The regulation of circRNA and lncRNAprotein binding in cardiovascular diseases: Emerging therapeutic targets.

Noncoding ribonucleic acids (ncRNAs) are a class of ribonucleic acids (RNAs) that carry cellular information and perform essential functions. This class encompasses various RNAs, such as small nuclear ribonucleic acids (snRNA), small interfering ribonucleic acids (siRNA) and many other kinds of RNA. Of these, circular ribonucleic acids (circRNAs) and long noncoding ribonucleic acids (lncRNAs) are two types of ncRNAs that regulate crucial physiological and pathological processes, including binding, in several organs through interactions with other RNAs or proteins. Recent studies indicate that these RNAs interact with various proteins, including protein 53, nuclear factor-kappa B, vascular endothelial growth factor, and fused in sarcoma/translocated in liposarcoma, to regulate both the histological and electrophysiological aspects of cardiac development as well as cardiovascular pathogenesis, ultimately leading to a variety of genetic heart diseases, coronary heart disease, myocardial infarction, rheumatic heart disease and cardiomyopathies. This paper presents a thorough review of recent studies on circRNA and lncRNAprotein binding within cardiac and vascular cells. It offers insight into the molecular mechanisms involved and emphasizes potential implications for treating cardiovascular diseases.

Proarrhythmic toxicity of low dose bisphenol A and its analogs in human iPSC-derived cardiomyocytes and human cardiac organoids through delay of cardiac repolarization.

Bisphenol A (BPA) and its analogs are common environmental chemicals with many potential adverse health effects. The impact of environmentally relevant low dose BPA on human heart, including cardiac electrical properties, is not understood. Perturbation of cardiac electrical properties is a key arrhythmogenic mechanism. In particular, delay of cardiac repolarization can cause ectopic excitation of cardiomyocytes and malignant arrhythmia. This can occur as a result of genetic mutations (i.e., long QT (LQT) syndrome), or cardiotoxicity of drugs and environmental chemicals. To define the impact of low dose BPA on electrical properties of cardiomyocytes in a human-relevant model system, we examined the rapid effects of 1 nM BPA in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) using patch-clamp and confocal fluorescence imaging. Acute exposure to BPA delayed repolarization and prolonged action potential duration (APD) in hiPSC-CMs through inhibition of the hERG K+ channel. In nodal-like hiPSC-CMs, BPA acutely increased pacing rate through stimulation of the If pacemaker channel. Existing arrhythmia susceptibility determines the response of hiPSC-CMs to BPA. BPA resulted in modest APD prolongation but no ectopic excitation in baseline condition, while rapidly promoted aberrant excitations and tachycardia-like events in myocytes that had drug-simulated LQT phenotype. In hiPSC-CM-based human cardiac organoids, the effects of BPA on APD and aberrant excitation were shared by its analog chemicals, which are often used in "BPA-free" products, with bisphenol AF having the largest effects. Our results reveal that BPA and its analogs have repolarization delay-associated pro-arrhythmic toxicity in human cardiomyocytes, particularly in myocytes that are prone to arrhythmias. The toxicity of these chemicals depends on existing pathophysiological conditions of the heart, and may be particularly pronounced in susceptible individuals. An individualized approach is needed in risk assessment and protection.

Atrial fibrillation and breast cancer-Vicious twins? A systematic review and meta-analysis.

