Comparison of bicarbonate Ringer's solution with lactated Ringer's solution among postoperative outcomes in patients with laparoscopic right hemihepatectomy: a single-centre randomised controlled trial.

The study was aimed to investigate the positive impact of bicarbonate Ringer's solution on postoperative outcomes in patients who underwent laparoscopic right hemihepatectomy. Patients in the two groups were infused with lactated Ringer's solution (LRS, n = 38) and the bicarbonate Ringer's solution (BRS, n = 38) at a rate of 5 ml·kg-1·h-1. The stroke volume was monitored and 200 ml of hydroxyethyl starch with 130/0.4 sodium chloride injection (Hes) of a bolus was given in the first 5-10 min. The main outcome was to test lactic acid (LAC) concentration before and after surgery. The concentrations of LAC in the LRS group were higher than in the BRS group at 2 h after operation began, at the end of the operation and 2 h after the operation. Overall, the parameters including pH, base excess (BE), HCO3-, aspartate transaminase (AST) and alanine transaminase (ALT) were improved. The values of bilirubin in the LRS group were higher and albumin were lower than in the BRS group at post-operation 1st and 2nd day (P<0.05). The time of prothrombin time (PT) and activated partial thromboplastin time (APTT) in the LRS group were longer than that in the BRS group at post-operation 1st and 2nd day (P<0.05). Likewise, the concentrations of Mg2+, Na+ and K+ also varied significantly. The length of hospital was reduced, and the incidence of premature ventricular contractions (P = 0.042) and total complications (P = 0.016) were lower in group BRS. TRIAL REGISTRATION: The study was registered at clinicalTrials.gov with the number ChiCTR2000038077 on 09/09/2020.

ST36 acupoint injection with anisodamine for postoperative nausea and vomiting in female patients after bariatric surgery: a prospective, randomized controlled trial.

BACKGROUND: The use of multimodal pharmacological prophylactic regimes has decreased postoperative nausea and vomiting (PONV) in general but it still occurs in over 60% of female patients after bariatric surgery. This study aimed to evaluate the efficacy of ST36 acupoint injection with anisodamine in prevention of PONV among female patients after bariatric surgery. METHODS: Ninety patients undergoing laparoscopic sleeve gastrectomy were randomly allocated to anisodamine or control group at the ratio of 2:1. Anisodamine or normal saline was injected into Zusanli (ST36) bilaterally after induction of general anesthesia. The incidence and severity of PONV were assessed during the first 3 postoperative days and at 3 months. The quality of early recovery of anesthesia, gastrointestinal function, sleep quality, anxiety, depression, and complications were also evaluated. RESULTS: Baseline and perioperative characteristics were comparable between two groups. In the anisodamine group, 25 patients (42.4%) experienced vomiting within postoperative 24 h compared with 21 (72.4%) in the control group (relative risk 0.59; 95% confidence interval 0.40-0.85). Time to first rescue antiemetic was 6.5 h in anisodamine group, and 1.7 h in the control group (P = 0.011). Less rescue antiemetic was required during the first 24 h in the anisodamine group (P = 0.024). There were no differences in either postoperative nausea or other recovery characteristics. CONCLUSIONS: The addition of ST36 acupoint injection with anisodamine significantly reduced postoperative vomiting without affecting nausea in female patients with obesity undergoing laparoscopic sleeve gastrectomy.

Use of a combination of diaphragmatic ultrasound and muscle relaxation monitoring in predicting post-extubation adverse respiratory events among elderly patients in an anesthesia intensive care unit.

