Effect of RhD and RhE sample phenotypic blood transfusion on the prognosis of hepatocellular carcinoma.

OBJECTIVE: This study aimed to analyze the therapeutic effects and clinical outcomes of HCC patients, who received both RhD and RhE same phenotypic blood transfusion during perioperative period. METHODS: Microcolumn gel technology (MGT) was used to detect Rh blood group phenotyping in 98 HCC patients. Patients received RhD and RhE same phenotypic transfusion were defined experimental group, and those received only RhD same phenotypic but RhE different phenotypic transfusion were included in control group. Hemoglobin (Hb) and hematocrit (HCT) before and after perioperative transfusion were analyzed. The occurrence of adverse transfusion reactions were observed. Survival analysis was performed using the Kaplan-Meier method. RESULTS: After the transfusion treatment, the Hb (118.9 ±â€…34.8 g/L vs 99.6 ±â€…26.9 g/L) and HCT [(34.0 ±â€…7.6)% vs (29.9 ±â€…8.8)%] of experimental group and the Hb (104.3 ±â€…36.2 g/L vs 94.8 ±â€…25.0 g/L) of control group were significantly higher than those before blood transfusion, respectively (all P < .05). In addition, Hb and HCT in experimental group were significantly higher than those in the control group after transfusion (P < .05). For the adverse blood transfusion reactions, the incidence of backache was reduced in the patients received Rh same phenotypic transfusion compared with those in control group (1.9% vs 15.2%, P = .024). The overall survival of patients in experimental group was better than that in control group (log-rank P = .036). CONCLUSION: Our study indicated that both RhD and RhE same phenotypic transfusion significantly increased Hb and HCT and reduced backache incidence than RhE different phenotypic transfusion in HCC patients. The overall survival of patients was improved by RhD and RhE same phenotypic transfusion.

New mechanism for mesenchymal stem cell microvesicle to restore lung permeability: intracellular S1P signaling pathway independent of S1P receptor-1.

BACKGROUND: Microvesicles (MVs) derived from human bone marrow mesenchymal stem cell (MSC) were demonstrated to restore lung protein permeability and attenuate acute lung injury. In our previous study, we found that MSC MV increased sphingosine-1-phosphate (S1P) kinase1 mRNA levels in injured human lung microvascular endothelial cells (HLMVEC) significantly. However, the role of S1P signaling in MSC MV to restore lung protein permeability is unknown. METHODS: In this study, we hypothesized that MSC MV might restore lung permeability in part through increasing intracellular S1P signaling pathway in injured HLMVEC independent of S1P receptors. We used the transwell co-culture system to study the effect of MSC MV on protein permeability of Lipopolysaccharide (LPS) damaged HLMVEC. RESULTS: Our results showed that LPS significantly increased the permeability of HLMVEC to FITC-dextran (70 kDa) within 24 h. MSC MV restores this permeability and, to a large extent, prevents the cytoskeleton protein F-actin from recombining into "actin stress fibers," and restores the positions of tight junctions and adhesion junctions in the damaged HLMVEC. This therapeutic effect of MSC MV was related to the increase in the S1P level in injured HLMVEC and was not eliminated when adding the antagonist of S1P receptor, suggesting that MSC MV to restore lung permeability was independent of S1P receptors on HLMVEC. Laser confocal further observed that Ca2+ mobilization and Rac1 activation in LPS injured HLMVEC were increased in parallel with the increase in intracellular S1P level after MSC MV treatment. CONCLUSIONS: In short, MSC MV partially restored protein permeability across HLMVEC through the intracellular S1P signaling pathway independent of S1P receptor-1.

Preoperative ICG Test to Predict Posthepatectomy Liver Failure and Postoperative Outcomes in Hilar Cholangiocarcinoma.

Preoperative evaluation of hepatic functional reserve in patients with hilar cholangiocarcinoma (hCCA) has vital clinical significance for prevention of posthepatectomy liver failure (PHLF) and mortality. The aim of the present study was to evaluate the clinical significance of the indocyanine green retention rate at 15 minutes (ICG R15) and related factors of postoperative outcomes in patients with hCCA. 147 patients who scheduled for hCCA resection underwent a preoperative ICG test between May 2015 and May 2020 and were prospectively analyzed. Single-factor analysis was used to evaluate the risk factors for PHLF and postoperative outcomes in hCCA. After univariate analysis, significant differences in ICG R15 were found between the PHLF group and the liver function recovered well (LFRW) group (P ≤ 0.05). In terms of postoperative complications, ICG R15 was also a risk factor for moderate-to-severe postoperative complications. Preoperative ICG R15 was significantly associated with PHLF and moderate-to-severe postoperative complications. ICG R15 may become an ideal clinical indicator for the evaluation of liver function reserve before hCCA and can better predict the postoperative complications.

