Diagnosis and cardiac transplantation of a Carney syndrome-induced cardiac myxoma combined with dilated cardiomyopathy: a case report.

BACKGROUND: Carney syndrome is an uncommon autosomal disorder closely linked to mutations in the PRKAR1A gene. Skin lesions are the most pronounced feature of Carney syndrome, affecting over 80% of individuals with this condition. This syndrome is characterized by a triad of myxomas, skin pigmentation, and endocrine hyperfunction, featuring multiple endocrine neoplasms with skin and cardiac involvement. Dilated cardiomyopathy, a primary cardiomyopathy, is defined as the dilation and impaired systolic function of the left or both ventricles. Its clinical presentation varies from being asymptomatic to heart failure or sudden cardiac death, making it a leading global cause of heart failure. Currently, Dilated cardiomyopathy has an estimated prevalence of 1/2500-1/250 individuals, predominantly affecting those aged 30-40 years, with a male-to-female ratio of 3:1. This case report describes a heart failure patient with cardiac myxoma caused by Carney syndrome combined with dilated cardiomyopathy. The patient was successfully treated for heart failure by heart transplantation. CASE PRESENTATION: Herein, we report a case of heart failure due to Carney syndrome that resulted in cardiac myxoma combined with dilated cardiomyopathy. A 35-year-old male was admitted to the hospital three years ago because of sudden chest tightness and shortness of breath. Echocardiography indicated myxoma, and a combination of genetic screening and physical examination confirmed Carney syndrome with cardiac myxoma. Following symptomatic management, he was discharged. Surgical interventions were not considered at the time. However, the patient's chest tightness and shortness of breath symptoms worsened, and he returned to the hospital. A New York Heart Association grade IV heart function was confirmed, and echocardiography indicated the presence of dilated cardiomyopathy accompanied by cardiac myxoma. Ultimately, the patient's heart failure was successfully treated with heart transplantation. CONCLUSIONS: Cardiac myxoma caused by Carney syndrome combined with heart failure caused by dilated cardiomyopathy can be resolved by heart transplantation.

A Retrospective Study of the No-Contact Technique to Obtain Radial Arteries for Coronary Artery Bypass Grafting.

BACKGROUND: To retrospectively study the experience with application of no-touch technique in radial artery (RA)-based coronary artery bypass grafting (CABG). METHODS: Clinical data of patients who underwent RA-based multi- (n = 45) or full-arterial CABG (n = 27) between January 2019 and June 2022 in the Affiliated Hospital of ZunYi Medical University were collected. The incidence of main cardiovascular events at 30-day follow-up, the antebrachial union condition and the vessel patency rate were analyzed. RESULTS: A total of 66 RAs were harvested and 70 RAs used as grafts. The number of RA used per patient was 1.46. Delayed antebrachial union occurred in 1 patient (1.45%). There was no death, cerebral infarction, myocardial infarction or revascularization at follow-up. Early coronary computed tomography (CT) after surgery revealed occlusion in 1 RA, with the patency rate being 98.57%. CONCLUSIONS: The No-touch RA harvesting technique, preservation and postoperative management applied in this study are effective and rational, and the application of RA as the graft in CABG is safe.

Primary pericardial mesothelioma complicated by pericardial calcification.

BACKGROUND: Pericardial calcification is usually a marker of chronic diseases, and its occurrence in rapidly progressing malignant primary pericardial mesothelioma (PPM) is extremely rare. Therefore, this atypical imaging appearance contributes to more frequent misdiagnosis of PPM. However, no systematic summary currently exists of the imaging characteristics of malignant pericardial calcification in PPM. In our report, its clinical characteristics are discussed in detail, to provide a reference to reduce the misdiagnosis rates of PPM. CASE PRESENTATION: A 50-year-old female patient was admitted to our hospital, presenting primarily with features suggestive of cardiac insufficiency. Chest computed tomography revealed significant pericardial thickening and localized calcification, suspicious of constrictive pericarditis. A chest examination performed through a midline incision showed a chronically inflamed and easily-ruptured pericardium that was closely adherent to the myocardium. Post-operative pathological examination confirmed a diagnosis of primary pericardial mesothelioma. Six weeks postoperatively, the patient experienced symptom recurrence and abandoned chemotherapy and radiation therapy. Nine months postoperatively, the patient died of heart failure. CONCLUSION: We report this case to highlight the rare finding of pericardial calcification in patients with primary pericardial mesothelioma. This case illustrated that confirmation of pericardial calcification cannot completely rule out rapidly developing PPM. Therefore, understanding the different radiological features of PPM can help to reduce its rate of early misdiagnosis.