OBJECTIVE: The purpose of this study was to examine the feasibility of using a combination of diaphragmatic ultrasound and muscle relaxation monitoring in predicting adverse respiratory events after extubation among elderly patients in an anesthetic intensive care unit (AICU). METHODS: The study participants were 120 elderly patients who were in the AICU after laparoscopic radical resection for colorectal cancer. Based on whether there were critical respiratory events (CREs) after extubation, they were divided into the adverse event group and the non-adverse event group. We used logistic regression to identify factors influencing the occurrence of CREs post-extubation in elderly patients. Using the receiver operating characteristic (ROC) curve, we analyzed the value of each indicator in predicting CREs post-extubation. RESULTS: We included 109 patients in the final analysis. In the adverse event group (n = 19), the age, proportion of females, and proportion of preoperative respiratory diseases were higher than in the non-adverse event group (n = 90). The muscle relaxation value, quiet breathing diaphragmatic excursion during extubation (DE-QB), deep breathing diaphragmatic excursion during extubation (DE-DB), and deep breathing diaphragmatic thickening fraction during extubation (DTF-DB) of patients in the adverse event group were significantly lower than those in the non-adverse event group (P < 0.05). Using binary logistic regression analysis, we identified muscle relaxation value, DE-DB, and DTF-DB during extubation as significant predictors of CREs post-extubation in elderly patients (P < 0.05). The area under the curve (AUC) of the combination of the muscle relaxation value, DE-DB, and DTF-DB during extubation for predicting CREs after extubation in elderly patients was 0.949, which was higher than that of any single indicator. CONCLUSION: The combination of diaphragmatic ultrasound and muscle relaxation monitoring was more accurate in predicting CREs post-extubation among elderly patients in the AICU.

Preemptive QP001, a fast-acting meloxicam formulation, provides analgesia and reduces opioid consumption following abdominal surgery: a randomized controlled trial.

BACKGROUND: QP001, a novel meloxicam formulation, has been developed to manage moderate to severe postoperative pain. This study aimed to evaluate the efficacy and safety of QP001 injections for moderate to severe pain following abdominal surgery. METHOD: This prospective, multicenter, randomized, double-blind, placebo-controlled clinical trial enlisted patients experiencing moderate to severe pain following abdominal surgery. These patients were randomized to receive either QP001 injections (30 mg or 60 mg) or a placebo pre-surgery. The primary efficacy endpoint was the total morphine consumption within 24 h after the first administration. RESULTS: A total of 108 patients were enrolled, and 106 patients completed the study. The total morphine consumption in the QP001 30 mg group and 60 mg group, versus placebo group, were significantly lower over the following 24 h (5.11[5.46] vs 8.86[7.67], P = 0.011; 3.11[3.08] vs 8.86[7.67], P < 0.001), respectively. The total morphine consumption in the QP001 30 mg and 60 mg groups, versus placebo group, was also significantly decreased over the following 48 h, including the 24-48 h period (P ≤ 0.001). The QP001 30 mg and 60 mg groups, versus placebo, showed a significant decrease in the area under the curve for pain intensity-time as well as a significant decrease in the effective pressing times of the analgesic pump over the 24 h and 48 h periods (P < 0.05). The QP001 groups, versus placebo, show no significant different in Adverse Events or Adverse Drug Reactions (P > 0.05). CONCLUSION: Preoperative/preemptive QP001 provides analgesia and reduces opioid consumption in patients with moderate to severe pain following abdominal surgery, while maintaining a favorable safety profile.

Comparison of Outcomes Following General Anesthesia and Spinal Anesthesia During Emergency Cervical Cerclage in Singleton Pregnant Women in the Second Trimester at a Single Center.

BACKGROUND Little information exists regarding the best anesthesia method for emergency cerclage. This single-center study aimed to compare the outcomes following general anesthesia and spinal anesthesia during emergency cervical cerclage in women in the second trimester of a singleton pregnancy. MATERIAL AND METHODS A total of 297 pregnant patients were recruited: 141 patients were assigned to the general anesthesia group and 156 patients were assigned to the spinal anesthesia group. Periprocedural data and obstetric outcomes were recorded and statistically analyzed. RESULTS Average duration of the cerclage procedure was shorter in the general anesthesia group than in the spinal anesthesia group (25.78±9.4 min versus 30.88±10.5 min; P<0.05). No severe maternal complications, such as hematosepsis or maternal death, occurred after the procedure for either group. The neutrophil-lymphocyte ratio and C-reactive protein (CRP) increased after emergency cerclage in both groups, but at no time did the 2 groups differ significantly (P>0.05). There was also no significant difference in the incidence of miscarriage or preterm delivery (delivery <34 gestational weeks) or in neonatal outcome between the 2 groups (P>0.05). CONCLUSIONS The results of this study showed that there were no significant differences in maternal and neonatal outcomes, rates of miscarriage, or preterm delivery between general anesthesia and spinal anesthesia during emergency cervical cerclage in women in the second trimester of a singleton pregnancy.

