Prevalencia de osteopenia del prematuro antes y después de la implementación de una estrategia temprana de manejo fosfocálcico / Prevalence of osteopenia of prematurity before and after implementing an early strategy with the use of calcium and phosphate

Introducción. Con el uso de la nutrición parenteral agresiva en recién nacidos de muy bajo peso, se detectaron alteraciones del metabolismo fosfocálcico. En 2016 se implementó una estrategia de prevención a través del monitoreo fosfocálcico y su suplementación temprana. El objetivo fue estudiar si esta estrategia disminuye la prevalencia de osteopenia e identificar factores de riesgo asociados. Población y métodos. Estudio cuasiexperimental que comparó la prevalencia de osteopenia entre dos grupos: uno después de implementar la estrategia de monitoreo y suplementación fosfocálcica (01/01/2017-31/12/2019), y otro previo a dicha intervención (01/01/2013-31/12/2015). Resultados. Se incluyeron 226 pacientes: 133 pertenecen al período preintervención y 93 al posintervención. La prevalencia de osteopenia global fue del 26,1 % (IC95% 20,5-32,3) y disminuyó del 29,3 % (IC95% 21,7-37,8) en el período preintervención al 21,5 % (IC95% 13,6-31,2) en el posintervención, sin significancia estadística (p = 0,19). En el análisis multivariado, el puntaje NEOCOSUR de riesgo de muerte al nacer, recibir corticoides posnatales y el período de intervención se asociaron de manera independiente a osteopenia. Haber nacido luego de la intervención disminuyó un 71 % la probabilidad de presentar fosfatasa alcalina >500 UI/L independientemente de las restantes variables incluidas en el modelo. Conclusión. La monitorización y suplementación fosfocálcica precoz constituye un factor protector para el desarrollo de osteopenia en recién nacidos con muy bajo peso al nacer.

Introduction. With the use of aggressive parenteral nutrition in very low birth weight infants, alterations in calcium and phosphate metabolism were detected. In 2016, a prevention strategy was implemented through calcium phosphate monitoring and early supplementation. Our objective was to study whether this strategy reduces the prevalence of osteopenia and to identify associated risk factors. Population and methods. Quasi-experiment comparing the prevalence of osteopenia between two groups: one after implementing the calcium phosphate monitoring and supplementation strategy (01/01/2017­12/31/2019) and another prior to such intervention (01/01/2013­12/31/2015). Results. A total of 226 patients were included: 133 in the pre-intervention period and 93 in the post-intervention period. The overall prevalence of osteopenia was 26.1% (95% CI: 20.5­32.3) and it was reduced from 29.3% (95% CI: 21.7­37.8) in the pre-intervention period to 21.5% (95% CI: 13.6­31.2) in the post-intervention period, with no statistical significance (p = 0.19). In the multivariate analysis, the NEOCOSUR score for risk of death at birth, use of postnatal corticosteroids, and the intervention period were independently associated with osteopenia. Being born after the intervention reduced the probability of alkaline phosphatase > 500 IU/L by 71%, regardless of the other variables included in the model. Conclusion. Calcium phosphate monitoring and early supplementation is a protective factor against the development of osteopenia in very low birth weight infants.

Efeitos da suplementação do cálcio sobre marcadores da pré-eclâmpsia: ensaio clínico randomizado / Efectos de los suplementos de calcio en marcadores de preeclampsia: ensayo clínico aleatorizado / Effects of calcium supplementation on markers of preeclampsia: randomized clinical trial

Resumo Objetivo Analisar os efeitos da suplementação de cálcio nos marcadores da pré-eclâmpsia ao longo do tempo, comparando o uso de cálcio em alta e baixa dosagem em mulheres grávidas com hipertensão. Métodos Trata-se de ensaio clínico randomizado com três grupos paralelos, placebo controlado, realizado no ambulatório de referência para o pré-natal de alto risco na Região Sul do Brasil, com análise de intenção de tratar e seguimento após quatro e oito semanas. A intervenção consistiu na ingestão de cálcio 500mg/dia, cálcio 1500mg/dia e placebo. Os dados foram analisados segundo um modelo generalizado de estimação de equações mistas adotando α 0,05. Resultados O efeito do cálcio em baixa e alta dosagem na evolução ao longo do tempo foi mantido entre os grupos, mesmo após o ajuste para os fatores de confusão. Houve diferença significativa nos parâmetros analisados na interação tempo e grupo (p <0,000) e diminuição nas médias de 12,3mmHg na PAS, 9,2 mmHg na PAD, 3,2 mg/dl creatinina e 7,2 mg/dl proteinúria para o grupo cálcio 500mg/dia. Os resultados foram semelhantes para o grupo com suplementação máxima. Conclusão O cálcio melhorou o prognóstico vascular em mulheres grávidas com hipertensão ao reduzir os níveis pressóricos e os marcadores da pré-eclâmpsia.