Successful management of Stanford type A aortic dissection with severe scoliosis in the setting of Marfan syndrome: a case report.

Background: Marfan syndrome (MFS) is a connective tissue disorder involving multiple organs. The most severe complications include aortic root dilatation and dissection. In the present report, we provide an uncommon case of acute aortic Stanford type A dissection (AADA) repair with severe scoliosis in an MFS patient and it is even more rare for such surgical treatment to be successfully completed along with holistic management that enables the patient to recover successfully. We offer a reference for future surgical therapy since the specific surgical treatment methods in this case have not been reported in the literature. Case Description: A 40-year-old Chinese female with MFS was rushed to our surgical clinic due to the sudden onset of intense chest pain. Physical examination revealed a diastolic murmur at the aortic valve area, increased arm and pectus carinatum deformity, severe scoliosis, acromicria, arachnodactyly, and planovalgus foot. Subsequently, AADA was discovered through computed tomography scan. In addition, echocardiogram revealed moderate aortic regurgitation and hydropericardium in small amount. Based on revised Ghent criteria, the patient was diagnosed with MFS complicated with aortic dissection. Emergency surgery was successfully performed for repair of the patient's aortic dissection and the diseased aortic valve. Postoperatively, the patient presented with a degree of respiratory insufficiency. However, the respiratory function was not greatly impaired, with good early intervention, such as taking deep breaths and coughing fully, active sputum suction, effective analgesia, ambulation and treadmill exercise. The patient finally recovered completely and was discharged 3 weeks later. Conclusions: We reported on a patient with severe scoliosis who successfully underwent surgical repair of AADA. Our report shows that the application of standard median sternotomy for repairing AADA offers the feasibility of implementation, on the basis of effectively solving various practical problems in the surgery brought about by scoliosis. It has been thoroughly assessed and addressed how the postoperative condition of such patients affects subsequent respiratory function and postoperative recovery. This report further provides a successful clinical reference for the implementation of this type of surgery and the postoperative management of respiratory function.

Dizziness Result From Anomalous Origin of Left Common Carotid Artery.

BACKGROUND: The anomalous origin of the left common carotid artery from the pulmonary artery is extremely scarce. At present, there are few relevant research and medical treatment data. This case is intended to provide relevant information and share treatment experiences. Case information: A 6-year-old child was diagnosed with patent ductus arteriosus and underwent surgery five years ago with occasional dizziness. After examination, it was found that the abnormality of her left common carotid artery originated from the pulmonary artery, and the patient underwent arterial ligation with the monitoring of cerebral oxygen consumption by near-infrared spectroscopy after careful preoperative evaluation. At present, it has been two years after the operation, and the patient is in good condition and has received regular follow-up. CONCLUSION: For patients with an abnormal left common carotid artery from the pulmonary artery, after careful preoperative evaluation such as cerebral angiography, under the monitoring of cerebral oxygen consumption by near-infrared spectroscopy, ligation of the proximal end of the artery of abnormal origin is safe and feasible.

Primary Osteosarcoma of Left Atrial Appendage in a Patient with Rheumatic Heart Disease.

Primary cardiac osteosarcoma is extremely rare, with all arising from the atrium, right ventricle, and cardiac valve, according to previous reports. We report a case of primary osteosarcoma of the left atrial appendage in a patient. We present a process of preoperative misdiagnosis, intraoperative confirmed diagnosis, and complete resection.

Case report: Traumatic ventricular aneurysm combining tricuspid valve avulsion in a child: Diagnostic findings and treatment protocols.

