A case report of pulmonary atresia with intact ventricular septum: an extraordinary finding of subsystemic right ventricle.

Background: Massive tricuspid regurgitation (TR) is the most common feature of pulmonary atresia with intact ventricular septum (PA/IVS), and mild or absent TR is observed in severe right ventricular (RV) dysplasia or RV-to-coronary fistulous connections, resulting in non-biventricular (BV) outcomes postnatally. Case summary: We report a case of fetal severe pulmonary stenosis with IVS diagnosed at 26 weeks of gestation. The severity of RV hypoplasia did not worsen or reach indications for intrauterine intervention, while the jet velocity of TR decreased significantly during pregnancy. The fetus was definitely diagnosed with PA/IVS with mild RV dysplasia after birth. Unusually, the fetus did not experience severe TR and myocardial sinusoids, the TR jet velocity was maintained at 2.0 m/s, and the coronary artery was almost normal. The incapable RV cannot pump blood into pulmonary circulation after RV decompression from valvular perforation and balloon dilation. It may be an extraordinary finding of subsystemic RV. Conclusion: PA/IVS is a heterogeneous disease with various degrees of RV dysplasia. Mild or no baseline TR is a reliable indicator with non-BV outcomes for fetal PA/IVS, even with acceptable dysplasia RV structures.

Neutrophil extracellular traps promote proliferation of pulmonary smooth muscle cells mediated by CCDC25 in pulmonary arterial hypertension.

BACKGROUND: Previous studies have indicated that neutrophil extracellular traps (NETs) play a pivotal role in pathogenesis of pulmonary arterial hypertension (PAH). However, the specific mechanism underlying the impact of NETs on pulmonary artery smooth muscle cells (PASMCs) has not been determined. The objective of this study was to elucidate underlying mechanisms through which NETs contribute to progression of PAH. METHODS: Bioinformatics analysis was employed in this study to screen for potential molecules and mechanisms associated with occurrence and development of PAH. These findings were subsequently validated in human samples, coiled-coil domain containing 25 (CCDC25) knockdown PASMCs, as well as monocrotaline-induced PAH rat model. RESULTS: NETs promoted proliferation of PASMCs, thereby facilitating pathogenesis of PAH. This phenomenon was mediated by the activation of transmembrane receptor CCDC25 on PASMCs, which subsequently activated ILK/ß-parvin/RAC1 pathway. Consequently, cytoskeletal remodeling and phenotypic transformation occur in PASMCs. Furthermore, the level of NETs could serve as an indicator of PAH severity and as potential therapeutic target for alleviating PAH. CONCLUSION: This study elucidated the involvement of NETs in pathogenesis of PAH through their influence on the function of PASMCs, thereby highlighting their potential as promising targets for the evaluation and treatment of PAH.

Bufalin targeting CAMKK2 inhibits the occurrence and development of intrahepatic cholangiocarcinoma through Wnt/ß-catenin signal pathway.

BACKGROUND: Intrahepatic cholangiocarcinoma (ICC) accounts for about 15% of primary liver cancer, and the incidence rate has been rising in recent years. Surgical resection is the best treatment for ICC, but the 5-year survival rate is less than 30%. ICC signature genes are crucial for the early diagnosis of ICC, so it is especially important to find its signature genes and therapeutic drug. Here, we studied that bufalin targeting CAMKK2 promotes mitochondrial dysfunction and inhibits the occurrence and metastasis of intrahepatic cholangiocarcinoma through Wnt/ß-catenin signal pathway. METHODS: IC50 of bufalin in ICC cells was determined by CCK8 and invasive and migratory abilities were verified by wound healing, cell cloning, transwell and Western blot. IF and IHC verified the expression of CAMKK2 between ICC patients and normal subjects. BLI and pull-down demonstrated the binding ability of bufalin and CAMKK2. Bioinformatics predicted whether CAMKK2 was related to the Wnt/ß-catenin pathway. SKL2001, an activator of ß-catenin, verified whether bufalin acted through this pathway. In vitro and in vivo experiments verified whether overexpression of CAMKK2 affects the proliferative and migratory effects of ICC. Transmission electron microscopy verified mitochondrial integrity. Associated Ca2+ levels verified the biological effects of ANXA2 on ICC. RESULTS: It was found that bufalin inhibited the proliferation and migration of ICC, and CAMKK2 was highly expressed in ICC, and its high expression was positively correlated with poor prognosis.CAMKK2 is a direct target of bufalin, and is associated with the Wnt/ß-catenin signaling pathway, which was dose-dependently decreased after bufalin treatment. In vitro and in vivo experiments verified that CAMKK2 overexpression promoted ICC proliferation and migration, and bufalin reversed this effect. CAMKK2 was associated with Ca2+, and changes in Ca2+ content induced changes in the protein content of ANXA2, which was dose-dependently decreasing in cytoplasmic ANXA2 and dose-dependently increasing in mitochondrial ANXA2 after bufalin treatment. In CAMKK2 overexpressing cells, ANXA2 was knocked down, and we found that reversal of CAMKK2 overexpression-induced enhancement of ICC proliferation and migration after siANXA2. CONCLUSIONS: Our results suggest that bufalin targeting CAMKK2 promotes mitochondrial dysfunction and inhibits the proliferation and migration of intrahepatic cholangiocarcinoma through Wnt/ß-catenin signal pathway. Thus, bufalin, as a drug, may also be used for cancer therapy in ICC in the future.