Background: Epidemiological studies suggest a bidirectional association between atrial fibrillation and breast cancer. This study aimed to conduct a meta-analysis to elucidate the prevalence of atrial fibrillation among breast cancer patients, and the bidirectional association between atrial fibrillation and breast cancer. Methods: PubMed, the Cochrane Library, and Embase were searched to identify studies reporting the prevalence, incidence, and bidirectional association between atrial fibrillation and breast cancer. The study was registered with PROSPERO (CRD42022313251). Levels of evidence and recommendations were assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE). Results: Twenty-three studies (17 retrospective cohort studies, 5 case-control studies and 1 cross-sectional study) involving 8,537,551 participants were included. Among patients with breast cancer, the prevalence of atrial fibrillation was 3% (11 studies; 95% CI: 0.6 to 7.1%) and the incidence was 2.7% (6 studies; 95% CI: 1.1 to 4.9%). Breast cancer was associated with increased risk of atrial fibrillation (5 studies; hazard ratio [HR]: 1.43, 95% CI: 1.12 to 1.82, I2 = 98%). Atrial fibrillation was also significantly associated elevated risk of breast cancer (5 studies HR: 1.18, 95% CI: 1.14 to 1.22, I2 = 0%). Grade assessment shown low certainty of the evidence for the risk of atrial fibrillation and moderate certainty of the evidence for the risk of breast cancer. Conclusion: Atrial fibrillation is not uncommon in patients with breast cancer and vice versa. There is a bidirectional association between atrial fibrillation (low certainty) and breast cancer (moderate certainty).

Acute exposure to low-dose bisphenol A delays cardiac repolarization in female canine heart - Implication for proarrhythmic toxicity in large animals.

Bisphenol A (BPA) is a common environmental chemical with a range of potential adverse health effects. The impact of environmentally-relevant low dose of BPA on the electrical properties of the hearts of large animals (e.g., dog, human) is poorly defined. Perturbation of cardiac electrical properties is a key arrhythmogenic mechanism. In particular, delay of ventricular repolarization and prolongation of the QT interval of the electrocardiogram is a marker for the risk of malignant arrhythmias. We examined the acute effect of 10-9 M BPA on the electrical properties of female canine ventricular myocytes and tissues. BPA rapidly delayed action potential repolarization and prolonged action potential duration (APD). The dose response curve of BPA on APD was nonmonotonic. BPA rapidly inhibited the IKr K+ current and ICaL Ca2+ current. Computational modeling indicated that the effect of BPA on APD can be accounted for by its suppression of IKr. At the tissue level, BPA acutely prolonged the QT interval in 4 left ventricular wedges. ERß signaling contributed to the acute effects of BPA on ventricular repolarization. Our results demonstrate that BPA has QT prolongation liability in female canine hearts. These findings have implication for the potential proarrhythmic cardiac toxicity of BPA in large animals.

Liver fibrosis scores and prognosis in patients with cardiovascular diseases: A systematic review and meta-analysis.

BACKGROUND: In patients with nonalcoholic fatty liver disease, liver fibrosis was associated with a higher risk of cardiovascular events. However, the relationship between liver fibrosis scores and clinical outcomes in patients with cardiovascular disease remains unclear. METHODS: Searching from PubMed, EMBASE and Cochrane Library databases yielded cohort studies that reported adjusted effect size between liver fibrosis scores (Fibrosis-4 score [FIB-4] or NAFLD fibrosis score [NFS]) and prognosis in patients with cardiovascular disease. The effect size was computed using a random-effects model. RESULTS: This meta-analysis included twelve cohort studies involving 25,252 patients with cardiovascular disease. Participants with the highest baseline level of FIB-4 or NFS had a significantly increased risk of cardiovascular events (FIB-4, HR: 1.75, 95% CI: 1.53-2.00, I 2  = 0%; NFS, HR: 1.92, 95% CI: 1.50-2.47, I 2  = 47%). This finding was consistent with the analysis of FIB-4 or NFS as a continuous variable (per 1-unit increment FIB-4, HR: 1.15, 95% CI: 1.06-1.24, I 2  = 72%; NFS, HR: 1.15, 95% CI: 1.07-1.24, I 2  = 71%). Furthermore, participants with the highest levels of FIB-4 or NFS had a greater risk of cardiovascular mortality (FIB-4, HR: 2.07, 95% CI: 1.19-3.61, I 2  = 89%; NFS, HR: 3.72, 95% CI: 2.62-5.29, I 2  = 60%) and all-cause mortality (FIB-4, HR: 1.81, 95% CI: 1.24-2.66, I 2  = 90%; NFS, HR: 3.49, 95% CI: 2.82-4.31, I 2  = 25%). This result was also consistent as a continuous variable. CONCLUSION: Higher levels of FIB-4 and NFS are related to an increased risk of cardiovascular events, cardiovascular mortality and all-cause mortality in patients with cardiovascular disease.

