An acute herb-drug interaction of Magnoliae Officinalis Cortex with methotrexate via inhibiting multidrug resistance-associated protein 2.

Magnoliae Officinalis Cortex (MOC), an herbal drug, contains polyphenolic lignans mainly magnolol (MN) and honokiol (HK). Methotrexate (MTX), a critical drug for cancers and autoimmune deseases, is a substrate of multidrug resistance-associated protein 2 (MRP2) and breast cancer resistance protein (BCRP). This study investigated the effect of coadministration of MOC on the pharmacokinetics of MTX and relevant mechanisms. Sprague-Dawley rats were orally administered MTX alone and with single dose (2.0 and 4.0 g/kg) and repeated seven doses of MOC (2.0 g/kg thrice daily for 2 days, the 7th dose given at 0.5 h before MTX). The serum concentrations of MTX were determined by a fluorescence polarization immunoassay. The results showed that a single dose of MOC at 2.0 g/kg significantly increased the AUC0-t and MRT of MTX by 352% and 308%, and a single dose at 4.0 g/kg significantly enhanced the AUC0-t and MRT by 362% and 291%, respectively. Likewise, repeated seven doses of MOC at 2.0 g/kg significantly increased the AUC0-t and MRT of MTX by 461% and 334%, respectively. Mechanism studies indicated that the function of MRP2 was significantly inhibited by MN, HK and the serum metabolites of MOC (MOCM), whereas BCRP was not inhibited by MOCM. In conclusion, coadministration of MOC markedly enhanced the systemic exposure and mean residence time of MTX through inhibiting the MRP2-mediated excretion of MTX.

Dental Occlusion Characteristics for Treatment Decision-Making Regarding Surgery-First Approach in Orthodontics.

The surgery-first approach (SFA) is conducted to decrease the difficulty and duration of orthodontic treatment by correcting the skeletal discrepancy at the initial stage of treatment. However, the indication of the SFA has not been well defined yet. This study explored the dental occlusion characteristics for treatment decision-making regarding the SFA. A total of 200 skeletal Class III patients were consecutively collected and divided into two groups: the orthodontic-first approach (OFA) group and the SFA group. The pretreatment digital dental models and lateral cephalograms were measured. Logistic regression was completed and receiver operating characteristic (ROC) curves were obtained to predict the probability of the SFA. Results showed that the ROC model with L1-MP, upper and lower arch length discrepancy, overbite, and asymmetric tooth number as influencing factors revealed that the sensitivity and specificity for determining SFA were 83.0% and 65.0%, respectively; the accuracy of prediction was 75.0%. In conclusion, our findings indicate that the six measurements from digital dental models and lateral cephalograms can be effectively applied in treatment decision-making for the SFA with satisfactory accuracy.

Therapeutic effects of methimazole on 3,4-methylenedioxymethamphetamine-induced hyperthermia and serotonergic neurotoxicity.

3,4-methylenedioxymethamphetamine (MDMA) is a popular recreational drug, however over 200 studies demonstrate that acute (e.g. hyperthermia, rhabdomyolysis) and chronic (e.g. neurotoxicity) toxicity effects of MDMA were observed in different animals. Methimazole (MMI), an inhibitor of thyroid hormone synthesis, was found to significantly reduce the HSP72 expression of heat stress induced in fibroblasts. Hence, we attempted to understand the effects of MMI on MDMA induced changes in vivo. Male SD rats were randomly divided into four groups as follows:(a) water-saline (b) water-MDMA (c) MMI-saline and (d) MMI-MDMA group. In the temperature analysis test, MMI was found to alleviate MDMA-induced hyperthermia and increase the heat loss index (HLI), revealing its peripheral vasodilation effect. PET experiment suggested that MDMA induced elevated glucose uptake by skeletal muscles, which was resolved by MMI pretreatment. IHC staining (serotonin transporter, SERT) showed the evidence of neurotoxicity caused by MDMA (serotonin fiber loss), which was alleviated by MMI. Furthermore, the animal behaviour test (forced swimming test, FST) showed higher swimming time but lower immobility time in MMI-MDMA and MMI-saline groups. Taken together, treatment of MMI shows benefits such as lowered body temperature, alleviation of neurotoxicity and excited behaviour. However, further investigations should be conducted in the future to provide in-depth evidence for its clinical use.

PDIA4, a novel ER stress chaperone, modulates adiponectin expression and inflammation in adipose tissue.