Resumen Objetivo Analizar los efectos de los suplementos de calcio en los marcadores de preeclampsia a lo largo del tiempo, comparando el uso de calcio en dosis altas y bajas en mujeres embarazadas con hipertensión. Métodos Se trata de un ensayo clínico aleatorizado con tres grupos paralelos, placebo controlado realizado en consultorios externos de referencia en el control prenatal de alto riesgo en la Región Sur de Brasil, con análisis de intención de tratar y seguimiento luego de cuatro y ocho semanas. La intervención consistió en la ingesta de calcio 500 mg/día, calcio 1500 mg/día y placebo. Los datos se analizaron de acuerdo con un modelo generalizado de estimación de ecuaciones mixtas adoptando α 0,05. Resultados El efecto del calcio en dosis bajas y altas en la evolución a lo largo del tiempo se mantuvo entre los grupos, inclusive después de los ajustes por los factores de confusión. Hubo diferencia significativa en los parámetros analizados en la interacción tiempo y grupo (p <0,000) y reducción de los promedios de 12,3 mmHg en la PAS, 9,2 mmHg en la PAD, 3,2 mg/dl creatinina y 7,2 mg/dl proteinuria en el grupo calcio 500 mg/día. Los resultados fueron parecidos en el grupo con suplemento en dosis máxima. Conclusión El calcio mejoró el pronóstico vascular en mujeres embarazadas con hipertensión al reducir los niveles de presión y los marcadores de preeclampsia. Registro Brasileiro de Ensaios Clínicos: RBR-9ngb95

Abstract Objective To analyze the effects of calcium supplementation on markers of preeclampsia over time by comparing the use of high- and low-dose calcium in hypertensive pregnant women. Methods This is a randomized clinical trial, placebo controlled, with three parallel groups carried out at the reference outpatient clinic for high-risk prenatal care in the South Region of Brazil, with intention-to-treat analysis and follow-up after four and eight weeks. The intervention consisted of ingesting calcium 500mg/day, calcium 1500mg/day and placebo. Data were analyzed according to a generalized mixed equation estimation model adopting α 0.05. Results The effect of low- and high-dose calcium on evolution over time was maintained between groups, even after adjustment for confounding factors. There was a significant difference in the parameters analyzed in the time and group interaction (p <0.000) and a decrease in the means of 12.3 mmHg in SBP, 9.2 mmHg in DBP, 3.2 mg/dl creatinine and 7.2 mg/dl proteinuria for the 500mg calcium/day group. The results were similar for the maximal supplementation group. Conclusion Calcium improved vascular prognosis in hypertensive pregnant women by reducing blood pressure levels and markers of preeclampsia. Brazilian Registry of Clinical Trials: RBR-9ngb95

Alterações osteometabólicas em pacientes em tratamento antineoplásico: revisão de escopo / Osteometabolic changes in patients under antineoplastic treatment: scoping review

Objetivo: sintetizar as principais evidências acerca das alterações osteometabólicas presentes nos pacientes em tratamento antineoplásico. Métodos: trata-se de uma revisão de escopo, seguindo a metodologia do Instituto Joanna Briggs, nas bases de dados PubMed/MedLine, Cochrane Library, LILACS, The British Library e Google Scholar. A revisão está protocolada no Open Science Framework. Resultados: muitos antineoplásicos possuem efeito na arquitetura óssea, reduzindo sua densidade, tais como moduladores seletivos de receptores de estrogênio, inibidores da aromatase, terapia de privação androgênica, e glicocorticoides. Para evitar tais desfechos, o tratamento e prevenção podem ser realizados pela suplementação de cálcio e vitamina D, exercícios físicos, uso de bifosfonatos, denosumab, e moduladores seletivos do receptor de estrogênio. Conclusão: pessoas com maior risco de desenvolver câncer também possuem maior risco de osteopenia e osteoporose, quando processo já estabelecido e em tratamento antineoplásico, devido ao compartilhamento de fatores de risco. Torna-se evidente a necessidade da densitometria óssea nos pacientes em tratamento contra o câncer para de prevenção e promoção de saúde óssea nesses pacientes, além de mais pesquisas com alto nivel de evidência para subsidiar tal uso.

Objective: To summarize the main evidence regarding osteometabolic changes in patients undergoing antineoplastic treatment. Methods: This is a scoping review, following the methodology of the Joanna Briggs Institute, using PubMed/MedLine, Cochrane Library, LILACS, The British Library, and Google Scholar. This review is registered in the Open Science Framework. Results: Many antineoplastics affect bone architecture by reducing its density, such as selective estrogen receptor modulators, aromatase inhibitors, androgen deprivation therapy, and glucocorticoids. To avoid such outcomes, treatment and prevention can be achieved by calcium and vitamin D supplementation, physical exercise, use of bisphosphonates, denosumab, and selective estrogen receptor modulators. Conclusion: people at a higher risk of developing cancer also have a higher risk of osteopenia and osteoporosis when the process is already established and undergoing antineoplastic treatment because of the grouping of risk factors. The need for bone densitometry in patients undergoing cancer treatment to prevent and promote bone health in these patients is evident, in addition to more research with a high level of evidence to support such use.

