Estimating Surgical Blood Loss Volume Using Continuously Monitored Vital Signs.

Background: There are currently no effective and accurate blood loss volume (BLV) estimation methods that can be implemented in operating rooms. To improve the accuracy and reliability of BLV estimation and facilitate clinical implementation, we propose a novel estimation method using continuously monitored photoplethysmography (PPG) and invasive arterial blood pressure (ABP). Methods: Forty anesthetized York Pigs (31.82 ± 3.52 kg) underwent a controlled hemorrhage at 20 mL/min until shock development was included. Machine-learning-based BLV estimation models were proposed and tested on normalized features derived by vital signs. Results: The results showed that the mean ± standard deviation (SD) for estimating BLV against the reference BLV of our proposed random-forest-derived BLV estimation models using PPG and ABP features, as well as the combination of ABP and PPG features, were 11.9 ± 156.2, 6.5 ± 161.5, and 7.0 ± 139.4 mL, respectively. Compared with traditional hematocrit computation formulas (estimation error: 102.1 ± 313.5 mL), our proposed models outperformed by nearly 200 mL in SD. Conclusion: This is the first attempt at predicting quantitative BLV from noninvasive measurements. Normalized PPG features are superior to ABP in accurately estimating early-stage BLV, and normalized invasive ABP features could enhance model performance in the event of a massive BLV.

The effect of mobile applications for improving adherence in cardiac rehabilitation: a systematic review and meta-analysis.

BACKGROUND: Despite of the established effectiveness, the acceptance and adherence of cardiac rehabilitation (CR) remains sub-optimal. Mobile technologies are increasingly used in promoting CR without any firm evidence of their safety and efficacy. This systematic review and meta-analysis were aimed to assess the effect of mobile applications as an intervention for improving adherence to CR. METHODS: Relevant studies were searched in PubMed, the Cochrane Library, Embase and Web of Science from inception to 29th December 2018. Eligible studies were the ones which used mobile applications as a stand-alone intervention or as the primary component for the intervention directed at improving CR adherence, without any limitations on outpatient or home-based CR. RESULTS: Eight studies were eligible for the systematic review including four randomized controlled trials (RCTs) as well as four before-after studies of which only one had control group. Four RCTs and 185 patients in experimental group were included in meta-analysis, which had evaluated the effect of mobile health applications on CR completion and had reported that the adherence of patients using mobile applications was 1.4 times higher than the control group (RR = 1.38; CI 1.16 to 1.65; P = 0.0003). Moreover, we also found mixed results in exercise capacity, mental health and quality of life. CONCLUSION: The use of mobile applications for improving the adherence of the CR might be effective. However, it appears to be in the initial stage of implementing mobile applications in CR and more research is essential to validate their effectiveness.

Arginine vasopressin differentially modulates GABAergic synaptic transmission onto temperature-sensitive and temperature-insensitive neurons in the rat preoptic area.

The preoptic area (POA) of the hypothalamus, containing temperature-sensitive and temperature-insensitive neurons, plays a key role in specific thermoregulatory responses. Although arginine vasopressin (AVP) has been shown to induce hypothermia by increasing the firing activities of warm-sensitive neurons and decreasing those of cold-sensitive and temperature-insensitive neurons, the effects of AVP on POA GABAergic transmission remain unknown. Herein, inhibitory postsynaptic currents (IPSCs) of temperature-sensitive and temperature-insensitive neurons in POA slices were recorded using whole-cell patch clamp. By monitoring changes in GABAergic transmission during AVP treatment, we showed that AVP decreased the amplitudes and frequencies of spontaneous IPSCs in mostly warm-sensitive neurons and in some temperature-insensitive neurons but increased these parameters in other temperature-insensitive neurons. The IPSC amplitude was reduced for only cold-sensitive neurons. RT-PCR and Western blot analyses further confirmed the POA expression of V1a receptors and GABAA receptors, including the subunits α1, α2, α3, ß2, ß3 and γ2. The effects of AVP on IPSCs in temperature-sensitive and temperature-insensitive neurons were dependent on G proteins and intracellular Ca2+ . AVP-mediated modulation was associated with changes in the kinetic parameters (decay time, 10-90% rise time, half-width). Together, these results suggest that AVP, acting via V1a receptors but not V1b receptors, differentially modulates GABAergic synaptic transmission and fine-tunes the firing activities of temperature-sensitive and temperature-insensitive neurons in the rat POA.