Applicability and effectiveness of ultrasound combined with nerve stimulator-guided lumbosacral plexus block in the supine versus lateral position during surgeries for lower limb fracture-a prospective randomized controlled trial.

BACKGROUND: Patients with lower limb fracture often have acute pain and discomfort from changes in position, and such pain affects early postoperative recovery. This study aimed to compare the applicability and effectiveness of ultrasound combined with nerve stimulator-guided lumbosacral plexus block (LSPB) in the supine versus lateral position during lower limb fracture surgery. METHODS: We included 126 patients who underwent elective internal fixation for lower limb fracture who were divided into the S group and the L group by the random number table method and underwent LSPB guided by ultrasound combined with a nerve stimulator in the supine and lateral positions, respectively. The primary outcome was the dose of sufentanil used in surgery. The secondary outcomes were the maximum VAS (visual analogue scale) pain score at position placing for LSPB, the time of position placing, the time for nerve block,the number of puncture attempts,the haemodynamic indicators, the VAS score at 1, 12, and 24 h following surgery, postoperative satisfactory degree to analgesia and adverse events related to nerve block. RESULTS: There was no statistically significant difference in dose of sufentanil used between the two groups(P = 0.142). The maximum VAS pain score at position placing(P < 0.01), the time of position placement(P < 0.01), the time for lumbar plexus block and the time of puncture attempts were significantly lower in the S group than in the L group (P < 0.01). However, the time for sacral plexus block was higher in the S group than in the L group (P = 0.029). There was no significant difference in haemodynamic indicators,number of puncture attempts for the sacral plexus, postoperative VAS scores, postoperative satisfactory degree to analgesia or adverse events related to nerve block between the two groups (all P > 0.05). CONCLUSIONS: Our study provides a more comfortable and better accepted anaesthetic regimen for patients undergoing lower limb fracture surgery. LSPB in the supine position is simple to apply and has definite anaesthetic effects. Additionally, it has a high level of postoperative analgesia and therefore should be widely applied. TRIAL REGISTRATION: The trial was registered prior to patient enrolment at the Chinese Clinical Trail Registry (Date:11/03/2021 Number: ChiCTR2100044117 ).

Performance of 68Ga-labeled prostate-specific membrane antigen ligand positron emission tomography/computed tomography in the diagnosis of primary prostate cancer: a systematic review and meta-analysis.

OBJECTIVE: To explore the feasibility of 68Ga-PSMA PET/CT in diagnosing primary prostate cancer. MATERIALS AND METHODS: Embase, PubMed and Cochrane Library databases were searched for studies published before July 2020. The studies that used 68Ga-PSMA PET/CT for detecting primary prostate cancer, and pathological biopsy as the reference standard were included. The selecting process used preferred reporting items for systematic reviews and meta-analyses (PRISMA). The quality of enrolled studies was assessed by the Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) tool. RESULTS: According to our search strategy, 9 studies were included for analysis. A total of 547 patients with primary prostate cancer and 443 lesion segments that underwent 68Ga-PSMA PET/CT scans were included and their pathological biopsies were compared. The results of these studies showed some differences. For instance, the lowest sensitivity of 68Ga-PSMA PET/CT in diagnosing primary prostate cancer was 67%, while the highest sensitivity recorded was 97%. CONCLUSIONS: Compared with conventional imaging examinations, 68Ga-PSMA PET/CT had higher sensitivity and specificity in detecting primary prostate cancer. At present, most of the studies that used 68Ga-PSMA PET/CT for detecting prostate cancer are retrospective studies. Based on its advantage of high detection rate, the use of 68Ga-PSMA PET/CT in the detection of primary prostate cancer is worthy of promotion.

Indirect comparison of the diagnostic performance of 18F-FDG PET/CT and MRI in differentiating benign and malignant ovarian or adnexal tumors: a systematic review and meta-analysis.

