Incidence and Risk Factors of Postoperative Severe Discomfort After Elective Surgery Under General Anesthesia: A Prospective Observational Study.

PURPOSE: Patient comfort is an important concern in patients receiving surgery, but the seriousness of discomfort during recovery is unknown. We investigated the incidence of postoperative discomfort based on the Standardized Endpoints in Perioperative Medicine initiative for patient comfort, and identified the risk factors. DESIGN: This was a single-center prospective observational study. METHODS: We enrolled adult patients who underwent elective surgery under general anesthesia between July and December 2018 at West China Hospital of Sichuan University (ChiCTR1800017324). The primary outcome was the incidence of postoperative severe discomfort (PoSD), defined as occurring when a patient experienced a severe rating in two or more domains in the six domains in the Standardized Endpoints in Perioperative Medicine initiative on the same day, including rest pain, postoperative nausea, and vomiting, dissatisfaction of gastrointestinal recovery, dissatisfaction of mobilization, sleep disturbance, and recovery. A generalized estimated equation was constructed to find risk factors of PoSD. FINDINGS: In total, 440 patients completed the study. The incidence of PoSD was 28% on postoperative day (POD) 1, 13% on POD 2, 9% on POD 3, and 3.6% on both POD 5 and 7. The most common discomfort was serious sleep disturbance, ranging from 43% to 10% in the first week after surgery. Longer operative time (odds ratio [95% confidence interval]: 1.56 [1.19 to 2.05], P = .001), gastrointestinal surgery (5.03[2.08,12.17], P < .001), orthopaedic surgery (3.03 [1.35,6.79], P = .007), ear, nose, and throat (ENT) surgery (3.50 [1.22,10.02], P = .020) and postoperative complications (1.77 [1.03-3.04], P = .038) were significant risk factors of PoSD. CONCLUSIONS: The incidence of PoSD after elective surgery under general anesthesia is high. Sleep disturbance was the most common problem identified. Anesthesia providers and perianesthesia nurses may need to optimize anesthetic application, combine different anesthesia methods, improve perioperative management, and provide interventions to reduce and to treat discomfort after surgeries.

Clinical Efficacy of Ultrasound-Mediated Transdermal Lidocaine and Capsaicin Delivery for the Treatment of Allodynia Caused by Herpes Zoster.

OBJECTIVE: To investigate the efficacy of ultrasound-mediated drug delivery for allodynia caused by herpes zoster. DESIGN: Unblinded randomized controlled study with two treatment groups and an additional control group. SUBJECTS: Patients hospitalized with allodynia caused by herpes zoster were enrolled. METHODS: Patients were randomly assigned to three groups: ultrasound-mediated transdermal drug delivery (group U), lidocaine intradermal injection (group I), or control group (group C). The primary outcome was pain intensity associated with allodynia, assessed with the visual analog scale (VAS) while brushing the skin with clothing after treatment stimulated allodynia. The secondary outcomes included an emotional functioning score (ES), average gabapentin consumption, and incidence of adverse events of each group. RESULTS: Sixty patients were enrolled in the study, but two of them failed to complete the treatment process. Therefore, 58 patients were included in the final analysis. All groups had lower VAS and ES scores after treatment compared with baseline. The VAS scores in groups U and I decreased significantly more than in group C (P < 0.05). Mean VAS scores in group U on days 1, 2, and 3 were lower than in group C (P < 0.01). ES was significantly lower in group U compared with groups I and C after treatment (P < 0.001). Average gabapentin consumption and incidence of adverse events in group C were higher than in the other two groups. CONCLUSIONS: In this study of treatment of allodynia caused by herpetic zoster, ultrasound-mediated lidocaine and capsaicin delivery provided better pain relief and improved emotional functioning compared with intradermal blockade with local anesthetics.

Impacts of Preoperative Smoking and Smoking Cessation Time on Preoperative Peripheral Blood Inflammatory Indexes and Postoperative Hospitalization Outcome in Male Patients with Lung Cancer and Surgery Treatment.