Bufalin targeting BFAR inhibits the occurrence and metastasis of gastric cancer through PI3K/AKT/mTOR signal pathway.

Gastric cancer (GC) is the most common malignant tumor of digestive system. Bufalin extracted from Venenum Bufonis is one of the most effective anticancer monomers, which has been proved to play anticancer roles in a variety of cancers such as ovarian cancer, prostate cancer and neuroblastoma. However, there are few studies on bufalin in GC, and lack of clear targets. The effect of bufalin on the proliferation and migration of GC cells was detected by CCK-8, scratch wound healing assay, transwell assay and Western blotting. The potential direct interaction proteins of bufalin were screened by human proteome microarray containing 21,838 human proteins. The target protein was determined by bioinformatics, and the binding sites were predicted by molecular docking technique. Biological experiments in vitro and in vivo were conducted to verify the effect of bufalin directly interaction protein and the mechanism of bufalin targeting the protein to inhibit the development of GC. The results showed that bufalin inhibited the proliferation and migration of MKN-45 and HGC-27 GC cell lines in vitro. BFAR, a direct interaction protein of bufalin has several potential binding sites to bufalin. BFAR is highly expressed in GC and promotes the occurrence and metastasis of GC by activating PI3K/AKT/mTOR signal pathway in vitro and in vivo. Bufalin reversed the promoting effect of BFAR on the carcinogenesis and metastasis of GC by down-regulating the expression of BFAR. Our results show that bufalin targeting BFAR inhibits the occurrence and metastasis of GC through PI3K/AKT/mTOR signal pathway. These results provide a new basis for bufalin as a promising drug for the treatment of GC.

Advances in protein glycosylation and its role in tissue repair and regeneration.

After tissue damage, a series of molecular and cellular events are initiated to promote tissue repair and regeneration to restore its original structure and function. These events include inter-cell communication, cell proliferation, cell migration, extracellular matrix differentiation, and other critical biological processes. Glycosylation is the crucial conservative and universal post-translational modification in all eukaryotic cells [1], with influential roles in intercellular recognition, regulation, signaling, immune response, cellular transformation, and disease development. Studies have shown that abnormally glycosylation of proteins is a well-recognized feature of cancer cells, and specific glycan structures are considered markers of tumor development. There are many studies on gene expression and regulation during tissue repair and regeneration. Still, there needs to be more knowledge of complex carbohydrates' effects on tissue repair and regeneration, such as glycosylation. Here, we present a review of studies investigating protein glycosylation in the tissue repair and regeneration process.

Using bioinformatics analysis to screen abnormal methylated differentially expressed hub genes of Kawasaki disease and construct diagnostic model.

