Cardiovascular effects and mechanisms of sodium-glucose cotransporter-2 inhibitors

Sodium-glucose cotransporter-2 inhibitors (SGLT2 inhibitors) are a new type of drug for the treatment of diabetes, and they have been proven to have a good hypoglycemic effect. Several lines of clinical evidence have shown that SGLT2 inhibitors can significantly reduce the risks of atherosclerosis, hospitalization for heart failure, cardiovascular death, and all-cause mortality and delay the progression of chronic kidney disease. Because of the protective effects of SGLT2 inhibitors on the heart and kidney, they are being studied for the treatment of heart failure and chronic kidney disease in patients without diabetes. Therefore, it is necessary for cardiologists, patients with diabetes, and nephrologists to fully understand this type of drug. In this review, we summarize the following three aspects of SGLT2 inhibitors: the recent clinical evidence of their cardiovascular benefits, their mechanisms of action, and their safety.     

Comparison Between Phenylephrine and Dopamine in Maintaining Cerebral Oxygen Saturation in Thoracic Surgery: A Randomized Controlled Trial

Fluid is usually restricted during thoracic surgery, and vasoactive agents are often administered to maintain blood pressure. One-lung ventilation (OLV) decreases arterial oxygenation; thus oxygen delivery to the brain can be decreased. In this study, we compared phenylephrine and dopamine with respect to maintaining cerebral oxygenation during OLV in major thoracic surgery.Sixty-three patients undergoing lobectomies were randomly assigned to the dopamine (D) or phenylephrine (P) group. The patients’ mean arterial pressure was maintained within 20% of baseline by a continuous infusion of dopamine or phenylephrine. Maintenance fluid was kept at 5 mL/kg/h. The depth of anesthesia was maintained with desflurane 1MAC and remifentanil infusion under bispectral index guidance. Regional cerebral oxygen saturation (rScO₂) and hemodynamic variables were recorded using near-infrared spectroscopy and esophageal cardiac Doppler.The rScO₂ was higher in the D group than the P group during OLV (OLV 60 min: 71 ± 6% vs 63 ± 12%; P = 0.03). The number of patients whose rScO₂ dropped more than 20% from baseline was 0 and 6 in the D and P groups, respectively (P = 0.02). The D group showed higher cardiac output, but lower mean arterial pressure than the P group (4.7 ± 1.0 vs 3.9 ± 1.2 L/min; 76.7 ± 8.1 vs 84.5 ± 7.5 mm Hg; P = 0.02, P = 0.02). Among the variables, age, hemoglobin concentration, and cardiac output were associated with rScO₂ by correlation analysis.Dopamine was superior to phenylephrine in maintaining cerebral oxygenation during OLV in thoracic surgery.     

The Effects of Expressing Religious Support Online for Breast Cancer Patients

The growth of online support groups has led to an expression effects paradigm within the health communication literature. Although religious support expression is characterized as a typical subdimension of emotional support, we argue that in the context of a life-threatening illness, the inclusion of a religious component creates a unique communication process. Using data from an online group for women with breast cancer, we test a theoretical expression effects model. Results demonstrate that for breast cancer patients, religious support expression has distinct effects from general emotional support messages, which highlights the need to further theorize expression effects along these lines.     

Helicobacter pylori induces epithelial-mesenchymal transition in gastric carcinogenesis via the AKT/GSK3β signaling pathway

