Case series of tracheal extubation in prone position after endoscopic retrograde cholangiopancreatography general anesthesia.

OBJECTIVE: The study aims to present a 15-patient case series of tracheal extubation in the prone position after endoscopic retrograde cholangiopancreatography (ERCP) general anesthesia. PATIENTS AND METHODS: Fifteen inpatients who underwent elective ERCP in our hospital were prospectively enrolled, and a series of case studies were conducted with the prone extubation technique after general anesthesia. All patients underwent routine operation of tracheal intubation under general anesthesia. After the surgery, when the train-of-four ratio (TOFr) ≥0.9, bispectral index (BIS) ≥80, tidal volume ≥6 ml/kg and the required actions could be performed, the endotracheal catheter was removed after sufficient negative pressure suction of oral secretions. After the endotracheal catheter was removed, the patient autonomously turned to the transport bed with the assistance of medical staff and was then admitted to the post-anesthesia care unit (PACU) for further observation. When the patient awoke, he had regained orientation, and presented stable vital signs, no nausea and vomiting, and no other discomfort symptoms, he/she was able to leave PACU and returned to the ward with a Steward score of ≥5. RESULTS: All 15 patients who underwent ERCP elective surgery were successfully extubated in the prone position after surgery. Transient hypoxemia with SpO2 below 90% occurred in 2 of the 15 patients and returned to normal with oxygen mask administration. 7 patients had coughs and were without special treatment. Another 1 patient showed transient abnormal hemodynamic fluctuations after extubation, mean airway pressure (MAP) was higher than 20% of the baseline value, and hemodynamics was stable after drug treatment. CONCLUSIONS: The prone extubation technique is feasible for ERCP general anesthesia patients. However, a larger sample size is needed to validate its safety and to verify whether there exist advantages of the extubation technique in a prone position over a supine position.

[Kindlin-2 regulates endometrium development via mTOR and Hippo signaling pathways in mice].

OBJECTIVE: To investigate the effects and mechanisms of Kindlin-2 on uterus development and reproductive capacity in female mice. METHODS: Cdh16-Cre tool mice and Kindlin-2flox/flox mice were used to construct the mouse model of uterus specific knockout of Kindlin-2, and the effects of Kindlin-2 deletion on uterine development and reproduction capacity of female mice were observed. High expression and knockdown of Kindlin-2 in endometrial cancer cell lines HEC-1 and Ish were used to detect the regulation of mammalian target of rapamycin (mTOR) signaling pathway. In addition, uterine proteins of the female mice with specific knockout of Kindlin-2 and female mice in the control group were extracted to detect the protein levels of key molecules of mTOR signaling pathway and Hippo signaling pathway. RESULTS: The mouse model of uterine specific knockout of Kindlin-2 was successfully constructed. The knockout efficiency of Kindlin-2 in mouse uterus was identified and verified by mouse tail polymerase chain reaction (PCR), Western blot protein identification, immunohistochemical staining (IHC) and other methods. Compared with the control group, the female mice with uterus specific deletion of Kindlin-2 lost weight, seriously impaired reproductive ability, and the number of newborn mice decreased, but the proportion of the female mice and male mice in the newborn mice did not change. Hematoxylin eosin staining (HE) experiment showed that the endometrium of Kindlin-2 knockout group was incomplete and the thickness of uterine wall became thinner. In terms of mechanism, the deletion of Kindlin-2 in endo-metrial cancer cell lines HEC-1 and Ish could downregulate the protein levels of mTOR, phosphorylated mTOR, adenosine monophosphate-activated protein kinase (AMPK), phosphorylated AMPK and phosphorylated ribosomal protein S6 (S6), and the mTOR signal pathway was inhibited. It was found that the specific deletion of Kindlin-2 could upregulate the protein levels of Mps one binding 1 (MOB1) and phosphorylated Yes-associated protein (YAP) in the uterus of the female mice, and the Hippo signal pathway was activated. CONCLUSION: Kindlin-2 inhibits the development of uterus by inhibiting mTOR signal pathway and activating Hippo signal pathway, thereby inhibiting the fertility of female mice.

Pretransplantation Cystatin C, but not Creatinine, Predicts 30-day Cardiovascular Events and Mortality in Liver Transplant Recipients With Normal Serum Creatinine Levels.

