Effect of Postoperative Prolonged sedation with Dexmedetomidine after successful reperfusion with Endovascular Thrombectomy on long-term prognosis in patients with acute ischemic stroke (PPDET): study protocol for a randomized controlled trial.

BACKGROUND: Endovascular thrombectomy (EVT) is a standard treatment for acute ischemic stroke (AIS) with large vessel occlusion. Hypertension and increased blood pressure variability within the first 24 h after successful reperfusion are related to a higher risk of symptomatic intracerebral hemorrhage and higher mortality. AIS patients might suffer from ischemia-reperfusion injury following reperfusion, especially within 24 h. Dexmedetomidine (DEX), a sedative commonly used in EVT, can stabilize hemodynamics by inhibiting the sympathetic nervous system and alleviate ischemia-reperfusion injury through anti-inflammatory and antioxidative properties. Postoperative prolonged sedation for 24 h with DEX might be a potential pharmacological approach to improve long-term prognosis after EVT. METHODS: This single-center, open-label, prospective, randomized controlled trial will include 368 patients. The ethics committee has approved the protocol. After successful reperfusion (modified thrombolysis in cerebral infarction scores 2b-3, indicating reperfusion of at least 50% of the affected vascular territory), participants are randomly assigned to the intervention or control group. In the intervention group, participants will receive 0.1~1.0 µg/kg/h DEX for 24 h. In the control group, participants will receive an equal dose of saline for 24 h. The primary outcome is the functional outcome at 90 days, measured with the categorical scale of the modified Rankin Scale, ranging from 0 (no symptoms) to 6 (death). The secondary outcome includes (1) the changes in stroke severity between admission and 24 h and 7 days after EVT, measured by the National Institute of Health Stroke Scale (ranging from 0 to 42, with higher scores indicating greater severity); (2) the changes in ischemic penumbra volume/infarct volume between admission and 7 days after EVT, measured by neuroimaging scan; (3) the length of ICU/hospital stay; and (4) adverse events and the all-cause mortality rate at 90 days. DISCUSSION: This randomized clinical trial is expected to verify the hypothesis that postoperative prolonged sedation with DEX after successful reperfusion may promote the long-term prognosis of patients with AIS and may reduce the related socio-economic burden. TRIAL REGISTRATION: ClinicalTrials.gov NCT04916197. Prospectively registered on 7 June 2021.

Airway management for a patient with tracheobronchomegaly undergoing lobectomy: a case report.

BACKGROUND: Tracheobronchomegaly (TBM) is a rare disorder mainly characterized by dilatation and malacia of the trachea and major bronchi with diverticularization. This will be a great challenge for airway management, especially in thoracic surgery requiring one-lung ventilation. Using a laryngeal mask airway and a modified double-lumen Foley catheter (DFC) as a "blocker" may achieve one-lung ventilation. This is the first report introducing this method in a patient with TBM. CASE PRESENTATION: We present a 64-year-old man with TBM receiving left lower lobectomy. Preoperative chest computed tomography demonstrated a prominent tracheobronchial dilation and deformation with multiple diverticularization. The most commonly used double-lumen tube or bronchial blocker could not match the distorted airways. After general anesthesia induction, a 4# laryngeal mask was inserted, through which the modified DFC was positioned in the left main bronchus with the guidance of a fiberoptic bronchoscope. The DFC balloon was inflated with 10 ml air and lung isolation was achieved without any significant air leak during one-lung or two-lung ventilation. However, the collapse of the non-dependent lung was delayed and finally achieved by low-pressure artificial pneumothorax. The surgery was successful and the patient was extubated soon after the surgery. CONCLUSIONS: Using a laryngeal mask airway with a modified double-lumen Foley catheter acted as a bronchial blocker could be an alternative method to achieve lung isolation.

Transcutaneous electrical acupoint stimulation in adult patients receiving gastrectomy/colorectal resection: A randomized controlled trial.