Helicobacter pylori (H. pylori) is a main risk factor for gastric cancer (GC). Epithelial-mesenchymal transition (EMT) is involved in the development and progression of H. pylori-associated GC. However, the exact molecular mechanism of this process remains unclear. The AKT/GSK3β signaling pathway has been demonstrated to promote EMT in several types of cancer. The present study investigated whether H. pylori infection induced EMT, and promoted the development and metastasis of cancer in the normal gastric mucosa, and whether this process was dependent on AKT activation. The expression levels of the EMT-associated proteins, including E-cadherin and N-cadherin, were determined in 165 gastric mucosal samples of different disease stages by immunohistochemical analysis. The expression levels of E-cadherin, N-cadherin, AKT, phosphorylated (p-)AKT (Ser473), GSK3β and p-GSK3β (Ser9) were further determined in H. pylori-infected Mongolian gerbil gastric tissues and cells co-cultured with H. pylori by immunohistochemical analysis and western blotting. The results indicated that the expression levels of the epithelial marker E-cadherin were decreased, whereas the expression levels of the mesenchymal marker N-cadherin were increased during gastric carcinogenesis. Their expression levels were associated with H. pylori infection. Furthermore, H. pylori infection resulted in downregulation of E-cadherin expression and upregulation of N-cadherin expression in Mongolian gerbils and GES-1 cells. In addition, an investigation of the associated mechanism of action revealed that p-AKT (Ser473) and p-GSK3β (Ser9) were activated in GES-1 cells following co-culture with H. pylori. Furthermore, following pretreatment of the cells with the AKT inhibitor VIII, the expression levels of E-cadherin, N-cadherin, p-AKT and p-GSK3β did not show significant differences between GES-1 cells that were co-cultured with or without H. pylori. The levels of p-AKT and p-GSK3β were increased in H. pylori-infected Mongolian gerbils. In conclusion, the present study demonstrated that H. pylori infection activated AKT and resulted in the phosphorylation and inactivation of GSK3β, which in turn promoted early stage EMT. These effects were AKT-dependent. This mechanism may serve as a prerequisite for GC development.     

HIFα Regulates Developmental Myelination Independent of Autocrine Wnt Signaling

The developing CNS is exposed to physiological hypoxia, under which hypoxia-inducible factor α (HIFα) is stabilized and plays a crucial role in regulating neural development. The cellular and molecular mechanisms of HIFα in developmental myelination remain incompletely understood. A previous concept proposes that HIFα regulates CNS developmental myelination by activating the autocrine Wnt/β-catenin signaling in oligodendrocyte progenitor cells (OPCs). Here, by analyzing a battery of genetic mice of both sexes, we presented in vivo evidence supporting an alternative understanding of oligodendroglial HIFα-regulated developmental myelination. At the cellular level, we found that HIFα was required for developmental myelination by transiently controlling upstream OPC differentiation but not downstream oligodendrocyte maturation and that HIFα dysregulation in OPCs but not oligodendrocytes disturbed normal developmental myelination. We demonstrated that HIFα played a minor, if any, role in regulating canonical Wnt signaling in the oligodendroglial lineage or in the CNS. At the molecular level, blocking autocrine Wnt signaling did not affect HIFα-regulated OPC differentiation and myelination. We further identified HIFα–Sox9 regulatory axis as an underlying molecular mechanism in HIFα-regulated OPC differentiation. Our findings support a concept shift in our mechanistic understanding of HIFα-regulated CNS myelination from the previous Wnt-dependent view to a Wnt-independent one and unveil a previously unappreciated HIFα–Sox9 pathway in regulating OPC differentiation.SIGNIFICANCE STATEMENT Promoting disturbed developmental myelination is a promising option in treating diffuse white matter injury, previously called periventricular leukomalacia, a major form of brain injury affecting premature infants. In the developing CNS, hypoxia-inducible factor α (HIFα) is a key regulator that adapts neural cells to physiological and pathologic hypoxic cues. The role and mechanism of HIFα in oligodendroglial myelination, which is severely disturbed in preterm infants affected with diffuse white matter injury, is incompletely understood. Our findings presented here represent a concept shift in our mechanistic understanding of HIFα-regulated developmental myelination and suggest the potential of intervening with an oligodendroglial HIFα-mediated signaling pathway to mitigate disturbed myelination in premature white matter injury.     

责任指数对口腔医学专业学生职业精神考核的设想

医学生的责任心体现在其一定行为表现上，是医学生职业精神培养的重要内涵，因此对影响医学生责任心的负向行为进行一定的干预具有重要意义。分析国内外医学院校应用责任指数考核在医学生行为督导养成的评价研究，遵循我国口腔医学专业人才培养的规律，结合口腔医学生成长的特点，借鉴职业精神考核的相关指标——责任指数考核法，试设计口腔医学生行为责任指数测评方案，并预设可行性，为拓宽口腔医学生职业精神的培养提供思路。