BACKGROUND: The connection between renal dysfunction and cardiovascular dysfunction has been consistently shown. In patients with liver cirrhosis, renal dysfunction shows a tight correlation with prognosis after liver transplantation (LT); therefore, precise renal assessment is mandatory. Cystatin C, a sensitive biomarker for assessing renal function, has shown superiority in detecting mild renal dysfunction compared to classical biomarker creatinine. In this study, we aimed to compare cystatin C and creatinine in predicting 30-day major cardiovascular events (MACE) and all-cause mortality in LT recipients with normal serum creatinine levels. PATIENTS AND METHODS: Between May 2010 and October 2015, 1181 LT recipients (mean Model for End-stage Liver Disease score 12.1) with pretransplantation creatinine level ≤1.4 mg/dL were divided into tertiles according to each renal biomarker. The 30-day MACE was a composite of troponin I >0.2 ng/mL, arrhythmia, congestive heart failure, death, and cerebrovascular events. RESULTS: The highest tertile of cystatin C (≥0.95 mg/L) was associated with a higher risk for a 30-day MACE event (odds ratio: 1.62; 95% confidence interval: 1.07 to 2.48) and higher risk of death (hazard ratio: 1.96; 95% confidence interval: 1.04 to 3.67) than the lowest tertile (<0.74 mg/L) after multivariate adjustments. However, the highest tertile of creatinine level showed neither increasing MACE event rate nor worse survival rate compared with the lowest tertile (both insignificant after multivariate adjustment). CONCLUSIONS: Pretransplantation cystatin C is superior in risk prediction of MACE and all-cause mortality in LT recipients with normal creatinine, compared to creatinine. It would assist further risk stratification which may not be detected with creatinine.

Application of the Revised Cardiac Risk Index to the Model for End-Stage Liver Disease Score Improves the Prediction of Cardiac Events in Patients Undergoing Liver Transplantation.

INTRODUCTION: Although the revised cardiac risk index (RCRI) is a useful tool for estimating the risk of postoperative cardiac events, whether it improves the prediction of cardiac events in patients undergoing liver transplantation (LT) has not been sufficiently demonstrated. METHODS: We retrospectively analyzed 1429 patients who underwent LT. Cardiac events were defined as myocardial infarction, death, or combined events within 30 days after surgery. The RCRI was defined as the number of independent predictors including high-risk surgery, ischemic heart disease, congestive heart failure, cerebrovascular disease, insulin treatment, and creatinine level >2 mg/dL. Multivariate logistic regression analysis was performed to identify factors independently associated with cardiac events. The additive predictability of RCRI for the Model for End-Stage Liver Disease (MELD) score was assessed using receiver operating characteristic curve analysis. RESULTS: Forty-four (3.1%) cardiac events occurred within 30 days after surgery. Both the MELD score (adjusted odds ratio [aOR], 1.05; P = .005) and RCRI (aOR, 4.35; P < .001 for RCRI score 2; aOR, 6.27; P = .009 for RCRI score 3 compared with RCRI score 1) independently predicted postoperative 30-day cardiac events. The model with MELD score plus RCRI was significantly more predictive for postoperative 30-day cardiac events than the model with MELD score alone (C-statistics 0.800 vs 0.757; P = .030). CONCLUSIONS: For preoperative risk stratification, RCRI showed additive value to MELD score in predicting postoperative 30-day cardiac events after LT.

Prevalence of Antiphospholipid Antibody Positivity and Association of Pretransplant Lupus Anticoagulant Positivity With Early Allograft Dysfunction in Liver Transplantation.

BACKGROUND: Antiphospholipid antibodies (aPL), including anticardiolipin (aCL), anti-ß2-glycoprotein I (anti-ß2GPI), and lupus anticoagulant (LA) antibodies, are frequently found in liver cirrhosis and associated with splanchnic vein thrombosis. Although the risk factors of early allograft dysfunction (EAD) are known, the association between EAD and aPL has been poorly investigated. We hypothesized that LA, potent aPL with thrombotic potential, may be associated with EAD development after living donor liver transplantation (LDLT). METHODS: Data of 719 patients who underwent LDLT from February 2014 to June 2016 at our center were retrospectively collected and analyzed. Patients were divided into 2 groups according to the positivity of LA screening test (LA group [n = 148] vs no-LA group [n = 571]). Risk factors for EAD were investigated using multivariable regression analysis and inverse probability of treatment weighting (IPTW) of propensity scores. RESULTS: The prevalence of LA screening positivity, confirmatory test positivity, and EAD was 20.6%, 1.1%, and 11.3%, respectively. aCL positivity rate was 7.5% and anti-ß2GPI positivity rate was 7.0%. The EAD prevalence in LA and no-LA group was 25.7% and 7.5%, respectively. However, multivariable and IPTW analyses showed no association between EAD and LA screening positivity (P = .263 and P = .825, respectively), although a significant association was found in univariate analysis (odds ratio, 4.242; P < .001). Model for End-stage Liver Disease score, operation time, and C-reactive protein level remained significant after multivariable analysis. CONCLUSION: A positive LA screening test result was associated with EAD only in the univariate analysis. Inflammation, based on C-reactive protein level, was more important for EAD development.