Objective: By using bioinformatics analysis, abnormal methylated differentially expressed genes (MDEGs) in Kawasaki disease (KD) were identified and a random forest diagnostic model for KD was established. Methods: The expression (GSE18606, GSE68004, GSE73461) and methylation (GSE109430) profiles was retrieved and download from Gene Expression Omnibus (GEO). We conducted enrichment analyses by using R software. In addition, we constructed a protein interaction network, and obtained 6 hub genes. We used expression profiles GSE100154 from GEO to verify the hub genes. Finally, we constructed a diagnostic model based on random forest. Results: We got a total of 55 MDEGs (43 hyper-methylated, low-expressing genes and 12 hypo-methylated, high-expressed genes). Six hub genes (CD2, IL2RB, IL7R, CD177, IL1RN, and MYL9) were identified by Cytoscape software. The area under curve (AUC) of the six hub genes was from 0.745 to 0.898, and the combined AUC was 0.967. The random forest diagnostic model showed that AUC was 0.901. Conclusion: The identification of 6 new hub genes improves our understanding of the molecular mechanism of KD, and the established model can be employed for accurate diagnosis and provide evidence for clinical diagnosis.

Valvuloplasty of fetal pulmonary atresia with intact ventricular septum and hypoplastic right heart: Mid-term follow-up results.

Objective: This study aimed to analyze and evaluate the results of mid-term follow-up after fetal pulmonary valvuloplasty (FPV) in fetuses with pulmonary atresia with intact ventricular septum (PA/IVS). Methods: From August 31, 2018, to May 31, 2019, seven fetuses with PA/IVS and hypoplastic right heart were included in this study. All underwent echocardiography by the same specialist and were operated on by the same team. Intervention and echocardiography data were collected, and changes in the associated indices noted during follow-up were analyzed. Results: All seven fetuses successfully underwent FPV. The median gestational age at FPV was 27.54 weeks. The average FPV procedural time was 6 â€‹min. Persistent bradycardia requiring treatment occurred in 4/7 procedures. Finally, five pregnancies were successfully delivered, and the other two were aborted. Compared to data before fetal cardiac interventions (FCI), tricuspid valve annulus diameter/mitral valve annulus diameter (TV/MV) and right ventricle diameter/left ventricle diameter (RV/LV) of all fetuses had progressively improved. The maximum tricuspid regurgitation velocity decreased from 4.60 â€‹m/s to 3.64 â€‹m/s. The average follow-up time was 30.40 â€‹± â€‹2.05 months. During the follow-up period, the diameter of the tricuspid valve ring in five children continued to improve, and the development rate of the tricuspid valve was relatively obvious from 6 months to 1 year after birth. However, the development of the right ventricle after birth was relatively slow. It was discovered that there were individual variations in the development of the right ventricle during follow-up. Conclusion: The findings support the potential for the development of the right ventricle and tricuspid valve in fetuses with PA/IVS who underwent FCI. Development of the right ventricle and tricuspid valve does not occur synchronously during pregnancy. The right ventricle develops rapidly in utero, but the development of tricuspid valve is more apparent after birth than in utero.

An investigation on bloom dynamics of Alexandrium catenella and A. pacificum and toxin accumulation in shellfish along the coast of Qinhuangdao, China.

The dinoflagellate genus Alexandrium comprises most of the toxic bloom-forming species producing paralytic shellfish toxins (PSTs) in the sea. Recently, repeated paralytic shellfish poisoning episodes have been recorded in Qinhuangdao located at the west coast of the Bohai Sea. To elucidate the relationship between toxic Alexandrium blooms and the poisoning episodes, a year-round investigation was carried out in this region from July 2020 to July 2021. Two qPCR assays were used to detect A. catenella and A. pacificum, and LC-MS/MS was applied to analyze PSTs in phytoplankton and shellfish samples. The blooms of A. catenella and A. pacificum were found in April and July, respectively, and PST content in three bivalves exhibited notable increase following the bloom of A. catenella. The results revealed bloom dynamics of the two toxic Alexandrium species in the Bohai Sea for the first time, and further confirmed A. catenella as the causative agent of poisoning episodes.

[Association between duration of fever before treatment and intravenous immunoglobulin resistance in Kawasaki disease]. / å·å´Žç— æ²»ç–—å‰å‘çƒ­æ—¶é—´ä¸Žä¸™ç§çƒè›‹ç™½è€è¯çš„ç›¸å ³æ€§ä¸´åºŠç ”ç©¶.

