Cross-cultural adaptation and validation of simplified Chinese version of the Waddell Disability Index for patients with nonspecific low back pain in Mainland China.

The current study aimed to translate the Waddell Disability Index (WDI) in a cross-cultural fashion, and evaluate the reliability and validity of the adapted simplified Chinese version (SC-WDI) for patients with nonspecific low back pain (LBP). The cross-cultural adaptation of the SC-WDI was conducted following international guidelines. The reliability and validity of the SC-WDI was assessed in a prospective observational study. The test-retest reliability was assessed by comparing the results of the first and final SC-WDI scales, 3 days interval. The discriminative, concurrent, and construct validity of the cross-cultural adapted questionnaire was evaluated. The relationship between the SC-WDI with SC-Oswestry Disability Index, SC-Roland-Morris Disability Questionnaire and visual analogue scale was assessed using the correlation coefficients. SPSS 18.0 (Chicago, IL) was used for statistical analysis. Two hundred eighty patients with LBP were included in current study. The mean age of participants was 48.4 years (range 25-82), and the mean disease duration was 1.3 years (range 0.5-24). The mean BMI was 24.6 ± 2.2. No floor or ceiling effects were noted for the SC-WDI. Cronbach's α for the total scale of was excellent with the value of 0.821. The intraclass correlation coefficient values of total SC-WDI was 0.74, which reflected a satisfactory test-retest reliability. SC-WDI had a good discriminative validity. It also indicated that the SC-WDI had a good concurrent criterion validity ( R = 0.681, 0.704, and 0.615, respectively) and construct validity with SC-Oswestry Disability Index, SC-Roland-Morris Disability Questionnaire, and visual analogue scale (all P values of < .0001). The SC-WDI demonstrated a good acceptability, score distribution, internal consistency, test-retest reliability and validity. It has high sensitivity in evaluating the HRQOL. Therefore, it is was considered as a satisfactory tool for evaluating HRQOL of Chinese patients with LBP.

Venoarterial extracorporeal membrane oxygenation improves survival in a rat model of acute myocardial infarction.

BACKGROUND: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been widely used in high-risk acute myocardial infarction (AMI) patients with promising outcomes. However, the underlying molecular mechanisms remain unknown and a VA-ECMO animal model has not yet been established. The purpose of this study was to establish a VA-ECMO model in AMI rats and evaluate long-term cardiac function. METHODS: We first established AMI in 20 Sprague-Dawley (SD) rats by ligating the left anterior descending coronary artery, while five rats underwent a thoracotomy to form the sham group. VA-ECMO was established after 30mins of AMI in 10 rats through the right jugular vein for venous drainage and right femoral artery for arterial infusion. Arterial blood pressure was monitored using a catheter in the left femoral artery, blood gas parameters were measured using a blood gas analyzer, while myocardial enzymes were detected using an ELISA Kit. Cardiac function was assessed through echocardiography on day 15. Masson staining and Western Blot were used for evaluating myocardial fibrosis, while histological injury was evaluated using hematoxylin and eosin staining. RESULTS: VA-ECMO support stabilized blood pressure, decreased the levels of myocardial enzymes including cTnI, cTnT, CK-MB, and was associated with a higher survival rate. In the long term, the VA-ECMO group showed improved cardiac function, significantly increased EF and FS but significantly decreased EDV and ESV compared to the AMI group. Furthermore, VA-ECMO significantly alleviated pathological damage and myocardial fibrosis. CONCLUSION: We established an economical, reliable, and reproducible VA-ECMO animal model in AMI rats, and demonstrated that VA-ECMO support prevents deteriorated cardiac function.

Del Nido cardioplegia for myocardial protection in adult cardiac surgery: a systematic review and update meta-analysis.