Possible therapeutics for Pseudomyxoma peritonei: a rare, lethal, and the least investigated disease

Pseudomyxoma peritonei (PMP) refers to a growth disorder characterized by glycoprotein neoplasm in the peritoneum, where mucin oversecretion occurs. The tumors of the appendix region are well associated with PMP; however, ovarian, colon, stomach, pancreas, and urachus tumors have also been linked to PMP. Other mucinous tumors in the pelvis, paracolic gutters, greater omentum, retrohepatic space, and Treitz ligament can be the reason for PMP. Despite being rare and having a slow growth rate, PMP can be lethal without treatment. It is treated with neoadjuvant chemotherapy with the option of cytoreductive surgery and intraperitoneal chemotherapy. In the current study, we hypothesize that there may be novel gentle ways to inhibit or eliminate the mucin. Dr. David Morris has used mucolytics - such as bromelain and N-acetyl cysteine to solubilize mucin. In the present review, we aimed to study the regulation of mucin expression by promoter methylation, and drugs that can inhibit mucin, such as boldine, amiloride, naltrexone, dexamethasone, and retinoid acid receptors antagonist. This review also explored some possible pathways, such as inhibition of Na + , Ca2+ channels and induction of DNA methyltransferase along with inhibition of ten-eleven translocation enzymes, which can be good targets to control mucin. Mucins are strong adhesive molecules that play great roles in clinging to cells or cell to cell. Besides, they have been greatly involved in metastasis and also act as disease markers for cancers. Diagnostic markers may have exclusive roles in disease initiation and progression. Therefore, the present review explores various drugs to control and target mucin in various diseases, specifically cancers. (AU)

Relación del consumo de calcio con el síndrome metabólico en adultos de la Amazonía Ecuatoriana / Relationship of calcium consumption with metabolic syndrome in adults from the Ecuadorian Amazon

Introducción. El Síndrome Metabólico (SM) comprende un conjunto de factores de riesgo cardiometabólico representado por obesidad central, dislipidemia, hipertensión arterial y glucosa alterada, se ha evidenciado que el consumo adecuado de calcio representa una disminución del riesgo para este síndrome. Objetivo. Analizar la relación entre el consumo de calcio total, de origen animal y vegetal con el SM y sus indicadores. Materiales y métodos. Estudio transversal de eje correlacional, con una muestra de 100 adultos de la región amazónica ecuatoriana, durante el último trimestre del 2020. La ingesta dietética de calcio se determinó mediante un recordatorio de 24 horas y el SM según los criterios de Adult Treatment Panel-IV (ATP-IV). Resultados. La población estuvo conformada por adultos maduros (40 a 60 años) que evidenciaron una ingesta de calcio deficiente (182,50 mg y 228,60 mg en mujeres y hombres respectivamente). Se evidenció, además, una relación directamente proporcional entre la circunferencia abdominal (r=0,391 ­ p=0,000), presión arterial sistólica (r=0,290 ­ p=0,000) y glucosa en ayuno (r=0,326 ­ p=0,000) con la edad. La ingesta de calcio total se relacionó positivamente con los triglicéridos, (r=0,221 ­ p=0,027). Conclusiones. La ingesta dietética de calcio en ambos sexos no alcanza el requerimiento diario y se relaciona positivamente con los triglicéridos(AU)

Introduction. The Metabolic Syndrome (MS) comprises a set of cardiometabolic risk factors represented by central obesity, dyslipidemia, high blood pressure and altered glucose, it has been shown that adequate calcium intake represents a decreased risk for this syndrome. Objective. To analyze the relationship between the consumption of total calcium, animal and vegetable origin, with MS and its indicators. Materials and methods. Cross-sectional study of correlational axis, with a sample of 100 adults from the Ecuadorian Amazon region, during the last quarter of 2020. Dietary calcium intake was determined through a 24-hour recall and the diagnosis of MS according to the Adult Treatment Panel- IV (ATP-IV) criteria. Results. The population consisted of mature adults (40 to 60 years) who showed a deficient calcium intake in both sexes (182.50 mg and 228.60 mg in women and men respectively). There is also evidence of a directly proportional relationship between abdominal circumference (r=0.391 - p=0.000), systolic blood pressure (r=0.290 - p=0.000) and fasting glucose (r=0.326 - p=0.000) with age. Total calcium intake was positively related to triglycerides (r=0.221 ­ p=0.027). Conclusions. Calcium dietary intake in both sexes does not reach the daily requirement and is positively related to triglycerides(AU)

Análisis descriptivos a partir del rotulo nutricional: calcio y facilitadores de su absorción en bebidas vegetales procesadas / Descriptive analysis based on nutritional label: calcium and absorption facilitators in processed vegetable beverages

Introducción: El calcio es el mineral más abundante e importante en el organismo. Los factores dietéticos que aumentan la absorción del calcio son: vitamina D, lactosa, lípidos, aminoácidos y citratos. Dado los escasos estudios en relación con los componentes facilitadores de la absorción del calcio en bebidas vegetales procesadas elaboradas a partir de leguminosas, cereales, coco, y frutos secos se pretendió conocer la cantidad, el tipo de calcio y los componentes facilitadores de su absorción en estas bebidas. Material y métodos: Se realizó un estudio cuantitativo y descriptivo a partir de una muestra de 49 bebidas vegetales presentes en las 3 cadenas de supermercados en la ciudad de Montevideo. Se estudiaron las variables cantidad y tipo de calcio adicionado, cantidad y tipo de facilitadores (proteínas, lípidos, vitamina C y D), declarados en el rotulado nutricional y en la lista de ingredientes respectivamente. Se calculó media, desvío estándar, coeficiente de variación para analizar los datos, test de Student, ANOVA, ANOVA Post Hoc, y correlación de Pearson. Resultados: El 31% de las bebidas vegetales procesadas en estudio se adicionaron con calcio (valor promedio: 120 mg). Predomina en la muestra el carbonato de calcio adicionado. Los componentes facilitadores están presentes en todas las bebidas muestra, siendo las de soja las que presentaron los cuatro facilitadores. Se observó diferencia significativa en el contenido de vitamina D en bebidas vegetales con adición y sin adición de calcio. Existe correlación positiva para el contenido de lípidos y vitamina D. El aporte de calcio y vitamina D de las BV adicionadas con calcio en una porción (200ml) representa el 26 % y 20% de la ingesta diaria recomendada respectivamente. Conclusiones: Conocer la composición nutricional de las bebidas vegetales procesadas según el contenido mineral y facilitadores de la absorción es relevante para la recomendación de este tipo de alimentos

