Amphiregulin in lung diseases: A review.

Amphiregulin is a member of the EGFR family, which is involved in many physiological and pathological processes through its binding with EGFR. Studies have found that amphiregulin plays an important role in the occurrence and development of lung diseases. This paper mainly reviews the structure and function of amphiregulin and focuses on the important role of amphiregulin in lung diseases.

Risk factors associated with surgical site infections in patients undergoing cardiothoracic surgery: A systematic review and meta-analysis.

Surgical site infections (SSIs) following cardiothoracic surgery can pose significant challenges to patient recovery and outcome. This systematic review and meta-analysis aim to identify and quantify the risk factors associated with SSIs in patients undergoing cardiothoracic surgery. A comprehensive literature search adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and based on the PICO paradigm was conducted across four databases: PubMed, Embase, Web of Science and the Cochrane Library, without any temporal restrictions. The meta-analysis incorporated studies detailing the risk factors for post-operative sternal infections, especially those reporting odds ratios (OR) or relative risks with 95% confidence intervals (CI). Quality assessment of the studies was done using the Newcastle-Ottawa Scale. Statistical analysis was executed using the chi-square tests for inter-study heterogeneity, with further analyses depending on I2 values. Sensitivity analyses were performed, and potential publication bias was also assessed. An initial dataset of 2442 articles was refined to 21 articles after thorough evaluations based on inclusion and exclusion criteria. Patients with diabetes mellitus have an OR of 1.80 (95% CI: 1.40-2.20) for the incidence of SSIs, while obese patients demonstrate an OR of 1.63 (95% CI: 1.40-1.87). Individuals who undergo intraoperative blood transfusion present an OR of 1.13 (95% CI: 1.07-1.18), and smokers manifest an OR of 1.32 (95% CI: 1.03-1.60). These findings unequivocally indicate a pronounced association between these factors and an elevated risk of SSIs post-operatively. This meta-analysis confirms that diabetes, obesity, intraoperative transfusion and smoking heighten the risk of SSIs post-cardiac surgery. Clinicians should be alert to these factors to optimise patient outcomes.

MitraClip used for severe mitral regurgitation after surgery for type A aortic dissection combined with Marfan syndrome.

Mitral regurgitation is a rare but catastrophic condition in patients after surgery for type A aortic dissection. The second thoracotomy to complete the mitral valve operation could be fatal. Here, we report a case of severe mitral regurgitation treated with MitraClip in a 53-year-old woman after surgery for type A aortic dissection combined with Marfan syndrome. She was discharged uneventfully, and a significant reduction of regurgitation of mitral valve and tricuspid valve was observed at the 6-month follow-up. MitraClip could be an alternative device for such high-risk patients.

Epigenetic regulation of temozolomide resistance in human cancers with an emphasis on brain tumors: Function of non-coding RNAs.

Brain tumors, which are highly malignant, pose a significant threat to health and often result in substantial rates of mortality and morbidity worldwide. The brain cancer therapy has been challenging due to obstacles such as the BBB, which hinders effective delivery of therapeutic agents. Additionally, the emergence of drug resistance further complicates the management of brain tumors. TMZ is utilized in brain cancer removal, but resistance is a drawback. ncRNAs are implicated in various diseases, and their involvement in the cancer is particularly noteworthy. The focus of the current manuscript is to explore the involvement of ncRNAs in controlling drug resistance, specifically in the context of resistance to the chemotherapy drug TMZ. The review emphasizes the function of ncRNAs, particularly miRNAs, in modulating the growth and invasion of brain tumors, which significantly influences their response to TMZ treatment. Through their interactions with various molecular pathways, miRNAs are modulators of TMZ response. Similarly, lncRNAs also associate with molecular pathways and miRNAs, affecting the efficacy of TMZ chemotherapy. Given their functional properties, lncRNAs can either induce or suppress TMZ resistance in brain tumors. Furthermore, circRNAs, which are cancer controllers, regulate miRNAs by acting as sponges, thereby impacting the response to TMZ chemotherapy. The review explores the correlation between ncRNAs and TMZ chemotherapy, shedding light on the underlying molecular pathways involved in this process.

Bestrophin3 Deficiency in Vascular Smooth Muscle Cells Activates MEKK2/3-MAPK Signaling to Trigger Spontaneous Aortic Dissection.