OBJECTIVE: Although the application of del Nido cardioplegia solution (DNC) in adult cardiac surgery is accumulating, the feasibility and safety of this myocardial protection strategy in adults remains controversial. We aimed to update our previous meta-analysis to determine the myocardial protective effect of DNC versus conventional cardioplegia (CC) in adult cardiac surgery. METHODS: A comprehensive literature search was performed using PubMed, EMBASE, the Cochrane Library, and International Clinical Trials Registry Platform databases through November 2020. RESULTS: Thirty-seven observational studies and four randomized controlled trials (RCTs) including 21,779 patients were identified. The DNC group was associated with decreased postoperative cardiac enzymes [troponin T (cTnT) and creatine kinase-MB (CK-MB)] [standardized mean differences (SMD): -0.59, 95% confidence interval (CI): -0.99 to -0.19, p = 0.004], cardiopulmonary bypass (CPB) time (MD: -9.31, 95% CI: -13.10 to -5.51, p < 0.00001), aortic cross-clamp (ACC) time (MD: -7.20, 95% CI: -10.31 to -4.09, p < 0.00001), and cardioplegia volume (SMD: -1.95, 95% CI: -2.46 to -1.44, p < 0.00001). Intraoperative defibrillation requirement was less in the DNC group [relative risk (RR): 0.50, 95% CI: 0.33 to 0.75, p = 0.0007]. The pooled analysis revealed no significant difference in operative mortality among the patients assigned to DNC and those undergoing CC. CONCLUSION: In adult cardiac surgery, compared to CC, myocardial protection used with DNC yield similar or better short-term clinical outcomes. More high-quality trials and RCTs reflecting long-term follow-up morbidity and mortality are required in the future to confirm these findings.

Establishment of a venovenous extracorporeal membrane oxygenation in a rat model of acute respiratory distress syndrome.

INTRODUCTION: Venovenous extracorporeal membrane oxygenation (VV ECMO) is now considered a reasonable option to salvage acute respiratory distress syndrome (ARDS). However, we lack a rodent model for experimental studies. This study was undertaken to establish an animal model of VV ECMO in ARDS rats. METHODS: A total of 18 Sprague-Dawley (SD) rats (350 ± 50 g) were used in this study. Using a rat model of oleic acid (OA)-induced ARDS, VV ECMO was established through cavoatrial cannulation of the right jugular vein for venous drainage and venous reinfusion with a specially designed three-cavity catheter. Continuous arterial pressure monitoring was implemented by using a catheter through cannulation of the right femoral artery. The central temperature was monitored with a rectal probe. Arterial blood gas monitoring was implemented by a blood gas analyzer at three-time points: at baseline, 1-hour (after OA modeling), and 3.5-hour (after VV ECMO support). Lung tissue and bronchoalveolar lavage fluid were harvested respectively for protein concentration and pulmonary histologic evaluation to confirm the alleviation of lung injury during VV ECMO. RESULTS: Following ARDS induced by OA, ten rats were successfully established on VV ECMO without failure and survived the ECMO procedure. VV ECMO alleviated lung injury and restored adequate circulation for the return of lung function and oxygenation. VV ECMO was associated with decreased lung injury score, wet/dry weight ratio, and fluid leakage into airspaces. CONCLUSION: We have established a reliable, economical, and functioning ARDS rat model of VV ECMO.

Oroxin A ameliorates the oleic acid-induced A549 cell injury through the suppression of pyroptosis and degradation of alveolar surfactant.

The destruction of the pulmonary epithelial barrier in acute respiratory distress syndrome is caused by the damage of the alveolar epithelial cells. Oroxin A is an effective flavonoid component derived from the medicinal plant Oroxylum indicum (L.) Kurz. In this study, the oleic acid (OA)-induced A549 cell injury model was established in vitro to explore the protective mechanism of Oroxin A. The experiment was divided into the following groups: control, OA and OA + Oroxin A group. The OA-induced A549 cell injury was dose (time)-dependent and was detected by the CCK-8 assay. The protein and mRNA expression levels associated with pyroptosis are detected by Western blotting and RT-qPCR. After Oroxin A treatment, the levels of IL-1ß, IL-18 and LDH released were significantly lower than the OA group. In terms of pyroptosis, Oroxin A can inhibit the expression of pyroptosis-related protein and mRNA. Significantly, the surfactant protein C (SPC) level in the OA + Oroxin A group was significantly higher than that in the OA group. The treatment with Oroxin A alleviates the OA-induced injury in the A549 cells, and its mechanism may be related to the inhibition of A549 cells pyroptosis and prevention of the degradation of the SPC.