OBJECTIVES: To examine the association between duration of fever before intravenous immunoglobulin (IVIG) treatment and IVIG resistance in children with Kawasaki disease (KD). METHODS: A retrospective analysis was performed on the medical data of 317 children with KD who were admitted from January 2018 to December 2020. According to the duration of fever before IVIG treatment, they were divided into two groups: short fever duration group (≤4 days) with 92 children and long fever duration group (>4 days) with 225 children. According to the presence or absence of IVIG resistance, each group was further divided into a drug-resistance group and a non-drug-resistance group. Baseline data and laboratory results were compared between groups. A multivariate logistic regression analysis was used to identify the influencing factors for IVIG resistance. RESULTS: In the short fever duration group, 19 children (20.7%) had IVIG resistance and 5 children (5.4%) had coronary artery aneurysm, and in the long fever duration group, 22 children (9.8%) had IVIG resistance and 19 children (8.4%) had coronary artery aneurysm, suggesting that the short fever duration group had a significantly higher rate of IVIG resistance than the long fever duration group (P<0.05), while there was no significant difference in the incidence rate of coronary artery aneurysm between the two groups (P>0.05). In the short fever duration group, compared with the children without drug resistance, the children with drug resistance had a significantly lower level of blood sodium and significantly higher levels of procalcitonin, C-reactive protein, and N-terminal B-type natriuretic peptide before treatment (P<0.05). In the long fever duration group, the children with drug resistance had significantly lower levels of blood sodium and creatine kinase before treatment than those without drug resistance (P<0.05). The multivariate logistic regression analysis showed that a reduction in blood sodium level was associated with IVIG resistance in the long fever duration group (P<0.05). CONCLUSIONS: IVIG resistance in children with KD varies with the duration of fever before treatment. A reduction in blood sodium is associated with IVIG resistance in KD children with a duration of fever of >4 days before treatment.

Advances in the development and optimization strategies of the hemostatic biomaterials.

Most injuries are accompanied by acute bleeding. Hemostasis is necessary to relieve pain and reduce mortality in these accidents. In recent years, the traditional hemostatic materials, including inorganic, protein-based, polysaccharide-based and synthetic materials have been widely used in the clinic. The most prominent of these are biodegradable collagen sponges (Helistat®, United States), gelatin sponges (Ethicon®, SURGIFOAM®, United States), chitosan (AllaQuixTM, ChitoSAMTM, United States), cellulose (Tabotamp®, SURGICEL®, United States), and the newly investigated extracellular matrix gels, etc. Although these materials have excellent hemostatic properties, they also have their advantages and disadvantages. In this review, the performance characteristics, hemostatic effects, applications and hemostatic mechanisms of various biomaterials mentioned above are presented, followed by several strategies to improve hemostasis, including modification of single materials, blending of multiple materials, design of self-assembled peptides and their hybrid materials. Finally, the exploration of more novel hemostatic biomaterials and relative coagulation mechanisms will be essential for future research on hemostatic methods.

Prediction of arrhythmia after intervention in children with atrial septal defect based on random forest.

BACKGROUND: Using random forest to predict arrhythmia after intervention in children with atrial septal defect. METHODS: We constructed a prediction model of complications after interventional closure for children with atrial septal defect. The model was based on random forest, and it solved the need for postoperative arrhythmia risk prediction and assisted clinicians and patients' families to make preoperative decisions. RESULTS: Available risk prediction models provided patients with specific risk factor assessments, we used Synthetic Minority Oversampling Technique algorithm and random forest machine learning to propose a prediction model, and got a prediction accuracy of 94.65 % and an Area Under Curve value of 0.8956. CONCLUSIONS: Our study was based on the model constructed by random forest, which can effectively predict the complications of arrhythmia after interventional closure in children with atrial septal defect.

Prognostic Value of Abnormal Ankle-Brachial Index in Patients With Coronary Artery Disease: A Meta-Analysis.