Immunotherapy or targeted therapy: What will be the future treatment for anaplastic thyroid carcinoma?

Anaplastic thyroid carcinoma (ATC) is a rare and aggressive form of thyroid carcinoma (TC). Currently, there are no effective treatments for this condition. In the past few years, targeted therapy and immunotherapy have made significant progress in ATC treatment. Several common genetic mutations have been found in ATC cells, involving different molecular pathways related to tumor progression, and new therapies that act on these molecular pathways have been studied to improve the quality of life of these patients. In 2018, the FDA approved dabrafenib combined with trametinib to treat BRAF-positive ATC, confirming its therapeutic potential. At the same time, the recent emergence of immunotherapy has also attracted wide attention from researchers. While immunotherapy for ATC is still in the experimental stage, numerous studies have shown that immunotherapy is a potential therapy for ATC. In addition, it has also been found that the combination of immunotherapy and targeted therapy may enhance the anti-tumor effect of targeted therapy. In recent years, there has been some progress in the study of targeted therapy or immunotherapy combined with radiotherapy or chemotherapy, showing the prospect of combined therapy in ATC. In this review, we analyze the response mechanism and potential effects of targeted therapy, immunotherapy, and combination therapy in ATC treatment and explore the future of treatment for ATC.

A multi-family cluster of COVID-19 associated with asymptomatic and pre-symptomatic transmission in Jixi City, Heilongjiang, China, 2020.

We investigated a multi-family cluster of 22 cases in Jixi, where pre-symptomatic and asymptomatic transmission resulted in at least 41% of household infections of SARS-CoV-2. Our study illustrates the challenge of controlling COVID-19 due to the presence of asymptomatic and pre-symptomatic transmission even when extensive testing and contact tracing are conducted.

Calreticulin induced endothelial ICAM-1 up-regulation associated with tristetraprolin expression alteration through PI3K/Akt/eNOS/p38 MAPK signaling pathway in rheumatoid arthritis.

The present study was undertaken to determine whether extracellular calreticulin (CRT) participates in the regulation of ICAM-1in rheumatoid arthritis (RA) and further explore the potential mechanism. Our results showed that ICAM-1 and VCAM-1 levels were positively correlated with CRT levels in RA serum and synovial fluid, respectively. In RA synovial tissue, increased co-expressions of CRT and ICAM-1 in vascular endothelium and perivascular areas and elevated co-location of CRT and VCAM-1 localized predominantly to lining layer were observed compared to those in OA. In in vitro HUVECs model, enhanced ICAM-1expression and increased phosphorylation levels of Akt and eNOS were detected in the presence of CRT. Increased phosphorylated eNOS was significantly inhibited by a PI3K inhibitor LY294002 and elevated ICAM-1expression was partially blocked by the inhibitors of both PI3K and eNOS (L-NAME). It has been certified that the RNA-binding protein TTP targets AU-rich elements in the ICAM-1 3'-UTR and suppresses ICAM-1 expression. Knocking down TTP in HUVECs led to an increased induction of ICAM-1 by CRT. We have currently known that activation of p38 downstream kinase MK-2 leads to phosphorylation and inactivation of human TTP. The block of p38 MAPK/MK-2 signaling led to decreased protein expression and mRNA stability of TTP and ICAM-1. Furthermore, L-NAME and/or LY294002 pre-treated HUVECs manifested decreased p38 and MK-2 phosphorylation, which was accompanied by reduced TTP and ICAM-1 protein expression as well as decreased mRNA stability. Our results suggested that CRT could promote ICAM-1 expression in endothelial cells through PI3K/Akt/eNOS/p38 MAPK signaling mediated TTP accumulation, probably in an inactive form, which may provide a possible proinflammatory mechanism of CRT in RA.

Author Correction: Linc-DYNC2H1-4 promotes EMT and CSC phenotypes by acting as a sponge of miR-145 in pancreatic cancer cells.

After publication of this article, the below errors were noticed:1. The SOX2 primer is incorrect in Table S2.2. The Poly(T) adaptor sequence of reverse transcription for miR-145 detection is missing in Table S2.This error did not impact the conclusions of the article. We apologize for any confusion or inconvenience to the readers.An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Linc-DYNC2H1-4 promotes EMT and CSC phenotypes by acting as a sponge of miR-145 in pancreatic cancer cells.