OBJECTIVE: To compare the value of fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) and magnetic resonance imaging (MRI) in differentiating benign and malignant ovarian or adnexal tumors. MATERIALS AND METHODS: English articles reporting on the diagnostic performance of MRI or 18F-FDG PET/CT in identifying benign and malignant ovarian or adnexal tumors published in PubMed and Embase between January 2000 and January 2021 were included in the meta-analysis. Two authors independently extracted the data. If the data presented in the study report could be used to construct a 2 × 2 contingency table comparing 18F-FDG PET/CT and MRI, the studies were selected for the analysis. The Quality Assessment of Diagnostic Accuracy Studies-2 (QUADAS-2) was used to evaluate the quality of the included studies. Forest plots were generated according to the sensitivity and specificity of 18F-FDG PET/CT and MRI. RESULTS: A total of 27 articles, including 1118F-FDG PET/CT studies and 17 MRI studies on the differentiation of benign and malignant ovarian or adnexal tumors, were included in this meta-analysis. The pooled sensitivity and specificity for 18F-FDG PET/CT in differentiating benign and malignant ovarian or adnexal tumors were 0.94 (95% CI, 0.87-0.97) and 0.86 (95% CI, 0.79-0.91), respectively, and the pooled sensitivity and specificity for MRI were 0.92 (95% CI: 0.89-0.95) and 0.85 (95% CI: 0.79-0.89), respectively. CONCLUSION: While MRI and 18F-FDG PET/CT both showed to have high and similar diagnostic performance in the differential diagnosis of benign and malignant ovarian or adnexal tumors, MRI, a promising non-radiation imaging technology, may be a more suitable choice for patients with ovarian or accessory tumors. Nonetheless, prospective studies directly comparing MRI and 18F-FDG PET/CT diagnostic performance in the differentiation of benign and malignant ovarian or adnexal tumors are needed.

Abnormal phosphorylation of tau protein and neuroinflammation induced by laparotomy in an animal model of postoperative delirium.

Postoperative delirium (POD) is an acute neuropsychological disturbance after surgery, whose prevalence is related with advancing age. Neuroinflammation and abnormal tau phosphorylation that commonly presenting in Alzheimer's disease (AD) may contribute to the progression and duration of POD. To study the acute influence of surgery on cognitive function, wild type male C57BL/6 N mice were randomly divided into three groups: Control (CON), Laparotomy at 4 h and 24 h (LAP-4 h, LAP-24 h), then subjected to laparotomy under sevoflurane anaesthesia. The cognitive performance, peripheral and central inflammatory responses and tau phosphorylation levels were evaluated at 4 h and 24 h postoperatively. When LAP4-hrs displayed anxiety behaviors with high mRNA levels of inflammatory cytokines, such as interleukin-1ß (IL-1ß), IL-6, IL-8, TNF-α and MCP-1 in the liver, and IL-8 in the hippocampus, results at 24 h were different. In the liver, only IL-10 protein was obviously elevated, but in the hippocampus, both pro- and anti-inflammatory cytokines were significantly decreased whilst the elimination of anxiety. The activity of major related kinases and phosphatases was remarkably changed which may contribute to the dephosphorylated tau protein. With tremendous neuropathological changes and significant numbers of activated microglias and astrocytes observed in the sub-regions of hippocampus, the memory impairment existed at both 4 h and 24 h. Since the association of dephosphorylated tau with POD, these findings may supply novel implications for the understanding of tauopathies and as a theoretical basis for preventions from the postoperative cognitive dysfunction (POCD).

Discovery of new chalone adamantyl arotinoids having RXRα-modulating and anticancer activities.

