Plasma SMOC2 Predicts Prognosis in Patients with Heart Failure: A Prospective Cohort.

Background: Heart failure (HF) is a chronic disease with a poor prognosis, making it extremely important to assess the prognosis of patients with HF for accurate treatment. Secreted modular calcium-binding protein 2 (SMOC2) is a cysteine-rich acidic secreted protein that plays a pathophysiological role in many diseases, including regulation of vascular growth factor activity. It has previously been found that SMOC2 plays an essential role in cardiac fibrosis in our previous preclinical study, but whether it can be used as a clinical marker in heart failure patients remains unclear. The purpose of this research was to evaluate the correlation between plasma levels of SMOC2 and the prognosis for individuals with HF. Methods: HF patients diagnosed with ischemic cardiomyopathy were enrolled from January to December 2021. Baseline plasma levels of SMOC2 were measured after demographic and clinical features were collected. Linear and nonlinear multivariate Cox regression models were used to determine the association between plasma SMOC2 and patient outcomes during follow-up. All analysis was performed using SPSS, EmpowerStats, and R software. Results: The study included 188 patients, and the average follow-up time was 489.5±88.3 days. The plasma SMOC2 concentrations were positively correlated with N-terminal pro-B-type Natriuretic Peptide (NT-proBNP), left ventricular end-diastolic diameter (LVEDd), and length of hospital stay and were negatively correlated with left ventricular ejection fraction (LVEF) at baseline. A total of 53 patients (28.2%) were rehospitalized due to cardiac deterioration, 14 (7.4%) died, and 37 (19.7%) developed malignant arrhythmias. A fully adjusted multivariate COX regression model showed that SMOC2 is associated with readmission (HR = 1.02, 95% CI:1.012-1.655). A significant increase in rehospitalization risk was observed in group Q2 (HR =1.064, 95% CI: 1.037, 3.662, p=0.005) and group Q3 (HR =1.085, 95% CI:1.086, 3.792, p=0.009) in comparison with group Q1. The p for trend also shows a linear correlation across the three models (P < 0.001). SMOC2 was associated with the severity of HF in patients, but not with all-cause deaths and arrhythmias during follow-up. Conclusion: Plasma SMOC2 is associated with the severity of HF and readmission rate, and is a good predictor of the risk of readmission in patients.

Room Temperature NH3 Selective Gas Sensors Based on Double-Shell Hierarchical SnO2@polyaniline Composites.

Morphology and structure play a crucial role in influencing the performance of gas sensors. Hollow structures, in particular, not only increase the specific surface area of the material but also enhance the collision frequency of gases within the shell, and have been studied in depth in the field of gas sensing. Taking SnO2 as an illustrative example, a dual-shell structure SnO2 (D-SnO2) was prepared. D-SnO2@Polyaniline (PANI) (DSPx, x represents D-SnO2 molar content) composites were synthesized via the in situ oxidative polymerization method, and simultaneously deposited onto a polyethylene terephthalate (PET) substrate to fabricate an electrode-free, flexible sensor. The impact of the SnO2 content on the sensing performance of the DSPx-based sensor for NH3 detection at room temperature was discussed. The results showed that the response of a 20 mol% D-SnO2@PANI (DSP20) sensor to 100 ppm NH3 at room temperature is 37.92, which is 5.1 times higher than that of a pristine PANI sensor. Moreover, the DSP20 sensor demonstrated a rapid response and recovery rate at the concentration of 10 ppm NH3, with response and recovery times of 182 s and 86 s.

Colchicine ameliorates short-term abdominal aortic aneurysms by inhibiting the expression of NLRP3 inflammasome components in mice.