Effects of non-invasive ventilation in subjects undergoing cardiac surgery on length of hospital stay and cardiac-pulmonary complications: a systematic review and meta-analysis.

BACKGROUND: Cardiac surgery often leads to pulmonary complications. Non-invasive ventilation (NIV) is a mechanical ventilation modality that may help to prevent the pulmonary complications, and the role of the prophylactic use of NIV in patients after cardiac surgery remains controversial. METHODS: We searched PubMed, Embase, Web of Science and Cochrane Central for randomized controlled trials comparing the use of NIV (continues positive airway pressure or bi-level positive airway pressure) with standard treatment in post-cardiac surgery subjects without language restriction. Two investigators screened the eligible studies up to July, 2019. Meta-analysis using random effect model or fixed effect model was conducted for pulmonary complications, mortality, rate of reintubation and cardiac complications, and mean difference (MD) or standard mean difference for length of hospital stay and length of ICU stay. RESULTS: We included nine randomized controlled trails with 830 subjects. The use of NIV failed to reduce the risk of pulmonary complications, including atelectasis [risk rate (RR) 0.60; 95% confidence interval (CI): 0.28 to 1.28, P=0.19] and pneumonia (RR 0.27; 95% CI: 0.05 to 1.64, P=0.16). However, it has shortened the length of ICU stay (MD -1.00 h, 95% CI: -1.38 to -0.63, P<0.00001) and the length of hospital stay (MD -1.00 d, 95% CI: -1.12 to -0.87, P<0.00001). NIV also failed to reduce the rate of reintubation (RR 0.68; 95% CI: 0.21 to 2.26, P=0.53) or the risk of cardiac complications (RR 0.81; 95% CI: 0.59 to 1.13, P=0.22). CONCLUSIONS: The prophylactic use of NIV immediately in post-cardiac subjects who underwent cardiac surgery might be able to shorten the length of hospital stay and the length of ICU stay, but it has no significant effect on pulmonary complications, rate of reintubation or cardiac complications.

Inhibition of Sphingosine Kinase 1 Attenuates Sepsis-induced Microvascular Leakage via Inhibiting Macrophage NLRP3 Inflammasome Activation in Mice.

BACKGROUND: Sepsis is the overwhelming inflammatory response to infection, in which nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome plays a crucial role. Shingosine-1-phosphate is reported to evoke NLRP3 inflammasome activation. Sphingosine kinase 1 (SphK1) is the major kinase that catalyzes bioactive lipid shingosine-1-phosphate formation and its role in sepsis remains uncertain. The authors hypothesize that SphK1 elicits NLRP3 inflammasome activation and exacerbates sepsis. METHODS: Peripheral blood mononuclear cells were isolated from septic patients and healthy volunteers to measure messenger RNA (mRNA) expression. In mice, sepsis was induced by cecal ligation and puncture. Bone marrow-derived macrophages were prepared from C57BL/6J wild-type, Casp1, Nlrp3 and SphK1 mice. PF-543 was used as the specific inhibitor of SphK1. Mortality, peripheral perfusion, lung Evan's blue dye index, lung wet/dry ratio, lung injury score, lung myeloperoxidase activity, NLRP3 activation, and function of endothelial adherens junction were measured. RESULTS: SphK1 mRNA expression was higher in cells from septic patients versus healthy volunteers (septic patients vs. healthy volunteers: 50.9 ± 57.0 fold change vs. 1.2 ± 0.1 fold change, P < 0.0001) and was positively correlated with IL-1ß mRNA expression in these cells (r = 0.537, P = 0.012) and negatively correlated with PaO2/FIO2 ratios (r = 0.516, P = 0.017). In mice that had undergone cecal ligation and puncture, the 5-day mortality was 30% in PF-543-treated group and 80% in control group (n = 10 per group, P = 0.028). Compared with controls, PF-543-treated mice demonstrated improved peripheral perfusion and alleviated extravascular Evan's blue dye effusion (control vs. PF-543: 25.5 ± 3.2 ng/g vs. 18.2 ± 1.4 ng/g, P < 0.001), lower lung wet/dry ratio (control vs. PF-543: 8.0 ± 0.2 vs. 7.1 ± 0.4, P < 0.0001), descending lung injury score, and weaker lung myeloperoxidase activity. Inhibition of SphK1 suppressed caspase-1 maturation and interleukin-1ß release through repressing NLRP3 inflammasome activation, and subsequently stabilized vascular endothelial cadherin through suppressing interleukin-1ß-evoked Src-mediated phosphorylation of vascular endothelial cadherin. CONCLUSIONS: SphK1 plays a crucial role in NLRP3 inflammasome activation and contributes to lung injury and mortality in mice polymicrobial sepsis.