In the present study, a new series of chalcone adamantly arotinoids (chalcone AdArs) derived from RAR antagonist MX781, are synthesized, characterized, and evaluated for the biological activities in vitro. The studies of antiproliferative activity and RXRα-binding affinity of target compounds result in the discovery of a lead candidate (WA15), which is a good RXRα binder (Kd = 2.89 × 10-6 M) with potent antiproliferative activity against human cancer cell lines (IC50 ≈ 10 µM) and low toxic to normal LO2 and MRC-5 cells (IC50 > 50 µM). Different from MX781, WA15 eliminates RARα antagonist activity but inhibits 9-cis-RA-induced RXRα transactivation activity in a dose-dependent manner. Compound WA15 is found to be a good apoptosis inducer in various cancer cells and promotes cell apoptosis in an RXRα-independent manner. Besides, WA15 shows the induction of proteasome-dependent RXRα degradation which might enhance the WA15-induced apoptosis. Finally, the immunoblotting indicates that WA15 can inhibit the TNFα-induced IKK activation and IκBα degradation, suggesting that the anticancer activity of WA15 might be related to the inhibition of IKK/NF-κB signal pathway.

Different Doses of Nalbuphine Combined with Dexmedetomidine in Laparoscopic Oophorocystectomy.

BACKGROUND The goal of this study was to investigate different doses of nalbuphine combined with dexmedetomidine in the postoperative treatment of laparoscopic oophorocystectomy. MATERIAL AND METHODS This prospective single-blinded randomized controlled study included 219 patients with benign ovarian cysts who received laparoscopic oophorocystectomy from March 2017 to October 2019. Patients were randomized into 4 groups: low (0.5 mg/kg), middle (1.0 mg/kg), and high (1.5 mg/kg) doses of nalbuphine combined with dexmedetomidine (4 µg/kg) (LND, MND, and HND groups, respectively) and a control group with sufentanil (2.5 µg/kg), with different patient-controlled intravenous analgesia pump (PCIA) strategies. Rest and active visual analog scale (VAS) scores measured postoperative pain, and Ramsay scores were used to measure sedation. RESULTS The HND group showed the lowest rest and cough VAS scores at 2 h, 8 h, 12 h, and 24 h after surgery, the lowest PCIA pressing time within 48 h after surgery, and the highest Ramsay scores at 2 h, 8 h, 24 h and 48 h after surgery. Rest and cough VAS scores decreased with higher nalbuphine doses in a dose-dependent manner. One day after surgery, IL-1ß and IL-6 levels increased in all groups, with the lowest levels of IL-1ß and IL-6 in the HND group. Hospitalization time was significantly shorter in the HND group compared with the LND and MND groups. There were no significant differences in complications among groups. CONCLUSIONS Combined nalbuphine and dexmedetomidine improved postoperative pain and sedative conditions, reduced inflammation in a nalbuphine dose-dependent manner, and might facilitate patient recovery.

Ribosomal protein small subunit 15A (RPS15A) inhibits the apoptosis of breast cancer MDA-MB-231 cells via upregulating phosphorylated ERK1/2, Bad, and Chk1.

AIM: To detect the expression and identify the role of Ribosomal protein S15A (RPS15A) in human breast cancer (BC). METHODS: Immunohistochemistry (IHC) was carried out for detecting the levels of RPS15A protein. Quantitative PCR was used to evaluate the mRNA level of RPS15A in one normal breast and three BC cell lines. Lentivirus-mediated shRNA targeting RPS15A was designed to investigate the impact of silencing RPS15A in MDA-MB-231 cell. RESULTS: Higher RPS15A expression was detected in tumor tissues than in para-cancer tissues, and higher RPS15A expression was related to larger tumor size and higher TNM stage. Also, RPS15A mRNA expression in all three BC cell lines was higher than that in normal breast cell (all P < .005). Further, RPS15A knockdown significantly suppressed MDA-MB-231 cell proliferation and induced apoptosis. Moreover, RPS15A knockdown increased the caspase-3/-7 activity, and suppressed the phosphorylated levels of ERK1/2, Bad, and Chk1 (all P < .01). CONCLUSION: RPS15A inhibits apoptosis via upregulating phosphorylated ERK1/2, Bad, and Chk1 in MDA-MB-231 cell line.

Minimum Alveolar Concentration-Awake of Sevoflurane Is Decreased in Patients With End-Stage Renal Disease.