BACKGROUND: Abdominal aortic aneurysms (AAA) are often associated with chronic inflammation and pose a significant risk to affected individuals. Colchicine, known for its anti-inflammatory properties, has shown promise in managing cardiovascular diseases. However, its specific role in the development of AAA remains poorly understood. METHODS AND RESULTS: In this study, we employed a short-term AAA model induced by angiotensin II (Ang II, 1000 ng/kg/min) and calcium chloride (CaCl2, 0.5 mol/l) in male ApoE-/- and C57BL/6 mice (8-12 weeks old) to investigate the effects of colchicine on AAA progression. Colchicine (0.4 mg/kg) was administered orally once daily, starting on the same day as AAA induction. After a 4-week duration, we observed a significant reduction in AAA diameter, degradation of elastic fibers, and expression of components related to the Nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome in the vessel wall of colchicine-treated mice compared to the saline group. Mechanistically, colchicine (5 µm/l, for 24h) inhibited the expression of NLRP3 inflammasome components through the P38-ERK/MicroRNA145-toll-like receptor 4 (TLR4) pathway in RAW264.7 cells. CONCLUSIONS: Our study demonstrates the effectiveness of colchicine in suppressing NLRP3 inflammasome components, thereby delaying AAA progression in the Ang II and CaCl2-induced short-term model. These findings suggest the potential of colchicine as a pharmacological treatment option for AAA.

A Review on the Pharmacological Aspects of Engeletin as Natural Compound.

Background: Engeletin (ENG) is a natural flavonoid compound known for its diverse physiological and pharmacological effects, such as anti-inflammatory, antioxidant, and immunomodulatory properties. It has garnered significant attention as a promising candidate for drug development. Objective: This article aims to comprehensively review the clinical application, pharmacological action, and potential mechanisms of ENG, while exploring its prospects in clinical pharmacology. Methods: We conducted a systematic search of PubMed, Science Direct, Google Scholar, Web of Science, Scopus, and MEDLINE for a thorough review of high-quality articles on the source, extraction, and application of ENG, or the primary active ingredient for improving bodily injuries. Results: ENG exhibits significant potential in treating a variety of diseases across different systems, attributed to its anti-inflammatory, antioxidant, anti-tumor, and metabolic regulatory activities. These effects are linked to direct or indirect interactions with multiple pathways involving key molecules upstream and downstream. Conclusion: While ENG shows promise, its development requires further exploration. Future studies should focus on elucidating its mechanisms of action, identifying targets through clinical studies, and optimizing compounds for drug development. These research directions are crucial for advancing the development and application of flavonoids. This review underscores the significant research potential of ENG, paving the way for its application in diverse clinical settings.

INTRA-AORTIC BALLOON PUMP REDUCES 30-DAY MORTALITY IN EARLY-STAGE CARDIOGENIC SHOCK COMPLICATING ACUTE MYOCARDIAL INFARCTION ACCORDING TO SCAI CLASSIFICATION.

ABSTRACT: Background: Cardiogenic shock complicating acute myocardial infarction (AMICS) remains a high 30-day mortality. Mechanical circulatory support devices are increasingly used in AMICS, but their effects on mortality vary partly because of shock severity. Aims: This study aimed to evaluate the association between intra-aortic balloon pump (IABP) and 30-day mortality in patients with early-stage AMICS. Methods: We retrospectively analyzed patients with ST-segment elevation myocardial infarction (STEMI) based on a multicenter clinical trial (NCT04996901). Patients were stratified by IABP use, and shock severity was classified according to the Society for Cardiovascular Angiography and Interventions (SCAI) SHOCK stages. The primary outcome was 30-day all-cause mortality. The association between IABP and 30-day mortality was evaluated across shock stages using propensity score matching, weighting, and logistic regression. Results: Five thousand three hundred forty-three patients were included, and 299 received IABP. The SCAI SHOCK stage was associated with 30-day mortality (odds ratio [OR], 20.19; 95% confidence interval [CI], 13.60-29.97; P < 0.001). In the 580 matched patients, a significant interaction between IABP and 30-day mortality at different shock stages was observed ( P = 0.005). Intra-aortic balloon pump was associated with lower 30-day mortality among patients with shock stage A/B (5.8% vs. 1.2%; OR, 0.19; 95% CI, 0.03-0.73; P = 0.034) but not stage C/D/E (29.3% vs. 38.1%; OR, 1.49; 95% CI, 0.84-2.65; P = 0.172). These results were confirmed by sensitivity analyses of the weighted cohort. Conclusions: Intra-aortic balloon pump reduced 30-day mortality in patients with early-stage AMICS. The SCAI SHOCK stage provides risk stratification for patients with STEMI and helps identify those who may respond well to IABP.