Objective s To investigate the effects of preoperative smoking and smoking cessation time on preoperative peripheral blood inflammatory indexes and postoperative hospitalization outcomes in male patients with lung cancer and surgery therapy.Methods We retrospectively enrolled 637 male patients who underwent curative-intent lung cancer resection between January 2014 and December 2016. Patients were classified as the current smokers, the never smokers, and the ex-smokers based on their smoking history, and the ex-smokers were allocated into five subgroups according to their smoking cessation times (CeT): CeT≤6 weeks, 6weeks10years. The preoperative peripheral blood white blood cells (WBCs), albumin, neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), intraoperative blood loss, 30-day mortality, in-hospital days, hospitalization costs, intensive care unit (ICU), admission days and placement time of closed thoracic drainage tube were compared among different groups.Results There were significant differences in WBC (F=5.275, P<0.001) and albumin (F=2.470, P<0.05) among patients of current smokers, ex-smokers with different smoking cessation time, and never-smokers. The blood WBC count in current smokers (7.7×10 9/L) was significantly higher than that in ex-smokers (7.0×10 9/L)and never-smokers (5.9×10 9/L) (t=-2.145, P<0.05; t=-6.073, P<0.01, respectively). The level of peripheral blood albumin in current smokers (41.1 g/L) was lower than that in ex-smokers (42.1 g/L) and never-smokers (43.2 g/L) (t=2.323, P<0.05; t=3.995, P<0.01, respectively). The level of peripheral blood NLR in current smokers (3.7) was higher than that in ex-smokers (3.1) and never smokers (2.8) (t=-1.836, P<0.05; t=-2.889, P<0.01, respectively). There was no significant difference in WBC, albumin and NLR among five subgroups of different smoking cessation time. No significant difference was observed in intraoperative blood loss, 30-day mortality, hospitalization costs, hospital stay, ICU stay and placement time of closed thoracic drainage tube among groups either. Conclusion Smoking increases the preoperative inflammatory indexes in peripheral blood of lung cancer patients. Smoking cessation has beneficial effect on reducing levels of these inflammatory indexes, which may be not impacted by the time length of smoking cessation. Therefore, lung cancer patients should be encouraged to quit smoking at any time.

Characterization of PD-L1 expression in Chinese non-small cell lung cancer patients with PTEN expression as a means for tissue quality screening.

The goal of this study is to evaluate PD-L1 prevalence and its association with major clinical characteristics in Chinese non-small cell lung cancer (NSCLC) patients to inform the clinical development of anti-PD1/PD-L1 agents in this population. We used phosphatase and tensin homolog (PTEN) expression through IHC as a surrogate tissue quality marker to screen surgical NSCLC samples in tissue microarray (TMA; 172 cases) or whole-section (268 cases) format. The samples were then analyzed with a clinically validated PD-L1 IHC assay. The results were correlated with baseline characteristics and clinical outcomes. PTEN IHC showed that 108 TMA samples and 105 whole-section samples qualified for PD-L1 IHC. With a clinically relevant cutoff, 41.7% of the TMA samples were PD-L1 positive. PD-L1 level was much lower in EGFR-mutant patients and seemed to be a favorable prognostic factor for both overall survival (OS) and recurrence-free survival (RFS). These findings were confirmed in the whole-section samples except that their survival data were not mature enough for correlation analysis. In summary, PD-L1 expression was detected in approximately 40% of PTEN-qualified Chinese NSCLC samples, negatively correlated with EGFR mutation and seemed to be a favorable prognostic factor for both OS and RFS. Notably, the different results from PTEN-qualified and PTEN-disqualified samples underscore the importance of tissue quality control prior to biomarker testing.

A comparison of exposure of Glottis using the Airtraq or the Macintosh Laryngoscope in Potentially difficult airway management: A self-controlled clinical trial.