Neuroprotective Effect of the Inhibitor Salubrinal after Cardiac Arrest in a Rodent Model.

Cardiac arrest (CA) yields poor neurological outcomes. Salubrinal (Sal), an endoplasmic reticulum (ER) stress inhibitor, has been shown to have neuroprotective effects in both in vivo and in vitro brain injury models. This study investigated the neuroprotective mechanisms of Sal in postresuscitation brain damage in a rodent model of CA. In the present study, rats were subjected to 6 min of CA and then successfully resuscitated. Either Sal (1 mg/kg) or vehicle (DMSO) was injected blindly 30 min before the induction of CA. Neurological status was assessed 24 h after CA, and the cortex was collected for analysis. As a result, we observed that, compared with the vehicle-treated animals, the rats pretreated with Sal exhibited markedly improved neurological performance and cortical mitochondrial morphology 24 h after CA. Moreover, Sal pretreatment was associated with the following: (1) upregulation of superoxide dismutase activity and a reduction in maleic dialdehyde content; (2) preserved mitochondrial membrane potential; (3) amelioration of the abnormal distribution of cytochrome C; and (4) an increased Bcl-2/Bax ratio, decreased cleaved caspase 3 upregulation, and enhanced HIF-1α expression. Our findings suggested that Sal treatment improved neurological dysfunction 24 h after CPR (cardiopulmonary resuscitation), possibly through mitochondrial preservation and stabilizing the structure of HIF-1α.

An LC-MS/MS method for quantification of HR011303, a novel highly selective urate transporter 1 inhibitor in beagle dogs and the application to a pharmacokinetic study.

HR011303 is a novel and highly selective urate transporter 1 (URAT1) inhibitor. In this study, a sensitive liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for quantification of HR011303 in beagle dog plasma. Plasma samples were pretreated with protein-precipitation extraction by acetonitrile and added with a trifluoromethyl substituted analog of HR011303 as internal standard. The chromatographic separation was performed on a Shiseido C18 column (100 × 4.6 mm, i.d., 5 µm) by mobile phases consisting of 5 mm ammonium-formic acid (100:0.1) and acetonitrile-formic acid (100:0.1) solutions in gradient elution. The MS detection was conducted in electrospray positive ionization with multiple reactions monitoring at m/z 338 → 240 for HR011303 and m/z 328 → 230 for the internal standard using 25 eV argon gas collision induced dissociation. The established LC-MS/MS method showed good selectivity, sensitivity, precision and accuracy. The plasma pharmacokinetics of HR011303 in beagle dogs following both oral and intravenous administration were then successfully evaluated using this LC-MS/MS method.

The efficacy of parenteral fish oil in critical illness patients with sepsis: a prospective, non-randomized, observational study.

BACKGROUND AND OBJECTIVES: To investigate the clinical outcomes in septic patients receiving parenteral fish oil. METHODS AND STUDY DESIGN: A prospective, non-randomized, observational clinical study was carried out in 112 patients with sepsis from March, 2013 to May, 2015 in the surgical intensive care unit (SICU) of a tertiaryreferral hospital. The patients were put into one of two groups; either the control or the study group. Patients received the standard treatment of sepsis based on guidelines in the control group. In the study group, patients received parenteral nutrition (PN) containing fish oil. The Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, the length of ICU and hospital stay, duration of mechanical ventilation, mortality, and readmission into the ICU were recorded. Tumor necrosis factor (TNF)-α and procalcitonin (PCT) levels were also evaluated. RESULTS: The study group showed a significant reduction for all-cause mortality (20.0% vs 10.0% in study and control groups, p=0.034) and APACHE II score on day 5 (p=0.015), day 7 (p=0.036) and day out of SICU (p=0.045) compared with the control group. The study group tended to show a shortened length of stay in the ICU compared to the control group. However, TNF-α and PCT level, 28 d mortality, the length of hospital stay and the duration of mechanical ventilation did not show statistical differences between the two groups. There were no drug-related adverse effects shown during the study. CONCLUSIONS: PN with fish oil is probably safe and may improve clinical outcome in critical ill patients with sepsis.