BACKGROUND: Aortic dissection (AD) is a fatal cardiovascular disorder without effective medications due to unclear pathogenic mechanisms. Bestrophin3 (Best3), the predominant isoform of bestrophin family in vessels, has emerged as critical for vascular pathological processes. However, the contribution of Best3 to vascular diseases remains elusive. METHODS: Smooth muscle cell-specific and endothelial cell-specific Best3 knockout mice (Best3SMKO and Best3ECKO, respectively) were engineered to investigate the role of Best3 in vascular pathophysiology. Functional studies, single-cell RNA sequencing, proteomics analysis, and coimmunoprecipitation coupled with mass spectrometry were performed to evaluate the function of Best3 in vessels. RESULTS: Best3 expression in aortas of human AD samples and mouse AD models was decreased. Best3SMKO but not Best3ECKO mice spontaneously developed AD with age, and the incidence reached 48% at 72 weeks of age. Reanalysis of single-cell transcriptome data revealed that reduction of fibromyocytes, a fibroblast-like smooth muscle cell cluster, was a typical feature of human ascending AD and aneurysm. Consistently, Best3 deficiency in smooth muscle cells decreased the number of fibromyocytes. Mechanistically, Best3 interacted with both MEKK2 and MEKK3, and this interaction inhibited phosphorylation of MEKK2 at serine153 and MEKK3 at serine61. Best3 deficiency induced phosphorylation-dependent inhibition of ubiquitination and protein turnover of MEKK2/3, thereby activating the downstream mitogen-activated protein kinase signaling cascade. Furthermore, restoration of Best3 or inhibition of MEKK2/3 prevented AD progression in angiotensin II-infused Best3SMKO and ApoE-/- mice. CONCLUSIONS: These findings unveil a critical role of Best3 in regulating smooth muscle cell phenotypic switch and aortic structural integrity through controlling MEKK2/3 degradation. Best3-MEKK2/3 signaling represents a novel therapeutic target for AD.

Multimodality CT imaging contributes to improving the diagnostic accuracy of solitary pulmonary nodules: a multi-institutional and prospective study.

BACKGROUND: Solitary pulmonary nodules (SPNs) are one of the most common chest computed tomography (CT) abnormalities clinically. We aimed to investigate the value of non-contrast enhanced CT (NECT), contrast enhanced CT (CECT), CT perfusion imaging (CTPI), and dual- energy CT (DECT) used for differentiating benign and malignant SPNs with a multi-institutional and prospective study. PATIENTS AND METHODS: Patients with 285 SPNs were scanned with NECT, CECT, CTPI and DECT. Differences between the benign and malignant SPNs on NECT, CECT, CTPI, and DECT used separately (NECT combined with CECT, DECT, and CTPI were methods of A, B, and C) or in combination (Method A + B, A + C, B + C, and A + B + C) were compared by receiver operating characteristic curve analysis. RESULTS: Multimodality CT imaging showed higher performances (sensitivities of 92.81% to 97.60%, specificities of 74.58% to 88.14%, and accuracies of 86.32% to 93.68%) than those of single modality CT imaging (sensitivities of 83.23% to 85.63%, specificities of 63.56% to 67.80%, and accuracies of 75.09% to 78.25%, all p < 0.05). CONCLUSIONS: SPNs evaluated with multimodality CT imaging contributes to improving the diagnostic accuracy of benign and malignant SPNs. NECT helps to locate and evaluate the morphological characteristics of SPNs. CECT helps to evaluate the vascularity of SPNs. CTPI using parameter of permeability surface and DECT using parameter of normalized iodine concentration at the venous phase both are helpful for improving the diagnostic performance.

A circular network of purine metabolism as coregulators of dilated cardiomyopathy.

BACKGROUND: The crosstalk of purine biosynthesis and metabolism exists to balance the cell energy production, proliferation, survival and cytoplasmic environment stability, but disorganized mechanics of with respect to developing heart failure (HF) is currently unknown. METHODS: We conducted a multi-omics wide analysis, including microarray-based transcriptomes, and full spectrum metabolomics with respect to chronic HF. Based on expression profiling by array, we applied a bioinformatics platform of quantifiable metabolic pathway changes based on gene set enrichment analysis (GSEA), gene set variation analysis (GSVA), Shapley Additive Explanations (SHAP), and Xtreme Gradient Boosting (XGBoost) algorithms to comprehensively analyze the dynamic changes of metabolic pathways and circular network in the HF development. Additionally, left ventricular tissue from patients undergoing myocardial biopsy and transplantation were collected to perform the protein and full spectrum metabolic mass spectrometry. RESULTS: Systematic bioinformatics analysis showed the purine metabolism reprogramming was significantly detected in dilated cardiomyopathy. In addition, this result was also demonstrated in metabolomic mass spectrometry. And the differentially expressed metabolites analysis showing the guanine, urea, and xanthine were significantly detected. Hub markers, includes IMPDH1, ENTPD2, AK7, AK2, and CANT1, also significantly identified based on XGBoost, SHAP model and PPI network. CONCLUSION: The crosstalk in the reactions involved in purine metabolism may involving in DCM metabolism reprogramming, and as coregulators of development of HF, which may identify as potential therapeutic targets. And the markers of IMPDH1, ENTPD2, AK7, AK2, and CANT1, and metabolites involved in purine metabolism shown an important role.