Introduction: Calcium is the most abundant and important mineral in the body. Dietary factors that increase calcium absorption are: vitamin D, lactose, lipids, amino acids, and citrates. In view of the scant studies on the components that facilitate calcium absorption in processed vegetable beverages made from legumes, cereals, coconut, and nuts, our intention was to determine the amount and type of calcium and of the components that facilitate its absorption in these beverages. Materials and methods: A quantitative and descriptive study was conducted from a sample of 49 vegetable drinks present in the three supermarket chains in Montevideo. The variables studied: amount and type of calcium added, and amount and type of facilitators (proteins, lipids, vitamin C and D), as declared in the nutritional labels and lists of ingredients, respectively. Mean, standard deviation, coefficient of variation were calculated to analyze the data, Student test, ANOVA, ANOVA Post Hoc, and Pearson correlation. Results: 31% of the processed vegetable beverages studied had calcium added (average value: 120 mg). Added calcium carbonate predominates in the sample. Facilitating components are present in all the vegetable beverages in the sample, with soy drinks presenting all four facilitators. A significant difference in vitamin D content was observed in vegetable beverages with and without calcium addition. There is a positive correlation for lipid content and vitamin D. The contribution of calcium and vitamin D of the BV with added calcium in one portion (200ml) represents 26% and 20% of the recommended daily intake respectively. Conclusions: Knowing the mineral content and the absorption facilitators in the nutritional composition of processed vegetable drinks is relevant when recommending this type of food

Prevalence of inadequacy and associated indicators with mineral intake in Brazilian adolescents and young adults / Prevalência de inadequação e fatores associados à ingestão adequada de minerais em adolescentes e adultos jovens brasileiros

ABSTRACT Objective To describe the prevalence of inadequate mineral intake and associated factors with calcium, iron, zinc, magnesium, phosphorus, and sodium intakes in individuals aged 15-24.9 years. Methods We analyzed 476 individuals from the Brazilian Study of Nutrition and Health, stratified into two age groups (adolescents aged 15-18.9 years and young adults aged 19-24.9 years). Mineral intake was obtained from two 24-hour Dietary Recalls. The values of the Estimated Average Requirement and the Tolerable Upper Intake Levels were considered to calculate the prevalence of inadequacy. Multiple logistic regression was used to determine associated factors with mineral intake. Results Calcium and magnesium had the highest prevalence of inadequacy (>83%) in both sexes and age groups. Sodium intake was above Tolerable Upper Intake Levels for the majority of the population studied (>68%). The intake of all minerals was different between the sexes for the two age groups (p<0.01), and it was not different between age groups (p>0.05). The associated factors with mineral intake were sex (calcium, iron, phosphorus, and sodium), age group (calcium, magnesium, phosphorus, and sodium), and physical activity (calcium, iron, and magnesium), followed by socioeconomic level (zinc and sodium) and body weight status (iron and sodium). Conclusion The expressive portion of the studied population is at nutritional risk for calcium, magnesium, and sodium. Such data can contribute to the national public policy revision that is related to micronutrient intake and the adoption of healthier habits by adolescents and young adults.

RESUMO Objetivo Descrever as prevalências de inadequação e fatores associados à ingestão de cálcio, ferro, zinco, magnésio, fósforo e sódio em indivíduos dos 15 aos 24,9 anos. Métodos Foram analisados 476 indivíduos do Estudo Brasileiro de Nutrição e Saúde, estratificados em dois grupos etários (adolescentes de 15-18,9 anos e adultos jovens de 19-24,9 anos). A ingestão de minerais foi obtida por meio de dois recordatórios de 24hs. Os valores de Requerimento Médio Estimado e do Limite Superior Tolerável de Ingestão foram considerados para calcular as prevalências de inadequação. Regressão logística múltipla foi utilizada para determinar os fatores associados à ingestão de minerais. Resultados Cálcio e magnésio tiveram elevadas prevalências de inadequação (>83%) em pacientes de ambos os sexos e grupos etários. A ingestão de sódio foi acima Limite Superior Tolerável de Ingestão para a maioria da população estudada (>68%). O consumo de todos os minerais foi diferente entre os sexos para os dois grupos etários (p<0,01) e não foi diferente entre os grupos etários (p>0,05). Os fatores associados à ingestão dos minerais foram sexo (cálcio, ferro, fósforo e sódio), grupo etário (cálcio, magnésio, fósforo e sódio) e atividade física (cálcio, ferro e magnésio), seguidos por nível socioeconômico (zinco e sódio) e estado de peso corporal (ferro e sódio). Conclusão Expressiva parcela da população estudada encontra-se em risco nutricional para cálcio, magnésio e sódio. Esses dados podem contribuir para a revisão de políticas públicas nacionais que se relacionam à ingestão de micronutrientes e à adoção de hábitos mais saudáveis pelos adolescentes e adultos jovens.