BACKGROUND: Acupuncture promotes the recovery of gastrointestinal function and provides analgesia after major abdominal surgery. The effects of transcutaneous electrical acupoint stimulation (TEAS) remain unclear. AIM: To explore the potential effects of TEAS on the recovery of gastrointestinal function after gastrectomy and colorectal resection. METHODS: Patients scheduled for gastrectomy or colorectal resection were randomized at a 2:3:3:2 ratio to receive: (1) TEAS at maximum tolerable current for 30 min immediately prior to anesthesia induction and for the entire duration of surgery, plus two 30-min daily sessions for 3 consecutive days after surgery (perioperative TEAS group); (2) Preoperative and intraoperative TEAS only; (3) Preoperative and postoperative TEAS only; or (4) Sham stimulation. The primary outcome was the time from the end of surgery to the first bowel sound. RESULTS: In total, 441 patients were randomized; 405 patients (58.4 ± 10.2 years of age; 247 males) received the planned surgery. The time to the first bowel sounds did not differ among the four groups (P = 0.90; log-rank test). On postoperative day 1, the rest pain scores differed significantly among the four groups (P = 0.04; Kruskal-Wallis test). Post hoc comparison using the Bonferroni test showed lower pain scores in the perioperative TEAS group (1.4 ± 1.2) than in the sham stimulation group (1.7 ± 1.1; P = 0.04). Surgical complications did not differ among the four groups. CONCLUSION: TEAS provided analgesic effects in adult patients undergoing major abdominal surgery, and it can be added to clinical practice as a means of accelerating postoperative rehabilitation of these patients.

Ginkgolide B improved postoperative cognitive dysfunction by inhibiting microgliosis-mediated neuroinflammation in the hippocampus of mice.

BACKGROUND: Postoperative cognitive dysfunction (POCD) are a common complication of the central nervous system following surgery and anesthesia. The specific pathogenesis and effective therapeutics of POCD need to be further studied. Ginkgolide B (GB), a platelet-activating factor receptor-specific antagonist, has been suggested to have strong anti-inflammatory effects. Here we tested the effects and mechanism of GB on POCD of aged rats. METHODS: Neurobehavioral tests were used to investigate the effect of GB pretreatment on POCD. The hippocampus were harvested to test the expression of proinflammatory cytokines by ELISA. The expression of the microglial marker ionized calcium-binding adaptor molecule-1 (Iba-1) in the hippocampus was evaluated by western blot assay and immunohistochemistry. A Nissl staining experiment was used to detect the neuronal numbers in the hippocampus. RESULTS: Surgery might result in the overexpression of platelet activating factor (PAF) in the plasma and hippocampus and might cause hippocampus-dependent memory impairment. GB pretreatment, inhibited the activation of microglia, reduced the levels of IL-1ß and TNF-α, decreased the loss of neurons after surgery, and prevented POCD in aged rats. CONCLUSION: Our findings suggested that PAF was involved in the development of POCD. Improvement of POCD by PAF antagonist GB was associated with the inhibition of microgliosis-mediated neuroinflammation and neuronal apoptosis in aged rats.

ED50 for intravenous midazolam-induced amnesia and its duration in surgical patients.