Reconstruction of aortic sinus using patches in patients with acute type A aortic dissection.

OBJECTIVES: Acute type A aortic dissection involving the aortic sinus is often combined with varying degrees of aortic regurgitation, while the structure of the aortic valve is often undamaged. The aim of this study was to evaluate the clinical effects of reconstruction of the aortic sinus using patches in patients with acute type A aortic dissection. METHODS: From January 2016 to December 2019, 52 patients with acute type A aortic dissection involving the aortic sinus were treated with aortic sinus reconstruction using pericardial or artificial vascular patches. The clinical and follow-up data were summarized. RESULTS: Bovine pericardial patches were used in 31 cases and artificial vascular patches were used in 21 cases for aortic sinus reconstruction. Cardiopulmonary bypass time was (250.4 ± 65.7) min, aortic cross clamp time was (143.7 ± 42.3) min, and hypothermic circulatory arrest time was (9.6 ± 8.1) min. Three patients died in hospital, with a mortality rate of 5.8%. Fifteen patients (28.8%) had mild postoperative aortic regurgitation. The follow-up duration was 40 ± 12 (range, 21-66) months. Five patients (10.2%) developed moderate to severe aortic regurgitation and 3 (6.1%) died during the follow-up period. CONCLUSIONS: The application of patches for aortic sinus reconstruction is a relatively easy method in aortic valve-sparing root reconstruction for acute type A aortic dissection involving the aortic sinus. The clinical and follow-up results are favorable.

Radiomics and Its Applications and Progress in Pancreatitis: A Current State of the Art Review.

Radiomics involves high-throughput extraction and analysis of quantitative information from medical images. Since it was proposed in 2012, there are some publications on the application of radiomics for (1) predicting recurrent acute pancreatitis (RAP), clinical severity of acute pancreatitis (AP), and extrapancreatic necrosis in AP; (2) differentiating mass-forming chronic pancreatitis (MFCP) from pancreatic ductal adenocarcinoma (PDAC), focal autoimmune pancreatitis (AIP) from PDAC, and functional abdominal pain (functional gastrointestinal diseases) from RAP and chronic pancreatitis (CP); and (3) identifying CP and normal pancreas, and CP risk factors and complications. In this review, we aim to systematically summarize the applications and progress of radiomics in pancreatitis and it associated situations, so as to provide reference for related research.

A comparative study on adsorption of cadmium and lead by hydrochars and biochars derived from rice husk and Zizania latifolia straw.

In this study, hydrochars and biochars were prepared from rice husk (RH) and Zizania latifolia straw (ZL) at various pyrolysis temperatures as absorbents, for removing toxic ions from single and competitive solutions of cadmium (Cd) and/or lead (Pb). The adsorption efficiencies of Cd and Pb in both hydrochars and biochars were lower in the competitive solution than in the single solution, and the absorbents had a stronger affinity for Pb than for Cd. Compared to hydrochars, biochars showed more favorable Cd and Pb adsorption capacities in the single or competitive solutions, and the ZL biochars had the maximum adsorption capacity among them. The SEM and FTIR analyses suggest that the predominant adsorption mechanisms of biochars and hydrochars are surfaces monolayer adsorption, precipitation, complexation, and coordination with π electrons. However, hydrochars derived from ZL exhibited an optimal additional Pb adsorption capacity in the high-level (5 ~ 10 mg L-1 Cd and Pb) competitive solution. This extra Pb adsorption of hydrochars was likely attributed to the Si-O-Si groups and more bumpy structure. Zizania latifolia straw biochar had a huge potential removal of Cd or/and Pb, and applying hydrochars as absorbents was beneficial to the removal of Cd and Pb in polluted solutions.

Aortic Repair Through a Left Thoracotomy in a 12-Year-Old Child with Traumatic Aortic Pseudoaneurysm: A Case Report.