Does Activated Clotting Time Help to Predict Innate Coagulopathy in End-Stage Liver Disease Patients?

BACKGROUND: Measuring activated clotting time (ACT) is widely performed to monitor heparin therapy. Regardless of anticoagulant use, ACT is affected by coagulopathies such as coagulation factor deficiency and thrombocytopenia. However, its use in end-stage liver disease (ESLD) with complex coagulopathy is not well characterized. We evaluated whether ACT could be used to detect innate coagulopathy in ESLD patients. METHODS: We retrospectively assessed Hemochron (International Technidyne, Edison, NJ, USA) ACT (FTCA 510, normal range 105-167 seconds) and INTEM clotting time (CT) of rotational thromboelastometry (ROTEM; ROTEM delta, Pentapharm GmbH, Munich, Germany) (100-240 seconds) in 366 liver transplantation (LT) recipients, simultaneously measured before anesthetic induction for LT. Multiple linear regression analyses helped identify the factors related to ACT in ESLD patients. The relationship between ACT and INTEM CT was evaluated by Spearman rank correlation analysis and receiver operating characteristic curve. RESULTS: Median ACT was 143 seconds (range 73-295 seconds), and 60 patients (16.4%) had ACTs of >167 seconds. Multiple regression analyses revealed that prolonged prothrombin time, activated partial thromboplastin time, low antithrombin III, and young age were associated with high ACT levels. INTEM CT was associated with ACT independent of liver disease severity, while EXTEM CT was not. ACT was moderately correlated with INTEM CT (r = 0.535), and the optimal cutoff value of ACT for predicting INTEM CT >240 seconds was 151 seconds (area under the curve = 0.787). CONCLUSIONS: In ESLD patients, ACT is effective in detecting prolonged INTEM CT. Therefore, ACT may be used to predict intrinsic pathway defects with a cutoff value of 151 seconds, suggesting feasibility when ROTEM is unavailable.

Prediction of Fluid Responsiveness by a Non-invasive Respiratory Systolic Time Interval Variation Using Heart Sound Signals in Recipients Undergoing Liver Transplantation.

BACKGROUND: The fluid management of cirrhotic patients undergoing liver transplantation (LT) is challenging. Phonocardiography, a graphic recording of heart sounds, provides valuable information concerning heart function and hemodynamic condition. We assessed whether the systolic time interval (STI) and its respiratory variation could predict fluid responsiveness in cirrhotic patients undergoing LT. METHODS: Thirty LT recipients who needed volume expansion were included. The fluid challenge consisted of 500 mL 5% albumin administered over a period of 10 minutes. STI was measured as the time interval between the maximal amplitude of each heart sound corrected with the corresponding RR interval (cSTI). The respiratory variation in STI (STV) induced by mechanical ventilation was calculated. Responders were defined as those showing a ≥10% increase in stroke volume index after volume expansion. RESULTS: In all, 14 of the 30 patients were responders. Significant increases in cSTI were observed after volume expansion in both responders (P < .001) and non-responders (P = .008). Responders showed significant decreases in STV (11.1% ± 4.3% vs 6.1% ± 2.6%, P < .001) after fluid loading, whereas STV in non-responders remained unchanged (6.4% ± 2.6% vs 6.4% ± 4.2%, P = .86). A cut-off value of ≥7.5% STV from baseline could predict fluid responsiveness with an area under the receiver operating characteristic curve of 0.804 (95% confidence interval, 0.618-0.925). CONCLUSIONS: Intra-operative STV can predict fluid responsiveness in patients undergoing LT. Beat-to-beat monitoring of STI and STV may be useful as a non-invasive hemodynamic index and for fluid management.

Pretransplant Resting Heart Rate and Its Association With All-Cause Mortality in Liver Transplant Recipients.

BACKGROUND: The importance of heart rate (HR) measurement as a prognostic factor has been recognized in many clinical conditions, such as hypertension, coronary artery disease, or heart failure. Patients with liver cirrhosis tend to have increased resting HR as consequence of hyperdynamic circulation. In the current study, we examined whether pretransplant resting increased HR is associated with overall mortality in cirrhotic patients following liver transplantation (LT). PATIENTS AND METHODS: We retrospectively collected and analyzed the data of 881 liver recipients who underwent LT surgery between October 2009 and September 2012. Patients were categorized into 3 groups by tertile of resting HR as follows: tertile 1 group, HR ≤ 65 beats per minute (bpm); tertile 2 group, HR 66 to 80 bpm; and tertile 3 group, HR > 80 bpm. RESULTS: Kaplan-Meier analysis showed that the all-cause mortality rate was significantly different according to tertiles of HR (P = .016, log-rank test). The multivariate Cox regression analysis showed that tertile 3 group was significantly associated with higher risk for all-cause mortality (hazard ratio 1.83, 95% confidence interval, 1.10-3.07; P = .021) compared with tertile 1 group, after adjusting for clinically significant variables in univariate analysis. CONCLUSIONS: Our results demonstrate that pretransplant resting tachycardia can identify patients at high risk of death in cirrhotic patients following LT, suggesting that further study will be need to clarify relationship between HR burden and sympathetic cardiac neuropathy.

