68.42%), with a median age of 2 years and 5 months (range: 7 months to 15 years and 9 months) and a median weight of 11.0 kg (5.7–36.5 kg). Partial VSD repair was recorded for 21 children (36.84%), including 4 children (19.05%) who underwent VSD closure in the later stages and 13 children (61.90%) who were under follow-up and waiting to undergo complete VSD closure. There was only one child (1.75%) with VSD left. After eliminating the data of four unqualified cases, the ROC curve for predicting VSD closure based on 53 pulmonary blood flow studies was obtained at a p value of

Stem cells provide a new strategy for the treatment of cardiac diseases; however, their effectiveness in dilated cardiomyopathy (DCM) has not been investigated. In this study, cardiosphere-derived cells (CDCs) were isolated from infants (≤ 24 months) and identified by the cell surface markers CD105, CD90, CD117 and CD45, which is consistent with a previous report, although increased CD34 expression was observed. The molecular expression profile of CDCs from infants was determined by RNA sequencing and compared with adult CDCs, showing that infant CDCs have almost completely altered gene expression patterns compared with adult CDCs. The upregulated genes in infant CDCs are mainly related to the biological processes of cell morphogenesis and differentiation. The molecular profile of infant CDCs was characterized by lower expression of inflammatory cytokines and higher expression of stem cell markers and growth factors compared to adult CDCs. After intramyocardial administration of infant CDCs in the heart of DCM rats, we found that infant CDCs remained in the heart of DCM rats for at least 7 days, improved DCM-induced cardiac function impairment and protected the myocardium by elevating the left ventricular ejection fraction and fraction shortening. However, the effectiveness of transplanted CDCs was reversed later, as increased fibrosis formation instead of angiogenesis was observed. We concluded that infant CDCs, with higher expression of stem cell markers and growth factors, exhibit non-durable heart protection due to limited residence time in the heart of DCM animals, suggesting that multiple administrations of the CDCs or post-regulation after transplantation may be the key for cell therapy in the future. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1007/s10616-019-00328-z) contains supplementary material, which is available to authorized users.

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.

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

Cancer has become the leading cause of death in recent years. As great advances in medical treatment, emerging therapies of various cancers have been developed. Current treatments include surgery, radiotherapy, chemotherapy, immunotherapy, and targeted therapy. Aptamers are synthetic ssDNA or RNA. They can bind tightly to target molecules due to their unique tertiary structure. It is easy for aptamers to be screened, synthesized, programmed, and chemically modified. Aptamers are emerging targeted drugs that hold great potentials, called therapeutic aptamers. There are few types of therapeutic aptamers that have already been approved by the US Food and Drug Administration (FDA) for disease treatment. Now more and more therapeutic aptamers are in the stage of preclinical research or clinical trials. This review summarized the screening and development of therapeutic aptamers against different types of cancer cells.

Human adenoviruses (HAdVs) causes infections predominantly in infants and young children, and severe HAdVs pneumonia results in high lethality rate in children. CircRNAs are novel identified long non-coding RNAs and play important roles in gene regulation and pathogenesis of disease. To elucidate the roles of circRNAs in HAdVs pneumonia, we analyzed the circRNAs profiles of healthy children and children with HAdVs pneumonia including mild and severe cases, and identified 139 significant upregulated circRNAs in children with HAdVs pneumonia vs healthy controls, and 18 significant upregulated circRNAs in children with severe HAdVs pneumonia vs mild HAdVs pneumonia. In particular, hsa_circ_0002171 was found differently expressed in both groups, which may be taken as diagnostic biomarkers for HAdVs pneumonia and severe HAdVs pneumonia. To identify the underlying mechanisms of circRNAs in HAdVs pneumonia, we analyzed the transcriptome of children with HAdVs pneumonia and established circRNA-mRNA regulatory network. Enrichment of the differentially expressed (DE) target mRNAs demonstrated that DE genes between healthy controls vs HAdVs pneumonia were mainly involved in RNA splicing, while DE genes between children with mild and severe HAdVs pneumonia were mainly from the regulation of lymphocyte activation. Receiver operating characteristic (ROC) curve analysis suggested that hsa_circ_0002171 had significant value in HAdVs pneumonia and severe cases diagnosis. Taken together, profile of circRNA expression was altered in children with HAdVs pneumonia and severe cases. These results demonstrate that hsa_circ_0002171 as a potential diagnostic biomarker of HAdVs pneumonia and severe cases and may be a novel therapeutic target.