The acquisition of epithelial-mesenchymal transition (EMT) and/or existence of a sub-population of cancer stem-like cells (CSC) are associated with malignant behavior and chemoresistance. To identify which factor could promote EMT and CSC formation and uncover the mechanistic role of such factor is important for novel and targeted therapies. In the present study, we found that the long intergenic non-coding RNA linc-DYNC2H1-4 was upregulated in pancreatic cancer cell line BxPC-3-Gem with acquired gemcitabine resistance. Knockdown of linc-DYNC2H1-4 decreased the invasive behavior of BxPC-3-Gem cells while ectopic expression of linc-DYNC2H1-4 promoted the acquisition of EMT and stemness of the parental sensitive cells. Linc-DYNC2H1-4 upregulated ZEB1, the EMT key player, which led to upregulation and downregulation of its targets vimentin and E-cadherin respectively, as well as enhanced the expressions of CSC makers Lin28, Nanog, Sox2 and Oct4. Linc-DYNC2H1-4 is mainly located in the cytosol. Mechanically, it could sponge miR-145 that targets ZEB1, Lin28, Nanog, Sox2, Oct4 to restore these EMT and CSC-associated genes expressions. We proved that MMP3, the nearby gene of linc-DYNC2H1-4 in the sense strand, was also a target of miR-145. Downregulation of MMP3 by miR-145 was reverted by linc-DYNC2H1-4, indicating that competing with miR-145 is one of the mechanisms for linc-DYNC2H1-4 to regulate MMP3. In summary, our results explore the important role of linc-DYNC2H1-4 in the acquisition of EMT and CSC, and the impact it has on gemcitabine resistance in pancreatic cancer cells.

Increased serum amyloid A and its association with autoantibodies, acute phase reactants and disease activity in patients with rheumatoid arthritis.

Determination of disease activity in patients with rheumatoid arthritis (RA) has become an important component for RA management. The aim of the present study was to investigate the association between circulating levels of serum amyloid A (SAA) and disease activity in RA patients. The types of disease and the respective number of patients enrolled in the present study were as follows: RA, 88; osteoarthritis (OA), 54; systemic lupus erythematosus (SLE), 43; and other autoimmune diseases, 30, as well as 50 healthy controls (HC). SAA levels were measured using an ELISA assay and western blot analysis was used to detect serum SAA levels. The correlations between SAA levels and disease activity score for 28 joints (DAS28), erythrocyte sedimentation rate (ESR) and C­reactive protein (CRP), respectively, were evaluated; in addition, the presence and absence of rheumatoid factor (RF) and anti­cyclic citrullinated peptide antibody (anti­CCP) were detected in respect to SAA levels. The results of the present study demonstrated that serum levels of SAA in RA patients were significantly increased compared to those of the OA, SLE, others and HC patients (P<0.05). SAA levels were found to be positively correlated with DAS28, ESR and CRP levels (R2=0.6174, 0.4422 and 0.3919, respectively). In addition, anti­CCP was not correlated with DAS28 (R2=0.0154). Furthermore, increased SAA levels were detected in patients with positive anti­CCP compared with those in anti­CCP negative subjects (P<0.01). In conclusion, the results of the present study provided further evidence for possible roles of SAA in RA, which indicated that it may be a useful biomarker for assessing disease severity and may provide additional information about disease activity.

An involvement of SR-B1 mediated p38 MAPK signaling pathway in serum amyloid A-induced angiogenesis in rheumatoid arthritis.

Serum amyloid A (SAA) has been reported high expression in autoimmune diseases, such as rheumatoid arthritis (RA). However, detailed molecular mechanisms induced by SAA in the pathogenesis of RA are still unclear. Herein, we focused on the role of SAA-SR-B1 mediated p38 MAPK signaling pathway in the process of RA angiogenesis. Our results showed that both SAA and SR-B1 predominantly localized to vascular endothelial cells, lining and sublining layers in RA synovium. In a series of in vitro experiments with human umbilical vein endothelial cells (HUVECs), SAA induced the endothelial cells (ECs) proliferation, migration and tube formation. However, blockage of SR-B1 and p38 MAPK inhibited SAA-induced cells proliferation, migration and tube formation. In conclusion, our data showed a possible molecular mechanism for SAA-SR-B1 induced angiogenesis events via p38 MAPK signaling pathway.