OBJECTIVE: To compare glottis exposure of the same patients with potentially difficult tracheal intubation (PDTI) subjected to Airtraq laryngoscopy and Macintosh laryngoscopy under consciousness and topical anesthesia. METHODS: A total of 147 PDTI patients with American Society of Anesthesiologists (ASA) I-III were subjected to Airtraq and Macintosh laryngoscopy performed by experienced anesthesiologists under consciousness and topical anesthesia. RESULTS: All patients were successfully intubated. Among them, three patients were intubated with fiberoptic bronchoscopy, 13 with Macintosh laryngoscopy and 131 with Airtraq laryngoscopy. Of the patients with Cormack and Lehance (C&L) Grade-I glottic view, 88 were subjected to Airtraq laryngoscopy and five to Macintosh laryngoscopy; Of the patients with C&L Grade-II glottic view, 56 were subjected to Airtraq laryngoscopy and 21 to Macintosh bronchoscopy; Of the patients with C&L Grade-III glottic view, three were subjected to Airtraq laryngoscopy and 112 to Macintosh bronchoscopy; Of the patients with C&L Grade-IV glottic view, none was subjected to Airtraq laryngoscopy and 9 to Macintosh laryngoscopy. CONCLUSIONS: Airtraq laryngoscopy could significantly improve the glottis exposure and reduce the difficulty of intubation for patients with potentially tracheal intubation compared to the traditional Macintosh laryngoscopy.

The pre-amputation pain and the postoperative deafferentation are the risk factors of phantom limb pain: a clinical survey in a sample of Chinese population.

BACKGROUND: To provide an overview of phantom limb pain (PLP) in China. This includes the prevalence of PLP and possible risk factors. METHODS: In a retrospective study, telephone interviews were conducted with 391 amputation patients who underwent extremity amputations at a tertiary hospital in China. RESULTS: PLP was found in 29% of the amputees. Pre-amputation pain (OR = 10.4, P = 0.002) and postoperative analgesia (OR = 4.9, P = 0.008) were identified as high-risk factors for PLP. 82.1% of PLP patients experienced pre-amputation pain. The average pain intensity of PLP was 5.1 ± 2.2, with 31.9% having severe intensity. The effects of PLP on the quality of the PLP patients were as follows: 7.8% of the patients had to limit their daily life and 29.0% of the patients had to limit their social activities. 17.3 and 25.7% of patients experienced depression and sleeping disorder respectively, while 18.9% had loss of interest and even 16.1% of PLP patients had attempted suicide. No effective treatments were found in 78.9% of these patients. CONCLUSIONS: PLP has markedly affected the lives of patients. Pre-amputation pain and postoperative epidural analgesia might be risk factors for the phantom limb pain after amputation. Prevention of pre-amputation pain and sudden post-amputation deafferentation should be recommended to the amputees.

Nerve Blockage Attenuates Postoperative Inflammation in Hippocampus of Young Rat Model with Surgical Trauma.

It is hypothesized that central nervous system inflammation induced by systematic inflammation due to surgical trauma plays a critical role in postoperative cognitive dysfunction. The potential inhibitory effect of nerve blockage with local anesthetics on peripheral inflammatory response has been reported. We hypothesize that nerve blockage may be effective in reducing postoperative inflammation and cognitive decline. The rats at the age of 4 weeks were subjected to general anesthesia and humeral fracture fixation, in combination with brachial plexus block, saline versus ropivacaine, respectively. The rats from control group underwent general anesthesia only. The expression of proinflammatory cytokines in plasma and in hippocampus was measured. Open field test and new object recognition task were performed before surgery and on postoperative days (POD) 1, 3, and 7. Compared with control group, the level of cytokines in plasma and hippocampus revealed an obvious increase in surgery groups. The effect of brachial plexus block on decreasing cytokines was observed. The rats exposed to surgery without brachial plexus block showed behavior impairment. Our results indicated that nerve blockage could downregulate proinflammatory cytokines in hippocampus after humeral fixation surgery, which may ameliorate the postoperative cognitive dysfunction in young rats.

Nerve injury-related autoimmunity activation leads to chronic inflammation and chronic neuropathic pain.