D-tagatose protects against oleic acid-induced acute respiratory distress syndrome in rats by activating PTEN/PI3K/AKT pathway.

Acute respiratory distress syndrome (ARDS) is characterized by disruption of the alveolar-capillary barrier, resulting in severe alveolar edema and inflammation. D-tagatose (TAG) is a low-calorie fructose isomer with diverse biological activities whose role in ARDS has never been explored. We found that TAG protects lung tissues from injury in the oleic acid-induced rat model of ARDS. Seventeen male Sprague-Dawley rats were randomly assigned to 3 groups: Sham (n = 5), ARDS (n = 6), and TAG + ARDS (n = 6). The treatment groups were injected with oleic acid to induce ARDS, and the TAG + ARDS group was given TAG 3 days before the induction. After the treatments, the effect of TAG was evaluated by blood gas analysis and observing the gross and histological structure of the lung. The results showed that TAG significantly improved the oxygenation function, reduced the respiratory acidosis and the inflammatory response. TAG also improved the vascular permeability in ARDS rats and promoted the differentiation of alveolar type II cells, maintaining the stability of the alveolar structure. This protective effect of TAG on the lung may be achieved by activating the PTEN/PI3K/AKT pathway. Thus, TAG protects against oleic acid-induced ARDS in rats, suggesting a new clinical strategy for treating the condition.

Venovenous extracorporeal membrane oxygenation promotes alveolar epithelial recovery by activating Hippo/YAP signaling after lung injury.

BACKGROUND: The preferred configuration for bridging patients with respiratory failure while awaiting lung transplantation is venovenous extracorporeal membrane oxygenation (VV ECMO). However, the protective effect of VV ECMO on the lung, as well as the underlying mechanisms, are still unknown. METHODS: We investigated the role of VV ECMO in preventing lung injury in vivo using a rat model. Additionally, the effects of Hippo/YAP signaling on alveolar epithelial type II cells (AT2)-mediated alveolar epithelial recovery in VV ECMO rats were also investigated. In the bronchoalveolar lavage fluid (BALF) and lung tissue, RNA sequencing, lung injury, edema, and cytokine expression were evaluated. RESULTS: VV ECMO significantly improved severe hypoxemia, reduced lung edema, and inflammatory response, and altered alveolar epithelial function, as indicated by reduced protein concentrations in BALF. This was associated with Hippo/YAP signaling activation, according to RNA sequencing analysis. Furthermore, we discovered that after VV ECMO, AT2 cells proliferated and differentiated, and this increase in AT2 cell activity was correlated to the increased nuclear expression of YAP, which is critical for alveolar epithelial recovery from lung injury. During VV ECMO, verteporfin-induced YAP inhibition and the loss of the oxygenator delayed lung alveolar epithelial recovery and led to a prolonged inflammatory response. CONCLUSIONS: These findings suggest that VV ECMO protects against lung injury by activating the Hippo/YAP signaling pathway. Strategies aimed at increasing YAP activity in AT2 cells could thus aid alveolar epithelial recovery, making VV ECMO easier for lung transplantation.

Dexamethasone Alleviates Myocardial Injury in a Rat Model of Acute Myocardial Infarction Supported by Venoarterial Extracorporeal Membrane Oxygenation.