This case report is an extremely rare case of a traumatic left ventricular aneurysm in a 3-year-old child who also had tricuspid valve avulsion due to blunt trauma. The diagnostic findings and treatment protocols are discussed to provide a clinical reference.

PEG2000-DBCO surface coating increases intracellular uptake of liposomes by breast cancer xenografts.

Given our interest in the utility of liposomes for molecular imaging and theranostics, we investigated how coating the outer layer of the liposome affects internalization by breast cancer cell lines in vitro and in breast tumor tissues in vivo. Indeed, we discovered that a remarkably high liposomal uptake can be achieved by DBCO (dibenzocyclooctyne) soft coating. Our data demonstrates that decorating the terminal lipid with a DBCO moiety at a specific density induces increased tumor uptake in vivo (tumor uptake ~ 50%) compared to conventional undecorated liposome (tumor uptake ~ 20%). In this study, we report improved visualization of breast cancer cells in vivo using a 4T1 orthotopic breast cancer model and primary breast tumor xenograft models MDA-MB-231 and MDA-MB-436. L-PEG2000-DBCO coated liposomes demonstrate increased accumulation in breast cancer cells independent of tumor size, type, position, receptor expression, as well as the condition of the host mice. We expect these findings to have a major positive impact on the practical utility of liposomes in image-guided applications and precision medicine theranostics.

Cerebral infarction after cardiac surgery.

Cerebral infarction, a common central nervous system complication after adult cardiac surgery, is one of the main factors leading to the poor prognosis of cardiac surgery patients besides cardiac insufficiency. However, there is currently no effective treatment for cerebral infarction. Therefore, early prevention and diagnosis of postoperative cerebral infarction are particularly important. There are many factors and mechanisms during and after cardiac surgery that play an important role in the occurrence of postoperative cerebral infarction, such as intraoperative embolism, systemic inflammatory response syndrome, atrial fibrillation, temperature regulation, blood pressure control, use of postoperative blood products, and so forth. The mechanism by which most risk factors act on the human body, leading to postoperative cerebral infarction, is not well understood, and further research is needed. Therefore, this paper aims to summarize and explain the relevant risk factors, mechanisms, clinical signs, imaging characteristics, and early diagnosis methods of cerebral infarction complications after cardiac surgery, and provides useful data for the establishment of related diagnosis and treatment standards.

Experience in curing refractory gastrointestinal bleeding due to type A aortic dissection combined with mesenteric artery malperfusion: a case report.

Aortic dissection (AD) is a cardiovascular emergency that seriously endangers human health. It has acute onset, dangerous condition and many complications. The mortality without treatment is very high, and the mortality within 24 hours is 25%. AD combined with mesenteric artery malperfusion has an incidence of only 5%, but a hospital mortality rate of up to 33-100%. Mesenteric artery malperfusion increases the mortality of acute AD by 3-4 times. Even after complete revascularization, ischemia/reperfusion injury still leads to frequent postoperative deaths. In this paper, we describe the case of a 60-year-old man with type A aortic dissection and mesenteric artery malperfusion who developed refractory gastrointestinal bleeding postoperatively. He was cured after conservative, interventional, and surgical hemostasis, finally recovered and discharged. This case provides a certain reference value for clinical treatment of such diseases. Aortic dissection combined with mesenteric artery malperfusion is a significant surgical challenge. Ischemia/reperfusion injury may still occur after thoracotomy, even when the blood supply is normalized. Immediate surgery is recommended for preventing death from acute AD, but the strategy should be modified according to the specific symptoms and ischemic severity. In addition, interventional/surgical treatment should be performed more actively in patients with refractory gastrointestinal bleeding after cardiac surgery and a poor response to conservative treatment.

Novel late-stage radiosynthesis of 5-[18F]-trifluoromethyl-1,2,4-oxadiazole (TFMO) containing molecules for PET imaging.