Background: The bioassay of thyroid-stimulating immunoglobulin was reported to have a similar performance to the commonly used thyroid-stimulating hormone binding inhibition assay, also known as thyroid receptor antibody assay. The normal reference range of thyroid receptor antibody levels indicates the withdrawal of anti-thyroid drugs in the recent clinical guidelines. Methods: A prospective, longitudinal observational study was conducted to evaluate the prognostic value of thyroid-stimulating immunoglobulin in patients with Graves’ disease. Results: A total of 77 patients with Graves’ disease treated with anti-thyroid drugs were in a continuous follow-up until 1 year after anti-thyroid drugs discontinuation. Commercial kits of thyroid-stimulating immunoglobulin and M22-thyroid-stimulating hormone binding inhibition assay were used and compared. Thyroid-stimulating immunoglobulin was all negative in healthy controls, Hashimoto thyroiditis, and subacute thyroiditis. Thyroid-stimulating immunoglobulin value was highest in untreated patients with Graves’ disease ( p Conclusion: Thyroid-stimulating immunoglobulin is a good predictor of relapse in patients with Graves’ disease treated with anti-thyroid drugs. It might be safer to discontinue anti-thyroid drugs when thyroid-stimulating immunoglobulin and thyroid receptor antibody were both negative.

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.

Objective: Adverse factors of postoperative hemodynamic and myocardial performance remain largely unexplored in children with congenital heart disease following cardiopulmonary bypass due to technical limitations. Pressure recording analytical method (PRAM) is a continuous hemodynamic and myocardial performance monitoring technique based on beat-to-beat arterial pressure waveform. Using PRAM, we examined the temporal trends and adverse factors, in clinical management, of these performances.Methods: We monitored blood pressure, cardiac index, cardiac cycle efficiency (CCE), dP/dTmax, and systematic vascular resistance index in 91 children (aged 186 ± 256 days) during their first 48 h after cardiopulmonary bypass. Above parameters, inotropic and vasoactive drug dosages, and serum lactate were recorded 3-hourly. NT-proBNP was measured daily.Results: CCE and dP/dTmax gradually increased (Ps < 0.0001), while systematic vascular resistance index, diastolic blood pressure and inotrope dosages decreased (Ps < 0.0001) over time. Cardiac index, systolic blood pressure, and heart rate did not change significantly (Ps ≥ 0.231). Patients undergoing deep hypothermic circulatory arrest had significantly higher heart rate and lower CCE (Ps ≤ 0.006) over time. Multivariate analyses indicated that epinephrine dose significantly correlated with systolic blood pressure, cardiac index, CCE, and dP/dTmax after polynomial transformation, with the peak ranging from 0.075 to 0.097.Conclusions: Systemic hemodynamic and myocardial performance gradually improved in the first 48 h after cardiopulmonary bypass without the “classic” nadir at 9–12 h. Deep hypothermic circulatory arrest and higher epinephrine doses were adversely associated with these performances. CCE, rather than cardiac index or other common-used parameters, was the most sensitive and consistent indicator.

ObjectiveTo probe markers and molecular mechanisms of the hypoplastic left heart (HLH) by single-cell RNA sequencing (scRNA-seq) and quantitative proteomics analysis.MethodsFollowing data preprocessing, scRNA-seq data of pluripotent stem cell (iPSC)-derived cardiomyocytes from one HLH patient and one control were analyzed by the Seurat package in R. Cell clusters were characterized, which was followed by a pseudotime analysis. Markers in the pseudotime analysis were utilized for functional enrichment analysis. Quantitative proteomics analysis was based on peripheral blood samples from HLH patients without heart failure (HLH-NHF), HLH patients with heart failure (HLH-HF), and healthy controls. Hub genes were identified by the intersection of pseudotime markers and differentially expressed proteins (DE-proteins), which were validated in the GSE77798 dataset, RT-qPCR, and western blot.ResultsCardiomyocytes derived from iPSCs were clustered into mesenchymal stem cells, myocardium, and fibroblast cells. Pseudotime analysis revealed their differentiation trajectory. Markers in the three pseudotime clusters were significantly associated with distinct biological processes and pathways. Finally, three hub genes (MMP2, B2M, and COL5A1) were identified, which were highly expressed in the left (LV) and right (RV) ventricles of HLH patients compared with controls. Furthermore, higher expression levels were detected in HLH patients with or without HF than in controls.ConclusionOur findings elucidate marker genes and molecular mechanisms of HLH, deepening the understanding of the pathogenesis of HLH.