BACKGROUND: Intraoperative awareness is a serious adverse event under general anesthesia. Midazolam has a good anterograde amnesia-inducing effect, can prevent and reduce the occurrence of intraoperative awareness. However, if the dosage of midazolam is improperly controlled, it may not produce forgetting effect, or bring obvious adverse side effects, such as respiratory depression, and delay of recovery. However, the half maximal effective dose (ED50 ) of midazolam for amnesia, the duration of amnesia and the factors affecting the duration of amnesia are still inconclusive. Therefore, it is of great clinical significance to observe and determine the dose, duration and influencing factors of amnesia induced by midazolam METHODS: A total of 106 patients who underwent ASA grades I-II elective operation under spinal-epidural anesthesia were intravenously injected with different doses of midazolam at 10 minutes after spinal-epidural anesthesia, every 5 minutes, the patient was presented with pictures or sounds as memory content, and heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP), mean blood pressure (MBP), blood oxygen saturation (SpO2), bispectral index (BIS), OAA/S and adverse events were recorded. The patient's forgetfulness was followed up in the early morning after operation. RESULTS: ED50 (the dose for amnesia in half of the subjects) was 0.031 mg/kg (95% CI: 0.027-0.036 mg/kg); ED95 (the dose for amnesia in 95% of the subjects) was 0.044 mg/kg (95% CI: 0.038-0.071 mg/kg). After the patients were injected intravenously with 0.04 mg/kg of midazolam, the respiratory and circulatory systems were basically stable, no serious adverse events occurred, and the forgetting rate was 88.5%. ET50 (the time for half of the subjects in a state of forgetfulness) was 23.77 minutes (95% CI: 20.18-27.07 min), and the corresponding BIS was 83.22; ET05 (the time for 5% of the subjects in a state of forgetfulness) was 53.90 minutes (95% CI: 48.54-61.47 min) and the corresponding BIS was 91.38. The amnesia-inducing effect of midazolam was correlated to sedation grade, BIS and age, and was not correlated to visual memory or auditory memory. CONCLUSION: In this study, the ED50 , ED95 and maintenance time of the forgetting effect of intravenous midazolam were preliminarily determined. KEY WORDS: Amnesia, Duration of amnesia, ED50, Midazolam.

The Association of Insomnia with Depression and Anxiety Symptoms in Patients Undergoing Noncardiac Surgery.

OBJECTIVE: Insomnia is common in patients undergoing surgery. It can increase the rate of postoperative complications, interfere with patient recovery, and decrease hospital satisfaction. However, there are few studies on perioperative insomnia. This study was conducted to investigate the differences in the demographic, health status, and clinical characteristics of patients with and without insomnia postoperatively, and to identify the potential risk factors of insomnia. METHODS: There were 299 non-cardiac surgery patients, 165 females, and 134 males, with a mean age of 55 years, enrolled in the study. The Insomnia Severity Index (ISI), Patient Health Questionnaire-9 (PHQ-9), Generalized Anxiety Disorder 7 (GAD-7), and Montreal Cognitive Assessment (MoCA) were administered to all the patients preoperatively. The Visual Analogue Scale (VAS) was used preoperatively, and at the end of the surgery, and then one day, two days, and three days after surgery. The PHQ-9, the GAD-7, and the ISI were repeated three days after surgery. Insomnia was diagnosed by the ISI as being a score of 8-28 (mild: 8-14; moderate-severe: 15-21; severe: 22-28). The patients were divided into group A (with insomnia, N=78) and group B (without insomnia, N=221) according to their ISI score three days after surgery. The general clinical data of the two groups were analyzed first, and then binary logistic regression analysis was conducted to assess the risk factors of insomnia. RESULTS: A total of 299 non-cardiac surgery patients with a mean age of 55 years were enrolled in the study. Of the included patients, the number of females was 165 and the number of the male was 134. The incidence of insomnia at 3 days postoperatively was 26.1% (78/299). The average points that group A patients scored in the ISI, PHQ-9, and the GAD-7 were significantly higher than those in group B. The VAS score three days after surgery was significantly higher in group A. The PHQ-9 and the GAD-7 three days after surgery showed significantly higher depression and anxiety scores in group A. Logistic regression showed that the ISI (p<0.001, 95% CI=1.218-1.500) and the GAD-7 (p=0.003, 95% CI=1.041-1.218) preoperatively, and the PHQ-9 postoperatively (p<0.001, 95% CI=1.226-1.555), were risk factors of insomnia. CONCLUSION: Insomnia is common and can worsen after surgery. The present study suggests that depression and anxiety are risk factors for insomnia after surgery. There is a need for further research and the development of strategies for depression and anxiety management to ensure better sleep quality for patients, which will be of significant benefit to their health. CLINICAL TRIAL REGISTRATION: The study was registered at clinical trial (NCT04027751); Trial registration: clinical trial, NCT04027751. Registered 22 July 2019; https://clinicaltrials.gov/ct2/show/NCT04027751?cond=NCT04027751&cntry=CN&draw=2&rank=1.

Cognitive Deficits and Clinical Symptoms with Hippocampal Subfields in First-Episode and Never-Treated Patients with Schizophrenia.