The prognostic value of the ankle-brachial index (ABI) in patients with coronary artery disease (CAD) remains undefined. This meta-analysis sought to investigate the association of abnormal ABI and adverse outcomes in patients with CAD. PubMed, Embase, China National Knowledge Infrastructure, VIP, and Wanfang databases were comprehensively searched for studies published from inception to September 10, 2019. All observational studies investigating the association of abnormal baseline ABI and risk of major adverse cardiovascular events (MACE) or all-cause mortality were selected. Normal ABI is usually defined as between 0.9 and 1.4. The prognostic values were summarized by pooling risk ratio (RR) with 95% confidence intervals (CIs) for abnormal versus normal ABI category. Nine (9384 patients with CAD) studies were included. Abnormal ABI was independently associated with MACE (RR: 2.46; 95% CI: 2.02-2.99) and all-cause mortality (RR: 1.74; 95% CI: 1.32-2.30). Subgroup analysis showed that the pooled RR for MACE was 2.34 (95% CI: 1.73-3.16) for an abnormal low ABI. Abnormal ABI predicts MACE and all-cause mortality in patients with CAD, even after adjusting conventional confounding factors. However, the prognostic value of abnormal ABI is mainly dominated by a low ABI rather than a high ABI.

Relation between high Ankle-Brachial Index and cardiovascular outcomes in the general population and cardiovascular disease: a meta-analysis.

INTRODUCTION: Conflicting findings have been reported on the association between high Ankle-Brachial Index (ABI) and cardiovascular outcomes. This meta-analysis aimed to assess the association of abnormally high ABI and cardiovascular outcomes in the general population and suspected or established cardiovascular disease (CVD) patients. EVIDENCE ACQUISITION: A comprehensive literature search was conducted in PubMed and Embase databases through November 10th, 2018. All observational studies evaluating the association of high ABI with cardiovascular events including stroke, coronary heart disease (CHD), congestive heart failure, and composite of CVD/all-cause mortality in the general population and suspected or established CVD patients were included. We pooled risk ratios (RR) with 95% confidence intervals (CI) for the abnormally high ABI (> 1.3 or >1.4) versus the reference normal ABI category. EVIDENCE SYNTHESIS: We identified 10 cohort studies enrolling 39,421 participants. A random effect model meta-analysis indicated that the pooled RR of composite of CVD/all-cause mortality was 1.07 (95% CI 0.83-1.38) in the general population and 1.26 (95% CI 1.03-1.55) in suspected or established CVD patients. Moreover, participants with abnormally high ABI did not increase the risk of stroke (RR 1.60; 95% CI 0.83-3.06) and CHD (RR 1.40; 95% CI 0.87-2.24) in the general population. CONCLUSIONS: Abnormally high ABI appears to be associated with an increased risk of a composite of CVD/all-cause mortality in suspected or established CVD patients but not in the general population. However, additional well-designed studies are required to support the current findings.

The relationship between endothelial progenitor cells and pulmonary arterial hypertension in children with congenital heart disease.

BACKGROUND: Pulmonary arterial hypertension (PAH) caused by congenital heart disease (CHD) is very common in clinics. Some studies have shown that PAH is related to the number of endothelial progenitor cells (EPCs), but there is no report on the relationship between PAH and the number of EPCs in children with CHD. METHODS: In this study, a total of 173 cases with CHD (from 0 to 6 years old) were collected. According to the mean pulmonary arterial pressure (mPAP) measured by right heart catheterization, these cases were divided into PAH groups (including high PAH group, mPAP> 25 mmHg, n = 32, and the middle PAH group, 20 mmHg ≤ mPAP≤25 mmHg, n = 30) and non-PAH group (mPAP< 20 mmHg, n = 111). Peripheral blood was taken for flow cytometry, and the number of EPCs (CD133+/KDR+ cells) was counted. The number of EPCs /µL of peripheral blood was calculated using the following formula: EPCs /µL = WBC /L × lymphocytes % × EPCs % × 10- 6. RESULTS: The median EPCs of the non-PAH group, middle PAH group and high PAH group is 1.86/µL, 1.30 /µL and 0.98/µL, respectively. The mPAP decreases steadily as the level of EPCs increases (P < 0.05). After adjustment of gender, age and BMI, the number of EPCs was significantly associated with a decreased risk of high PAH (OR = 0.37, 95% CI: 0.16-0.87, P < 0.05). However, EPCs was not significantly associated with middle PAH (P > 0.05). CONCLUSION: The findings revealed that the EPCs and high PAH in patients with CHD correlate significantly and EPCs may become an effective treatment for PAH in patients with CHD. EPCs may be a protective factor of high PAH for children with CHD.