BACKGROUND: End-stage renal disease (ESRD) has been shown to be associated with abnormal neural function. Clinically used inhaled anesthetic agents typically exert their effect through multiple target receptors in the central nervous system. Pathological changes in the brain may alter sensitivity to inhaled anesthetic agents. This study aimed to determine the minimum alveolar concentration-awake (MACawake) of sevoflurane in patients with ESRD compared to patients with normal renal function. METHODS: Patients underwent inhalational induction of anesthesia and received sevoflurane at a preselected concentration according to a modified Dixon "up-and-down" method starting at 1.0% with a step size of 0.2%. The concentration of sevoflurane used for each consecutive patient was increased or decreased based on a positive or negative response to verbal command in the previous patient. Serum neuron-specific enolase, a biomarker of impaired neurons, was also measured. RESULTS: Forty-one patients were enrolled: 20 with ESRD and 21 as controls. The MACawake of sevoflurane in patients with ESRD was significantly lower than that observed in the control group (0.56% [standard deviation {SD} = 0.10%] vs 0.67% [SD = 0.08%]; P = .031). Patients with ESRD exhibited higher serum neuron-specific enolase levels compared to the control group (16.4 ng/mL [SD = 5.0] vs 8.7 ng/mL [SD = 2.9]; P < .001). CONCLUSIONS: MACawake of sevoflurane is somewhat lower in patients with ESRD compared to those with normal renal function. Impaired cerebral function may partly contribute to the reduction in anesthetic requirement.

Cholesterol inhibits entotic cell-in-cell formation and actomyosin contraction.

Cell-in-cell structure is prevalent in human cancer, and associated with several specific pathophysiological phenomena. Although cell membrane adhesion molecules were found critical for cell-in-cell formation, the roles of other membrane components, such as lipids, remain to be explored. In this study, we attempted to investigate the effects of cholesterol and phospholipids on the formation of cell-in-cell structures by utilizing liposome as a vector. We found that Lipofectamine-2000, the reagent commonly used for routine transfection, could significantly reduce entotic cell-in-cell formation in a cell-specific manner, which is correlated with suppressed actomyosin contraction as indicated by reduced ß-actin expression and myosin light chain phosphorylation. The influence on cell-in-cell formation was likely dictated by specific liposome components as some liposomes affected cell-in-cell formation while some others didn't. Screening on a limited number of lipids, the major components of liposome, identified phosphatidylethanolamine (PE), stearamide (SA), lysophosphatidic acid (LPA) and cholesterol (CHOL) as the inhibitors of cell-in-cell formation. Importantly, cholesterol treatment significantly inhibited myosin light chain phosphorylation, which resembles the effect of Lipofectamine-2000, suggesting cholesterol might be partially responsible for liposomes' effects on cell-in-cell formation. Together, our findings supporting a role of membrane lipids and cholesterol in cell-in-cell formation probably via regulating actomyosin contraction.

TEM8 functions as a receptor for uPA and mediates uPA-stimulated EGFR phosphorylation.

BACKGROUND: TEM8 is a cell membrane protein predominantly expressed in tumor endothelium, which serves as a receptor for the protective antigen (PA) of anthrax toxin. However, the physiological ligands for TEM8 remain unknown. RESULTS: Here we identified uPA as an interacting partner of TEM8. Binding of uPA stimulated the phosphorylation of TEM8 and augmented phosphorylation of EGFR and ERK1/2. Finally, TEM8-Fc, a recombinant fusion protein comprising the extracellular domain of human TEM8 linked to the Fc portion of human IgG1, efficiently abrogated the interaction between uPA and TEM8, blocked uPA-induced migration of HepG2 cells in vitro and inhibited the growth and metastasis of human MCF-7 xenografts in vivo. uPA, TEM8 and EGFR overexpression and ERK1/2 phosphorylation were found co-located on frozen cancer tissue sections. CONCLUSIONS: Taken together, our data provide evidence that TEM8 is a novel receptor for uPA, which may play a significant role in the regulation of tumor growth and metastasis.

Aggregation of Ribosomal Protein S6 at Nucleolus Is Cell Cycle-Controlled and Its Function in Pre-rRNA Processing Is Phosphorylation Dependent.