Myocardial ischemia causes myocardial inflammation. Research indicates that the venoarterial extracorporeal membrane oxygenation (VA ECMO) provides cardiac support; however, the inflammatory response caused by myocardial ischemia remains unresolved. Dexamethasone (Dex), a broad anti-inflammatory agent, exhibits a cardioprotective effect. This study aims to investigate the effect of Dex on a rat model of acute myocardial infarction (AMI) supported by VA ECMO. Male Sprague-Dawley rats (300-350 g) were randomly divided into three groups: Sham group (n = 5), ECMO group (n = 6), and ECMO + Dex group (n = 6). AMI was induced by ligating the left anterior descending (LAD) coronary artery. Sham group only thoracotomy was performed but LAD was not ligated. The ECMO and ECMO + Dex groups were subjected to 1 h of AMI and 2 h of VA ECMO. In the ECMO + Dex group, Dex (0.2 mg/kg) was intravenously injected into the rats after 1 h of AMI. Lastly, myocardial tissue and blood samples were harvested for further evaluation. The ECMO + Dex group significantly reduced infarct size and levels of cTnI, cTnT, and CK-MB. Apoptotic cells and the expression levels of Bax, Caspase3, and Cle-Caspase3 proteins were markedly lower in the ECMO + Dex group than that in the ECMO group. Neutrophil and macrophage infiltration was lower in the ECMO + Dex group than in the ECMO group. A significant reduction was noted in ICAM-1, C5a, MMP-9, IL-1ß, IL-6, and TNF-α. In summary, our findings revealed that Dex alleviates myocardial injury in a rat model of AMI supported by VA ECMO.

Natural Compound Library Screening Identifies Oroxin A for the Treatment of Myocardial Ischemia/Reperfusion Injury.

Myocardial ischemia/reperfusion injury (MI/RI) is a serious pathophysiological process relating to cardiovascular disease. Oroxin A (OA) is a natural flavonoid glycoside with various biological activities. However, its effect on the pathophysiological process of MI/RI has not yet been reported. The aim of this study was to determine whether OA could alleviate MI/RI induced inflammation and pyroptosis in vivo and in vitro, providing a novel therapeutic regimen for the treatment of MI/RI. A high-throughput drug screening strategy was employed to test 2,661 natural compound libraries that can alleviate MI/RI in vivo and in vitro. The rat model of MI/RI was established by ligating the left anterior descending (LAD) coronary artery. H9c2 cells were subjected to oxygen-glucose deprivation/reperfusion (OGD/R) to simulate MI/RI. The results show that OA is able to significantly inhibit apoptosis, pyroptosis and the inflammation response (TNF-α, IL-6, IL-8, IL-10, IL-1ß, IL-18) in vivo and in vitro, and reduce the release of myocardial enzymes (cTnI, cTnT, CK-MB, LDH, AST). In the rat MI/RI model, OA can not only improve cardiac function and reduce inflammatory cell infiltration but also reduce myocardial infarct size. The results revealed that OA is an effective remedy against MI/RI as it reduces the inflammatory response and inhibits pyroptosis. This may provide a new therapeutic target for the clinical treatment of MI/RI.

Risk Factors for Dysphagia after Anterior Cervical Discectomy and Fusion with the Zero-P implant system: A Study with Minimum of 2 Years Follow-up.

OBJECTIVE: To evaluate the risk factors for dysphagia after anterior cervical discectomy and fusion (ACDF) with the Zero-P Implant System by multidimensional analysis and investigated the predictive values of these risk factors for dysphagia. METHODS: A retrospective analysis of 260 patients who underwent ACDF with the Zero-P Implant System and had at least 2 year of follow-up were performed. All patients were divided into a non-dysphagia group and a dysphagia group. Sex, age, body mass index (BMI), intraoperative time, estimated blood loss, diabetes mellitus, hypertension, smoking, alcohol consumption, prevertebral soft-tissue thickness, the levels of surgery, O-C2 angle, C2-7 angle, T1 slope and segmental angle were analyzed. The Modified Japanese Orthopaedic Association (JOA) scoring system was used to determine functional status. NDI was used to evaluate neck pain and disability. The Bazaz grading system was chosen to evaluate dysphagia after surgery. Postoperative cerebrospinal fluid (CSF) leakage, infection, and dysphagia were recorded in both groups. An independent t-test was used to compare quantitative variables, a chi-square test was used to compare qualitative data between the two groups. To eliminate the influence of confounding factors, logistic regression was performed for multifactor regression of factors. The results were regarded as significant when the P-values were less than 0.05 in this study. RESULTS: In total, the non-dysphagia group comprised 70 patients and the dysphagia group comprised 190 patients, with an average age of 58.33 ± 4.68 years (ranging, 42-82 years). These patients were followed up for 28.5 ± 3.5 months (range, 24-32 months). For clinical outcomes, both groups demonstrated significant improvement in the NDI and JOA scores (P < 0.001). According to the Bazaz dysphagia grading system, mild, moderate, and severe dysphagia were found in 50, 17, and 3 patients, respectively. In total, 37.1% (n = 26) had resolved by 3 month, 38.6% (n = 27) by 6 months, and 17.1% (n = 12) by 12 months. Chi-square test results indicated that number of operated levels, operation time dT1 slope, dO-C2 angle, dC2-7 angle, segmental angle and dPSTT were associated with a high incidence of dysphagia. Multivariate logistic regression analysis showed that number of operated levels, operation time, dC2-7 angle and dPSTT were significantly associated with postoperative dysphagia. CONCLUSIONS: More operated levels, more operation time, more dC2-7 angle and dPSTT were the risk factors for postoperative dysphagia. In additional, sufficient preoperative preparation, evaluation combined with proficient and precise surgical treatment were suggested to reduce the incidence of postoperative dysphagia when ACDF was performed.