13-Cis Retinoic Acid Induces Neuronal Differentiation in Daoy (Medulloblastoma) Cells Through Epigenetic Regulation of Topoisomerase IIß.

Medulloblastoma (MB) is a malignant tumor of the cerebellum that occurs in children and infants. Abnormal neuronal differentiation can lead to brain tumors, and topoisomerase IIß (Top IIß) plays an important role in neuronal differentiation. The aim of this study was to investigate the molecular mechanism of 13-cis retinoic acid (13-cis RA) promoting the expression of Top IIß and inducing neuronal differentiation in human MB Daoy cells. The results showed that 13-cis RA inhibited the cell proliferation and induced cell cycle arrest in G0/G1 phase. The cells differentiated into a neuronal phenotype, with high expression of the neuronal marker microtubule-associated protein 2 (MAP2) and abundant Top IIß, and obvious neurite growth. Chromatin immunoprecipitation (ChIP) assay showed that histone H3 lysine 27 tri-methylation (H3K27me3) modification in Top IIß promoter decreased after 13-cis RA-induced cell differentiation, while jumonji domain-containing protein 3 (JMJD3) binding in Top IIß promoter increased. These results suggest that H3K27me3 and JMJD3 can regulate the expression of Top IIß gene, which is related to inducing neural differentiation. Our results provide new insights into understanding the regulatory mechanisms of Top IIß during neuronal differentiation and imply the potential application of 13-cis RA in the clinical treatment of MB.

Dapagliflozin protects against dilated cardiomyopathy progression by targeting NLRP3 inflammasome activation.

Dilated cardiomyopathy (DCM) is the major cause of heart failure and has a poor prognosis. The accumulating evidence points to an essential role of the inflammatory component in the process of DCM. Inhibitors of sodium-glucose cotransporter 2 (SGLT2) are widely used to treat heart failure patients due to their cardiac benefits. However, their role in DCM remains unclear. We used the doxorubicin (Dox)-induced DCM model for our study. The SGLT2 inhibitor dapagliflozin (Dapa) improved cardiac function in mice treated with doxorubicin and attenuated the activation of the nucleotide-binding oligomerization domain-like receptor family protein 3 (NLRP3) inflammasome pathway and the expression of inflammatory factors. In addition, dapagliflozin suppresses NLRP3 activation by decreasing p38-dependent toll-like receptor 4 (TLR4) expression. In our study, dagliflozin improves cardiac function in DCM by inhibiting the activity of the NLRP3 inflammasome.

Nano-Resveratrol Liposome: Physicochemical Stability, In Vitro Release, and Cytotoxicity.

Nano-resveratrol liposome (RES-LIP) was prepared by the thin film rotary-evaporated method combined with ultrasonication and characterized by transmission electron microscopy (TEM), zeta potential, dynamic light scattering (DLS), and Fourier-transform infrared (FT-IR). The physicochemical stability, in vitro release, antioxidant activity, and cytotoxicity of RES-LIP were studied. Data showed that RES-LIP was a spherical vesicle with a diameter of less than 100 nm, the zeta potential was - 60 mV and the encapsulation efficiency was 86.78%. The physicochemical stability of RES-LIP was determined by Ea, ΔG, ΔH, and ΔS, which suggested that the process of RES-LIP degradation was spontaneous and endothermic. The in vitro release of RES-LIP was pH-dependent, belonged to the Weibull model, and was non-Fick diffusion. The antioxidant activity of RES-LIP was stronger than free resveratrol. The MTT assay and flow cytometry results suggested that resveratrol decreased cytotoxicity after being encapsulated by liposome. The prepared RES-LIP had high encapsulation efficiency, was sustained-release, had low cytotoxicity, was pH-targeted, and had potential usage in food and medicine fields.