Memory dysfunction and associated hippocampal disturbances play crucial roles in cognitive impairment of schizophrenia. To examine the relationships between cognitive function and the hippocampal subfields (HSs) in first-episode never-treated (FENT) schizophrenia patients, the HSs were segmented in 39 FENT patients and 30 healthy controls using a state-of the-art automated algorithm. We found no significant differences in any HSs between the patients and controls. However, multivariate regression analysis showed that the left cornu ammonis 1 (CA1), left hippocampal tail, left presubiculum, and right molecular layer contributed 40% to the variance of the PANSS negative symptom score. After adjusting for sex, age, education, and intracranial volume, the partial correlation analysis showed that the volumes of left CA1, CA3, CA4, molecular layer, granule cell layer and both left and right subiculum were negatively correlated with the MATRICS consensus cognitive battery (MCCB) Hopkins Verbal Learning Test (HVLT). Multiple regression analysis showed that the left CA1 and CA3 hippocampal abnormalities contributed 66% to the variance of the HVLT. Our results suggest no detectable HS deficits were found in FENT schizophrenia patients. However, the HSs may be involved in the symptoms and cognitive deficits of schizophrenia patients in the early phase of their illness.

Comparison of adverse events between video and direct laryngoscopes for tracheal intubations in emergency department and ICU patients-a systematic review and meta-analysis.

OBJECTIVE: This systematic review and meta-analysis was designed to determine whether video laryngoscope (VL) compared with direct laryngoscope (DL) could reduce the occurrence of adverse events associated with tracheal intubation in the emergency and ICU patients. METHODS: The current issue of Cochrane Central Register of Controlled Trials, PubMed, EMBASE, and Web of Science (from database inception to October 30, 2018) were searched. The RCTs, quasi-RCTs, observational studies comparing VL and DL for tracheal intubation in emergency or ICU patients and reporting the rates of adverse events were included. The primary outcome was the rate of esophageal intubation (EI). Review Manager 5.3 software was used to perform the pooled analysis and assess the risk of bias for each eligible RCT. The ACROBAT-NRSi Cochrane Risk of Bias Tool was applied to assess the risk of bias for each eligible observational study. RESULTS: Twenty-three studies (13,117 patients) were included in the review for data extraction. Pooled analysis showed a lower rate of EI by using VL (relative risk [RR], 0.24; P < 0.01; high-quality evidence for RCTs and very low-quality evidence for observational studies). Subgroup analyses based on the type of studies, whether a cardiopulmonary resuscitation study, or operators' expertise showed a similar lower rate of EI by using VL compared with DL in all subgroups (P < 0.01) except for experienced operators (RR, 0.44; P = 0.09). There were no significant differences between devices for other adverse events (P > 0.05), except for a lower incidence of hypoxemia when intubation was performed with VL by inexperienced operators (P = 0.03). CONCLUSIONS: Based on the results of this analysis, we conclude that compared with DL, VL can reduce the risk of EI during tracheal intubation in the emergency and ICU patients, but does not provide significant benefits on other adverse events associated with tracheal intubation.

Perioperative Ulinastatin helps preserve endothelial glycocalyx layer in periampullary carcinoma patients undergoing Traditional Whipple Procedure.

BACKGROUND: Damage-associated molecular patterns (DAMPs) generated by major surgery can induce global inflammation response and may degrade the vascular endothelial glycocalyx layer (EGL); in turn, the resulting EGL fragments can act as DAMPs, in a destructive positive feedback loop, to promote exacerbation of inflammation. Ulinastatin (UTI) may attenuate EGL shedding by inhibiting serine proteases and hyaluronidase. OBJECTIVE: This trail evaluates whether EGL shedding elicited by Traditional Whipple Procedure (TWP) could be decreased by using UTI. METHODS: We divided 60 patients undergoing TWP into a control group and a UTI group (n = 30 for both). Blood samples were collected before (T0), near the end (T1), and 1 hour after (T2) surgery. Levels of syndecan-1, ICAM-1, VCAM-1, IL-6, C-reactive protein, thrombomodulin, Hbg and serum albumin were measured and plasma albumin leakage was estimated. RESULTS: IL-6 levels significantly elevated at T1 and T2 in the control group compared with T0, but not the UTI group. Syndecan-1 levels significantly elevated at T1 and T2 in the control group but only T2 in the UTI group compared with T0. CONCLUSIONS: We found global inflammation reaction and EGL degradation during TWP. Perioperative UTI treatment can attenuate this EGL shedding and might alleviate plasma albumin leakage.