Efficacy of left ventricular unloading strategies during venoarterial extracorporeal membrane oxygenation in patients with cardiogenic shock: a protocol for a systematic review and Bayesian network meta-analysis.

INTRODUCTION: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) has been widely used for patients with refractory cardiogenic shock. A common side effect of this technic is the resultant increase in left ventricular (LV) afterload which could potentially aggravate myocardial ischaemia, delay ventricular recovery and increase the risk of pulmonary congestion. Several LV unloading strategies have been proposed and implemented to mitigate these complications. However, it is still indistinct that which one is the best choice for clinical application. This Bayesian network meta-analysis (NMA) aims to compare the efficacy of different LV unloading strategies during VA-ECMO. METHODS AND ANALYSIS: PubMed, Embase, the Cochrane Library and the International Clinical Trials Registry Platform will be explored from their inception to 31 December 2020. Random controlled trials and cohort studies that compared different LV unloading strategies during VA-ECMO will be included in this study. The primary outcome will be in-hospital mortality. The secondary outcomes will include neurological complications, haemolysis, bleeding, limb ischaemia, renal failure, gastrointestinal complications, sepsis, duration of mechanical ventilation, length of intensive care unit and hospital stays. Pairwise and NMA will respectively be conducted using Stata (V.16, StataCorp) and Aggregate Data Drug Information System (V.1.16.5), and the cumulative probability will be used to rank the included LV unloading strategies. The risk of bias will be conducted using the Cochrane Collaboration's tool or Newcastle-Ottawa Quality Assessment Scale according to their study design. Subgroup analysis, sensitivity analysis and publication bias assessment will be performed. The Grading of Recommendations Assessment, Development and Evaluation will be conducted to explore the quality of evidence. ETHICS AND DISSEMINATION: Either ethics approval or patient consent is not necessary, because this study will be based on literature. The results will be disseminated through peer-reviewed publications and conference presentations. PROSPERO REGISTRATION NUMBER: CRD42020165093.

Synthesis and Biological Evaluation of a Series of Bile Acid Derivatives as FXR Agonists for Treatment of NASH.

Farnesoid X receptor (FXR) has become a particularly attractive target for the discovery of drugs for the treatment of liver and metabolic diseases. Obeticholic acid (INT-747), a FXR agonist, has advanced into clinical phase III trials in patients with nonalcoholic steatohepatitis (NASH), but adverse effects (e.g., pruritus, LDL increase) were observed. Pruritus might be induced by Takeda G-protein-coupled receptor 5 (TGR5, GPBAR1), and there are chances to develop FXR agonists with higher selectivity over TGR5. In this letter, novel bile acids bearing different modifications on ring A and side chain of INT-747 are reported and discussed. Our results indicated that the side chain of INT-747 is amenable to a variety of chemical modifications with good FXR potency in vitro. Especially, compound 18 not only showed promising FXR potency and excellent pharmacokinetic properties, but also proved superior pharmacological efficacy in the HFD + CCl4 model.