Increasing evidence supporting a causal link between obesity and endoplasmic reticulum (ER) stress in adipose tissue is being reported. Protein disulfide isomerase 4 (PDIA4) is a novel ER chaperone involved in the pancreatic ß-cells pathogenesis in diabetes. However, the role of PDIA4 in obesity progression remains poorly understood. To assess the relationship between PDIA4, adiponectin, and metformin, we used the palmitate-induced inflammation in hypertrophic adipocytes and the high-fat diet-induced obesity mouse model. Our results revealed that palmitate-induced hypertrophic adipocytes exhibit obesity-associated conditions such as increased lipid accumulation, inflammation, and reduced glucose uptake. Pharmacological and genetic inhibition of PDIA4 significantly reverses these obesity-associated conditions in adipocytes. PDIA4 mechanistically promotes obesity progression via adiponectin downregulation. Furthermore, metformin modulates PDIA4 and adiponectin expression and improves obesity-associated conditions in both in vitro adipocytes and in vivo mouse models. Serum PDIA4 concentrations are also associated with body mass index, adiponectin, triglycerides, and inflammatory cytokines in humans. This is the first study demonstrating that PDIA4 modulates adipocytes by downregulating adiponectin. Moreover, metformin may serve as a potential therapeutic for preventing obesity via PDIA4-targeting.

Circulating protein disulfide isomerase family member 4 is associated with type 2 diabetes mellitus, insulin sensitivity, and obesity.

AIMS: Endoplasmic reticulum (ER) stress is associated with obesity and type 2 diabetes mellitus (T2DM) and increasing evidence demonstrates that some ER stress markers can represent the severity of metabolic dysfunction in either cellular or animal models. However, no appropriate molecule has been identified to demonstrate these relationships in clinical practice. METHODS: To determine whether the serum level of the ER chaperone, protein disulfide isomerase family A, member 4 (PDIA4), is associated with type 2 diabetes mellitus, obesity, and insulin sensitivity, we conducted a cross-sectional study for which a total of 553 adults, including 159 with normal glucose tolerance (NGT), 169 with prediabetes (Pre-DM), and 225 with newly diagnosed T2DM, were recruited. RESULTS: Serum PDIA4 levels were significantly higher in patients with T2DM than in those with NGT (P < 0.001), even after adjustment for potential confounders. These levels correlated positively with fasting plasma glucose, BMI, waist circumference as well as high-sensitivity C-reactive protein levels, and negatively and strongly correlated with insulin sensitivity. In a multivariate logistic regression analysis, higher serum PDIA4 concentration was observed to be significantly associated with an increased risk of T2DM. CONCLUSIONS: Our findings provide new mechanistic insights linking ER stress, T2DM, insulin sensitivity, and obesity, which may, in part, account for the ER chaperone properties associated with PDIA4. The results suggest that PDIA4 may serve as a potential instigator of and a putative therapeutic target for T2DM.

A novel method of skin graft fixation using adhesive hydrofiber foam.

OBJECTIVE: Conventional skin graft fixation uses a tie-over bolus dressing with splint fixation. However, splints are highly uncomfortable and contribute considerably to medical waste. Previous study has shown positive results using hydrofiber for skin graft fixation. The aim of this study was to assess the effectiveness of using adhesive hydrofiber foam for skin graft fixation. METHOD: In this retrospective study, patients reconstructed with split-thickness skin graft that was fixated only with adhesive hydrofiber foam from April 2017 until April 2019 were included. RESULTS: A total of 44 patients took part, of whom 32 were male and 12 female, with a mean age of 56±19 years. The mean operative time was 77.5±91 minutes. The average defect size was 42±37cm2. The mean skin graft take was 97±5%. The mean length of hospital admission after skin grafting until discharge was 8.5±9.2 days. Excluding those patients undergoing other procedures at the same time as the skin graft gave a total of 34 patients. Their mean operative time was 32±20 minutes, and mean length of hospital stay after skin grafting was 4.0±4.7 days. CONCLUSION: Adhesive hydrofiber foam for skin graft fixation was technically very easy to apply, resulting in a waterproof, non-bulky, secure dressing. Splints were not required. Patients were allowed to mobilise. This method resulted in increased patient comfort and decreased medical waste. From these findings, we believe that this is an extremely simple and effective method of skin graft fixation.

Associations between Sex and Risk Factors for Predicting Chronic Kidney Disease.