Small molecules that contain the (TFMO) moiety were reported to specifically inhibit the class-IIa histone deacetylases (HDACs), an important target in cancer and the disorders of the central nervous system (CNS). However, radiolabeling methods to incorporate the [18F]fluoride into the TFMO moiety are lacking. Herein, we report a novel late-stage incorporation of [18F]fluoride into the TFMO moiety in a single radiochemical step. In this approach the bromodifluoromethyl-1,2,4-oxadiazole was converted into [18F]TFMO via no-carrier-added bromine-[18F]fluoride exchange in a single step, thus producing the PET tracers with acceptable radiochemical yield (3-5%), high radiochemical purity (> 98%) and moderate molar activity of 0.33-0.49 GBq/umol (8.9-13.4 mCi/umol). We validated the utility of the novel radiochemical design by the radiosynthesis of [18F]TMP195, which is a known TFMO containing potent inhibitor of class-IIa HDACs.

Mitochondria-associated protein LRPPRC exerts cardioprotective effects against doxorubicin-induced toxicity, potentially via inhibition of ROS accumulation.

Doxorubicin (DOX) has been widely employed to treat cancer, particularly solid tumors and hematological malignancies, owing to its high efficacy; however, chemotherapy has been indicated to be cardiotoxic and induce adverse effects, including mitochondrial dysfunction and DNA damage, which limits its application. The mitochondria-associated protein leucine-rich pentatricopeptide repeat-containing (LRPPRC) has been reported to serve critical regulatory roles in physiological processes via regulating mitochondrial function. The aim of the present study was to investigate the possible protective effects of LRPPRC against DOX-induced cardiac injury. In a DOX-induced cardiotoxicity model in H9C2 cells, LRPPRC was indicated to be transcriptionally upregulated and stabilize Bcl-2 and Bax. LRPPRC overexpression exhibited protective effects against proliferation and both apoptotic and non-apoptotic cell death following DOX treatment, but not under normal conditions. It was additionally observed that overexpressed LRPPRC reversed the decreases in ATP synthesis, mitochondrial mass and transcriptional activity, which were induced by DOX exposure. Overexpressed LRPPRC also decreased the accumulation of reactive oxygen species (ROS) under DOX treatment and inhibited cell death to a similar extent as N-acetyl-L-cysteine, which is a known ROS scavenger, indicating that LRPPRC potentially exerts protective effects via inhibiting ROS accumulation. Moreover, LRPPRC overexpression protected H9C2 cells against oxidative stress induced by H2O2, which also indicated its ROS-scavenging function. The present study demonstrated for the first time, to the best of our knowledge, that DOX-induced LRPPRC may exert cardioprotective effects via inhibiting ROS accumulation, thereby maintaining mitochondrial function.

Hypoxia modifies the polarization of macrophages and their inflammatory microenvironment, and inhibits malignant behavior in cancer cells.

Macrophages are a heterogeneous group of phagocytes that play critical roles in inflammation, infection and tumor growth. Macrophages respond to different environmental factors and are thereby polarized into specialized functional subsets. Although hypoxia is an important environmental factor, its impact on human macrophage polarization and subsequent modification of the inflammatory microenvironment have not been fully established. The present study aimed to elucidate the effect of hypoxia exposure on the ability of human macrophages to polarize into the classically activated (pro-inflammatory) M1, and the alternatively activated (anti-inflammatory) M2 phenotypes. The effect on the inflammatory microenvironment and the subsequent modification of A549 lung carcinoma cells was also investigated. The presented data show that hypoxia promoted macrophage polarization towards the M2 phenotype, and modified the inflammatory microenvironment by decreasing the release of proinflammatory cytokines. Modification of the microenvironment by proinflammatory M1 macrophages under hypoxia reversed the inhibition of malignant behaviors within the proinflammatory microenvironment. Furthermore, it was identified p38 signaling (a major contributor to the response to reactive oxygen species generated by hypoxic stress), but not hypoxia-induced factor, as a key regulator of macrophages under hypoxia. Taken together, the data suggest that hypoxia affects the inflammatory microenvironment by modifying the polarization of macrophages, and thus, reversing the inhibitory effects of a proinflammatory microenvironment on the malignant behaviors of several types of cancer cell.

Role of Phosphorylated AMP-Activated Protein Kinase (AMPK) in Myocardial Insulin Resistance After Myocardial Ischemia-Reperfusion During Cardiopulmonary Bypass Surgery in Dogs.