The Predictive Value of the CHA2DS2-VASc Score for In-Stent Restenosis Among Patients with Drug-Eluting Stents Implantation.

Objective: The CHA2DS2-VASc score, a system which has been initially recommended for the assessment of thromboembolic risk in patients with atrial fibrillation (AF), arouses attention in the field of adverse coronary events. The purpose of this study was to explore the predictive value of preprocedural CHA2DS2-VASc score on ISR in patients after drug-eluting stent (DES) implantation. Methods: To further investigate the relationship between CHA2DS2-VASc scores and ISR after DES, a retrospective study of DES was carried on. Additionally, the preoperative variables for the ISR and control groups were contrasted. Predictive factors were chosen using the optimal subset regression. We validate the model using internal validation. The prediction model was evaluated using the receiver operator characteristic (ROC) analysis. Results: We used a 3:7 ratio to create an experimental group and a validation group, and then ran a stepwise regression with the data from each of the two groups. The results showed that CHA2DS2-VASc score was an independent risk factor for ISR in both the experimental (p = 0.0139) and validation groups (p = 0.0014), and both had significant predictive value for ISR. The area of the ROC curve was greater than 0.5 in both groups (AUC = 0.78, 0.719, respectively) indicating that the model fit was good in both groups. Conclusion: The CHA2DS2-VASc score is a reliable predictor of in-stent restenosis (ISR) after DES implantation.

Differential influences of serum vitamin C on blood pressure based on age and sex in normotensive individuals.

Aim: Hypertension is among the most prevalent chronic diseases with diverse etiology, affecting over 1 billion people globally. In numerous studies, vitamin C inversely correlated with blood pressure and was suspected to have antihypertensive properties. Currently, there is conflicting evidence regarding the relationship between vitamin C and blood pressure, with most studies being conducted on hypertensive subjects. The principal objective of this project was to investigate the relationship between vitamin C and blood pressure in normotensive adult subjects. Methods: A total of 2,533 individuals aged 20 years and above were enrolled in the present study from the National Health and Nutrition Examination Survey (NHANES) 2017-2018. Outcome variables were systolic blood pressure (SBP) and diastolic blood pressure (DBP). Serum vitamin C was regarded as an independent variable. EmpowerStats software and R (version 3.4.3) were used to examine the association between vitamin C and SBP or DBP. Results: Vitamin C was reversely correlated with both SBP (ß = -0.02, 95% CI: -0.03 to -0.00, p = 0.0306) and DBP (ß = -0.02, 95% CI: -0.04 to -0.01, p = <0.0011) after adjusting all covariates. This reverse relationship may be affected by a number of factors, including a person's gender, age, race, and ethnicity. A U-shaped association between vitamin C and SBP in females and an inverted one between vitamin C and DBP in males were detected, respectively. We further calculated the inflection points at 90.3 µmol/L for females and 40 µmol/L for males. It is somewhat surprising that a reverse U-shaped distribution between vitamin C and SBP and DBP in people over 50 was detected, and the point of inflection of vitamin C were all located at 40 µmol/L. Conclusion: Vitamin C was negatively correlated with both SBP and DBP in this cross-sectional analysis. However, a U-shaped relationship and an inverted one were also observed in certain people, which implied that, though vitamin C is considered a vital antioxidant, maintaining vitamin C at appropriate levels may be beneficial according to different populations.

Dual-targeted repetitive transcranial magnetic stimulation modulates brain functional network connectivity to improve cognition in mild cognitive impairment patients.