Ribosomal protein S6 (rpS6) has long been regarded as one of the primary r-proteins that functions in the early stage of 40S subunit assembly, but its actual role is still obscure. The correct forming of 18S rRNA is a key step in the nuclear synthesis of 40S subunit. In this study, we demonstrate that rpS6 participates in the processing of 30S pre-rRNA to 18S rRNA only when its C-terminal five serines are phosphorylated, however, the process of entering the nucleus and then targeting the nucleolus does not dependent its phosphorylation. Remarkably, we also find that the aggregation of rpS6 at the nucleolus correlates to the phasing of cell cycle, beginning to concentrate in the nucleolus at later S phase and disaggregate at M phase. J. Cell. Biochem. 117: 1649-1657, 2016. © 2015 Wiley Periodicals, Inc.

Lineage tracing reveals conversion of liver sinusoidal endothelial cells into hepatocytes.

Although liver sinusoidal endothelial cells (LSECs) have long been known to contribute to liver regeneration following injury, the exact role of these cells in liver regeneration remains poorly understood. In this work, we performed lineage tracing of LSECs in mice carrying Tie2-Cre or VE-cadherin-Cre constructs to facilitate fate-mapping of LSECs in liver regeneration. Some YFP-positive LSECs were observed to convert into hepatocytes following a two-thirds partial hepatectomy (PH). Furthermore, human umbilical vein endothelial cells (HUVECs) could be triggered to convert into cells that closely resembled hepatocytes when cultured with serum from mice that underwent an extended PH. These findings suggest that mature non-hepatocyte LSECs play an essential role in mammalian liver regeneration by converting to hepatocytes. The conversion of LSECs to hepatocyte-like (iHep) cells may provide a new approach to tissue engineering.

DNA in serum extracellular vesicles is stable under different storage conditions.

BACKGROUND: Extracellular vesicles (EVs), including exosomes, microvesicles, and apoptotic bodies, can be secreted by most cell types and released in perhaps all biological fluids. EVs contain multiple proteins, specific lipids and several kinds of nucleic acids such as RNAs and DNAs. Studies have found that EVs contain double-stranded DNA and that genetic information has a certain degree of consistency with tumor DNA. Therefore, if genes that exist in exosomes are stable, we may be able to use EVs genetic testing as a new means to monitor gene mutation. METHODS: In this study, EVs were extracted from serum under various storage conditions (4 °C, room temperature and repeated freeze-thaw). We used western blotting to examine the stability of serum EVs. Then, we extracted DNA from EVs and tested the concentration changing under different conditions. We further assessed the stability of EVs DNA s using polymerase chain reaction (PCR) and Sanger sequencing. RESULTS: EVs is stable under the conditions of 4 °C (for 24 h, 72 h, 168 h), room temperature (for 6 h, 12 h, 24 h, 48 h) and repeated freeze-thaw (after one time, three times, five times). Also, serum DNA is mainly present in EVs, especially in exosomes, and that the content and function of DNA in EVs is stable whether in a changing environment or not. We showed that EVs DNA stayed stable for 1 week at 4 °C, 1 day at room temperature and after repeated freeze-thaw cycles (less than three times). However, DNA from serum EVs after 2 days at room temperature or after five repeated freeze-thaw cycles could be used for PCR and sequencing. CONCLUSIONS: Serum EVs and EVs DNA can remain stable under different environments, which is the premise that EVs could serve as a novel means for genetic tumor detection and potential biomarkers for cancer diagnostics and prognostics.

Postconditioning with sevoflurane ameliorates spatial learning and memory deficit after hemorrhage shock and resuscitation in rats.