A simple method to remove a remnant sewing needle from the posterior pericardial cavity without cardiac arrest.

We reported a case of removing a remnant sewing needle without cardiac arrest from the posterior pericardial cavity after open-heart surgery for a 17-year-old male patient with atrial septal defect.

Visualizing the down-regulation of hTERT mRNA expression using gold-nanoflare probes and verifying the correlation with cancer cell apoptosis.

The human telomerase reverse transcriptase catalytic subunit (hTERT) is the rate-limiting subunit of the telomerase holoenzyme. Down-regulating the expression of hTERT mRNA by antisense oligonucleotides would reduce the expression of hTERT, inhibit telomerase activity, and impair the growth of cancer cells in vitro. In this work, we propose a locked nucleic acid-functionalized gold nanoparticle flare probe (AuNP-probe). After transferring these probes into cells by endocytosis of the gold nanoparticles, the binding process of the antisense locked nucleic acid with hTERT mRNA along with gene regulation can be visualized by fluorescence recovery of flare-sequences. A significant decline in hTERT mRNA levels and the hTERT content occurred in cancer cells after treatment with the AuNP-probes, and only approximately 25% of the original level of hTERT mRNA remained after 72 h. AuNP-probe treated cancer cells were arrested in the G1 phase of the cell cycle and underwent apoptosis; cell viability decreased obviously compared with that of telomerase-negative normal cells.

Dietary inflammatory index and depression: a meta-analysis.

OBJECTIVE: The purpose of the present meta-analysis was to evaluate the association between the inflammatory potential of diet, determined by the dietary inflammatory index (DII®) score, and depression. DESIGN: Systematic review and meta-analysis. SETTING: A comprehensive literature search was conducted in PubMed, Web of Science and EMBASE databases up to August 2018. All observational studies that examined the association of the DII score with depression/depressive symptoms were included. SUBJECTS: Four prospective cohorts and two cross-sectional studies enrolling a total of 49 584 subjects. RESULTS: Overall, individuals in the highest DII v. the lowest DII category had a 23 % higher risk of depression (risk ratio (RR)=1·23; 95 % CI 1·12, 1·35). When stratified by study design, the pooled RR was 1·25 (95 % CI 1·12, 1·40) for the prospective cohort studies and 1·16 (95 % CI 0·96, 1·41) for the cross-sectional studies. Gender-specific analysis showed that this association was observed in women (RR=1·25; 95 % CI 1·09, 1·42) but was not statistically significant in men (RR=1·15; 95 % CI 0·83, 1·59). CONCLUSIONS: The meta-analysis suggests that pro-inflammatory diet estimated by a higher DII score is independently associated with an increased risk of depression, particularly in women. However, more well-designed studies are needed to evaluate whether an anti-inflammatory diet can reduce the risk of depression.

In situ monitoring of cytoplasmic precursor and mature microRNA using gold nanoparticle and graphene oxide composite probes.

This study strategically fabricates a nucleic acid functionalized gold nanoparticle and graphene oxide composite probe (AuNP/GO probe) to achieve both the recognition and in situ monitoring of cytoplasmic target precursor microRNAs (pre-miRNAs) and mature microRNAs (miRNAs) in living cells. The pre-miRNA-21 detection with AuNP probes has a good linear range of 0-300 nM and a limit of detection (LOD) of 4.5 nM, whereas the GO probe has a linear relationship with mature miRNA-21 from 0.1 to 10 nM with a LOD of 1.74 nM. This assay was utilized to directly visualize the relative expression levels of pre- and mature forms of miRNA-21 and let-7a. The results suggested that the expression levels of precursor miRNAs remain constant in cancer cells and normal cells. However, the expression levels of mature miRNAs vary widely, demonstrating the "up-regulation" of miRNA-21 and "down-regulation" of let-7a in cancer cells in contrast to that in normal cells. The practicality of this strategy was verified by in situ monitoring changes in cytoplasmic pre-miRNA-21 and mature miRNA-21 in response to small-molecule inhibitors of miRNA-21.