Hydrogels for localized chemotherapy of liver cancer: a possible strategy for improved and safe liver cancer treatment.

The systemic drug has historically been preferred for the treatment of the majority of pathological conditions, particularly liver cancer. Indeed, this mode of treatment is associated with adverse reactions, toxicity, off-target accumulation, and rapid hepatic and renal clearance. Numerous efforts have been made to design systemic therapeutic carriers to improve retention while decreasing side effects and clearance. Following systemic medication, local administration of therapeutic agents allows for higher 'effective' doses with fewer side effects, kidney accumulation, and clearance. Hydrogels are highly biocompatible and can be used for both imaging and therapy. Hydrogel-based drug delivery approach has fewer side effects than traditional chemotherapy and can deliver drugs to tumors for a longer time. The chemical and physical flexibility of hydrogels can be used to achieve disease-induced in situ accumulation as well as subsequent drug release and hydrogel-programmed degradation. Moreover, they can act as a biocompatible depot for localized chemotherapy when stimuli-responsive carriers are administrated. Herein, we summarize the design strategies of various hydrogels used for localized chemotherapy of liver cancer and their delivery routes, as well as recent research on smart hydrogels.

IL-6 and IL-8 are likely associated with psychological status in treatment naïve general population.

BACKGROUND: Levels of inflammatory markers are elevated in patients with psychological disorders. However, anti-psychological drugs have an effect on proinflammatory cytokine production and disturb their relationship. Limited evidence focuses on the inflammatory marker profile of psychological status before treatment. This study aimed to investigate the inflammatory biomarker profiles of psychological treatment-naive individuals. METHODS: We included 790 psychological treatment-naive individuals from a longitudinal cohort study of Midlife in the United States (MIDUS). Symptoms of depression, anxiety, and stress were assessed by the Center for Epidemiologic Studies Depression Scale (CES-D) subscales, the Social Anxiety Scale (STAI), and Liebowitz Social Anxiety Scale (LSAS), the Perceived Stress Scale (PSS), respectively. RESULTS: Spearman correlation analysis showed that a higher CESD total score was correlated with higher CRP (p=0.009), IL-6 (p=0.007), fibrinogen (p=0.036), E-selectin (p=0.018), ICAM-1 (p=0.013), and IL-8 (p=0.05) levels. Multivariate linear regression analysis showed that the CESD total score was positively associated with the levels of IL-6 (p=0.024) after adjustments. Moreover, the perceived stress score (PSS) was negatively associated with the levels of IL-8 (p=0.025). However, these associations were not significant after multiple testing (p=0.088, 0.091, respectively). LIMITATIONS: The casual relationship cannot be drawn due to the cross-sectional design CONCLUSION: Overall, our results suggested IL-6 and IL-8 might play a important role in the pathogenesis of psychological disorder. Larger and longitude studies are needed to confirm our results.

Effectiveness and Safety of DOACs vs. VKAs in AF Patients With Cancer: Evidence From Randomized Clinical Trials and Observational Studies.