BACKGROUND: Severe hemorrhage shock and resuscitation are a systemic ischemia-reperfusion phenomenon which can induce learning and memory deficit in human and rats. Sevoflurane postconditioning has been proved to offer neuroprotection under different setting of cerebral ischemia-reperfusion in rats. The aim of this study was to investigate whether sevoflurane postconditioning could improve spatial learning and memory ability after hemorrhage shock and resuscitation in rats. METHODS: Thirty-five male rats were randomized into five groups: sham group, shock group, low concentration (sevo1, 1.2%), middle concentration (sevo2, 2.4%), and high concentration (sevo3, 3.6%) of sevoflurane postconditioning groups. The spatial learning and memory ability of rats were measured by Morris water maze 3 d after the operation. The expression of choline acetyltransferase (CHAT) and acetylcholinesterase (ACHE) in the hippocampus CA1 region was observed by immunohistochemistry method after the Morris water maze test. RESULTS: The ability of spatial learning and memory of rats and the expression of CHAT was significantly declined, while the expression of ACHE increased in the shock group compared with the sham group (P < 0.05). Sevoflurane postconditioning with the concentrations of 2.4% and 3.6% significantly ameliorated the spatial learning and memory ability and increased the expression of CHAT and decreased the expression of ACHE in hippocampal CA1 region when compared with shock group (P < 0.05). CONCLUSIONS: Postconditioning with sevoflurane at the concentrations of 2.4% and 3.6% which improved the ability of spatial learning and memory after hemorrhage shock and resuscitation in rats may involve the protection of the cholinergic neurons in hippocampal CA1 region.

Dexmedetomidine Combined with General Anesthesia Provides Similar Intraoperative Stress Response Reduction When Compared with a Combined General and Epidural Anesthetic Technique.

BACKGROUND: Epidural anesthesia may attenuate the sympathetic hyperactivity and stress response from surgery. In this study, we compared the stress response, hemodynamic variables, and recovery profiles of patients undergoing total IV anesthesia (TIVA) and intraoperative dexmedetomidine with those receiving epidural anesthesia and TIVA. METHODS: Ninety patients undergoing elective open gastrectomy under TIVA were recruited. The dexmedetomidine group (group D, n = 30) received IV dexmedetomidine 0.6 µg/kg before the induction of general anesthesia, followed by dexmedetomidine 0.4 µg/kg/h until peritoneal closure. The control group (group C, n = 30) received volume-matched normal saline infusion as placebo. The epidural group (group E, n = 30) received epidural anesthesia with 0.375% ropivacaine combined with TIVA. The hemodynamic variables and recovery characteristics during emergence were evaluated. Blood samples for norepinephrine (NE), epinephrine (E), cortisol (Cor), and cytokines (tumor necrosis factor-α [TNF-α], interleukin [IL]-6, and IL-10) were obtained before the administration of dexmedetomidine or epidural anesthesia (baseline), immediately after tracheal intubation, upon incision, at the time of celiac exploration, and at tracheal extubation. RESULTS: Compared with group E, there were no differences in the plasma concentration levels of NE, E, Cor, and cytokines (TNF-α, IL-6, and IL-10) in group D at all time points. The levels of NE and E in groups D and E were significantly lower than that in group C, at all time points following induction (all P < 0.0001 except at incision which were P = 0.001 and P = 0.004), and the level of Cor in groups D and E was significantly lower than that in group C at celiac exploration (P = 0.017 and P = 0.019) and immediately after tracheal extubation (P < 0.0001). The levels of TNF-α, IL-6, and IL-10 increased after the celiac exploration in the 3 groups. The levels of plasma TNF-α, IL-6, and IL-6/IL-10 ratio were higher in group C than in groups D and E at celiac exploration and tracheal extubation (all P < 0.0001 except at celiac exploration which were P = 0.005 and P =0.038 for TNF-α and P = 0.049 and P = 0.038 for IL-6/IL-10 ratio). In group D, the heart rate was significantly slower after commencing dexmedetomidine and remained significantly slower throughout the operative course (all P < 0.0001 except at tracheal extubation which was P = 0.032). The number of patients who required intervention because of intraoperative hypotension was significantly higher in group E (36.7%) compared with groups D and C (13.3% and 10.0%) (P = 0.037, P = 0.015). The times to eye opening and tracheal extubation were similar in all groups. There were fewer incidences of agitation in group D (6.7 %) than in group C (26.6%) (P = 0.038). CONCLUSIONS: When used in conjunction with TIVA, intraoperative dexmedetomidine blunts surgical stress responses to an extent comparable to combined epidural and general anesthesia without compromising hemodynamic stability and with minimal adverse effects during the intraoperative period.