BACKGROUND: Peripheral nerve injuries that provoke neuropathic pain are associated with chronic inflammation and nervous lesions. The authors hypothesized that chronic neuropathic pain might be caused by chronic inflammation resulting from a nervous autoimmune reaction triggered by nerve injury. METHODS: The authors observed chronic inflammation and neuropathic behaviors for up to 12 weeks after nerve injury in T lymphocyte-deficient nude mice and their heterozygous littermates. Lymphocyte proliferation and Schwann cell apoptosis were examined after coculture of each population with various neural tissues from normal rats and those with nerve injury. RESULT: Nude mice recovered faster and exhibited less thermal hyperalgesia after nerve injury compared to their heterozygous littermates. A large number of IL-17 cells indicative of lymphocyte activation were found in the injured sciatic nerve and spinal cord (L4-6) of heterozygous littermates, but far fewer of these populations were found in nude mice. In vitro lymphocyte proliferation was enhanced after coculture with nerve tissues from normal rats compared to nerve tissue-free phosphate-buffered saline controls. In particular, coculture with sciatic nerve tissue enhanced proliferation by 80%, dorsal root ganglion by 46%, and spinal cord by 14%. Moreover, neural tissues from rats with nerve injury markedly increased the lymphocyte proliferation compared to coculture with tissues from corresponding normal rats. Schwann cell apoptosis was triggered in vitro when cocultured with lymphocytes from neuropathic rats. CONCLUSION: Our study suggests that chronic neuropathic pain might be caused by chronic inflammation resulting from a nervous autoimmune reaction triggered by nerve injury.

Comparison of S-ketamine and midazolam for intravenous preoperative sedative and anxiolytic effects in preschool children: study protocol for a randomized controlled clinical trial.

BACKGROUND: Preoperative anxiety management is gaining particular attention in paediatric anaesthesia. Pharmacological and non-pharmacological resorts can be implemented to address this special issue. Despite the various approaches currently used for preoperative sedation in children, the different sedative and anti-anxiety effects between the newly marketed anaesthetic, S-ketamine, and the traditional sedative, midazolam, are still unclear. METHODS: This is a patient- and assessor-blinded randomized controlled clinical trial. Participants (n = 110) will receive S-ketamine (0.5 mg/kg) or midazolam (0.08 mg/kg) intravenously administrated at a ratio of 1:1 in the anaesthesia holding area. The primary outcome of this study is the sedative effect evaluated via the change in the modified Yale preoperative anxiety scale. It will be performed at two timepoints: in the pre-anaesthetic holding area before premedication (baseline, marked as T0) and about 5 min after premedication in the operating room without the existence of their guardians (marked as T1). Our secondary objectives include the parent separation anxiety score, postoperative agitation, caregivers' and anaesthesia care providers' satisfaction, and mask compliance. DISCUSSION: This randomized controlled trial is the first study to compare the anti-anxiety effect of intravenous S-ketamine and midazolam. We will provide a new approach for the clinical management of preoperative anxiety in preschool children posted for elective surgery. TRIAL REGISTRATION: ChiCTR2300069998. Registered on 30 March 2023.

[Effects of pretreatment of lipid, midazolam and propofol on ropivacaine-induced convulsion and LD50 in rats].