BACKGROUND The aim of this study was to determine the role of AMP-activated protein kinase (AMPK) in myocardial insulin resistance after myocardial ischemia-reperfusion during cardiopulmonary bypass surgery in dogs. MATERIAL AND METHODS Twenty-four mongrel dogs were randomly assigned to 4 groups. The control group did not undergo aortic cross-clamping; the model group underwent 60 mins of aortic cross-clamping with 150 ml cardioplegic solution. The treatment group, the inhibition group respectively with 0.11mg/kg AICAR (AMPK agonist) in 150 ml cardioplegic solution and 0.11mg/kg Compound C (AMPK inhibitor) in 150 ml cardioplegic solution. The blood flow was determined and left ventricular myocardial tissue were taken at pre-bypass, 15, 60, and 90 min after aorta declamping, respectively. Expression of AMPK mRNA, p-AMPK and GLUT-4 proteins was determined by RT-PCR, IHC and WB. RESULTS Compared with the control group, receiving 60 min ischemia at 15 min after reperfusion, Myocardial Glucose Extraction Ratio were significantly decreased in the other 3 groups, it was significantly decreased from 20.0% to 1.2% at 60 min of reperfusion, and recovered to 6.1% after 90 min reperfusion in model group, while recovered to 4.1%, 12.0% after 90 min reperfusion respectively exposed to Compound C and AICAR. The expressions of p-AMPK, GLUT-4 protein and AMPK mRNA in myocardium were decreased in different experiment groups, but these changes occurred to a lesser extent in the treatment group. CONCLUSIONS The inability of GLUT-4 expression induced by the decreases in p-AMPK protein expression that may be one of the reasons for myocardial insulin resistance.

Dual complementary liposomes inhibit triple-negative breast tumor progression and metastasis.

Distinguishing malignant cells from non-neoplastic ones is a major challenge in triple-negative breast cancer (TNBC) treatment. Here, we developed a complementary targeting strategy that uses precisely matched, multivalent ligand-receptor interactions to recognize and target TNBC tumors at the primary site and metastatic lesions. We screened a panel of cancer cell surface markers and identified intercellular adhesion molecule-1 (ICAM1) and epithelial growth factor receptor (EGFR) as optimal candidates for TNBC complementary targeting. We engineered a dual complementary liposome (DCL) that precisely complements the molecular ratio and organization of ICAM1 and EGFR specific to TNBC cell surfaces. Our in vitro mechanistic studies demonstrated that DCLs, compared to single-targeting liposomes, exhibited increased binding, enhanced internalization, and decreased receptor signaling. DCLs consistently exhibited substantially increased tumor targeting activity and antitumor efficacy in orthotopic and lung metastasis models, indicating that DCLs are a platform technology for the design of personalized nanomedicines for TNBC.

Peptide density targets and impedes triple negative breast cancer metastasis.

The C-X-C chemokine receptor type 4 (CXCR4, CD184) pathway is a key regulator of cancer metastasis. Existing therapeutics that block CXCR4 signaling are dependent on single molecule-receptor interactions or silencing CXCR4 expression. CXCR4 localizes in lipid rafts and forms dimers therefore CXCR4 targeting and signaling may depend on ligand density. Herein, we report liposomes presenting a CXCR4 binding peptide (DV1) as a three-dimensional molecular array, ranging from 9k to 74k molecules µm-2, target triple negative breast cancer (TNBC). TNBC cells exhibit a maxima in binding and uptake of DV1-functionalized liposomes (L-DV1) in vitro at a specific density, which yields a significant reduction in cell migration. This density inhibits metastasis from a primary tumor for 27 days, resulting from peptide density dependent gene regulation. We show that complementing cell membrane receptor expression may be a strategy for targeting cells and regulating signaling.

Nanoparticle elasticity directs tumor uptake.