Background: Mild cognitive impairment (MCI) is a condition between normal aging and dementia; nearly 10-15% of MCI patients develop dementia annually. There are no effective interventions for MCI progression. Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that has attempted to improve the overall cognitive function of MCI patients. However, it does not affect episodic memory improvement. Methods: In this study, we engaged 15 clinically diagnosed MCI patients and normal controls to explore the effect of dual-targeted rTMS on progressing cognitive function, particularly episodic memory in MCI patients. Resting-state EEG recordings and neuropsychological assessments were conducted before and after the intervention. EEG features were extracted using an adaptive algorithm to calculate functional connectivity alterations in relevant brain regions and the mechanisms of altered brain functional networks in response to dual-target rTMS. Results: The study revealed that the functional brain connectivity between the right posterior cingulate gyrus (PCC) and the right dorsal caudate nucleus (DC) was significantly reduced in MCI patients compared to normal controls (p < 0.001). Dual-target rTMS increased the strength of the reduced functional connectivity (p < 0.001), which was related to cognitive enhancement (p < 0.05). Conclusion: This study provides a new stimulation protocol for rTMS intervention. Improving the functional connectivity of the right PCC to the right DC is a possible mechanism by which rTMS improves overall cognitive and memory function in MCI patients.

The Relationship Between Plasma Selenium, Antioxidant Status, Inflammatory Responses and Ischemic Cardiomyopathy: A Case-Control Study Based on Matched Propensity Scores.

Background: Ischemic cardiomyopathy (ICM) with high morbidity and mortality is closely associated with an abnormal equilibrium of circulation selenium levels. The oxidative stress theory is the most accepted theory of selenium causing ischemic cardiomyopathy. However, the role of inflammatory responses in ICM has received limited attention. Methods: This study included 119 subjects, 43 of whom were patients with ICM, and 76 were healthy controls. Blood specimens were collected from subjects and serum levels of inflammatory and oxidative stress indicators and plasma levels of selenium were measured. Results: When plasma selenium and indicators of inflammation and oxidative stress were compared between groups, plasma selenium levels were significantly lower in the ICM group than in the control group (68.83874 vs 104.39775, p=0.02032), while indicators of inflammation such as tumour necrosis factor-alpha (TNF-α) (79.09773 vs 46.15634, p<0.001), interleukin-6 (IL-6) (49.41484 vs 38.46923, p<0.01) and neutrophil/lymphocyte ratio (3.696574 vs 2.383658, p<0.001) were significantly higher in the ICM group than in the control group (all of these results were statistically different). Additionally, malondialdehyde (MDA), a marker of oxidative stress, was considerably higher in the ICM group than in the control group (61.63078 vs 39.0609, p<0.01). In contrast, there were no significant differences in superoxide dismutase (SOD) levels between groups (p>0.05). The Poisson regression analysis revealed a significant association between selenium and high levels of MDA, IL-6 and TNF-α (p<0.05). Additionally, selenium was negatively connected with SOD levels and the neutrophil/lymphocyte ratio, but this relationship was not statistically significant (p=0.96, 0.15, respectively). Conclusion: Selenium deficiency is strongly associated with the development of ICM, and with levels of inflammation and oxidative stress in patients with ICM. Selenium can prevent the development and delay the progression of ICM by alleviating inflammatory responses.

Birth weight influences differently on systolic and diastolic blood pressure in children and adolescents aged 8-15.

AIM: Globally, hypertension is one of the main threats to public health and a significant risk factor predisposing individuals to various cardiovascular conditions. Hypertension in the young is particularly complex and challenging. Accumulating evidence has implicated that low birth weight is vital for elevated blood pressure, and birth weight was negatively correlated with blood pressure. However, fewer studies with conflicting results have addressed the associations between birth weight and blood pressure in children and adolescents, and there is no relevant research conducted in the NHANES population. The principal objective of this project was to investigate the relationship between birth weight and blood pressure in children and adolescents in NHANES. METHODS: A total of 7600 subjects aged 8 to15 were enrolled in the present study from the National Health and Nutrition Examination Survey (NHANES) 2007-2018. Outcome variables were systolic blood pressure(SBP) and diastolic blood pressure(DBP). Birth weight was regarded as an independent variable. EmpowerStats software and R (version 3.4.3) were performed to examine the association between birth weight and SBP or DBP. RESULTS: Birth weight was negatively correlated with SBP in the fully-adjusted model(ß = -0.02, 95%CI: -0.04 to -0.04, p = 0.0013), especially in non-Hispanic White (ß = -0.03, 95%CI: -0.06 to -0.00,p = 0.0446), aged between 13 to 15(ß = -0.03, 95%CI: -0.04 to -0.01, p = 0.0027), and male individuals(ß = -0.03, 95%CI: -0.05 to -0.01, p = 0.0027). However, there was no unidirectional association between birth weight and DBP in the fully adjusted model(ß = -0.01, 95%CI: -0.03 to 0.02, p = 0.5668) and in sub-analysis. An inverted U-shaped and J-shaped relationship was uncovered between birth weight and DBP in those aged 13 or above and Mexican Americans, respectively. The inflection point calculated by a recursive algorithm of birth weight in these groups was all 105 oz. CONCLUSIONS: The current study identified that birth weight was negatively related to SBP but not significantly related to DBP in children and adolescents aged 8 to 15, highlighting different potential mechanisms behind high SBP and high DBP in the young. However, an inverted U-shaped and J-shaped relationship between birth weight and DBP was observed, suggesting that targeted intervention measures should be taken for different groups of people rather than generalizations.