Ferulic acid enhances insulin secretion by potentiating L-type Ca2+ channel activation / 中西医结合学报

OBJECTIVE@#To investigate the effect of ferulic acid, a natural compound, on pancreatic beta cell viability, Ca2+ channels, and insulin secretion.@*METHODS@#We studied the effects of ferulic acid on rat insulinoma cell line viability using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide viability assay. The whole-cell patch-clamp technique and enzyme-linked immunosorbent assay were also used to examine the action of ferulic acid on Ca2+ channels and insulin secretion, respectively.@*RESULTS@#Ferulic acid did not affect cell viability during exposures up to 72 h. The electrophysiological study demonstrated that ferulic acid rapidly and concentration-dependently increased L-type Ca2+ channel current, shifting its activation curve in the hyperpolarizing direction with a decreased slope factor, while the voltage dependence of inactivation was not affected. On the other hand, ferulic acid have no effect on T-type Ca2+ channels. Furthermore, ferulic acid significantly increased insulin secretion, an effect inhibited by nifedipine and Ca2+-free extracellular fluid, confirming that ferulic acid-induced insulin secretion in these cells was mediated by augmenting Ca2+ influx through L-type Ca2+ channel. Our data also suggest that this may be a direct, nongenomic action.@*CONCLUSION@#This is the first electrophysiological demonstration that acute ferulic acid treatment could increase L-type Ca2+ channel current in pancreatic β cells by enhancing its voltage dependence of activation, leading to insulin secretion.

Immunology of a unique biological structure: the Echinococcus laminated layer

The larval stages of the cestode parasites belonging to the genus Echinococcus grow within internal organs of humans and a range of animal species. The resulting diseases, collectively termed echinococcoses, include major neglected tropical diseases of humans and livestock. Echinococcus larvae are outwardly protected by the laminated layer (LL), an acellular structure that is unique to this genus. The LL is based on a fibrillar meshwork made up of mucins, which are decorated by galactose-rich O-glycans. In addition, in the species cluster termed E. granulosus sensu lato, the LL features nano-deposits of the calcium salt of myo-inositol hexakisphosphate (Insp6). The main purpose of our article is to update the immunobiology of the LL. Major recent advances in this area are (i) the demonstration of LL "debris" at the infection site and draining lymph nodes, (ii) the characterization of the decoy activity of calcium Insp6 with respect to complement, (iii) the evidence that the LL mucin carbohydrates interact specifically with a lectin receptor expressed in Kupffer cells (Clec4F), and (iv) the characterization of what appear to be receptor-independent effects of LL particles on dendritic cells and macrophages. Much information is missing on the immunology of this intriguing structure: we discuss gaps in knowledge and propose possible avenues for research.

Suxiao Jiuxin Pills Prevent Ventricular Fibrillation from Inhibiting L-type Calcium Currents CaV1.2 in vivo and in vitro / 中国结合医学杂志

OBJECTIVE@#To investigate whether Suxiao Jiuxin Pills (SJP), a Chinese herbal remedy, is an anti-ventricular fibrillation (VF) agent.@*METHODS@#VF was induced by isoproterenolol (ISO) intraperitoneal injection followed by electrical pacing in mice and rabbits. The effects of SJP on the L-type calcium channel current (CaV1.2), voltage-dependent sodium channel current (INa), rapid and slow delayed rectifier potassium channel current (IKr and IKs, respectively) were studied by whole-cell patch-clamp method. Computer simulation was implemented to incorporate the experimental data of SJP effects on the CaV1.2 current into the action potential (AP) and pseudo-electrocardiography (pseudo-ECG) models.@*RESULTS@#SJP prevented VF induction and reduced VF durations significantly in mice and rabbits. Patch-clamp experiments revealed that SJP decreased the peak amplitude of the CaV1.2 current with a half maximal concentration (IC50) value of 16.9 mg/L (SJP-30 mg/L, -32.8 ± 6.1 pA; Verapamil, -16.2 ±1.8 pA; vs. control, -234.5 ±16.7 pA, P<0.01, respectively). The steady-state activation curve, inactivation curve, and the recovery from inactivation of the CaV1.2 current were not shifted significantly. Specifically, SJP did not altered INa, IKr, and IKs currents significantly (SJP vs. control, P>0.05). Computer simulation showed that SJP-reduced CaV1.2 current shortened the AP duration, transiting VF into sinus rhythm in pseudo-ECG.@*CONCLUSION@#SJP reduced VF via inhibiting the CaV1.2 current with in vivo, in vitro, and in silico studies, which provide experimental basis for SJP anti-VF clinical application.