Traumatic pseudoaneurysm of the descending aorta is a rare but life-threatening disease, especially in children. Open surgical replacement and thoracic endovascular repair in treating traumatic pseudoaneurysm to prevent aortic rupture rarely have been reported in children. Here, we present a rare case of aortic pseudoaneurysm caused by trauma in a 12-year-old child treated with an alternative surgical strategy. Aortic repair without an implant assisted by distal perfusion was performed through a left thoracotomy. The child satisfactorily recovered, was discharged, and remained in a good condition during the follow-up period.

PGAM5-Mediated PHB2 Dephosphorylation Contributes to Diabetic Cardiomyopathy by Disrupting Mitochondrial Quality Surveillance.

Disruption of the mitochondrial quality surveillance (MQS) system contributes to mitochondrial dysfunction in diabetic cardiomyopathy (DCM). In this study, we observed that cardiac expression of phosphoglycerate mutase 5 (PGAM5), a mitochondrial Ser/Thr protein phosphatase, is upregulated in mice with streptozotocin-induced DCM. Notably, DCM-related cardiac structural and functional deficits were negated in cardiomyocyte-specific Pgam5 knockout (Pgam5CKO ) mice. Hyperglycemic stress impaired adenosine triphosphate production, reduced respiratory activity, and prolonged mitochondrial permeability transition pore opening in acutely isolated neonatal cardiomyocytes from control Pgam5f/f mice, and these effects were markedly prevented in cardiomyocytes from Pgam5CKO mice. Likewise, three main MQS-governed processes-namely, mitochondrial fission/fusion cycling, mitophagy, and biogenesis-were disrupted by hyperglycemia in Pgam5f/f , but not in Pgam5CKO , cardiomyocytes. On the basis of bioinformatics prediction of interaction between PGAM5 and prohibitin 2 (PHB2), an inner mitochondrial membrane-associated scaffolding protein, co-immunoprecipitation, and immunoblot assays demonstrated that PGAM5 dephosphorylates PHB2 on Ser91. Transfection of cardiomyocytes with phosphodefective or phosphomimetic Ser91 mutants of PHB2 confirmed a critical role for PGAM5-mediated dephosphorylation of PHB2 in mitochondrial dysfunction associated with hyperglycemic stress. Furthermore, knockin mice expressing phosphomimetic PHB2S91D were resistant to diabetes-induced cardiac dysfunction. Our findings highlight the PGAM-PHB2 axis as a novel and critical regulator of mitochondrial dysfunction in DCM.

Outcomes of long versus short stent cronus hybrid prosthesis in type A aortic dissection: A single centre experience.

OBJECTIVES: The frozen elephant trunk (FET) technique has become an important tool in the treatment of acute type A aortic dissection. The aim of this study was to evaluate the effect of long FET on spinal cord injury (SCI) and distal aortic remodeling after acute type A aortic dissection based on clinical and radiological outcomes. METHODS: From January 2018 to November 2019, 158 patients (mean age 51.8 years [range: 32-78 years], 88.6% male) with acute type A aortic dissection were treated by FET with 100 mm (n = 113) or 150 mm (n = 45) open hybrid stent graft prosthesis. Patients were divided into two groups according to the length of FET. The clinical and radiological outcomes of the patients were reviewed retrospectively. RESULTS: Postoperative outcomes did not differ significantly: in-hospital mortality (9.7% vs. 6.7%, p = .758) and SCI (5.3% vs. 2.2%, p = .674). Aortic remodeling, which was evaluated by aortic diameter, true lumen diameter, false lumen (FL) diameter and the rate of FL complete thrombosis, was more positive in long FET group in the descending thoracic aorta during the follow-up period. At the abdominal level, there was no statistically significant difference between the two groups. CONCLUSIONS: The long version of FET does not increase the risk of SCI in patients with acute type A aortic dissection. The application of long FET can achieve better results in terms of remodeling of the thoracic aorta in the short- and medium-term follow-up.

The Pulsatile Modification Improves Hemodynamics and Attenuates Inflammatory Responses in Extracorporeal Membrane Oxygenation.