OBJECTIVE: To assess the effects of lipid on ropivacaine-induced convulsion and LD50 in rats and compare with those of the traditional anticonvulsants midazolam and propofol. METHODS: Protocol 1: A total of 120 SD rats (60 males, 60 females), weighing 200-300 g, were randomly assigned into 4 groups with equal males and females: lipid (L), midazolam (M) and propofol (P) and control (C). Rats were pretreated with 10 ml/kg lipid intravenously in group L, saline and 0.23 mg/kg midazolam (10 ml/kg in volume) sequentially in group M, saline and 4 mg/kg propofol (10 ml/kg in volume) in group P and saline 10 ml/kg in group C. Then ropivacaine 44 mg/kg (0.75%) was injected intraperitoneally into each rat. The convulsion rate in each group and the time of convulsion after ropivacaine injection were observed. Meanwhile, the plasma concentration of ropivacaine at the time of convulsion was measured. Protocol 2: Additional 100 male SD rats were used for the measurements of ropivacaine LD50 with different pretreatments including lipid, midazolam, propofol and saline through the up-and-down method. Rats were randomly assigned into 4 groups similarly as protocol 1. The doses of ropivacaine in each group were determined according to our pilot study and 6 dosage levels with the same interval ratio 8.5 was applied in each group. The doses of these pretreatment drugs and administration methods were similarly as protocol 1. RESULTS: The convulsion rate after 44 mg/kg ropivacaine ip injection was 43.3% in group C, 0% in group M, 13.3% in group P and 70% in group L. Lipid increased the convulsion rate significantly. The plasma concentration of ropivacaine at the time of convulsion was 1.65 ± 0.30 µg/kg in group C, 1.73 ± 0.14 µg/kg in group P and 3.45 ± 0.26 µg/kg in group L. The LD50 of ropivacaine in group C was 64.39 mg/kg, 88.40 mg/kg in group M and 90.20 mg/kg in group P and 55.45 mg/kg in group L. CONCLUSIONS: Midazolam and propofol not only decrease the convulsion rate of ropivacaine, but also increase its LD50. Lipid not only increases the convulsion rate of ropivacaine, but also decreases its LD50. The application of lipid for the prevention of local anesthetic toxicity has potential risks.

[Atropine treatment of hypoxic bradycardia accelerated the occurrence of cardiac arrest].

OBJECTIVE: To explore the therapeutic effects of atropine for hypoxic bradycardia during the occurrence of cardiac arrest. METHODS: Sixty-four adult New Zealand rabbits were selected and allocated randomly into 2 groups: instant resuscitation group and 8-minute resuscitation group. Each animal was anesthetized by an intravenous injection of sodium pentobarbital and intubated through tracheostomy. The tracheostomy tube was then clamped off to induce acute hypoxia. At soon as heart rate (HR) decreased to a half of basic-heart-rate, either atropine 50 µg/kg or 0.9% normal saline as control was randomly administered intravenously. In instant resuscitation group (group T1), the tracheostomy tube was unclamped and cardiopulmonary resuscitation (CPR) initiated for the occurrence of cardiac arrest (MAP < 10 mm Hg). In 8-minute resuscitation group (group T2), the tracheostomy tube was clamped for 8 minutes and then CPR initiated. The statistical data were analyzed by SPSS 10.0. All data were reported as x(-) ± s. T test was used to compare the means of cardiac arrest time between two groups, one-way ANONA to compare HR & mean arterial pressure (MAP) and Fisher's exact probabilities test to compare the survival rates between two groups. A value of P < 0.05 was considered statistically significant. RESULTS: The heart rate of atropine treated group was higher than that of normal saline group for about 90 minutes post-dosing. In atropine group, the MAP decrease was significantly faster than that of normal saline group (P < 0.01). Most importantly, after the clamping of tracheostomy tube, the average time of cardiac arrest occurred at (335.43 ± 43.25) s in atropine group versus (371 ± 55) s in normal saline group (P = 0.006). CONCLUSION: Although atropine treatment of severe hypoxic bradycardia improves the decrease of HR for a short time, it decreases MAP and accelerates the occurrence of cardiac arrest result from acute hypoxia. But the mortality rate is not improved by the treatment of atropine.

Dexmedetomidine and Netrin-1 Combination Therapy Inhibits Endoplasmic Reticulum Stress by Regulating the ERK5/MEF2A Pathway to Attenuate Cerebral Ischemia Injury.