The Gut Microbial-Derived Metabolite Trimethylamine N-Oxide and Atrial Fibrillation: Relationships, Mechanisms, and Therapeutic Strategies.

Accumulating evidence has demonstrated that gut microbial-derived metabolite trimethylamine N-oxide (TMAO) plays a crucial role in the pathogenesis of many diseases and can be served as a prognostic biomarker for several cardiovascular disorders, including arrhythmia. Recently, some studies have documented that TMAO was associated with the occurrence, progression, recurrence, and embolism risk of atrial fibrillation (AF). The activation of related inflammatory signal pathways and the cardiac sympathetic nervous system (CSNS) caused by elevated TAMO may be the underlying mechanism. It is worth noting that intervention in the metabolic pathway of TMAO may be an underlying therapeutic target of AF. In addition, standardized and individualized treatment strategies in clinical practice may be of great significance for AF patients, particularly those with high serum TMAO concentrations. However, there are also contradictions in the current research on TMAO and AF. Moreover, notwithstanding the positive preclinical and clinical findings, data supporting a direct association between TMAO and AF is a paucity. Thus, conclusive evidence from preclinical studies and multi-center randomized controlled trials to reveal the essential relationship between TMAO and AF is needy. In this review, we have attempted to summarize recent studies on TMAO and AF, highlighted the potential therapeutic strategies for AF patients, followed by a discussion on directions for future research in this field.

The relationship between high-density lipoprotein cholesterol (HDL-C) and glycosylated hemoglobin in diabetic patients aged 20 or above: a cross-sectional study.

AIM: The incidence rate of diabetes is increasing year by year, seriously threatening human health. As a predictor of glycemic control, glycated hemoglobin is reported to be related to various complications and prognoses of diabetes. Besides, HDL-C dyslipidemia is a component of metabolic syndrome and may be related to various cardiovascular and cerebrovascular diseases. The principal objective of this project was to investigate the relationship between HDL-C and glycosylated hemoglobin in adult diabetic patients. METHODS: A total of 3171 adult diabetic patients aged 20 years and above were included in the present study from the National Health and Nutrition Examination Survey (NHANES). HDL-C and glycosylated hemoglobin were regarded as independent and dependent variables, respectively. EmpowerStats software and R (version 3.4.3) were used to examine the association between HDL-C and glycosylated hemoglobin. RESULTS: HDL-C was inversely associated with glycohemoglobin after adjusting for other covariates (ß = - 0.004, 95% CI:- 0.008 to - 0.000, p = 0.044). Race/ethnicity and age were considered the most prominent interactive factors that affect the relationship between HDL and glycosylated hemoglobin by the interaction analysis. A U-shaped association was detected between HDL-C and glycosylated hemoglobin for people of other race/ethnicity or aged 60 and above, which had an inflection point of HDL-C at 60 mg/dL. In contrast, we observed an inverted U-shaped distribution between HDL-C and glycosylated hemoglobin in people under 40 with point of inflection located at 60 mg/dL as well. CONCLUSIONS: HDL-C in diabetic patients is inversely associated with glycosylated hemoglobin and may be relevant to glycemic control. However, a U-shaped relationship was also observed in a certain kind of people, which implied that, though HDL-C is considered as metabolism and anti-atherogenic property, for diabetics, it is not the higher, the better.