Gender is an important risk factor in predicting chronic kidney disease (CKD); however, it is under-researched. The purpose of this study was to examine whether gender differences affect the risk factors of early CKD prediction. This study used data from 19,270 adult health screenings, including 5101 with CKD, to screen for 11 independent variables selected as risk factors and to test for the significant effects of statistical Chi-square test variables, using seven machine learning techniques to train the predictive models. Performance indicators included classification accuracy, sensitivity, specificity, and precision. Unbalanced category issues were addressed using three extraction methods: manual sampling, the synthetic minority oversampling technique, and SpreadSubsample. The Chi-square test revealed statistically significant results (p < 0.001) for gender, age, red blood cell count in urine, urine protein (PRO) content, and the PRO-to-urinary creatinine ratio. In terms of classifier prediction performance, the manual extraction method, logistic regression, exhibited the highest average prediction accuracy rate (0.8053) for men, whereas the manual extraction method, linear discriminant analysis, demonstrated the highest average prediction accuracy rate (0.8485) for women. The clinical features of a normal or abnormal PRO-to-urinary creatinine ratio indicated that PRO ratio, age, and urine red blood cell count are the most important risk factors with which to predict CKD in both genders. As a result, this study proposes a prediction model with acceptable prediction accuracy. The model supports doctors in diagnosis and treatment and achieves the goal of early detection and treatment. Based on the evidence-based medicine, machine learning methods are used to develop predictive model in this study. The model has proven to support the prediction of early clinical risk of CKD as much as possible to improve the efficacy and quality of clinical decision making.

6M50LSG Scoring System Increased the Proportion of Adequate Excess Body Weight Loss for Suspected Poor Responders After Laparoscopic Sleeve Gastrectomy in Asian Population.

PURPOSE: We aimed to evaluate the efficacy of the predictive tool, 6M50LSG scoring system, to identify suspected poor responders after laparoscopic sleeve gastrectomy (LSG). METHODS: The 6M50LSG scoring system has been applied since 2019. Suspected poor responders are defined by EBWL at 1 month < 19.5% or EBWL at 3 months < 37.7% based on the 6M50LSG scoring system. Our analysis included 109 suspected poor responders. Based on the date of LSG, the patients were separated into two groups: the 2016-2018 group (before group, BG, with regular care) and the 2019-2020 group (after group, AG, with upgrade medical nutrition therapy). RESULTS: At the end of the study, the AG group had a significantly higher proportion of adequate weight loss, which was defined as EBWL ≥ 50% at 6 months after LSG, than that in the BG group (18.92% in BG vs. 48.57% in AG, p = 0.003). The AG group demonstrated significantly more 3-months-TWL (BG: 15.22% vs. AG: 17.54%, p < 0.001) and 6-months-TWL (BG: 21.08% vs. AG: 25.65%, p < 0.001). In multivariate analyses and adjustments, the scoring system (AG) resulted in significantly higher chances of adequate weight loss in suspected poor responders (adjusted OR 3.392, 95% CI = 1.345-8.5564, p = 0.010). One year after LSG, suspected poor responders in AG had a significantly higher weight loss than those in BG (BG vs. AG: TWL 27.17% vs. 32.20%, p = 0.014) . CONCLUSION: This study confirmed that the 6M50LSG scoring system with upgraded medical nutrition therapy increased the proportion of suspected poor responders with adequate weight loss after LSG.

Cerebral Venous Thrombosis Mimicking Acute Ischemic Stroke in the Emergency Assessment of Thrombolysis Eligibility: Learning from a Misdiagnosed Case.

PURPOSE: Cerebral venous thrombosis (CVT) occasionally presents with acute focal neurologic signs, mimicking arterial stroke syndrome. Diagnosing CVT in the setting of thrombolysis eligibility evaluation is challenging. We reported this case to discuss the promptly recognizing CVT in the setting of thrombolysis eligibility evaluation, and review the literature of thrombolytic therapy in CVT patients. CASE REPORT: A 57-year-old man presented with acute-onset right upper extremity monoparesis, right facial palsy, and aphasia. He underwent emergent thrombolysis with recombinant tissue plasminogen activator according to American Stroke Association guidelines. Subsequently, CVT was identified on multiphase computed tomography (CT) angiography. His symptoms initially improved but subsequently deteriorated because of intracranial hemorrhage. Cryoprecipitate and tranexamic acid were immediately administered. Anticoagulation was started 24 hours after the onset of hemorrhage. His modified Rankin Scale score was 4 at 120 days after the hemorrhage. CONCLUSION: Patients with CVT have a higher risk of thrombolysis-related intracranial hemorrhage than other stroke mimics. A greater focus on noncontrast brain CT and the venous phase of CT angiography help identifying this stroke mimic before thrombolysis.