The complexity of hard-to-treat diseases such as ischemic stroke strongly undermines the therapeutic potential of available treatment options. Therefore, current developments have gently shifted from a focus on monotherapy to combined or multiple therapies. Both dexmedetomidine and Netrin-1 have anti-neuronal apoptosis effects, but the mechanism is still unclear. The study aimed to estimate the efficacy of dexmedetomidine and Netrin-1 combination therapy against ERS-induced apoptosis after cerebral ischemia injury in vivo and in vitro, and whether the mechanism is related to the ERK5/MEF2A pathway. Adult male Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) in vivo, 90 min ischemia and 24 h reperfusion. The hippocampus slices used to establish oxygen-glucose deprivation (OGD) injury model in vitro. Neterin-1 and Dexmedetomidine were pretreated and post-treated, respectively, before and after the model establishment. MEF2A knockdown was performed by microinjection of AAV9-MEF2A RNAi vector. Orthodromic population spike (OPS) at the end of reoxygenation were recorded. Neurobehavioral tests, TTC staining, Nissl staining, TUNEL staining were performed to assess the effect of the drugs. The expression of CHOP, GRP78, MEF2A, ERK5, and p-ERK5 were investigated by Western blot and immunofluorescence staining. Neurological deficit score, infarct volume, the expression of GRP78, CHOP, and neural apoptotic rate of MCAO group increased markedly. Combination of dexmedetomidine and Netrin-1 resulted in lower infarct volumes and fewer neurological impairments, higher OPS recovery rate, and less damaged and apoptotic cells after cerebral ischemia injury. Furthermore, expression levels of GRP78 and CHOP decreased in the combination therapy group, and it was more effective than the single drug group. Meanwhile, Combination of dexmedetomidine and Netrin-1 increased MEF2A expression and promoted ERK5 phosphorylation. However, the protective effect of dexmedetomidine combined with Netrin-1 in improving neurological function was significantly eliminated by pre-knockdown MEF2A. The neuroprotective effects of dexmedetomidine combined with Netrin on cerebral ischemia-reperfusion injury and hippocampal hypoxia injury in terms of ERS. The synergistic effect of combination therapy is related to the activation of ERK5/MEF2A signaling pathway.

Pharmacokinetic and pharmacodynamic properties of ciprofol emulsion in Chinese subjects: a single center, open-label, single-arm dose-escalation phase 1 study.

We conducted a single-center, single-arm, open-label, dose-escalation phase 1 clinical trial to evaluate the tolerability of a single intravenous injection of ciprofol emulsion for the induction of short-term general anesthesia. Four doses of ciprofol (0.15 mg/kg, n = 2; 0.4 mg/kg, n = 10; 0.6 mg/kg, n = 6; 0.9 mg/kg, n = 6) were administered. Twenty-four subjects were enrolled, with 18 subjects in the 0.4 to 0.9 mg/kg dosage groups included in the data analysis. In total, 37 mild and 4 moderate adverse events (AEs), including 9 abnormal limb movements (3 moderate cases), 8 cases of sinus bradycardia, 11 cases of prolonged QTcF interval (including 1 moderate case), and 1 case of hypotension, were found, but no serious AEs were reported. The Modified Observer's Assessment of Alertness/Sedation (MOAA/S) scores rapidly decreased after ciprofol administration. The duration of recovery of the verbal response, loss of verbal response duration, the duration of MOAA/S ≤1 and the duration until the return of responsiveness were all increased in a dose-dependent manner. The durations of bispectral index values <60 (6, 8 and 12 min) were similar to the durations of loss of verbal response (6, 8 and 14 min) and MOAA/S ≤1 (5, 5.5 and 13.5 min) in the 0.4, 0.6 and 0.9 mg/kg dose groups, respectively. The plasma concentration reached a peak value approximately 2 min after injection in the 0.4-0.9 mg/kg groups and all subjects fully recovered after ciprofol administration, with the shortest time being 9.2 min in the 0.4 mg/kg group. A ciprofol dosing regimen of 0.4-0.9 mg/kg was well-tolerated and exhibited rapid onset and recovery properties.

[Association of immunization and thermal latencies in rats with chronic constriction injury].