Calcitonin increases hepatic hepcidin expression through the BMP6 of kidney in mice.

BACKGROUND: Osteoporosis is frequently accompanied by iron disorders. Calcitonin (CT) was approved as a clinical drug to treat osteoporosis. Hepcidin is a peptide hormone that is secreted by the liver and controls body iron homeostasis. Hepcidin deficiency leads to iron overload diseases. This study was aimed at investigating the effect of CT on hepatic hepcidin and the mechanism by which CT modulates hepatic hepcidin pathways and iron metabolism. METHOD: RT-PCR, Western blot, ELISA and siRNA were used to detect the effect of CT on iron metabolism in vivo and in vitro. In addition, the regulatory signal molecules of hepcidin were measured to explore the molecular mechanism of its regulation. RESULTS: The results showed that CT strongly increased hepcidin expression and altered iron homeostasis, after mice were intraperitoneal injection of CT. In response to CT administration, BMP6 level in kidney and the serum BMP6 was increased significantly. The phosphorylation of Smad1/5/8 proteins in liver was increased at 3 h and 6 h. Moreover, the Bmp inhibitor LDN-193,189 pretreatment significantly attenuated the CT-mediated increases in phosphorylated Smad1/5/8 and Hamp1 mRNA levels. Calcitonin receptor (CTR) siRNA transfection significant suppressed the role of CT on BMP6 expression in Caki-1 cells. CONCLUSION: Our results suggest that CT strongly induces hepcidin expression and affected iron metabolism. It will provide a new strategy for the treatment of calcium iron related diseases.

Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC) Probably Caused by DSG2 p.Val149Ile Mutation as Genetic Background When Carrying with Heterozygous PRRT2 p.Arg217ProfsTer8 Mutation: A Case Report.

BACKGROUND: ARVC is a rare genetic-related disease characterized by fibrous fat replacement in the ventricular myocardium, caused by mutations in genes encoding for the desmosomal proteins, such as the desmoglein-2 gene (DSG2). It is reported in the literature that other genetic factors may play a role in disease penetrance. Herein, we report a Chinese proband with ARVC, which was probably caused by DSG2 p.Val149Ile mutation as genetic background when carrying heterozygous PRRT2 p.Arg217ProfsTer8 mutation. CASE PRESENTATION: A 17-year-old male with a history of paroxysmal kinesigenic dyskinesia (PKD) presented to the hospital for syncope induced by ventricular tachycardia. According to relevant clinical data and the diagnostic criteria of ARVC, a precise positive diagnosis of ARVC was finally made. Gene testing revealed that the patient carried a DSG2 heterozygous missense mutation (NM_001943: exon5: c.445G>A, p.Val149Ile) as well as frameshift mutation of PRRT2 (NM_001256442: exon2: p. Arg217Profs Ter8). CONCLUSION: This is the first time to report a Chinese proband with ARVC and a history of PKD carrying both DSG2 p. val149ile mutation and PRRT2 p. Arg217ProfsTer8 mutation, which can provide a new direction for gene screening of patients with ARVC and further supplements for its diagnostic criteria.

Hypothyroidism and Complicated Sick Sinus Syndrome and Acute Severe Psychiatric Disorder: A Case Report.