Comparison of Percutaneous Dilatational Tracheostomy Guided by Ultrasound and Bronchoscopy in Critically Ill Obese Patients.

OBJECTIVES: This study aimed to compare the efficacy and safety of percutaneous dilatational tracheostomy (PDT) with ultrasound (US) or bronchoscopic guidance for critically ill patients, notably obese patients. METHODS: This work was a retrospective study. The study included mechanically ventilated patients who underwent PDT from August 2013 to July 2015 in the Department of Critical Care Medicine of Zhongshan Hospital. The patients were classified according to the different guidance methods during tracheotomy and their body mass index in the following 4 groups: normal bronchoscopy group, normal US group, obese bronchoscopy group, and obese US group. The parameters, including operation time, number of punctures, intraoperative and postoperative complications, duration of the intensive care unit stay, hospitalization time, and mortality, were recorded and compared between groups. RESULTS: Compared with the obese bronchoscopy group, the obese US group had a significantly shorter PDT operation time (mean ± SD, 12.8 ± 4.8 versus 16.2 ± 4.4 minutes; P = .026), fewer punctures (P = .011), and a lesser amount of intraoperative hemorrhage (12.1 ± 4.6 versus 16.8 ± 4.3 mL; P = .009). There were no significant differences in these parameters between the normal US and normal bronchoscopy groups. CONCLUSIONS: Ultrasound-guided PDT significantly reduced the number of punctures and the operation time compared with bronchoscopy-guided PDT, and it decreased intraoperative hemorrhage in critically ill obese patients. Percutaneous dilatational tracheostomy with US guidance was a faster, safer, and more accurate method of airway management.

Effective component of Salvia miltiorrhiza in promoting cardiomyogenic differentiation of human placenta­derived mesenchymal stem cells.

Our previous study indicated that Salvia miltiorrhiza (SM) induced human placenta­derived mesenchymal stem cells (hPDMSCs) to differentiate into cardiomyocytes, however, the effective component of SM in promoting cardiomyogenic differentiation remained to be elucidated. In the present study, the most commonly examined components of SM, including danshensu, salvianolic acid B, protocatechuic aldehyde, tanshinone I (TS I), TS IIA and cryptotanshinone, were used to determine the effective components of SM in promoting cardiomyogenic differentiation. The above components of SM slowed cell growth rate and altered cell morphology with a spindle or irregular shape to different degrees. The cells treated with the above components of SM showed increasing of cardiac protein expression to differing degrees, including GATA­binding protein 4, atrial natriuretic factor, α­sarcomeric actin and cardiac troponin­I. Among the components of SM, TS IIA induced the most marked effects. In addition, the above components of SM increased the expression of phosphorylated glycogen synthase kinase­3ß, but decreased the expression of ß­catenin to different degrees, with TS IIA also having the most marked effects. In conclusion, the results of the present study suggested that TS IIA was the most effective active component of SM in inducing hPDMSCs to differentiate into cardiomyocytes, and that Wnt/ß­catenin signaling was important in the process of TS IIA promoting cardiomyogenic differentiation.

The predictive value of plasma cytokines on gastroesophageal anastomotic leakage at an early stage in patients undergoing esophagectomy.

BACKGROUND: It's difficult to diagnose gastroesophageal anastomotic leakage (GAL) at early postoperative stage. This study was conducted to evaluate the early predictive value of plasma cytokines levels on GAL in patients undergoing esophagectomy. METHODS: Consecutive esophageal cancer patients who underwent esophagectomy and admitted to Surgical Intensive Care Unit (SICU) just after surgery were retrospectively analyzed. The baseline and postoperative 1 day plasma cytokine levels were collected and analyzed to evaluate the predictive value for clinically important anastomotic leakage. Area under receiver operating characteristic curve (AUROC) analysis was also performed. RESULTS: A total of 183 patients were included. Sixteen patients (8.74%) experienced GAL (GAL group) and the others did not (non-GAL group). The concentrations of tumor necrosis factor-alpha (TNF-α), interleukin (IL)-2R, IL-6, IL-8 and IL-10 in plasma on the first postoperative day significantly increased in the GAL group than in the non-GAL group (P<0.05). IL-6, IL-8 and IL-10 were fair predictors of GAL (AUROC >0.7) and the other two cytokines were poorly predictive (AUROC <0.7). The mean length of ICU and hospital stay were significantly longer in the GAL group than in the non-GAL group (P<0.05). CONCLUSIONS: Plasma concentrations of IL-6, IL-8 and IL-10 on the first postoperative day can predict clinically important GAL in patients undergoing esophagectomy.