Pyroglutamate aminopeptidase (PGP) specifically cleaves the peptide bond of pyroglutamic acid linked to the N-terminal end of a polypeptide or protein. Previous studies showed that PGP was associated with several physiological processes and diseases especially those involving inflammation. Utilizing a ‘caging’ strategy, we designed and synthesized a bioluminescence probe (PBL) with a limit-of-detection of 3.7 * 10−4 mU/mL. In vivo imaging in a mouse model of inflammatory liver disease revealed that the probe has excellent sensitivity and selectivity and provides a powerful tool for studying the physiological and pathological processes involving PGP.

A hypertrophic scar (HS) is a severe fibrotic skin disease that causes disfigurement and deformity. It occurs after deep cutaneous injury and presents a major clinical challenge. The present study aimed to evaluate the effects of umbilical cord-derived mesenchymal stem cells (UCMSCs) on hypertrophic scar fibroblasts (HSFs), one of the main effector cells for HS formation, in a co-culture system and to investigate the potential underlying molecular mechanism. Cultured HSFs were divided into control and co-culture groups. The proliferation ability of HSFs was evaluated using cell counting kit-8 and the percentage of Ki67-positive fibroblasts was assessed by immunofluorescence. The apoptosis of HSFs was determined using a TUNEL assay and by assessing the expression of capase-3 via western blotting. A scratch wound healing assay was employed to examine the migration of HSFs. The expression levels of HS-associated genes (collagen type Iα 2 chain, collagen type IIIα 1 chain and actin α 2 smooth muscle) and proteins (collagen I, collagen III and α-smooth muscle actin) were measured by reverse transcription-quantitative PCR (RT-qPCR) and western blotting, respectively, to assess the pro-fibrotic phenotype of HSFs. The modulation of the transforming growth factor β1 (TGF β1)/Smad3 pathway in HSFs was evaluated by measuring the protein levels of TGF β1, Smad3 and phosphorylated Smad3 using western blotting, and the mRNA levels of TGFβ1 and several other target genes (cellular communication network factor 2, metalloproteinase inhibitor 1 and periostin) were measured by RT-qPCR. The proliferative and migratory ability of co-cultured HSFs was suppressed compared with controls, and no significant difference in apoptosis was observed between the two groups. The pro-fibrotic phenotype of co-cultured HSFs was inhibited due to a decline in expression levels of HS-associated genes and proteins. Furthermore, co-culture with UCMSCs inhibited the activation of the TGF β1/Smad3 pathway. In conclusion, the present study indicated that UCMSCs may exert an anti-fibrotic action on HSFs in co-culture through inhibition of the TGF β1/Smad3 pathway, which suggests a potential use for UCMSCs in HS therapy.

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

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

Background: To identify alarming symptoms that could potentially lead to severe form of COVID-19 pneumonia (i.e. novel coronavirus pneumonia: NCP), a disease that is now having pandemic spread. Methods: Articles from PubMed, Embase, Cochrane database and Google up to 24 February 2020 were systematically reviewed. 18 publications that had documented cases of COVID-19 pneumonia were identified. The relevant data were extracted, systematically reviewed and further evaluated using meta-analysis. We define severe COVID-19 pneumonia as the disease status that requires admission to the intensive care unit (ICU) and respiratory/circulatory support, which is in align with the guideline from the World Health Organization (WHO). Results: 14 studies including 1,424 patients were considered eligible and analyzed. Symptoms such as fever (89.2%), cough (67.2%), fatigue (43.6%) were quite common; but dizziness, hemoptysis, abdominal pain and conjunctival congestion/conjunctivitis were relatively rare. The incidence of dyspnea was significantly higher in patients with severe than non-severe COVID-19 pneumonia (42.7% vs.16.3%, p

Background: To identify alarming symptoms that could potentially lead to severe form of COVID-19 pneumonia (i.e. novel coronavirus pneumonia: NCP), a disease that is now having pandemic spread.Methods: Articles from PubMed, Embase, Cochrane database and Google up to 24 February 2020 were systematically reviewed. 18 publications that had documented cases of COVID-19 pneumonia were identified. The relevant data were extracted, systematically reviewed and further evaluated using meta-analysis. We define severe COVID-19 pneumonia as the disease status that requires admission to the intensive care unit (ICU) and respiratory/circulatory support, which is in align with the guideline from the World Health Organization (WHO).Results: 14 studies including 1,424 patients were considered eligible and analyzed. Symptoms such as fever (89.2%), cough (67.2%), fatigue (43.6%) were quite common; but dizziness, hemoptysis, abdominal pain and conjunctival congestion/conjunctivitis were relatively rare. The incidence of dyspnea was significantly higher in patients with severe than non-severe COVID-19 pneumonia (42.7% vs.16.3%, pConclusion: Dyspnea, fever and diarrhea are significantly more prevalent in patients with severe COVID-19 pneumonia, suggesting they are alarming symptoms that warrant close attention and timely management.