Dysregulation of the miR-30a/BiP axis by cigarette smoking accelerates oral cancer progression.

BACKGROUND: Cigarette smoking is the most significant cause of oral cancer progression. Cigarette smoke condensate (CSC) has been shown to induce endoplasmic reticulum (ER) stress. Binding immunoglobulin protein (BiP) being as an ER stress regulator, has been reported to be implicated in malignant behaviors. Therefore, the aim of this study was to investigate the role of the ER stress-responsive protein, BiP, in CSC-induced oral squamous cell carcinoma (OSCC) malignancy. METHODS: The biological role of BiP in CSC-induced tumor progression was investigated in OSCC cells (YD38 and SCC25) and in a tumor xenograft mouse model. The expressions of related genes were investigated using quantitative RT-PCR and Western blot analysis. Cell migration and invasion were assessed using scratch wound healing and Transwell invasion assays. The effects of conditioned media from OSCC cells on the angiogenic activities of endothelial cells were analyzed using a tube formation assay. The interaction between miR-30a and BiP mRNA was detected using a luciferase reporter assay. RESULTS: Our results demonstrated that CSC increased the expression of BiP in time- and dose-dependent manners in YD38 and SCC25 cells, and that silencing BiP abrogated CSC-induced cell invasion and tumor-associated angiogenesis. Notably, the putative miR-30a binding site was observed in the 3'untranslated region (UTR) of BiP mRNA, and miR-30a suppressed BiP expression by targeting 3'UTR of BiP transcript. In addition, CSC increased the expression of BiP in OSCC cells by downregulating miR-30a. We also showed that BiP promoted invasion and tumor-associated angiogenesis by increasing the production and secretion of vascular endothelial growth factor in CSC-exposed OSCC cells. Moreover, BiP inhibition suppressed OSCC growth and reduced tumor vessel density in tumor-bearing mice administered with CSC. CONCLUSIONS: These observations suggest that epigenetic regulation of BiP via miR-30a downregulation is involved in CSC-induced OSCC progression.

Obesity-associated leptin promotes chemoresistance in colorectal cancer through YAP-dependent AXL upregulation.

Obesity results from an imbalance between caloric intake and energy expenditure, and it is highly associated with colorectal carcinogenesis and therapeutic resistance in patients with colorectal cancer (CRC). Dysregulation of adipokine production in obesity has been reported to cause malignant behaviors in CRC. Leptin, which is the principal hormone secreted by adipocytes and an obesity-associated adipokine, is significantly overexpressed in CRC tissues. However, the effect of leptin on chemoresistance in CRC is unclear. Therefore, the aim of this study was to clarify the role of leptin and the underlying mechanisms in mediating 5-fluorouracil (5-FU) resistance in CRC. We used palmitate to artificially generate obese adipocytes. As expected, lipid accumulation was significantly increased in obese adipocytes. We demonstrated that CRC cells incubated with conditioned media (CM) harvested from obese adipocytes were associated with increased resistance to 5-FU. Notably, this increase in resistance to 5-FU was through the elevated production and secretion of leptin. Leptin could further stimulate the expression of AXL and activate its downstream signaling molecule, PLCγ, thereby resulting in an increased expression of p-glycoprotein (P-gp) in CRC cells. Mechanistically, leptin induced AXL expression via the inhibition of AMPK and subsequent increase in YAP activation and nuclear translocation. In addition, nuclear YAP interacted with TEAD and promoted the occupancy of TEAD on the AXL promoter, thereby stimulating AXL promoter activity after leptin treatment. Furthermore, leptin neutralization rescued the sensitivity of CRC tumors to 5-FU in mice fed on a high-fat diet (HFD). These results indicated that leptin mediated 5-FU resistance through YAP-dependent AXL overexpression in CRC.

Risk Prediction of Second Primary Endometrial Cancer in Obese Women: A Hospital-Based Cancer Registry Study.

Due to the high effectiveness of cancer screening and therapies, the diagnosis of second primary cancers (SPCs) has increased in women with endometrial cancer (EC). However, previous studies providing adequate evidence to support screening for SPCs in endometrial cancer are lacking. This study aimed to develop effective risk prediction models of second primary endometrial cancer (SPEC) in women with obesity (body mass index (BMI) > 25) and included datasets on the incidence of SPEC and the other risks of SPEC in 4480 primary cancer survivors from a hospital-based cancer registry database. We found that obesity plays a key role in SPEC. We used 10 independent variables as predicting variables, which correlated to obesity, and so should be monitored for the early detection of SPEC in endometrial cancer. Our proposed scheme is promising for SPEC prediction and demonstrates the important influence of obesity and clinical data representation in all cases following primary treatments. Our results suggest that obesity is still a crucial risk factor for SPEC in endometrial cancer.