Mechanistic insights into δ-opioid-induced cardioprotection: Involvement of caveolin translocation to the mitochondria.

AIMS: The cardioprotective effects of preconditioning against ischemia-reperfusion (I/R) injury depend on the structural integrity of membrane caveolae and signaling through G protein-coupled receptors (GPCRs). However, the mechanisms underlying opioid preconditioning are not fully understood. Here, we examined whether caveolins transmitted opioid-GPCR signals to the mitochondria to mediate cardioprotection. MAIN METHODS: Mice were treated with pertussis toxin (PTX) or saline. Thirty-six hours later, mice from each group were randomly assigned to receive the δ-opioid receptor agonist SNC-121 or saline intraperitoneally 15 min before in vivo I/R. Infarct sizes in each group were compared, and immunoblot analysis was used to detect caveolin expression. The structures of caveolae and mitochondria were determined by electron microscopy (EM). The opening degree of the mitochondrial permeability transition pore (mPTP) was assessed by colorimetry, and mitochondrial respiratory function was assessed by Oxygraph-2k. KEY FINDINGS: Treatment with an opioid receptor agonist reduced the myocardial infarct size after I/R injury, increased caveolin expression, decreased mitochondrial mPTP opening, and improved mitochondrial respiratory function. EM analysis revealed that opioids induced caveolae formation in myocytes and tended to promote translocation to mitochondria. However, these protective effects were blocked by PTX. SIGNIFICANCE: Opioid-induced preconditioning depended on Gi signaling, which promoted caveolin translocation to mitochondria, supported their functional integrity, and enhanced cardiac stress adaption. Verification of this pathway will establish new targets for opioid agents in the field of cardiac protection.

Videolaryngoscopy versus direct laryngoscopy for nasotracheal intubation: A systematic review and meta-analysis of randomised controlled trials.

STUDY OBJECTIVE: Nasotracheal intubation (NTI) is a common practice in the oral and maxillofacial surgeries. A systematic review and meta-analysis was performed to determine whether videolaryngoscopy (VL) compared with direct laryngoscopy (DL) can lead to better outcomes for NTI in adult surgical patients. MEASUREMENTS: Only randomised controlled trials comparing VL and DL for NTI were included. The primary outcome was overall success rate and the second outcomes were first-attempt success rate, intubation time, rate of Cormack and Lehane classification 1, rate of Magill Forceps used, rate of postoperative sore throat, and ease of intubation. MAIN RESULTS: Fourteen studies with 20 comparisons (n = 1052) were included in quantitative synthesis. The overall success rate was similar between two groups (RR, 1.03; p = 0.14; moderate-quality evidence). VL was associated with a higher first-attempt success rate (RR 1.09; p = 0.04; low-quality evidence), a shorten intubation time (MD-6.72 s; p = 0.0001; low-quality evidence), a higher rate of Cormack and Lehane classification 1 (RR, 2.11; p < 0.01; high-quality evidence), a less use of the Magill forceps (RR, 0.11; p < 0.01; high-quality evidence) and a lower incidence of postoperative sore throat (RR, 0.50; p = 0.03; high-quality evidence). Subgroup analysis based on whether with a difficult airway showed higher overall success (p < 0.01) and first-attempt success rates with VL (p = 0.04) in patients with difficult airways; however, these benefits was not shown in patients with a normal airway (p > 0.05); Subgroup analysis based on operators' experience showed that success rate did not differ between groups (p > 0.05), but intubation time was shortened by more than 50s by non-experienced operators (p < 0.05). Subgroup analysis based on different devices used showed that only non-integrated VL led to a shorter intubation time (p < 0.05). CONCLUSIONS: The use of VL does not increase the overall success rate of NTI in adult patients with general anesthesia, but it improves the first-attempt success rate and laryngeal visualization, and shortens the intubation time. VL is particularly beneficial for patients with difficult airways.