Relationship between the gene polymorphism of osteoprotegerin and bone mineral density in hemodialysis patients.

OBJECTIVE: To investigate the relationship between the gene polymorphism of osteoprotegerin (OPG) and bone mineral density (BMD) in hemodialysis patients. PATIENTS AND METHODS: A total of 147 patients with end-stage renal disease (ESRD) who were admitted to the Weifang People's Hospital for maintenance hemodialysis between January 2014 and December 2015 were enrolled. Peripheral blood was collected from the subjects for assay of the polymorphism of A163G and G1181C loci of OPG. The measurements of the levels of RANK, RANKL, TNF-α, IL-6, PINP, CTX-I, CTX-II and TRACP5 in the isolated serum were taken. RESULTS: For the polymorphism of A163G locus on the OPG gene, the BMDs of left femoral neck and lumbar poster anterior L1-L4 of the AA genotype were significantly higher than those of the AG and GG genotypes. There was no significant difference in comparison of BMDs at the forearm (distal 1/3) between the AA genotype and AG and GG genotypes. No significant differences were found in the comparison of BMDs at all sites between AG and GG genotypes. The serum level of RANKL of the AA genotype was significantly higher than levels of AG and GG genotypes, but the levels of RANK, TNF-α, IL-6, PINP, CTX-I, CTX-II and TRACP5 were prominently lower than those levels of AG and GG genotypes. For the polymorphism of G1181C locus on the OPG gene, the BMDs of left femoral neck and lumbar poster anterior L1-L4 of the CC genotype were significantly higher than the BMDs of GG and GC genotypes, There was no significant difference in the comparison of BMDs at the forearm (distal 1/3) between the CC genotype and GG and GC genotypes. No significant differences were found in the comparison of BMDs at all sites between GG and GC genotypes. The serum level of RANKL of the CC genotype was significantly higher than the level of GG and GC genotypes. However, the levels of RANK, TNF-α, IL-6, PINP, CTX-I, CTX-II and TRACP5 were prominently lower than those levels of GG and GC genotypes. CONCLUSIONS: The polymorphisms of A163G and G1181C loci on the OPG gene were correlated with the BMD of hemodialysis patients. The genotype AA of A163G and genotype CC of G1181C were identified as the protective factors for BMD.

Pretransplant Left Ventricular Dysfunction Adversely Affects Perioperative Outcomes in Pediatric Liver Transplantation: A Retrospective Observational Study.

BACKGROUND: Although left ventricular diastolic dysfunction (LVDD) is a pronounced feature of adult cirrhotic cardiomyopathy and a major predictor of poor outcomes following liver transplantation (LT), little is known about if pretransplant cardiac dysfunction affects perioperative outcomes in pediatric LT. METHODS: We retrospectively evaluated pretransplant clinical and Doppler echocardiographic data for 45 consecutive pediatric LT recipients who were treated between 2007 and 2013 (median age = 15 months; interquartile range = 9 to 78 months). LVDD was defined according to the cirrhotic cardiomyopathy criteria, and the myocardial performance index (MPI) was measured using tissue Doppler imaging. Intraoperative data and hospitalization days following LT were compared. RESULTS: LVDD and MPI ≥0.5 (defined as a z score ≥2) were observed in 13% and 27% of patients, respectively. Patients with an MPI ≥0.5 demonstrated the increased accumulation of lactate at the end of their LT operation (mean = 2.48 vs 0.82; P = .026) compared with patients with an MPI <0.5. The hospital stay was longer in patients with LVDD (median = 46 days vs 30 days; P = .041) and patients with an MPI ≥0.5 (median = 38 days vs 29 days; P = .014) compared with patients without LVDD and MPI <0.5, respectively. CONCLUSIONS: LVDD might be less prevalent (13%) in pediatric patients compared with adults. However, pretransplant cardiac dysfunction in patients with LVDD and an MPI ≥0.5 adversely affects perioperative outcomes, necessitating that such pediatric LT recipients be cautiously observed perioperatively.

Expression of APPL1 is correlated with clinicopathologic characteristics and poor prognosis in patients with gastric cancer.

