Background: Postoperative cognitive dysfunction (POCD) is a serious complication after surgery, especially in elderly patients. The anesthesia technique is a potentially modifiable risk factor for POCD. This study assessed the effects of dexmedetomidine, propofol or midazolam sedation on POCD in elderly patients who underwent hip or knee replacement under spinal anesthesia. Methods: The present study was a prospective randomized controlled preliminary trial. From July 2013 and December 2014, a total of 164 patients aged 65 years or older who underwent hip or knee arthroplasty at China-Japan Friendship Hospital and 41 non-surgical controls were included in this study. Patients were randomized in a 1:1:1 ratio to 3 sedative groups. All the patients received combined spinal-epidural anesthesia (CSEA) with midazolam, dexmedetomidine or propofol sedation. The sedative dose was adjusted to achieve light sedation (bispectral index[BIS] score between 70 and 85). All study participants and controls completed a battery of 5 neuropsychological tests before and 7 days after surgery. One year postoperatively, the patients and controls were interviewed over the telephone using the Montreal cognitive assessment 5-minute protocol. Results: In all, 60 of 164 patients (36.6%) were diagnosed with POCD 7 days postoperatively, POCD incidence in propofol group was significantly lower than that in dexmedetomidine and midazolam groups (18.2% vs. 40.0%, 51.9%, χ 2 = 6.342 and 13.603, P = 0.012 and < 0.001). When the patients were re-tested 1 year postoperatively, the incidence of POCD was not significantly different among the 3 groups (14.0%, 10.6% vs. 14.9%, χ 2 = 0.016 and 0.382, P = 0.899 and 0.536). Conclusion: Among dexmedetomidine, propofol and midazolam sedation in elderly patients, propofol sedation shows a significant advantage in term of short-term POCD incidence.

Inflammatory breast carcinoma (IBC) isOur screening methods for certain types of breast cancer such as inflammatory breast cancer (IBC) have not impacted the disease's age-adjusted 5 year mortality because these types of breast cancer do not remain organconfined before they are detected. 1 One telltale sign of lack of organ confinement is the presence of lymphovascular invasion, a finding that is most pronounced in IBC. 2 Lymphovascular invasion is defined by tumor emboli within lymphovascular spaces. 3 These emboli have a unique microscopic appearance of compact clumps of tumor cells retracted away from the surrounding endothelial cell layer lining the lymphovascular space. The molecular determinants of this phenotype remain undefined. Recently our laboratory established a human SCID model of IBC (MARY-X) that exhibited florid lymphovascular tumor emboli in vivo and compact spheroids in vitro. 4,5 We have characterized, in part, the molecular basis of the IBC phenotype using this model. Our initial studies indicated that MARY-X overexpressed both Ecadherin and MUC1. 4 We chose to focus on E-cadherin initially and demonstrated that both the tumor cell emboli and the in vitro spheroids formed on the basis of an intact and overexpressed E-cadherin/␣,␤-catenin axis that mediated tumor cell adhesion analogous to the embryonic blastocyst. 5 Disruption of the E-cadherin/␣,␤-catenin axis with either anti-E-cadherin antibodies or E-cadherin dominant-negative mutant approaches caused complete disadherence of the tumor emboli in vivo. Furthermore in addition to these two manipulations, trypsin proteolysis and Ca ϩϩ depletion caused complete disadherence of the spheroids in vitro. In the present study we decided to investigate the role of overexpressed MUC1 and a possible mechanism that might explain the apparent lack of binding of the tumor embolus to the surrounding endothelium.

Postoperative cognitive dysfunction (POCD), a long-lasting cognitive decline after surgery, is currently a major clinical problem with no clear pathophysiological mechanism or effective therapy. Accumulating evidence suggests that neuroinflammation plays a critical role in POCD. After surgery, alarmins are leaked from the injury sites and proinflammatory cytokines are increased in the peripheral circulation. Neurons in the hippocampus, which is responsible for learning and memory, can be damaged by cytokines transmitted to the brain parenchyma. Microglia, bone marrow-derived macrophages, mast cells, and T cells in the central nervous system (CNS) can be activated to secrete more cytokines, further aggravating neuroinflammation after surgery. Conversely, blocking the inflammation network between these immune cells and related cytokines alleviates POCD in experimental animals. Thus, a deeper understanding of the roles of immune cells and the crosstalk between them in POCD may uncover promising therapeutic targets for POCD treatment and prevention. Here, we reviewed several major immune cells and discussed their functional roles in POCD.

No abstract

Pain is the most common symptom in patients with rheumatoid arthritis (RA). Although in recent years, through the implementation of targeted treatment and the introduction of disease-modifying antirheumatic drugs (DMARDs), the treatment of RA patients has made a significant progress, a large proportion of patients still feel pain. Finding appropriate treatment to alleviate the pain is very important for RA patients. Current research showed that, in addition to inflammation, RA pain involves peripheral sensitization and abnormalities in the central nervous system (CNS) pain regulatory mechanisms. This review summarized the literature on pain mechanisms of RA published in recent years. A better understanding of pain mechanisms will help to develop new analgesic targets and deploy new and existing therapies.

No abstract

(Abstracted from Genet Med 2019;21:2293–2302) Noninvasive prenatal screening for aneuploidy using cell-free DNA (cfDNA) has been used since 2011 to identify fetal genetic disorders such as trisomies 13, 18, and 21. However, these tests can give false-positive results or fail all together when other conditions, such as maternal cancer, are present.

Background/Aims: Arctigenin possesses biological activities, but its underlying mechanisms at the cellular and ion channel levels are not completely understood. Therefore, the present study was designed to identify the anti-arrhythmia effect of arctigenin in vivo, as well as its cellular targets and mechanisms. Methods: A rat arrhythmia model was established via continuous aconitine infusion, and the onset times of ventricular premature contraction, ventricular tachycardia and death were recorded. The Action Potential Duration (APD), sodium current (I_Na), L-type calcium current (I_{Ca, L}) and transient outward potassium current (I_to) were measured and analysed using a patch-clamp recording technique in normal rat cardiomyocytes and myocytes of arrhythmia aconitine-induced by. Results: Arctigenin significantly delayed the arrhythmia onset in the aconitine-induced rat model. The 50% and 90% repolarisations (APD₅₀ and APD₉₀) were shortened by 100 µM arctigenin; the arctigenin dose also inhibited the prolongation of APD₅₀ and APD₉₀ caused by 1 µM aconitine. Arctigenin inhibited I_Na and I_Ca,L and attenuated the aconitine-increased I_Na and I_Ca,L by accelerating the activation process and delaying the inactivation process. Arctigenin enhanced I_to by facilitating the activation process and delaying the inactivation process, and recoverd the decreased I_to induced by aconitine. Conclusions: Arctigenin has displayed anti-arrhythmia effects, both in vivo and in vitro. In the context of electrophysiology, I_Na, I_{Ca, L}, and I_to may be multiple targets of arctigenin, leading to its antiarrhythmic effect.