BACKGROUND: COVID-19 is still a worldwide pandemic and extracorporeal membrane oxygenation (ECMO) is vital for extremely critical COVID-19 patients. Pulsatile flow impacts greatly on organ function and microcirculation, however, the effects of pulsatile flow on hemodynamics and inflammatory responses during ECMO are unknown. An in vivo study was launched aiming at comparing the two perfusion modes in ECMO. METHODS: Fourteen beagles were randomly allocated into two groups: the pulsatile group (n=7) and the non-pulsatile group (n=7). ECMO was conducted using the i-Cor system for 24 hours. Hemodynamic parameters including surplus hemodynamic energy (SHE), energy equivalent pressure (EEP), oxygenator pressure drop (OPD), and circuit pressure drop (CPD) were monitored. To assess inflammatory responses during ECMO, levels of tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, IL-8, and transforming growth factor-ß1 (TGF-ß1) were measured. RESULTS: EEP and SHE were markedly higher in pulsatile circuits when compared with the conventional circuits. Between-group differences in both OPD and CPD reached statistical significance. Significant decreases in TNF-α were seen in animals treated with pulsatile flows at 2 hours, 12 hours, and 24 hours as well as a decrease in IL-1ß at 24 hours during ECMO. The TGF-ß1 levels were significantly higher in pulsatile circuits from 2 hours to 24 hours. The changes in IL-6 and IL-8 levels were insignificant. CONCLUSION: The modification of pulsatility in ECMO generates more hemodynamic energies and attenuates inflammatory responses as compared to the conventional non-pulsatile ECMO.

Astilbin Protects Against Carbon Tetrachloride-Induced Liver Fibrosis in Rats.

BACKGROUND: Hepatic fibrosis is an inflammatory liver disease, and there is no effective therapy at present. Astilbin is a bioactive ingredient found in many medicinal and food plants, with antioxidative, anti-inflammatory, and antitumor properties. OBJECTIVES: This study aimed to investigate the protective effect and related molecular mechanism of astilbin against carbon tetrachloride (CCl4)-induced liver fibrosis in rats. METHODS: Liver fibrosis was induced by injection of CCl4 in male Sprague-Dawley rats, and those rats were then treated with astilbin at different concentrations. Pathological changes, collagen production, inflammatory cytokine, and oxidative stress were evaluated to evaluate the effects of astilbin on CCl4-induced hepatic fibrosis. Real-time PCR and western blot were performed to detect the mRNA and protein expression of indicated genes. RESULTS: We discovered that CCl4 caused significant fibrosis damage in rat liver, and astilbin dose-dependently improved the liver functions and fibrosis degree. Astilbin treatment significantly decreased collagen production, inflammatory response, and oxidative stress in vivo. Mechanically, administration of astilbin obviously elevated the hepatic levels of Nrf2 and its downstream components, including NAD(P)H:quinone oxidoreductase 1 (Nqo1), heme oxygenase (HO-1), glutamate-cysteine ligase catalytic subunit, and glutamate cysteine ligase modifier. CONCLUSIONS: Taken together, these findings demonstrate that astilbin could protect against CCL4 induced-liver fibrosis in rats.

An aorto-oesophageal fistula treated with total arch repair combined with oesophageal repair.

Aorto-oesophageal fistula is a rare but fatal disease. Open surgical repair or endotube repair of aorta and oesophagus save patients from circulatory deterioration, major haematemesis and severe infection. Here we present a rare case of an aorto-oesophageal fistula in the right hemi-arch caused by a fish bone treated with an alternative surgical strategy. Total aortic arch repair using the frozen elephant trunk procedure combined with oesophageal repair were performed. No aortic fistula, oesophageal fistula or artificial graft infection occurred in the follow-up.

Dihydroquercetin Activates AMPK/Nrf2/HO-1 Signaling in Macrophages and Attenuates Inflammation in LPS-Induced Endotoxemic Mice.

Dihydroquercetin (DHQ) is a flavonoid compound known for its anti-oxidant effects. Oxidative stress plays a dominant role in regulating the pathways associated with systemic inflammatory immune activation during endotoxemia. Whether and how DHQ regulates inflammatory responses in endotoxemia remains elusive. Here we show DHQ pretreatment effectively reduced the Ten-day mortality in bacterial endotoxin lipopolyssacharide (LPS)-challenged mice, suppressing LPS-induced inflammatory responses reflected by impaired production of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in the serum of mice. In Raw 264.7 cells, DHQ pretreatment significantly inhibited the transcriptional upregulation of TNF-α, interferon-γ (IFN-γ), interleukin-10 (IL-10) and toll-like receptor 4 (TLR-4) after LPS stimulation. Additionally, knockdown of heme oxygenase-1 (HO-1), one of the most important DHQ induced antioxidant genes, cancelled the inhibition of DHQ treatment on LPS induced TNF-α, IFN-γ production. Nuclear factor erythroid 2-related factor 2 (Nrf2) expression and AMP-activated protein kinase (AMPK) phosphorylation were both enhanced by DHQ in Raw 264.7 cells, indicating a DHQ induced AMPK/Nrf2/HO-1 signal axis. In conclusion, DHQ pretreatment could protect mice against the inflammation and mortality associated with endotoxemia.