Videolaryngoscopy versus fiberoptic bronchoscope for awake intubation - a systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Awake intubation with videolaryngoscopy (VL) is a novel method that is drawing more and more attention as an alternative to awake intubation with fiberoptic bronchoscope (FOB). This meta-analysis is designed to determine the performance of VL compared to the FOB for awake intubation. METHODS: The Cochrane Central Register of Controlled Trials, PubMed, Embase, and Web of science were searched from database inception until October 30, 2017. Randomized controlled trials comparing VL and FOB for awake intubation were selected. The primary outcome was the overall success rate. Rev-Man 5.3 software was used to perform the pooled analysis and assess the risk of bias for each eligible study. The GRADE system was used to assess the quality of evidence for all outcomes. RESULTS: Six studies (446 patients) were included in the review for data extraction. Pooled analysis did not show any difference in the overall success rate by using VL and FOB (relative risk [RR], 1.00; P=0.99; high-quality evidence). There was no heterogeneity among studies (I 2=0). Subgroup analyses showed no differences between two groups through nasal (RR, 1.00; P=1.00; high-quality evidence) and oral intubations (RR, 1.00; P=0.98; high-quality evidence). The intubation time was shorter by using VL than by using FOB (mean difference, -40.4 seconds; P<0.01; low-quality evidence). There were no differences between groups for other outcomes (P>0.05). CONCLUSION: For awake intubation, VL with a shorter intubation time is as effective and safe as FOB. VL may be a useful alternative to FOB.

The Role of Long Noncoding RNAs in Central Nervous System and Neurodegenerative Diseases.

Long noncoding RNAs (lncRNAs) refer to a group of noncoding RNAs (ncRNAs) that has a transcript of more than 200 nucleotides in length in eukaryotic cells. The lncRNAs regulate gene expression at epigenetic, transcriptional, and post-transcriptional levels by multiple action modes. In this review, we describe the diverse roles reported for lncRNAs, and discuss how they could mechanistically be involved in the development of central nervous system (CNS) and neurodegenerative diseases. Further studies on the function of lncRNAs and their mechanism will help deepen our understanding of the development, function, and diseases of the CNS, and provide new ideas for the design and development of some therapeutic drugs.

Median effective volume of ropivacaine 0.5% for ultrasound-guided adductor canal block.

Objective This study aimed to identify the median effective volume of ropivacaine 0.5% for ultrasound-guided adductor canal block (ACB). Methods Thirty-two patients received ultrasound-guided ACB for knee arthroscopic meniscectomy. The criterion for successful ACB was the loss of pinprick sensation in the saphenous area (medial knee, leg, and foot). The volume of ropivacaine 0.5% in each case was determined using the up-down method and used for calculating the median effective dose. Results The mean age, weight, and height of patients were 28.6 ± 7.1 years, 68.2 ± 10.6 kg, and 172.5 ± 6.4 cm, respectively. Among patients who received 18- and 15-mL doses, ACB was successful in all four cases. Among patients who received a 12-mL dose, ACB was effective in eight and ineffective in two cases. Among patients who received a 10-mL dose, ACB was successful in six and unsuccessful in seven cases. In patients who received an 8-mL dose, ACB was ineffective in all five cases. The median effective volume of ropivacaine 0.5% was 10.4 mL (95% confidence interval, 9.1-11.4 mL). In all effective cases, the median quadriceps strength was grade 5. Conclusions The median effective volume of ropivacaine 0.5% is 10.4 mL for ultrasound-guided ACB.

Research progress on the roles of microRNAs in governing synaptic plasticity, learning and memory.