Effect of Erxian Decoction-containing serum on H_2O_2-induced proliferation and osteogenic differentiation of MC3T3-E1 cells via BK channels / 中国中药杂志

This study aimed to investigate the effects of Erxian Decoction(EXD)-containing serum on the proliferation and osteogenic differentiation of MC3T3-E1 cells under oxidative stress through BK channels. The oxidative stress model was induced in MC3T3-E1 cells by H_2O_2, and 3 mmol·L~(-1) tetraethylammonium(TEA) chloride was used to block the BK channels in MC3T3-E1 cells. MC3T3-E1 cells were divided into a control group, a model group, an EXD group, a TEA group, and a TEA+EXD group. After MC3T3-E1 cells were treated with corresponding drugs for 2 days, 700 μmol·L~(-1) H_2O_2 was added for treatment for another 2 hours. CCK-8 assay was used to detect cell proliferation activity. The alkaline phosphatase(ALP) assay kit was used to detect the ALP activity of cells. Western blot and real-time fluorescence-based quantitative PCR(RT-qPCR) were used to detect protein and mRNA expression, respectively. Alizarin red staining was used to detect the mineralization area of osteoblasts. The results showed that compared with the control group, the model group showed significantly blunted cell proliferation activity and ALP activity, reduced expression of BK channel α subunit(BKα), collagen Ⅰ(COL1), bone morphogenetic protein 2(BMP2), osteoprotegerin(OPG), and phosphorylated Akt, decreased mRNA expression levels of Runt-related transcription factor 2(RUNX2), BMP2, and OPG, and declining area of calcium nodules. EXD-containing serum could significantly potentiate the cell proliferation activity and ALP activity, up-regulate the protein expression of BKα, COL1, BMP2, OPG, and phosphorylated Akt, and forkhead box protein O1(FoxO1), promote the mRNA expression of RUNX2, BMP2, and OPG, and enlarge the area of calcium nodules. However, BK channel blockage by TEA reversed the effects of EXD-containing serum in promoting the protein expression of BKα, COL1, BMP2, OPG, and phosphorylated Akt and FoxO1, increasing the mRNA expression of RUNX2, BMP2, and OPG, and enlarging the area of calcium nodules. EXD-containing serum could improve the proliferation activity, osteogenic differentiation, and mineralization ability of MC3T3-E1 cells under oxidative stress, which might be related to the regulation of BK channels and downstream Akt/FoxO1 signaling pathway.

Incremental value of epicardial fat volume on predicting obstructive coronary artery disease with myocardial ischemia / 中华心血管病杂志

Objective: This study aimed to investigate the association between epicardial fat volume (EFV) and obstructive coronary artery disease (CAD) with myocardial ischemia, and evaluate the incremental value of EFV on top of traditional risk factors and coronary artery calcium (CAC) in predicting obstructive CAD with myocardial ischemia. Methods: This study was a retrospective cross-sectional study. Patients with suspected CAD who underwent coronary angiography (CAG) and single photon emission computerized tomography-myocardial perfusion imaging (SPECT-MPI) at the Third Affiliated Hospital of Soochow University from March 2018 to November 2019 were consecutively enrolled. EFV and CAC were measured by non-contrast chest computed tomography (CT) scan. Obstructive CAD was defined as coronary artery stenosis≥50% in at least one of the major epicardial coronary arteries, and myocardial ischemia was defined as reversible perfusion defects in stress and rest MPI. Obstructive CAD with myocardial ischemia was defined in patients with coronary stenosis severity≥50% and reversible perfusion defects in the corresponding areas of SPECT-MPI. Patients with myocardial ischemia bot without obstructive CAD were defined as none-obstructive CAD with myocardial ischemia group. We collected and compared the general clinical data, CAC and EFV between the two groups. Multivariable logistic regression analysis was performed to identify the relationship between EFV and obstructive CAD with myocardial ischemia. ROC curves were performed to determine whether addition of EFV improved predictive value beyond traditional risk factors and CAC for obstructive CAD with myocardial ischemia. Results: Among the 164 patients with suspected CAD, 111 patients were males, and average age was (61.4±9.9) years old. 62 (37.8%) patients were included into the obstructive CAD with myocardial ischemia group. 102 (62.2%) patients were included into the none-obstructive CAD with myocardial ischemia group. EFV was significantly higher in obstructive CAD with myocardial ischemia group than in none-obstructive CAD with myocardial ischemia group ((135.63±33.29)cm3 and (105.18±31.16)cm3, P<0.01). Univariate regression analysis showed the risk of obstructive CAD with myocardial ischemia increased by 1.96 times for each SD increase in EFV(OR 2.96; 95%CI, 1.89-4.62; P<0.01). After adjustment for traditional risk factors and CAC, EFV remained as an independent predictor for obstructive CAD with myocardial ischemia (OR, 4.48, 95%CI, 2.17-9.23; P<0.01). Addition of EFV to CAC and traditional risk factors was related to larger AUC for predicting obstructive CAD with myocardial ischemia (0.90 vs. 0.85, P=0.04, 95%CI: 0.85-0.95) and the global chi-square increased by 21.81 (P<0.05). Conclusions: EFV is an independent predictor for obstructive CAD with myocardial ischemia. Addition of EFV to traditional risk factors and CAC has incremental value for predicting obstructive CAD with myocardial ischemia in this patient cohort.