To date, the role of elasticity in drug delivery remains elusive due to the inability to measure microscale mechanics and alter rheology without affecting chemistry. Herein, we describe the in vitro cellular uptake and in vivo tumor uptake of nanolipogels (NLGs). NLGs are composed of identical lipid bilayers encapsulating an alginate core, with tunable elasticity. The elasticity of NLGs was evaluated by atomic force microscopy, which demonstrated that they exhibit Young's moduli ranging from 45 ± 9 to 19,000 ± 5 kPa. Neoplastic and non-neoplastic cells exhibited significantly greater uptake of soft NLGs (Young's modulus <1.6 MPa) relative to their elastic counterparts (Young's modulus >13.8 MPa). In an orthotopic breast tumor model, soft NLGs accumulated significantly more in tumors, whereas elastic NLGs preferentially accumulated in the liver. Our findings demonstrate that particle elasticity directs tumor accumulation, suggesting that it may be a design parameter to enhance tumor delivery efficiency.

Effects of RNA silencing of matrix metalloproteinase-2 on the growth of esophageal carcinoma cells in vivo.

Esophageal carcinoma is one of the most common malignancies in China. Previous studies reported that matrix metalloproteinases (MMPs) have important roles in the progression and invasion of numerous types of solid tumors. Among the MMPs, MMP-2 has been closely associated with tumor growth and invasion. In the present study, a short hairpin RNA (shRNA) lentiviral expression vector targeting the MMP-2 gene was constructed in order to observe the inhibitory effect of MMP-2 gene silencing on the growth of the KYSE150 esophageal carcinoma cell line in vivo. Three small hairpin RNA sequences targeting MMP-2 were designed and cloned into lentiviral vectors. Following transfection of the lentiviral vectors into KTSE150 cells, MMP-2 mRNA and protein expression levels were examined by reverse transcription-quantitative polymerase chain reaction and western blotting, and the growth rate of cells was analyzed by MTT assays. Subsequently, tumor growth was assessed in nude mice. Lentivirus-mediated RNA interference effectively inhibited the expression of MMP-2 mRNA and protein in KYSE150 esophageal carcinoma cells, and suppressed the growth of esophageal carcinoma cells in vivo. The results of the present study suggested that lentivirus-mediated gene therapy targeting MMP-2 may be an attractive strategy for the treatment of esophageal carcinoma and justifies the performance of further studies on the application of lentivirus vectors to cancer gene therapy.

Cancer targeted therapeutics: From molecules to drug delivery vehicles.

The pitfall of all chemotherapeutics lies in drug resistance and the severe side effects experienced by patients. One way to reduce the off-target effects of chemotherapy on healthy tissues is to alter the biodistribution of drug. This can be achieved in two ways: Passive targeting utilizes shape, size, and surface chemistry to increase particle circulation and tumor accumulation. Active targeting employs either chemical moieties (e.g. peptides, sugars, aptamers, antibodies) to selectively bind to cell membranes or responsive elements (e.g. ultrasound, magnetism, light) to deliver its cargo within a local region. This article will focus on the systemic administration of anti-cancer agents and their ability to home to tumors and, if relevant, distant metastatic sites.

Metabolism targeting therapy of dichloroacetate-loaded electrospun mats on colorectal cancer.

Differences in energy metabolism between tumor cells and normal cells offer an attractive avenue of research into drug targets for tumor therapy. The use of a metabolic modulator (sodium dichloroacetate, DCA), administered in situ, to reverse the "Warburg effect" of tumor cells has been demonstrated as an effective tumor therapy. Herein, DCA and diisopropylamine dichloroacetate (DADA) were incorporated separately into polylactide (PLA) electrospun mats and applied to C26 tumor-bearing mice via in situ administration. After 12 d of treatment, the tumor suppression rates of 75% and 84% were achieved in the DC group (treated with a DCA-loaded mat) and the DA group (treated with a DADA-loaded mat), respectively. With tolerable physiologic toxicity under high local concentration, the DA group showed a 95% tumor suppression rate without any recurrence after 15 d of therapy. The desirable therapeutic effects of these metabolic modulators should ascribe to the energy-central metabolism-targeting effects of DCA and DADA, which were demonstrated both in vitro and in vivo. Therefore, DCA- and DADA-loaded mats are the effective anti-cancer drugs dosages to discriminate between tumor cells and normal cells for minimizing systemic toxicity.