Background: The use of direct oral anticoagulants (DOACs) is recommended as the preferred treatment drug in patients with nonvalvular atrial fibrillation (AF). However, the effectiveness and safety of DOACs compared with vitamin K antagonists (VKAs) in patients with cancer and AF are still controversial. Therefore, we performed a meta-analysis regarding the effectiveness and safety of DOACs vs. VKAs in AF patients with cancer. Methods: A search of the Pubmed and EMBASE databases until August 2021 was performed. Adjusted risk ratios (RRs) and 95% confidence intervals (CIs) were pooled using a random-effects model with an inverse variance method. Results: Thirteen studies were deemed to meet the criteria. For the effectiveness outcomes, the use of DOACs compared with VKAs use was significantly associated with decreased risks of stroke or systemic embolism (RR = 0.66, 95% CI: 0.54-0.80) and venous thromboembolism (RR = 0.40, 95% CI: 0.26-0.61), but not ischemic stroke (RR = 0.79, 95% CI: 0.56-1.11), myocardial infarction (RR = 0.78, 95% CI: 0.56-1.11), cardiovascular death (RR = 0.76, 95% CI: 0.53-1.09), and all-cause death (RR = 0.82, 95% CI: 0.43-1.56). For the safety outcomes, compared with VKAs use, the use of DOACs was associated with reduced risks of intracranial bleeding (RR = 0.60, 95% CI: 0.50-0.71) and gastrointestinal bleeding (RR = 0.87, 95% CI: 0.80-0.95). There were no significant differences in major bleeding (RR = 0.87, 95% CI: 0.74-1.04), major or nonmajor clinically relevant bleeding (RR = 0.87, 95% CI: 0.74-1.01), and any bleeding (RR = 0.88, 95% CI: 0.76-1.03). Conclusion: Compared with VKAs, DOACs appeared to have significant reductions in stroke or systemic embolism, venous thromboembolism, intracranial bleeding, and gastrointestinal bleeding, but comparable risks of ischemic stroke, myocardial infarction, cardiovascular death, all-cause death, major bleeding, major or nonmajor clinically relevant bleeding, and any bleeding in patients with AF and cancer.

Dose-response relationship among body mass index, abdominal adiposity and atrial fibrillation in patients undergoing cardiac surgery: a meta-analysis of 35 cohorts.

BACKGROUND: Whether overweight increases the risk of postoperative atrial fibrillation (POAF) is unclear, and whether adiposity independently contributes to POAF has not been comprehensively studied. Thus, we conducted a meta-analysis to clarify the strength and shape of the exposure-effect relationship between adiposity and POAF. METHODS: The PubMed, Cochrane Library, and EMBASE databases were searched for revelant studies (randomized controlled trials (RCTs), cohort studies, and nest-case control studies) reporting data regarding the relationship between adiposity and the risk of POAF. RESULTS: Thirty-five publications involving 33,271 cases/141,442 patients were included. Analysis of categorical variables showed that obesity (RR: 1.39, 95% CI [1.21-1.61]; P < 0.001), but not being underweight (RR: 1.44, 95% CI [0.90-2.30]; P = 0.13) or being overweight (RR: 1.03, 95% CI [0.95-1.11]; P = 0.48) was associated with an increased risk of POAF. In the exposure-effect analysis (BMI) was 1.09 (95% CI [1.05-1.12]; P < 0.001) for the risk of POAF. There was a significant linear relationship between BMI and POAF (Pnonlinearity = 0.44); the curve was flat and began to rise steeply at a BMI of approximately 30. Notably, BMI levels below 30 (overweight) were not associated with a higher risk of POAF. Additionally, waist obesity or visceral adiposity index was associated with the risk of POAF. CONCLUSION: Based on the current evidence, our findings showed that high body mass index or abdominal adiposity was independently associated with an increased risk of POAF, while underweight or overweight might not significantly increase the POAF risk.

Impaired Right Ventricular Calcium Cycling Is an Early Risk Factor in R14del-Phospholamban Arrhythmias.

The inherited mutation (R14del) in the calcium regulatory protein phospholamban (PLN) is linked to malignant ventricular arrhythmia with poor prognosis starting at adolescence. However, the underlying early mechanisms that may serve as prognostic factors remain elusive. This study generated humanized mice in which the endogenous gene was replaced with either human wild type or R14del-PLN and addressed the early molecular and cellular pathogenic mechanisms. R14del-PLN mice exhibited stress-induced impairment of atrioventricular conduction, and prolongation of both ventricular activation and repolarization times in association with ventricular tachyarrhythmia, originating from the right ventricle (RV). Most of these distinct electrocardiographic features were remarkably similar to those in R14del-PLN patients. Studies in isolated cardiomyocytes revealed RV-specific calcium defects, including prolonged action potential duration, depressed calcium kinetics and contractile parameters, and elevated diastolic Ca-levels. Ca-sparks were also higher although SR Ca-load was reduced. Accordingly, stress conditions induced after contractions, and inclusion of the CaMKII inhibitor KN93 reversed this proarrhythmic parameter. Compensatory responses included altered expression of key genes associated with Ca-cycling. These data suggest that R14del-PLN cardiomyopathy originates with RV-specific impairment of Ca-cycling and point to the urgent need to improve risk stratification in asymptomatic carriers to prevent fatal arrhythmias and delay cardiomyopathy onset.