BACKGROUND: Thyroxine is closely related to cardiovascular diseases, such as coronary heart disease, ventricular arrhythmia, atrioventricular block, myocardial systolic weakness, pericardial effusion, low cardiac output and hypertension. Previous studies have also found that hypothyroidism can also lead to mental disorders. Here, we present a rare case of severe hypothyroidism patient accompanied by sick sinus syndrome (SSS) as a cardiovascular manifestation needing cardiac pacing and severe mental disorders. CASE PRESENTATION: A 42-year-old female patient, previously healthy, was referred to our hospital because of bradycardia complicated with sick sinus syndrome which requiring cardiac pacing and severe mental disorders. Her clinical features along with laboratory findings strongly suggested that the patient had severe hypothyroidism with sick sinus syndrome and mental disorders, both of which were reversible and successfully treated with levothyroxine. CONCLUSION: This is the first reported case of hypothyroidism with sick sinus syndrome requiring pacemakers and psychiatric disorders, and the symptoms can be improved and reversed after thyroxine supplementation. This case highlights the importance of hypothyroidism screening when faced with unexplained psychosis or sick sinus syndrome, especially if combined.

Association between sleep structure and amnesic mild cognitive impairment in patients with insomnia disorder: a case-control study.

STUDY OBJECTIVES: To examine the association between sleep structure and amnesic mild cognitive impairment (aMCI) in patients with insomnia disorder. METHODS: A total of 256 patients with insomnia disorder were diagnosed by neurologists, 45 of whom were diagnosed with aMCI according to the Petersen criteria, and 45 participants with intact cognition were chosen as controls matched for age and education. A case-control study was conducted to compare sleep structure between aMCI and control patients with insomnia disorder. We evaluated self-reported sleep problems by the Insomnia Severity Index and objective sleep features by polysomnography. Logistic regression models were used to estimate the associations between sleep parameters and aMCI in patients with insomnia disorder. RESULTS: There was no significant difference in Insomnia Severity Index scores between the aMCI and control groups. In the logistic regression after adjustment for covariates, people with a longer sleep duration (adjusted odds ratio [aOR] = 0.56, 95% confidence interval [CI]: 0.36-0.89), greater sleep efficiency (aOR = 0.50, 95% CI: 0.32-0.77), and a higher percentage of total sleep time in stage 3 of non-rapid eye movement sleep (N3%) (aOR = 0.02, 95% CI: 0.01-0.15) have a lower relative probability of having aMCI. By contrast, higher N1% (aOR = 2.28, 95% CI: 1.36-3.82) and wake after sleep onset (aOR = 1.31, 95% CI: 1.11-1.55) may be risk factors for aMCI in patients with insomnia. CONCLUSIONS: In patients with insomnia disorder, sleep duration, sleep fragmentation, sleep efficiency, N1% and N3% were independently associated with the presence of aMCI. In the clinical setting, if patients with insomnia show much more serious abnormalities in these sleep indices, clinicians should pay attention to their cognitive function. In-depth research would also be worthwhile to elaborate the causality between sleep and cognitive decline.

Effect of environmental factors on survival and population growth of ciliated parasite, Mesanophrys sp. (Ciliophora: Scuticociliatia) infecting Portunus trituberculatus.

Mesanophrys sp. is a newly identified parasitic ciliate infecting farmed swimming crab. To demonstrate the correlation between parasite development and environmental conditions, this study aimed to investigate the effect of temperature, salinity, pH and frequency of passage of parasite on survival, growth and body size of Mesanophrys sp. in vitro. The results revealed that survival, population density and growth rate of the parasite were highest at 12°C and decreased with increasing temperature from 16 to 26°C. In addition, the survival, population density and growth rate of Mesanophrys sp. were high at 20‰. When salinity was adjusted to levels lower (0-10‰) and higher (40-60‰) than 20‰, the parasite's survival and growth rate gradually declined. The optimal pH for parasite survival was 8.0, whereas its survival was inhibited at <4.5 or >9.5. Our result also showed that parasite body proportions (length:width) were significantly smaller at the highest temperature compared to the lower temperature, whereas different salinities had no significant effect. Furthermore, we introduced dynamic parasite culture systems in vitro where Mesanophrys sp. was cultured in medium-containing culture plates through continually reducing and halving the old medium into fresh. Application of this optimized dilution timing technique with fresh medium and sub-cultured enabled a continuous culture of parasites. Under this optimized condition, the highest population density and exponential growth rate of the parasite were achieved than that of a control group. This study will help to understand the ciliated parasite infection dynamics and provides new possibilities for in vitro parasite-associated studies.