The relationship between serum uric acid and risk of stroke is still controversial. Therefore, we conducted a meta-analysis based on the cohort study to explore the relationship between serum uric acid and risk of stroke, and further illuminate whether there is a linear or non-linear relationship between them. We manually searched the database including Cochrane, PubMed, Embase, Web of Science, and selected cohort studies focusing on the relationship between serum uric acid and stroke risk. Random effect model was used for statistical analysis. Twenty-one cohort studies involving 818,098 participants were included. The pooled relative risk for the high-vs-low categories was 1.22 (95% CI: 1.15-1.30). In addition, there was a non-linear dose-response relationship between uric acid and stroke risk. Serum uric acid was in the range of 3-5 mg/dl, with the lowest risk of stroke. In conclusion, high serum uric acid level increases the risk of stroke, with a non-linear dose-response relationship.

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

BACKGROUND Assessment of left ventricular (LV) diastolic function is part of routine echocardiographic examinations. Accuracy of the 2016 ASE/EACVI algorithm to detect LV diastolic dysfunction in patients with a normal LV ejection fraction (LVEF) has been examined but simultaneous measurements of LV pressures and echocardiographic parameters of diastolic function are sparse. METHODS The accuracy of multiple echo parameters of diastolic dynamics and the 2016 guidelines were assessed by simultaneous transthoracic echocardiography and LV pressure recordings in 120 patients (derivation cohort) and 60 patients (validation cohort) with suspected coronary artery disease and normal LVEF. Receiver-operating characteristic (ROC) curves defined optimal cut points for each echocardiographic parameter. A new algorithm was proposed to estimate LV diastolic pressures using 5 parameters based on ROC data: tricuspid regurgitation velocity >280cm/s, average e' 13, velocity of pulmonary vein A-wave reversal >32 cm/s, and left atrial volume index >32 mL/m2 . Performances of the 2016 guidelines and a proposed algorithm were examined for detecting a LV pre-A >12 and LV end-diastolic pressure (LVEDP) >15 mm Hg. RESULTS In the derivation cohort, the 2016 algorithm identified an elevated LVEDP >15 mm Hg with an accuracy of 74.2% (63.8-82.9); the modified algorithm improved accuracy to 86.0% (77.6-92.1), P

ObjectiveTo compare the difference between severe and non-severe COVID-19 pneumonia and figure out the potential symptoms lead to severity.MethodsArticles from PubMed, Embase, Cochrane database, and google up-to 24 February 2020 were systematically reviewed. Eighteen Literatures were identified with cases of COVID-19 pneumonia. The extracted data includes clinical symptoms, age, gender, sample size and region et al were systematic reviewed and meta analyzed.Results14 eligible studies including 1,424 patients were analyzed. Symptoms like fever (89.2%), cough (67.2%), fatigue (43.6%) were common, dizziness, hemoptysis, abdominal pain and conjunctival congestion/conjunctivitis were rare. Polypnea/dyspnea in severe patients were significantly higher than non-severe (42.7% vs.16.3%, PConclusionsFever, cough and fatigue are common symptoms in COVID-19 pneumonia. Compared with non-severe patients, the symptoms as fever, polypnea/dyspnea and diarrhea are potential symptoms lead to severity.

Granulomatous lobular mastitis (GLM) is a chronic inflammatory breast condition that is characterized by granulomatous inflammation. GLM remains a refractory disease due to its failure to respond to routine anti-inflammatory therapies and its high recurrence rate. Thus, the present study aimed to investigate the application of local heat therapy in GLM as a potential therapeutic strategy. The results revealed that the application of local heat therapy was associated with a shortened remission time for GLM, while the remission and recurrence rates were similar to those of existing therapies. The median first remission time following local heat therapy was significantly decreased compared with that following corticosteroid therapy (5.30 months vs. 11.27 months; P0.05). In addition, the recurrence rates were not statistically different between the groups (local heat therapy, 8.3%; extensive excision, 10%; and corticosteroid therapy, 10%; P>0.05). The local heat therapy showed mild adverse effects and shortened healing times compared to the other therapies; however, further confirmation is required.