Hydrogen sulfide restores sevoflurane postconditioning mediated cardioprotection in diabetic rats: Role of SIRT1/Nrf2 signaling-modulated mitochondrial dysfunction and oxidative stress.

Diabetic hearts are vulnerable to myocardial ischemia/reperfusion injury (IRI), but are insensitive to sevoflurane postconditioning (SPC), activating peroxiredoxins that confer cardioprotection. Previous studies have demonstrated that hydrogen sulfide (H2 S) can suppress oxidative stress of diabetic rats through increasing the expression of silent information regulator factor 2-related enzyme 1 (SIRT1), but whether cardioprotection by SPC can be restored afterward remains unclear. Diabetic rat was subjected to IRI (30 min of ischemia followed by 120 min reperfusion). Postconditioning treatment with sevoflurane was administered for 15 min upon the onset of reperfusion. The diabetic rats were treated with GYY4137 (H2 S donor) 5 days before the experiment. Myocardial infarct size, mitochondrial structure and function, ATP content, activities of complex I-IV, marker of oxidative stress, SIRT1, nuclear factor E2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NADPH Oxidase-2 (Nox-2) protein expression were detected after reperfusion, and cardiac function was evaluated by echocardiography at 24 h after reperfusion. After H2 S activated SIRT1 in the impaired myocardium of diabetic rats, SPC significantly upregulated the expression of Nrf2 and its downstream mediator HO-1, thus reduced the expression of Nox-2. In addition, H2 S remarkably increased cytoplasmic and nuclear SIRT1 which was further enhanced by SPC. Furthermore, H2 S combined with SPC reduced the production of reactive oxygen species, increased the content of ATP, and maintained mitochondrial enzyme activity. Finally, myocardial infarct size and myocardium damage were decreased, and cardiac function was improved. Taken together, our study proved that H2 S could restore SPC-induced cardioprotection in diabetic rats by enhancing and promoting SIRT1/Nrf2 signaling pathway mediated mitochondrial dysfunction and oxidative stress.

Inhibition of AMPK-related kinase 5 (ARK5) enhances cisplatin cytotoxicity in non-small cell lung cancer cells through regulation of epithelial-mesenchymal transition.

Lung cancer incidence and mortality rates are amongst the highest of all malignant tumors worldwide. ARK5 is a member of the human AMP-activated protein kinase (AMPK) family which is implicated in tumor survival and progression. The current study was designed to explore the role of ARK5 in resistance of non-small cell lung cancer (NSCLC) to cisplatin. We studied the sensitivity of two NSCLC cell lines, NCI-H1229 and A549, to cisplatin by using proliferation and cell viability assays. We then examined expression of ARK5, Twist, and the epithelial to mesenchymal transition (EMT) biomarkers, E-cadherin and Vimentin, by Western blot and immunofluorescence. We found that ARK5 downregulation significantly increased the cisplatin chemosensitivity of NSCLC cells, and that NCI-H1299 cells, which express high levels of ARK5 and possess a mesenchymal phenotype, were more resistant to cisplatin than A549 cells, which show low expression ARK5. Furthermore, siRNA-mediated silencing of ARK5 resulted in altered EMT patterns in NSCLC cells. These data support a role for ARK5 in regulating EMT in NSCLC cells. Together, our findings suggest that ARK5 is a potential drug target for combating drug resistance and regulating EMT in NSCLC cells.

Progesterone Protects Against Bisphenol A-Induced Arrhythmias in Female Rat Cardiac Myocytes via Rapid Signaling.