Evaluation of the relationship between cardiac calcification and cardiovascular disease using the echocardiographic calcium score in patients undergoing peritoneal dialysis: a cross-sectional study

INTRODUCTION@#An echocardiographic calcium score (ECS) predicts cardiovascular disease (CVD) in the general population. Its utility in peritoneal dialysis (PD) patients is unknown.@*METHODS@#This cross-sectional study assessed 125 patients on PD. The ECS (range 0-8) was compared between subjects with CVD and those without.@*RESULTS@#Among the subjects, 54 had CVD and 71 did not. Subjects with CVD were older (69 years vs. 56 years, P < 0.001) and had a higher prevalence of diabetes mellitus (DM) (81.5% vs. 45.1%, P < 0.001). They had lower diastolic blood pressure (72 mmHg vs. 81 mmHg, P < 0.001), lower phosphate (1.6 mmol/L vs. 1.9 mmol/L, P = 0.002), albumin (30 g/L vs. 32 g/L, P = 0.001), parathyroid hormone (34.4 pmol/L vs. 55.8 pmol/L, P = 0.002), total cholesterol (4.5 vs. 4.9, P = 0.047), LDL cholesterol (2.4 mmol/L vs. 2.8 mmol/L, P = 0.019) and HDL cholesterol (0.8 mmol/L vs. 1.1 mmol/L, P = 0.002). The ECS was found to be higher in subjects with CVD than in those without (2 vs. 1, P = 0.001). On multivariate analysis, only DM and age were independently associated with CVD.@*CONCLUSION@#The ECS was significantly higher in PD patients with CVD than in those without, reflecting a higher vascular calcification burden in the former. It is a potentially useful tool to quantify vascular calcification in PD patients.

Disseminated intravascular coagulation phenotype is regulated by the TRPM7 channel during sepsis

BACKGROUND: Sepsis is an uncontrolled inflammatory response against a systemic infection that results in elevated mortality, mainly induced by bacterial products known as endotoxins, producing endotoxemia. Disseminated intravascular coagulation (DIC) is frequently observed in septic patients and is associated with organ failure and death. Sepsis activates endothelial cells (ECs), promoting a prothrombotic phenotype contributing to DIC. Ion channel mediated calcium permeability participates in coagulation. The transient reception potential melastatin 7 (TRPM7) non-selective divalent cation channel that also contains an α-kinase domain, which is permeable to divalent cations including Ca2+, regulates endotoxin-stimulated calcium permeability in ECs and is associated with increased mortality in septic patients. However, whether endothelial TRPM7 mediates endotoxemia-induced coagulation is not known. Therefore, our aim was to examine if TRPM7 mediates coagulation during endotoxemia. RESULTS: The results showed that TRPM7 regulated endotoxin-induced platelet and neutrophil adhesion to ECs, dependent on the TRPM7 ion channel activity and by the α-kinase function. Endotoxic animals showed that TRPM7 mediated neutrophil rolling on blood vessels and intravascular coagulation. TRPM7 mediated the increased expression of the adhesion proteins, von Willebrand factor (vWF), intercellular adhesion molecule 1 (ICAM-1), and P-selectin, which were also mediated by the TRPM7 α-kinase function. Notably, endotoxin-induced expression of vWF, ICAM-1 and P-selectin were required for endotoxin-induced platelet and neutrophil adhesion to ECs. Endotoxemic rats showed increased endothelial TRPM7 expression associated with a procoagulant phenotype, liver and kidney dysfunction, increased death events and an increased relative risk of death. Interestingly, circulating ECs (CECs) from septic shock patients (SSPs) showed increased TRPM7 expression associated with increased DIC scores and decreased survival times. Additionally, SSPs with a high expression of TRPM7 in CECs showed increased mortality and relative risk of death. Notably, CECs from SSPs showed significant results from the AUROC analyses for predicting mortality in SSPs that were better than the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) scores. CONCLUSIONS: Our study demonstrates that sepsis-induced DIC is mediated by TRPM7 in ECs. TRPM7 ion channel activity and α-kinase function are required by DIC-mediated sepsis-induced organ dysfunction and its expression are associated with increased mortality during sepsis. TRPM7 appears as a new prognostic biomarker to predict mortality associated to DIC in SSPs, and as a novel target for drug development against DIC during infectious inflammatory diseases.

Chemoprevention of colorectal cancer in general population and high-risk population: a systematic review and network meta-analysis / 中华医学杂志(英文版)

BACKGROUND@#Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer (CRC). We performed a network meta-analysis to summarize such evidence and assess the efficacy and safety of these agents.@*METHODS@#We searched PubMed, Embase, and the Cochrane Library for studies published in English until October 31, 2021 that fit our inclusion criteria. We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of candidate agents (low-dose aspirin [Asp], high-dose Asp, cyclooxygenase-2 inhibitors [coxibs], calcium, vitamin D, folic acid, ursodeoxycholic acid [UDCA], estrogen, and progesterone, alone or in combination) for preventing colorectal adenoma and CRC. Cochrane risk-of-bias assessment tool was employed to evaluate the quality of each included study.@*RESULTS@#Thirty-two randomized controlled trials (278,694 participants) comparing 13 different interventions were included. Coxibs significantly reduced the risk of colorectal adenoma (risk ratio [RR]: 0.59, 95% confidence interval [CI]: 0.44-0.79, six trials involving 5486 participants), advanced adenoma (RR: 0.63, 95% CI: 0.43-0.92, four trials involving 4723 participants), and metachronous adenoma (RR: 0.58, 95% CI: 0.43-0.79, five trials involving 5258 participants) compared with placebo. Coxibs also significantly increased the risk of severe adverse events (RR: 1.29, 95% CI: 1.13-1.47, six trials involving 7109 participants). Other interventions, including Asp, folic acid, UDCA, vitamin D, and calcium, did not reduce the risk of colorectal adenoma in the general and high-risk populations compared with placebo.@*CONCLUSIONS@#Considering the balance between benefits and harms, regular use of coxibs for prevention of colorectal adenoma was not supported by the current evidence. Benefit of low-dose Asp for chemoprevention of colorectal adenoma still requires further evidence.@*REGISTRATION@#PROSPERO, No. CRD42022296376.