Congenital heart disease (CHD) is 1 of the most common congenital malformations, and considerable numbers of infants and young children with CHD undergo cardiopulmonary bypass surgery. It has been increasingly realized that perioperative nutrition support plays an important role in improving clinical outcomes. The purpose of this review, by searching PubMed, was to examine the nutrition conditions in perioperative children with CHD and the main problems in nutrition management in the cardiac intensive care unit (CICU), based on which future directions were proposed. We found that preoperative poor nutrition status is common. This limited reserve of energy and protein is further compounded by the complex metabolic alterations with hypermetabolism, hypercatabolism, and hypoanabolism in the early postoperative course. Knowledge about energy and protein metabolism and requirements in children after cardiopulmonary bypass remains very limited. The current nutrition recommendations in the CICU are based on little evidence. Insufficient energy and protein supply to meet demands remains a norm in the immediate postoperative period. The commonly used predictive equations do not provide accurate estimate of energy requirement in individual patients during the highly dynamic postoperative course. Indirect calorimetry can provide the best estimate of energy requirements for children with CHD in the CICU. Measurement of nitrogen balance is the recommended method to determine the minimal protein requirement. During the early postoperative period, daily measurements of resting energy expenditure using indirect calorimetry and nitrogen balance in each individual child are essential to optimize energy and protein supply to meet requirements.

Disordered proliferation and angiogenesis of pulmonary artery endothelial cells is an important stage in the development of pulmonary arterial hypertension. Recent studies revealed that GDF11 (growth differentiation factor 11) induces endothelial cells proliferation and migration; however, whether GDF11 is directly involved in the pathogenesis of pulmonary arterial hypertension remains unknown. Here, we found that GDF11 was significantly upregulated and activated in 2 experimental pulmonary arterial hypertension models and cultured pulmonary artery endothelial cells. Genetic ablation ofgdf11in endothelial cells rescued pulmonary arterial hypertension features, as demonstrated by right ventricle hypertrophy, right ventricular systolic pressure, hemodynamics, cardiac function, and vascular remodeling. Moreover, we found that hypoxia significantly increased cell cycle progression, proliferation, migration, adhesion, and tube formation, which were significantly inhibited by GDF11 small interfering RNA. These events could be reproduced using cultured pulmonary artery endothelial cells and were dependent on Smad signaling. Moreover, hypoxia-induced GDF11 expression was regulated by the transcription factor zinc finger protein 740, which assisted RNA polymerase in recognizing and binding to the GDF11 promoter sequence located at a site (−753/−744; CCCCCCCCAC) upstream of the gene. This study identified a novel growth and differentiation factor signaling pathway involved in the zinc finger protein 740/GDF11/transforming growth factor-β receptor I/Smad signaling axis and involved in pulmonary artery endothelial cells proliferation and angiogenesis. These results provide critical insights for the development of novel therapeutic strategies for pulmonary arterial hypertension involving components of the GDF11 signaling system.

Dysfunction and injury of endothelial cells play critical roles in pulmonary arterial hypertension, including aberrant proliferation, suppressed apoptosis, and excessive angiogenesis. The 12-lipoxygenase and 12-hydroxyeicosatetraenoic acid pathway, which has been considered as a crucial mediator, elevates pulmonary vascular resistance and pulmonary arterial pressure. However, the mechanisms underlying the bioactivity of 12-hydroxyeicosatetraenoic acid in pulmonary vasculature, especially in endothelial cells, are still elusive. Thus we aim to determine the key role of 12-lipoxygenase/12-hydroxyeicosatetraenoic acid in angiogenesis and survival of pulmonary artery endothelial cells and ascertain the signaling pathways participating in the pathological process. Here we establish that hypoxia increases the formation of endogenous 12-hydroxyeicosatetraenoic acid through stimulation of 12-lipoxygenase. Furthermore, we put forward new information that 12-hydroxyeicosatetraenoic acid promotes endothelial cell migration and tube formation, whereas it inhibits the serum deprivation-induced apoptotic responses under hypoxia. Particularly, the regulatory effects of 12-lipoxygenase/12-hydroxyeicosatetraenoic acid on pulmonary artery endothelial cells, at least in part, depend on phosphatidylinositol 3-kinase (PI3K)/Akt signaling activation. Taken together, these results may have significant implications for understanding of pulmonary hypertension and offer a potential therapeutic concept focusing on the 12-lipoxygenase/12-hydroxyeicosatetraenoic acid signaling system.