Bisphenol A (BPA) is an estrogenic endocrine-disrupting chemical (EDC) that has a range of potential adverse health effects. Previously we showed that acute exposure to BPA promoted arrhythmias in female rat hearts through estrogen receptor rapid signaling. Progesterone (P4) and estrogen have antagonistic or complementary actions in a number of tissues and systems. In the current study, we examined the influence and possible protective effect of P4 on the rapid cardiac actions of BPA in female rat cardiac myocytes. Preincubation with physiological concentration (1 nM) of P4 abolished BPA-induced triggered activities in female cardiac myocytes. Further, P4 abrogated BPA-induced alterations in Ca2+ handling, including elevated sarcoplasmic reticulum Ca2+ leak and Ca2+ load. Key to the inhibitory effect of P4 is its blockade of BPA-induced increase in the phosphorylation of phospholamban. At myocyte and protein levels, these inhibitory actions of P4 were blocked by pretreatment with the nuclear P4 receptor (nPR) antagonist RU486. Analysis using membrane-impermeable bovine serum albumin-conjugated P4 suggested that the actions of P4 were mediated by membrane-initiated signaling. Inhibitory G (Gi) protein and phophoinositide-3 kinase (PI3K), but not tyrosine protein kinase activation, were involved in the observed effects of P4. In conclusion, P4 exerts an acute protective effect against BPA-induced arrhythmogenesis in female cardiac myocytes through nPR and the Gi/PI3K signaling pathway. Our findings highlight the importance of considering the impact of EDCs in the context of native hormonals and may provide potential therapeutic strategies for protection against the cardiac toxicities associated with BPA exposure.

Rapid responses and mechanism of action for low-dose bisphenol S on ex vivo rat hearts and isolated myocytes: evidence of female-specific proarrhythmic effects.

BACKGROUND: Bisphenol S (BPS) has increasingly been used as a substitute for bisphenol A (BPA) in some "BPA-free" consumer goods and in thermal papers. Wide human exposure to BPS has been reported; however, the biological and potential toxic effects of BPS are poorly understood. OBJECTIVE: In this study, we sought to elucidate the sex-specific rapid effect of BPS in rat hearts and its underlying mechanism. METHODS: We examined the rapid effects of BPS in rat hearts using electrophysiology, confocal and conventional fluorescence imaging, and immunoblotting. Treatment was administered via acute perfusion of excised hearts or isolated cardiac myocytes. RESULTS: In female rat hearts acutely exposed to 10-9 M BPS, the heart rate was increased; in the presence of catecholamine-induced stress, the frequency of ventricular arrhythmia events was markedly increased. BPS-exposed hearts showed increased incidence of arrhythmogenic-triggered activities in female ventricular myocytes and altered myocyte Ca2+ handling, particularly spontaneous Ca2+ release from the sarcoplasmic reticulum. The dose responses of BPS actions were inverted U-shaped. The impact of BPS on myocyte Ca2+ handling was mediated by estrogen receptor ß signaling and by rapid increases in the phosphorylation of key Ca2+ handling proteins, including ryanodine receptor and phospholamban. The proarrhythmic effects of BPS were female specific; male rat hearts were not affected by BPS at the organ, myocyte, or protein levels. CONCLUSION: Rapid exposure to low-dose BPS showed proarrhythmic impact on female rat hearts; these effects at the organ, cellular, and molecular levels are remarkably similar to those reported for BPA. Evaluation of the bioactivity and safety of BPS and other BPA analogs is necessary before they are used as BPA alternatives in consumer products.

The prevalence and influence factors of inter-ankle systolic blood pressure difference in community population.