Effect of Early Full-Calorie Nutrition Support Following Esophagectomy: A Randomized Controlled Trial.

BACKGROUND: Early use of enteral nutrition (EN) is indicated following surgical resection of esophageal cancer. However, early EN support does not always meet the optimal calorie or protein requirements, and the benefits of supplementary parenteral nutrition (PN) remain unclear. We aimed to evaluate the efficacy and safety of early supplementary PN following esophagectomy. MATERIALS AND METHODS: We enrolled 80 consecutive patients who underwent esophagectomy. Resting energy expenditure and body composition measurements were performed in all patients preoperatively and postoperatively. EN was administered after surgery, followed by randomization to either EN+PN or EN alone. The amount of PN administered was calculated to meet the full calorie requirement, as measured by indirect calorimetry, and 1.5 g protein/kg fat-free mass (FFM) per day was added as determined by body composition measurement. The clinical characteristics were compared between the 2 groups. RESULTS: Patients in the EN+PN group but not in the EN group preserved body weight (0.18 ± 3.38 kg vs -2.15 ± 3.19 kg, P < .05) and FFM (1.46 ± 2.97 kg vs -2.08 ± 4.16 kg) relative to preoperative measurements. Length of hospital stay, postoperative morbidity rates, and standard blood biochemistry profiles were similar. However, scores for physical functioning (71.5 ± 24.3 vs 60.4 ± 27.4, P < .05) and energy/fatigue (62.9 ± 19.5 vs 54.2 ± 23.5, P < .05) were higher in the EN+PN group 90 days following surgery. CONCLUSION: Early use of supplemental PN to meet full calorie requirements of patients who underwent esophagectomy led to better quality of life 3 months after surgery. Moreover, increased calorie and protein supplies were associated with preservation of body weight and FFM.

Low molecular weight heparin once versus twice for thromboprophylaxis following esophagectomy: a randomised, double-blind and placebo-controlled trial.

BACKGROUND: Venous thromboembolism (VTE) remained common complication following surgical resection of esophageal cancer. In this prospective randomized double-blind placebo-controlled trial (NCT01267305), we aim to compare the safety and efficacy between low molecular weight heparin (LMWH) once-daily (QD) and twice-daily (BID) for the prophylaxis of VTE following esophagectomy. METHODS: During August 2012 to July 2013, patients underwent esophagectomy were randomly assigned to nadroparin calcium QD (4,100 AxaIU qd + placebo qd, group QD), or nadroparin calcium BID (4,100 AxaIU q12h, group BID) in the prophylaxis of VTE. All patients received thrombelastography (TEG) before and 0/24/48/72 hours after operation. Daily vascular ultrasound of lower extremities was followed during the first 7 postoperative days to confirm the suspected deep venous thrombosis (DVT). Cumulatively postoperative chest drainage at 72 hours after the surgery was collected to identify the difference in volume and red blood cell (RBC) counts between the two groups. Any bleeding events and thromboembolic events were also documented. RESULTS: A total of 117 patients were enrolled in this study, and 111 eligible patients were randomly assigned (group QD: 55 patients; group BID: 56 patients). Patients' clinical features were close between the two groups. TEG analysis [R time, K time, alpha angel and maximum amplitude (MA)] before and instantly after operation showed nearly identical results. However, compared with group QD, all TEG measurements of 24/48/72 hours postoperatively showed significantly prolonged R time and K time, and decreased alpha angel in group BID. In ultrasound follow-ups, a total of four cases of DVT (four cases in group QD and no case in group BID) were found in this cohort (7.27% versus 0%, P=0.046), and one case of pulmonary embolism (PE) (in group QD) was observed. The incidence of VTE was lower in group BID (9.09% versus 0%, P=0.032). At 72 hours after surgery, the cumulative volume of chest drainage were close between these two groups (1,001.39±424.58 versus 1,133.61±513.93 mL, P=0.406). RBC counts in chest drainage were also identical between two groups [(2.56±1.98)×10(5) versus (2.71±4.67)×10(5), P=0.61]. No patient died due to VTE or bleeding events. CONCLUSIONS: For the prophylaxis of VTE, BID LMWH provided more potent efficacy and equal safety when compared to QD LMWH in patients undergoing selective esophagectomy. Further study based on larger population is required to confirm these findings.