Wang L, Chen X, Sun X, Suo J. Onco Targets Ther.2020:13:7555–7569 The authors have advised Figure 6E on page 7565 isincorrect. Due to an error at the time of figure assemblyone of the images from 6G was used as a placeholderand not replaced later. The correct Figure 6 is shownbelow. The authors apologize for this error and advise it does notaffect the results of the paper. Read the original article

Human biliverdin reductase (hBVR), is an enzyme, that converts biliverdin to bilirubin, and has been implicated in epithelial-mesenchymal transition (EMT) in breast cancer. However, few studies have investigated the role of hBVR in cell apoptosis in other cancers. Therefore, the aim of this study was to investigate the effects of hBVR in several lines of cancer cells. The results of this study showed that hBVR expression was up-regulated in breast, lung, and liver cancers, but not ovarian cancer. Moreover, hBVR inhibition by small interfering RNA (si-hBVR) attenuated cell survival and increased caspase-3 protein expression, which was mediated by the ERK1/2 signaling pathway in relative cancer cells. In addition, the mitochondrial membrane potential and mitochondrial membrane proteins Bcl-2 and BAX were found to be necessary for activation of the mitochondria dependent apoptosis pathway. Collectively, these findings indicated, for the first time, that the anti-apoptotic effect of hBVR in cancers which portend new strategies for developing novel biomarkers and effective treatment ways for cancer patients.

Transforming growth factor-β (TGF-β), recognized as a crucial factor in regulating fibrosis and tissue remodeling, plays a role in thyroid-associated ophthalmopathy (TAO). Pentraxin-3 (PTX3), a member of pentraxins, was recently implicated in many autoimmune and fibrotic diseases. Thus, we hypothesize if there is a potential correlation between TGF-β and PTX3 in orbital fibroblasts (OFs). Several strains of OFs obtained from patients with TAO (n = 8) and healthy donors (n = 3) were established as the study model. Recombinant TGF-β1 was exerted as an intervention and the expression of PTX3 was detected. To uncover the underlying mechanism, specific inhibitors of TGF-β and siRNA knockdown of Smads were utilized. We found that TGF-β1 can reduce PTX3 protein expression in OFs. We also demonstrated that this downregulation was mediated at a pretranslational level, and PTX3 mRNA was inhibited in a time- and concentration-dependent manner by TGF-β1. Interestingly, the basic level of PTX3 and the magnitude of suppression were not significantly different between TAO and control groups. Furthermore, the TGF-β receptor complex (type I:type II) and the Smad2/3-Smad4-dependent pathway are essential for TGF-mediated PTX3 repression. These findings indicated that TGF-β1 can inhibit PTX3 expression in human OFs, which may participate in inflammation and fibrosis in patients with TAO and provide a potential target for the antifibrotic treatment.

Introduction Inguinal hernia is the most common disease in pediatric surgery and is induced by congenital processus vaginalis patency. Almost all inguinal hernias are inguinal indirect hernias, and herniorrhaphy has accounted for about 15% of all pediatric operations. In the past 20 years, with the development of minimally invasive technology, laparoscopic inguinal herniorrhaphy has been emerging in China and in other countries. Aim To introduce a new technique for treating inguinal hernia in children, and evaluate the feasibility and surgical efficacy of a transumbilical single-port laparoscopic water-injection hernia crochet needle in treating pediatric inguinal hernia. Material and methods Clinical data of 136 inguinal hernial children treated using a transumbilical single-port laparoscopic water-injection hernia crochet needle in our hospital from June 2017 to December 2018 were retrospectively analyzed. Results All procedures were successfully accomplished, and no case was converted to a different procedure; the average operation time was 16 min for one side and 35 min for both sides. Patients were followed for an average of 10 months after surgery. One patient had a line-knot reaction at the inguinal puncture point 3 months after surgery and recovered after conservative treatment, and no recurrent case was observed after surgery. Conclusions It is feasible to treat pediatric inguinal hernia through a transumbilical single-port laparoscopic water-injection hernia crochet needle, which is associated with safety, less trauma, rapid recovery, no obvious scar, and satisfactory efficacy. Therefore, it is worthy of being promoted and applied in clinical practice.