YAP-Dependent BiP Induction Is Involved in Nicotine-Mediated Oral Cancer Malignancy.

Cigarette smoking is a significant risk factor for the development and progression of oral cancer. Previous studies have reported an association between nicotine and malignancy in oral cancer. Recent studies have also demonstrated that nicotine can induce endoplasmic reticulum (ER) stress in tumor cells. Binding immunoglobulin protein (BiP) acts as a master regulator of ER stress and is frequently overexpressed in oral cancer cell lines and tissues. However, the effect of nicotine on BiP in oral cancer is unknown. Therefore, this study aimed to evaluate the role of BiP and its underlying regulatory mechanisms in nicotine-induced oral cancer progression. Our results showed that nicotine significantly induced the expression of BiP in time- and dose-dependent manners in oral squamous cell carcinoma (OSCC) cells. In addition, BiP was involved in nicotine-mediated OSCC malignancy, and depletion of BiP expression remarkably suppressed nicotine-induced malignant behaviors, including epithelial-mesenchymal transition (EMT) change, migration, and invasion. In vivo, BiP silencing abrogated nicotine-induced tumor growth and EMT switch in nude mice. Moreover, nicotine stimulated BiP expression through the activation of the YAP-TEAD transcriptional complex. Mechanistically, we observed that nicotine regulated YAP nuclear translocation and its interaction with TEAD through α7-nAChR-Akt signaling, subsequently resulting in increased TEAD occupancy on the HSPA5 promoter and elevated promoter activity. These observations suggest that BiP is involved in nicotine-induced oral cancer malignancy and may have therapeutic potential in tobacco-related oral cancer.

Post-Moore Memory Technology: Sneak Path Current (SPC) Phenomena on RRAM Crossbar Array and Solutions.

The sneak path current (SPC) is the inevitable issue in crossbar memory array while implementing high-density storage configuration. The crosstalks are attracting much attention, and the read accuracy in the crossbar architecture is deteriorated by the SPC. In this work, the sneak path current problem is observed and investigated by the electrical experimental measurements in the crossbar array structure with the half-read scheme. The read margin of the selected cell is improved by the bilayer stacked structure, and the sneak path current is reduced ~20% in the bilayer structure. The voltage-read stress-induced read margin degradation has also been investigated, and less voltage stress degradation is showed in bilayer structure due to the intrinsic nonlinearity. The oxide-based bilayer stacked resistive random access memory (RRAM) is presented to offer immunity toward sneak path currents in high-density memory integrations when implementing the future high-density storage and in-memory computing applications.

Spatiotemporal Dynamics of Cerebral Vascular Permeability in Type 2 Diabetes-Related Cerebral Microangiopathy.

Aims: Diabetes-related cerebral microangiopathy can manifest as cerebral small vessel disease (CSVD) and exhibit cognitive decline. To find the early change of function in advance, this study examined the spatiotemporal dynamics of cerebral vascular permeability (Ktrans) in the progression of type 2 diabetes mellitus (T2DM). Methods: Ktrans was cross-sectionally measured in T2DM and non-diabetes groups with or without CSVD using dynamic contrast-enhanced MRI (DCE-MRI). Results: In all patients with T2DM, the Ktrans of white matter (WM) was increased, whereas the Ktrans of gray matter (GM) was increased only in T2DM with CSVD. The involvement of WM was earlier than GM and was before the CSVD features could be visualized on MRI. Among the commonly available four CSVD items of MRI, microbleeds were the most sensitive, indicating the increased permeability in all patients. Increased Ktrans in T2DM was more associated with moderate WM hyperintensity but less with the presence of lacunae or multiple perivascular spaces, in contrast to patients without diabetes. The differential correlation suggested distinct mechanisms underlying diabetes-related CSVD and other CSVDs. Conclusions: This study highlights the early development of cerebral microangiopathy with increased BBB leakage in T2DM, before the CSVD features can be visualized on MRI. The results may increase the proactivity of clinicians in recognizing the subsequent neurological comorbidities.

Correction to: Gamma synuclein is a novel nicotine responsive protein in oral cancer malignancy.

[This corrects the article DOI: 10.1186/s12935-020-01401-w.].