The importance of non-coding RNA involved in biological processes has become apparent in recent years and the mechanism of transcriptional regulation has also been identified. MicroRNAs (miRNAs) represent a class of small regulatory non-coding RNAs of 22bp in length that mediate gene silencing by identifying specific sequences in the target messenger RNAs (mRNAs). Many miRNAs are highly expressed in the central nervous system in a spatially and temporally controlled manner in normal physiology, as well as in certain pathological conditions. There is growing evidence that a considerable number of specific miRNAs play important roles in synaptic plasticity, learning and memory function. In addition, the dysfunction of these molecules may also contribute to the etiology of several neurodegenerative diseases. Here we provide an overview of the current literatures, which support non-coding RNA-mediated gene function regulation represents an important but underappreciated, layer of epigenetic control that facilitates learning and memory functions.

Ozonated autohemotherapy modulates the serum levels of inflammatory cytokines in gouty patients.

OBJECTIVES: Ozonated autohemotherapy (O3-AHT) has been used to effectively treat gout, but the underlying therapeutic mechanisms remain unknown. In this study, as an initial effort to understand the therapeutic mechanisms of O3-AHT, we aim to examine the effect of O3-AHT on serum inflammatory cytokine levels in gouty patients. PATIENTS AND METHODS: Three groups of patients and healthy subjects were recruited, including the gouty (n=10), hyperuricemia (n=10), and healthy control (n=11) groups. Cytometric bead array was applied to examine 12 cytokines before (T0), during (T1), and after (T2) therapies. RESULTS: Three cytokines, IL-8, IL-12, and MCP-1, were detectable in all participants. Before O3-AHT, the average serum levels of IL-8 and MCP-1 were higher in the gout group than in the hyperuricemia and healthy control groups, confirming the inflammation status in gouty patients. After the 5th course of O3-AHT (T1), IL-8 level was significantly increased compared to that at T0. IL-12 level was also raised at T1, although the difference did not reach statistical significance. After completing the therapy, both IL-8 and IL-12 levels decreased to levels lower than those at T0. MCP-1 level remained essentially unchanged during and after treatment. CONCLUSION: Our results indicate that O3-AHT induces a significant change in serum cytokine levels, suggesting that modulating the inflammatory process is one of the therapeutic mechanisms underlying O3-AHT. In addition, the sensitive response of serum IL-8 and IL-12 levels to O3-AHT suggests that these cytokines may be developed as biomarkers to evaluate the therapeutic effect of O3-AHT in gouty patients.

Changes in duration of action of rocuronium following decrease in hepatic blood flow during pneumoperitoneum for laparoscopic gynaecological surgery.

BACKGROUND: A moderate insufflation pressure and deep neuromuscular blockade (NMB) have been recommended in laparoscopic surgery in consideration of the possible reduction in splanchnic perfusion due to the CO2-pneumoperitoneum. Since the liver is the major organ for rocuronium metabolism, the question of whether NMB of rocuronium would change with the variation of liver perfusion during pneumoperitoneum during laparoscopic surgery merits investigation. METHODS: In this prospective study, a total of sixty female patients scheduled for either selective laparoscopic gynaecological surgery (group laparoscopy) or laparotomy for gynaecological surgery (group control) were analyzed. Rocuronium was administered with closed-loop feedback infusion system, which was also applied to monitor NMB complied with good clinical research practice (GCRP). The onset time, clinical duration, and recovery index were measured. Hepatic blood flow was assessed by laparoscopic intraoperative ultrasonography before insufflation/after entering the abdominal cavity (T1), 5 min after insufflation in the Trendelenburg position/5 min after skin incision (T2), 15 min after insufflation in the Trendelenburg position/15 min after skin incision (T3), 30 min after insufflation in the Trendelenburg position/30 min after skin incision (T4), and 5 min after deflation/before closing the abdomen (T5) in group laparoscopy/group control respectively. The relationship between the clinical duration of rocuronium and portal venous blood flow was analyzed using linear or quadratic regression. RESULT: The clinical duration and RI of rocuronium were both prolonged significantly in group laparoscopy (36.8 ± 8.3 min; 12.8 ± 5.5 min) compared to group control (29.0 ± 5.8 min; 9.8 ± 4.0 min) (P < 0.0001; P = 0.018). A significant decrease was found in portal venous blood flow during the entire pneumoperitoneum period in group laparoscopy compared with group control (P < 0.0001). There was a significant correlation between the clinical duration of rocuronium and portal venous blood flow (Y = 51.800-0.043X + (1.86E-005) X 2; r2 = 0.491; P < 0.0001). CONCLUSION: Rocuronium-induced NMB during laparoscopic gynaecological surgery might be prolonged due to the decrease in portal venous blood flow induced by CO2-pneumoperitoneum. Less rocuronium could be required to achieve a desirable NMB in laparoscopic gynaecological surgery. TRIAL REGISTRATION: ChiCTR. Registry number: ChiCTR-OPN-15007524 . Date of registration: December 4, 2015.