BACKGROUND: Although appl1 is overexpressed in many cancers, its status in gastric cancer (gc) is not known. In the present study, we used relevant pathologic and clinical data to investigate appl1 expression in patients with gc. METHODS: In 47 gc and 27 non-gc surgical specimens, immunohistochemistry was used to detect the expression of appl1, and reverse-transcriptase polymerase chain reaction (rt-pcr) was used to detect messenger rna (mrna). A scatterplot visualized the relationship between survival time and mrna expression in gc patients. The log-rank test and other survival statistics were used to determine the association of appl1 expression with the pathologic features of the cancer and clinical outcomes. RESULTS: In gc, appl1 was expressed in 28 of 47 specimens (59.6%), and in non-gc, it was expressed in 7 of 23 specimens (30.4%, p < 0.05). The expression of mrna in gc was 0.82 [95% confidence interval (ci): 0.78 to 0.86], and in non-gc, it was 0.73 (95% ci: 0.69 to 0.77; p < 0.05). Immunohistochemistry demonstrated that, in gc, appl1 expression was correlated with depth of infiltration (p = 0.005), lymph node metastasis (p = 0.017), and TNM stage (p = 0.022), but not with pathologic type (p = 0.41). Testing by rt-pcr demonstrated that, in gc, appl1 mrna expression was correlated with depth of infiltration (p = 0.042), lymph node metastasis (p = 0.031), and TNM stage (p = 0.04), but again, not with pathologic type (p = 0.98). The correlation coefficient between survival time and mrna expression was -0.83 (p < 0.01). Overexpression of appl1 protein (hazard ratio: 3.88; 95% ci: 1.07 to 14.09) and mrna (hazard ratio: 4.23; 95% ci: 3.09 to 15.11) was a risk factor for death in patients with gc. CONCLUSIONS: Expression of appl1 is increased in gc. Overexpression is prognostic for a lethal outcome.

Relationship between 5-HTTLPR polymorphism and post-stroke depression.

Post-stroke depression (PSD) is a mental illness characterized by subjective feelings of depression, cognitive dysfunction, and decreased interest. The serotoninergic system is involved in the pathogenesis of depressive disorders and is regulated by the serotonin transporter gene. The serotonin transporter-linked polymorphic region (5-HTTLPR) has been examined as a factor associated with depression and other mental disorders. This study was performed to explore the relationship between 5-HTTLPR and PSD in a Han Chinese population. In total, 199 patients with PSD and 202 unrelated non-PSD patients were recruited from psychiatric hospitals. Depression was diagnosed using the Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition. Blood samples were collected from all patients for 5-HTTLPR genotyping. Genotype and allele frequencies were compared between the two groups. SS genotype frequency was significantly higher in the PSD group than in the non-PSD group. LL genotype frequency was significantly higher in the non-PSD group than in the PSD group (P < 0.01). This study describes a positive association between 5-HTTLPR and PSD in a Han Chinese population and provides genetic evidence to support the genetic susceptibility of PSD.

Quantification of Both Platelet Count and Fibrinogen Concentration Using Maximal Clot Firmness of Thromboelastometry During Liver Transplantation.

BACKGROUND: Rotation thromboelastometry (ROTEM®) is increasingly used in liver transplantation (LT). Of the ROTEM® parameters, maximum clot firmness (MCF) of EXTEM (MCFEXT) and INTEM (MCFINT) are influenced by both platelet count (PLT) and fibrinogen concentration (FIB), whereas MCF of FIBTEM (MCFFIB) is solely influenced by FIB. We aimed to determine whether using MCFs of thromboelastometry could reliably predict both PLT and FIB and to evaluate their relations in patients with thrombocytopenia and hypofibrinogenemia during LT. METHODS: A total of 4100 retrospective ROTEM® assays with simultaneous standard laboratory tests performed during LT were analyzed in 295 patients. The optimal cut-off values of PLT and FIB according to the ROTEM® transfusion guideline were determined by area under the curve (AUC) of receiver operating characteristic (ROC) curve analysis. RESULTS: MCFEXT and MCFINT showed good correlation with platelet count (r = 0.79 and 0.80, respectively, P < .001) and with fibrinogen concentration (r = 0.67 and 0.66, respectively, P < .001). MCFFIB and fibrinogen concentration were highly correlated (r = 0.84, P < .001). Additionally, PLT and FIB were calculated mathematically: PLT (/µL) = 14827 + 3.93 (MCFEXT)(2.5); FIB (mg/dL) = 63 + 0.00082 (MCFEXT)(3.0); FIB (mg/dL) = 29 + 13.3 MCFFIB. MCFEXT <35 mm predicted PLT of 43 × 10(3)/µL (AUC = 0.89) and FIB of 91 mg/dL (AUC = 0.78), whereas MCFEXT <45 mm predicted PLT of 52 × 10(3)/µL (AUC = 0.89) and FIB of 121 mg/dL (AUC = 0.86), MCFFIB <8 mm predicted FIB of 128 mg/dL (AUC = 0.94). MCFINT showed almost the same cut-off values as MCFEXT. CONCLUSIONS: Both PLT and FIB can be reliably quantified by MCFs of thromboelastometry, reducing the needs for additional laboratory tests to know values of thrombocytopenia and hypofibrinogenemia in patients undergoing LT.