AIM: The aim of this study was to investigate the prevalence of interankle systolic blood pressure difference (sIAND) and its influencing factors in community population. METHODS: This study included 2849 (65.1±9.4 y) subjects. Blood pressure (BPs) of four limbs was simultaneously measured with 4 electronic sphygmomanometers after 10 min rest in supine position. The difference of systolic BP (SBP) between two ankles was calculated as DETASBP. The criterion for abnormal sIAND was ≥10 mmHg of absolute DeltaSBP, in which the criterion for 1o sIAND was 10-19 mmHg and for 2o sIAND was ≥20 mmHg. Age, gender, smoking, hypertension, family histories of hypertension and diabetes were recorded. Fasting blood glucose and lipids, circumference of hip and waist, and body mass index (BMI) were measured. RESULTS: The SBP was higher in the right ankle than in the left ankle (158.9±21.8 vs 157.3±21.6 mmHg, P<0.05) and mean DeltaSBP was 6.08±6.26 mmHg. Similar difference was found in both genders. The prevalence of abnormal was 18.5%, in which, the prevalence 1o sIAND was 15.3% and that of 2o sIAND was 3.1%. Multivariate regression analysis showed that age, waist circumference and blood glucose level were the positive factors for DeltaSBP. The normal upper limit for DeltaSBP was 16.7 mmHg in this population, the prevalence of sIAND by≥16 mmHg was 5.8%. CONCLUSION: Aging, hypertension, obesity and abnormal glucose metabolism are positive factors for inter-ankle SBP difference.

[SCN5A mutation in patients with Brugada electrocardiographic pattern induced by fever].

OBJECTIVE: To explore the relationship between SCN5A, SCN1b, SCN3b and GPD1L genotypes and the risk of malignant arrhythmia in patients with Brugada electrocardiographic pattern induced by fever. METHODS: The clinical data and peripheral blood of patients with Brugada electrocardiographic pattern induced by fever were collected. Patients with depolarization abnormality associated with hypertension, coronary heart disease, drugs and other factors were excluded. The direct DNA sequencing was used to screen the mutation of candidate gene SCN5A, SCN1b, SCN3b and GPD1L. If gene variation was found, mutation or polymorphism was then determined by comparison with 200 control individuals. The relationship between genotype and phenotype as well as the risk of malignant arrhythmia were analyzed. RESULTS: Five eligible patients with fever-induced Brugada ECG pattern were included in this study. TypeI Brugada ECG was presented in all five patients in fibrile state and disappeared in normothermia. No sudden cardiac death (SCD) occurred and no ventricular arrhythmia was presented in Holter monitor during the 3 to 5 years follow-up period. Six gene variants were found including a novel missense mutation of base C to T, named Arg965 Cys (R965C), which located in 965 codon of the 17 exon in SCN5A, and five SCN5A polymorphisms including A29A (c.87A>G), R1193Q (c.3578G>A), D1819D (c.5457T>C), exon11 -24G>A, exon23 +4A>G. CONCLUSION: SCN5A mutation is related to fever-induced Brugada ECG pattern. However, individuals with Brugada ECG pattern induced by fever bear low risk of malignant arrhythmia and SCD during fibrile state and follow up in this small patient cohort.

[Peutz-Jeghers syndrome complicated with pulmonary mucinous adenocarcinoma: a case report and review of the literature].

OBJECTIVE: To explore the clinical characteristics, complications and prognosis of Peutz-Jeghers syndrome. METHODS: The clinical manifestations, imaging characteristics and pathological data of one patient with Peutz-Jeghers syndrome treated in Shaoxing People's Hospital were presented, and 3 cases of Peutz-Jeghers syndrome complicated with lung cancer reported in the literature were reviewed. The literature review was carried out by searching the Pubmed and CBMdisc database with Peutz-Jeghers syndrome and lung cancer as the key words. RESULTS: The patient treated in our hospital was a 30-year-old female. The primary manifestations were cough, sputum production and hemoptysis. Multiple gastrointestinal hamartomatous polyps were found, and associated with melanin pigmentation of the buccal mucosa, the lips, the hands and the feet. Therefore the diagnosis of Peutz-Jeghers syndrome was made. Chest CT scan showed a peripheral nodule at the right lower lobe, which was confirmed to be lung mucinous adenocarcinoma by surgery and pathology. The 3 cases reported in the literature were males aging from 22 to 43 years old. Cough, expectoration and hemoptysis were defined as the manifestations for 2 patients, and another case was found by physical check-up. They all died within a short period. Pathological study revealed adenocarcinoma of the lung in all the cases. CONCLUSION: Peutz-Jeghers syndrome complicated with lung cancer is rare and has a poor prognosis.