Gamma synuclein is a novel nicotine responsive protein in oral cancer malignancy.

BACKGROUND: The mechanisms of neuronal protein γ-synuclein (SNCG) in the malignancy of oral squamous cell carcinoma (OSCC) are not clear. This study tested the hypothesis that SNCG is involved in nicotine-induced malignant behaviors of OSCC. The effect of nicotine on SNCG expression and epithelial-to-mesenchymal transition (EMT) markers were examined. METHODS: Short hairpin RNA (shRNA) and an antagonist specific for α7-nicotine acetylcholine receptors (α7-nAChRs) were used to examine the role of α7-nAChRs in mediating the effects of nicotine. Knockdown of SNCG in nicotine-treated cells was performed to investigate the role of SNCG in cancer malignancy. The in vivo effect of nicotine was examined using a nude mouse xenotransplantation model. RESULTS: Nicotine increased SNCG expression in a time- and dose-dependent manner. Nicotine treatment also increased E-cadherin and ZO-1 and decreased fibronectin and vimentin expression. After specific knockdown of α7-nAChRs and inhibition of the PI3/AKT signal, the effect of nicotine on SNCG expression was attenuated. Silencing of SNCG abolished nicotine-induced invasion and migration of OSCC cells. The xenotransplantation model revealed that nicotine augmented tumor growth and SNCG expression. CONCLUSION: Nicotine upregulated SNCG expression by activating the α7-nAChRs/PI3/AKT signaling that are participated in nicotine-induced oral cancer malignancy.

Advanced Machine Learning in Prediction of Second Primary Cancer in Colorectal Cancer.

Colorectal cancer (CRC) ranked third among most commonly diagnosed cancers worldwide. The onset of second primary cancer (SPC) is an important indicator in treating CRC. We tried to use the advanced machine learning method in order to find the factors of SPC. Patients with CRC from three medical centers were identified from cancer registries in Taiwan. The classifier of A Library for Support Vector Machines (LIBSVM) and Reduced Error Pruning Tree (REPTree) were applied to analyze the relationship of clinical features with category by constructing the optimized model of every classified issue. Machine learning can be used to rank the factor affecting the secondary primary malignancy. In the clinical practice, physician should be of aware the possibility of cancer recurrence and routine checkups for early second primary malignancy detection is recommended. The accuracy rate of the may need more big data. The machine learning method is feasible in detecting/predicting potential second primary cancer in the future.

Can we predict patient outcome before extracorporeal membrane oxygenation for refractory cardiac arrest?

BACKGROUND: Refractory cardiac arrest resistant to conventional cardiopulmonary resuscitation (C-CPR) has a poor outcome. Although previous reports showed that extracorporeal cardiopulmonary resuscitation (E-CPR) can improve the clinical outcome, there are no clinically applicable predictors of patient outcome that can be used prior to the implementation of E-CPR. We aimed to evaluate the use of clinical factors in patients with refractory cardiac arrest undergoing E-CPR to predict patient outcome in our institution. METHODS: This is a single-center retrospective study. We report 112 patients presenting with refractory cardiac arrest resistant to C-CPR between January 2012 and November 2017. All patients received E-CPR for continued life support when a cardiogenic etiology was presumed. Clinical factors associated with patient outcome were analyzed. Significant pre-ECMO clinical factors were extracted to build a patient outcome risk prediction model. RESULTS: The overall survival rate at discharge was 40.2, and 30.4% of patients were discharged with good neurologic function. The six-month survival rate after hospital discharge was 36.6, and 25.9% of patients had good neurologic function 6 months after discharge. We stratified the patients into low-risk (n = 38), medium-risk (n = 47), and high-risk groups (n = 27) according to the TLR score (low-flow Time, cardiac arrest Location, and initial cardiac arrest Rhythm) that we derived from pre-ECMO clinical parameters. Compared with the medium-risk and high-risk groups, the low-risk group had better survival at discharge (65.8% vs. 42.6% vs. 0%, p < 0.0001) and at 6 months (60.5% vs. 38.3% vs. 0%, p = 0.0001). The low-risk group also had a better neurologic outcome at discharge (50% vs. 31.9% vs. 0%, p = 0.0001) and 6 months after discharge (44.7% vs. 25.5% vs. 0%, p = 0.0003) than the medium-risk and high-risk groups. CONCLUSIONS: Patients with refractory cardiac arrest receiving E-CPR can be stratified by pre-ECMO clinical factors to predict the clinical outcome. Larger-scale studies are required to validate our observations.