[Under hypoxia condition contactin-1 regulates migration of MKN45 cells through RhoA pathway].

Recent studies have suggested that contactin-1 has a key role in cancer cell proliferation and migration, however the detailed mechanism of this process is still unclear. Here, human gastric cancer cell line MKN45 was employed. It was found that under hypoxia conditions contactin-1 mRNA and protein levels were both up-regulated by HIF-1alpha expression. Furthermore, although hypoxia increased the migration rate of MKN45 cells, contactin-1 (CNTN1) shRNA reversed this process. Meanwhile, RhoA V14 and RhoA V14N19 mutation constructs were employed, and it was found that constitutively active form of RhoA reversed the cell migration suppression induced by contactin-1 knockdown, while dominant-negative form of RhoA blocked hypoxia induced hypermigration. Apart from this, contactin-1 displayed the ability to phosphorylate the RhoA activator p115 RhoGEF. Thus, under hypoxia conditions, elevated HIF-1alpha seems to up-regulate contactin-1 expression and by this activate RhoA and facilitate migration of cancer cells.

Electroacupuncture inhibits excessive interferon-γ evoked up-regulation of P2X4 receptor in spinal microglia in a CCI rat model for neuropathic pain.

BACKGROUND: Although electroacupuncture (EA) is effective in the relief of neuropathic pain, the underlying mechanisms remain unclear. Previous studies have reported immunomodulatory effects of EA in rats. Since excessive release of interferon-γ (IFN-γ) after nerve injury transforms quiescent spinal microglia into an activated state with more neuropathic pain, associated with purinergic receptor P2X4 expression, it is possible that EA may mediate its analgesic effect by attenuating IFN-γ release and subsequent generation of P2X4R(+) microglia. METHODS: Male rats underwent chronic constriction injury (CCI) or IFN-γ intrathecal injection and von Frey tests were performed to evaluate the effect of EA on pain thresholds. Spinal IFN-γ and P2X4R expression levels were measured by immunohistochemistry, real-time PCR, enzyme immunoassay, and/or western blots. In vitro primary cultures of microglia were used to examine IFN-γ activation of P2X4R(+) cells. RESULTS: In CCI rats, EA treatment significantly increased paw withdrawal threshold relative to control. IFN-γ facilitated P2X4R(+) microglia activation both in vitro and in vivo. EA also down-regulated both P2X4R and IFN-γ expression in the spinal cord after CCI. However, EA did not exert the same analgesic effect after intrathecal IFN-γ injection. CONCLUSIONS: EA ameliorated tactile allodynia after peripheral nerve injury by down-regulating excessive expression of IFN-γ in the spinal cord and subsequently reducing expression of P2X4R.

Acute kidney injury after infrarenal abdominal aortic aneurysm surgery: a comparison of AKIN and RIFLE criteria for risk prediction.

BACKGROUND: Although both Acute Kidney Injury Network (AKIN) and risk, injury, failure, loss, and end-stage (RIFLE) kidney disease criteria are frequently used to diagnose acute kidney injury (AKI), they have rarely been compared in the diagnosis of AKI in patients undergoing surgery for infrarenal abdominal aortic aneurysm (AAA). This study investigated the incidence of, and risk factors for, AKI, defined by AKIN and RIFLE criteria, and compared their ability to predict mortality after infrarenal AAA surgery. METHODS: This study examined 444 patients who underwent infrarenal AAA surgery between January 1999 and December 2011. Risk factors for AKI were assessed by multivariable analyses, and the impact of AKI on overall mortality was assessed by a Cox's proportional hazard model with inverse probability of treatment weighting (IPTW). Net reclassification improvement (NRI) was used to assess the performance of AKIN and RIFLE criteria in predicting overall mortality. RESULTS: AKI based on AKIN and RIFLE criteria occurred in 82 (18.5%) and 55 (12.4%) patients, respectively. The independent risk factors for AKI were intraoperative red blood cell (RBC) transfusion and chronic kidney disease (CKD) by AKIN criteria, and age, intraoperative RBC transfusion, preoperative atrial fibrillation, and CKD by RIFLE criteria. After IPTW adjustment, AKI was related to 30 day mortality and overall mortality. NRI was 15.2% greater (P=0.04) for AKIN than for RIFLE criteria in assessing the risk of overall mortality. CONCLUSIONS: Although AKI defined by either AKIN or RIFLE criteria was associated with overall mortality, AKIN criteria showed better prediction of mortality in patients undergoing infrarenal AAA surgery.