MiR-7684-5p leads to surgery-induced cognitive decline in mice probably through the downregulation of SorLA.

BACKGROUND: Postoperative cognitive dysfunction is a postoperative severe complication caused by many factors. However, its specific pathogenesis remains unclear. MicroRNAs (miRNAs), which are involved in the pathogenesis of neurodegenerative diseases, may also affect POCD. METHODS: In this research, microarray technology was used to screen 26 miRNAs that had a differential expression in the hippocampus of mouse between the surgery group and control group. The qRT-PCR verification on the hippocampuses of 10 pairs of mouse testifies the high expression of miR-7684-5p in the surgery group (identical with the result of chip). RESULTS: Surgical trauma was found to induce the expression of miR-7684-5p with the accumulation of Aß in the hippocampus. Furthermore, miR-7684-5p knockdown effectively reduced the levels of Aß triggered by surgery, and attenuated hippocampal-dependent memory impairment. Moreover, we testify that sorLA is a target gene of miR-7684-5p through bioinformatics prediction and dual-luciferase report gene experiment. CONCLUSIONS: Our data indicate that decreased postoperative cognitive function may be caused by the increased generation of Aß by reducing sorLA expression. Our work implicates miR-7684-5p as a potential biomarker and a novel therapeutic target.

Pneumonia relevant to lung transplantation and pathogen distribution.

BACKGROUND: Pneumonia is the most common cause of morbidity and mortality in lung transplant (LT) recipients. The aim of the present study was to evaluate the incidence, etiology, risk factors and prognosis of pneumonia in LT recipients. METHODS: The LT cohort consisted of 28 recipients receiving LT in Beijing Chao-Yang Hospital from August 2005 to April 2011. Data collected included demographic data, underlying disorders, time and type of transplant, follow-up information, date of last follow-up, and patient status. A retrospective analysis was made of observational data that were prospectively collected. RESULTS: Twenty-two patients of 28 LT recipients had 47 episodes of pneumonia throughout the study period. Thirtyeight episodes of pneumonia in 19 recipients occurred post-LT with a median follow-up of 257.5 days (1-2104 days), the incidence of pneumonia was 192.4 episodes per 100 LT/year and its median time of onset was 100.5 days (0-946 days) post-transplantation. Bacteria, virus and fungi accounted for 62%, 16% and 15% of the microbial pathogens, respectively. The most frequent were Pseudomonas aeruginosa (20%), cytomegalovirus (CMV) (15%), and Aspergillus fumigatus (10%). A total of 29% (11/38) of pneumonias occurred in the first month post-LT, and then the incidence decreased gradually. The incidence of CMV pneumonia was 25% (7/28) with a median time of 97 days (10-971 days). More than one bacterial infection and CMV infection were independent risk factors for aspergillus infection. The incidence of pulmonary tuberculosis (TB) was 18% (5/28), and the history of TB was a risk factor for TB relapse. There were 58% (7/12) of recipients who died of infection, and 71% (5/7) of these died in the first year after LT. CONCLUSIONS: Pneumonia is still a major cause of morbidity and mortality in LT recipients. The most frequent microorganisms were Pseudomonas aeruginosa, CMV, and Aspergillus fumigates. The incidence of CMV pneumonia decreases with a delayed median time of onset. More than one incidence of bacterial infection and CMV infection are independent risk factors for aspergillus infection. LT recipients are at high risk for TB, and the history of TB is a risk factor for TB relapse.