Connexin 43-modified bone marrow stromal cells reverse the imatinib resistance of K562 cells via Ca 2+ -dependent gap junction intercellular communication / 中华医学杂志(英文版)

BACKGROUND@#Imatinib mesylate (IM) resistance is an emerging problem for chronic myeloid leukemia (CML). Previous studies found that connexin 43 (Cx43) deficiency in the hematopoietic microenvironment (HM) protects minimal residual disease (MRD), but the mechanism remains unknown.@*METHODS@#Immunohistochemistry assays were employed to compare the expression of Cx43 and hypoxia-inducible factor 1α (HIF-1α) in bone marrow (BM) biopsies of CML patients and healthy donors. A coculture system of K562 cells and several Cx43-modified bone marrow stromal cells (BMSCs) was established under IM treatment. Proliferation, cell cycle, apoptosis, and other indicators of K562 cells in different groups were detected to investigate the function and possible mechanism of Cx43. We assessed the Ca 2+ -related pathway by Western blotting. Tumor-bearing models were also established to validate the causal role of Cx43 in reversing IM resistance.@*RESULTS@#Low levels of Cx43 in BMs were observed in CML patients, and Cx43 expression was negatively correlated with HIF-1α. We also observed that K562 cells cocultured with BMSCs transfected with adenovirus-short hairpin RNA of Cx43 (BMSCs-shCx43) had a lower apoptosis rate and that their cell cycle was blocked in G0/G1 phase, while the result was the opposite in the Cx43-overexpression setting. Cx43 mediates gap junction intercellular communication (GJIC) through direct contact, and Ca 2+ is the key factor mediating the downstream apoptotic pathway. In animal experiments, mice bearing K562, and BMSCs-Cx43 had the smallest tumor volume and spleen, which was consistent with the in vitro experiments.@*CONCLUSIONS@#Cx43 deficiency exists in CML patients, promoting the generation of MRD and inducing drug resistance. Enhancing Cx43 expression and GJIC function in the HM may be a novel strategy to reverse drug resistance and promote IM efficacy.

Impact of statin use on major adverse cardiovascular events in patients with normal stress myocardial perfusion imaging and elevated coronary artery calcium score

INTRODUCTION@#Normal stress myocardial perfusion imaging (MPI) carries a favourable prognosis. Conversely, elevated coronary artery calcium (CAC) is associated with increased major adverse cardiovascular events (MACE). There is limited information on the prognosis and management of patients with elevated CAC and normal MPI. We aimed to assess the outcomes of patients with elevated CAC and normal MPI in relation to post-MPI statin use.@*METHODS@#A retrospective review of normal MPI with CAC score >300 was performed between 1 March 2016 and 31 January 2017 in a Singapore tertiary hospital. Patients with known atherosclerotic cardiovascular disease or left ventricular ejection fraction <50% on MPI were excluded. Patient demographics, prescriptions and MACE (cardiac death, nonfatal myocardial infarction and/or ischaemic stroke) at 24 months after MPI were traced using electronic records. Binary logistic regression was used to evaluate for independent predictors of MACE.@*RESULTS@#We included 311 patients (median age 71 years, 56.3% male), of whom 65.0% were on moderate to high-intensity statins (MHIS) after MPI. MACE was significantly lower in the post-MPI MHIS group (3.5% vs. 9.2%, P = 0.035). On univariate binary logistic regression, post-MPI MHIS use was the only significant predictor for MACE (odds ratio [OR] 0.355 [95% confidence interval (CI) 0.131-0.962], P = 0.042), even after multivariate adjustment (adjusted OR 0.363, 95% confidence interval 0.134-0.984, P = 0.046).@*CONCLUSION@#Post-MPI MHIS use is associated with lower MACE and is an independent negative predictor for 24-month MACE among patients with normal MPI and CAC >300.

Hypercalcium crisis and postoperative hungry bone syndrome caused by primary hyperparathyroidism: a case report / 临床耳鼻咽喉头颈外科杂志

To review the diagnosis and treatment of a case of hypercalcium crisis caused by primary hyperparathyroidism（PHPT） and prophylactic treatment of hungry bone syndrome. In a 32-year-old male with hypercalcemia, the main manifestations were loss of appetite, nausea, polyuria, polydipsia, fatigue, lethargy, etc. parathyroid hormone, serum calcium increased, thyroid function was normal, thyroid color ultrasound and MRI showed space-occupying behind the right thyroid, radionuclide examination showed abnormal imaging agent concentration in the right parathyroid area, there was a history of pathological fracture. Clinically diagnosed as hypercalcemia crisis secondary to PHPT.