Attenuated benzodiazepine-sensitive tonic GABAA currents of supraoptic magnocellular neuroendocrine cells in 24-h water-deprived rats.

In supraoptic nucleus (SON) magnocellular neurosecretory cells (MNCs), γ-GABA, via activation of GABAA receptors (GABAA Rs), mediates persistent tonic inhibitory currents (Itonic ), as well as conventional inhibitory postsynaptic currents (IPSCs, Iphasic ). In the present study, we examined the functional significance of Itonic in SON MNCs challenged by 24-h water deprivation (24WD). Although the main characteristics of spontaneous IPSCs were similar in 24WD compared to euhydrated (EU) rats, Itonic , measured by bicuculline (BIC)-induced Iholding shifts, was significantly smaller in 24WD compared to EU rats (P < 0.05). Propofol and diazepam prolonged IPSC decay time to a similar extent in both groups but induced less Itonic in 24WD compared to EU rats, suggesting a selective decrease in GABAA receptors mediating Itonic over Iphasic in 24WD rats. THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol), a preferential δ subunit agonist, and L-655,708, a GABAA receptor α5 subunit selective imidazobenzodiazepine, caused a significantly smaller inward and outward shift in Iholding , respectively, in 24WD compared to EU rats (P < 0.05 in both cases), suggesting an overall decrease in the α5 subunit-containing GABAA Rs and the δ subunit-containing receptors mediating Itonic in 24WD animals. Consistent with a decrease in 24WD Itonic , bath application of GABA induced significantly less inhibition of the neuronal firing activity in 24WD compared to EU SON MNCs (P < 0.05). Taken together, the results of the present study indicate a selective decrease in GABAA Rs functions mediating Itonic as opposed to those mediating Iphasic in SON MNCs, demonstrating the functional significance of Itonic with respect to increasing neuronal excitability and hormone secretion in 24WD rats.

Five-minute parameter of thromboelastometry is sufficient to detect thrombocytopenia and hypofibrinogenaemia in patients undergoing liver transplantation.

BACKGROUND: Early detection of coagulopathy is important to prevent bleeding during liver transplantation (LT). Rotation thromboelastometry (ROTEM(®)) provides the earliest parameter of clot amplitudes at 5 min (A5). We evaluated whether A5 correlates with platelet count (PLT) and fibrinogen concentration (Fib) and can predict thrombocytopenia and hypofibrinogenaemia in hypocoagulable patients undergoing living-donor LT (LDLT). METHODS: A total of 3446 retrospective ROTEM(®) measurements, including 1139 EXTEM, 1182 INTEM, and 1125 FIBTEM, with simultaneously measured PLT and Fib, were analysed during LDLT in 239 patients. The correlations between A5 and maximum clot firmness (MCF) index, PLT, and Fib were calculated. Receiver operating characteristic analysis with area under the curve (AUC) was used to assess A5 thresholds predictive of PLT and Fib. RESULTS: The median PLT was 47 000 mm(-3) and the median Fib was 100 mg dl(-1) during LDLT. The A5 parameters of EXTEM (A5EXTEM) and INTEM (A5INTEM) were highly correlated with MCF (r=0.96 and r=0.95, respectively), PLT (r=0.76 and r=0.77, respectively), and Fib (r=0.63 and r=0.64, respectively). A5 of FIBTEM (A5FIBTEM) was also correlated with MCF (r=0.91) and Fib (r=0.75). A5EXTEM thresholds of 15 and 19 mm predicted PLT<30 000 mm(-3) (AUC=0.90) and <50 000 mm(-3) (AUC=0.87), respectively, whereas A5FIBTEM 4 mm predicted Fib<100 mg dl(-1) (AUC=0.86). Biases from A5EXTEM and A5FIBTEM to their MCFs were 16.4 and 1.3 mm, respectively. CONCLUSIONS: A5 as an early variable of clot firmness is effective in detecting critically low PLT and Fib. A5 can therefore be a reliable fast index guiding transfusion therapy in hypocoagulable patients undergoing LDLT.

Factors affecting intraoperative changes in regional cerebral oxygen saturation in patients undergoing liver transplantation.

BACKGROUND: Regional oxygen saturation (rSO(2)) is a sensitive marker of cerebral hypoperfusion during liver transplantation. However, bilirubin absorbs near-infrared light, resulting in falsely low rSO(2) values. We sought to determine whether rSO(2) values vary in response to bilirubin concentrations during liver transplantation and to assess whether rSO(2) changes were associated with factors reflecting cerebral oxygen delivery in patients with hyperbilirubinemia. METHODS: Measurements of rSO(2) values continuous cardiac output (CO), mean arterial pressure, central venous pressure, body temperature, arterial blood gas analysis, and laboratory parameters were simultaneously performed at 1 hour after the surgical incision (baseline) and at 3 predetermined times during the anhepatic and neohepatic phases in 95 end-stage liver disease patients including 67 males of Child A/B/C/29/29/37 categories respectively. Relationships between changes in parameters were evaluated by correlation and multivariate regression analyses. RESULTS: The 273 measurements revealed changes in rSO(2) (range, -18% to 40%) to correlate significantly with alterations in hemoglobin (Hb), serum glucose, lactate, prothrombin time, pH, partial arterial CO(2) pressure (PaCO(2)), and CO, but not with serum total bilirubin (TB). Multivariate linear regression analysis revealed that changes in Hb, CO, PaCO(2), and pH were independent of rSO(2) changes during liver transplantation. CONCLUSIONS: Our findings showed that rSO(2) changes were independently associated with factors reflecting cerebral oxygen delivery, such as Hb, CO, PaCO(2), and pH, whereas rSO(2) values did not correlate with changes in bilirubin concentrations, indicating that rSO(2) changes reveal cerebral oxygen balance regardless of TB levels among patients undergoing liver transplantation.

First Report of Powdery Mildew Caused by Leveillula taurica on Cynanchum kashgaricum in China.

Cynanchum kashgaricum Liou f., belonging to the family Apocynaceae, is an endemic herbaceous perennial and extremely endangered plant species, only found in the wild in desert regions of Xinjiang, China (3), and is valuable for sand stabilization. In August 2010, a previously unknown and widespread powdery mildew disease was observed on C. kashgaricum growing in the Taklimakan Desert in Xinjiang, China. Disease symptoms included the appearance of a white mycelial coating on the upper surfaces of leaves, while the corresponding abaxial surfaces of infected leaves became chlorotic. As the disease progressed, the infected leaves turned yellow and necrotic. In this survey, the incidence of affected C. kashgaricum plants was 60%. On the basis of microscopic examination, the morphology of the fungus can be described as follows: the primary conidia of the fungus were lanceolate or clavate, with a pointed apex and rounded base, measuring 40.4 to 82.5 × 11.1 to 24.6 µm, with an irregular surface covered by warts; the secondary conidia varied in shape from subcylindrical to cylindrical, with rounded ends, and had lateral borders that were parallel to each other with rounded or truncate bases, measuring 40.5 to 73.5 × 11.2 to 23.9 µm. The ascomata were nearly gregarious and globe-shaped, of dust-colored appearance, and 113 to 267 µm in diameter; they were immersed in dense mycelial tomentum with numerous asci (usually 10 to 18 per ascoma). Numerous, well-developed appendages were present on the lower half of the ascomata; these appendages were irregularly branched and their length was 0.15 to 0.3 times the diameter of the ascomata. The asci were stalked, long or wide ellipsoidal in shape, and 93 to 140 × 27.6 to 52.9 µm. The asci usually contained two ellipsoidal ascospores 24.5 to 49.5 × 18.3 to 29.5 µm. On the basis of morphologic characteristics, the fungus was identified as Leveillula taurica (2). A voucher specimen of the fungus under the identifier HMTU09021 was deposited in the Mycological Herbarium of Tarim University (HMTU). To verify the identity of the fungus, the internal transcribed spacer (ITS) rDNA was amplified and sequenced, and the sequences were deposited as GenBank Accession No. JN861731. Comparison with sequences in the GenBank database revealed that the ITS sequence showed 100% homology with the sequence of L. taurica on Capsicum annuum (Accession No. GQ167201) and Lepidium latifolium (Accession No. AB044349). Thus, the pathogen was identified as L. taurica on the basis of the anamorphic and teleomorphic morphological characters and the ITS sequence. To our knowledge, while L. taurica infection in plants of the family Apocynaceae has been reported around the world (1), in east Asia only a single report of C. glaucum infection in this genus has occurred, in Afghanistan (1). This is the first report of L. taurica infection of C. kashgaricum. Outbreaks of this powdery mildew could not only threaten growth of the endangered plant but also accelerate local ecological deterioration. References: (1) K. Amano. Host Range and Geographical Distribution of the Powdery Mildew Fungi, 2nd ed. Japan Scientific Societies Press, Tokyo, Japan, 1986. (2) U. Braun. A Monograph of the Erysiphales (Powdery Mildews). Nova Hedwigia Beiheft 89:1, 1987. (3) F. Ying et al. Acta Bot. Boreali-Occidentalia Sin. 23:263, 2003.