OBJECTIVE: To observe the change of thermal latencies, spinal cord morphology and quantity of microglia following the treatment of lipopolysaccharide (LPS) or cyclosporin A (CsA) in rats with established neuropathic pain through chronic constriction injury (CCI). METHODS: A total of 36 male SD rats with CCI of sciatic nerve were randomly divided into LPS group, CsA group and NS group, and injected with LPS (1 mg/kg), CsA (6 mg/kg), and NS (2 mL) per day respectively since the 3rd day post operation. The thermal latencies and mechanical thresholds of the rats were measured preoperatively and on the 3rd, 5th, 7th, 10th, 13th and 14th day post operation. The rats were sacrificed on the 14th day and the L4 of spinal cords were harvested for CD11b IHC examination of microglia. RESULTS: The thermal latencies went down steadily in rats treated with LPS, but went up in rats treated with CsA since the 3rd day after nerve injury. More active microglia were found in the white and grey matter of the spinal cord L4 in rats treated with LPS and NS than in rats treated with CsA. The majority of microglia were inactive in rats treated with CsA. CONCLUSION: Immunomodulator might affect the thermal latencies of CCI rat model, perhaps through microglia in the central nerve system.

The Critical Role of Cannabinoid Receptor 2 in URB602-Induced Protective Effects Against Renal Ischemia-Reperfusion Injury in the Rat.

Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury (AKI) and even induces remote organ damage. Accumulating proofs demonstrates that the endocannabinoid system may provide a promising access for treatment strategy of renal IRI associated AKI. In the current study, using the established renal IRI model of rat, we tested the hypothesis that pretreatment of URB602, 30 min before renal IRI, alleviates kidney injury and relevant distant organ damage via limiting oxidative stress and inflammation. Using Western blot analysis and LC-MS/MS, renal IRI showed to increase the levels of 2-arachidonoylglycerol (2-AG) in kidneys as well as COX-2, PGE2, TXA2, and decrease N-arachidonoylethanolamine (anandamide, AEA); the expressions of renal cannabinoid receptor 1 (CB1) and cannabinoid receptor 2 (CB2) were unchanged. The URB602 pretreatment in renal IRI, further enhanced renal 2-AG which is high affinity to both CB1 and CB2, and reduced renal COX-2 which is involved in the regulation of renal perfusion and inflammation. AM630 (CB2 antagonist) almost blocked all the antioxidant, anti-inflammatory and nephroprotective effects of URB602, whereas AM251 (CB1 antagonist) showed limited influence, and parecoxib (COX-2 inhibitor) slightly ameliorated renal function at the dose of 10 mg/kg. Taken together, our data indicate that URB602 acts as a reactive oxygen species scavenger and anti-inflammatory media in renal IRI mainly depending on the activation of CB2.

Astrocyte morphology: Diversity, plasticity, and role in neurological diseases.

Astrocytes are the most abundant glial cells in the central nervous system (CNS) and participate in synaptic, circuit, and behavioral functions. The well-developed protoplasmic astrocytes contain numerous processes forming well-delineated bushy territories that overlap by as little as 5% at their boundaries. This highly complex morphology, with up to approximately 80% of the cell's membrane constituted by fine processes with dimensions on the tens of nanometer scale and high surface area to volume ratios, comes in contact with synapses, blood vessels, and other glial cells. Recent progress is challenging the conventional view that astrocytes are morphologically homogeneous throughout the brain; instead, they display circuit- and region-specific morphological diversity that may contribute to the heterogeneous astrocyte-neuron spatiotemporal interplay in different brain areas. Further, the fine structure of astrocytes is found to be highly plastic and activity-dependent. We are beginning to understand how astrocyte structural plasticity contributes to brain functions. The change/loss of astrocyte morphology, traditionally known as a hallmark for reactive astrogliosis, is a common pathological feature in many neurological disorders. However, recent data suggest the fine structural deficits preceding reactive astrogliosis may drive disease progression. This review summarizes recent advances in astrocyte morphological diversity, plasticity, and disease-related deficits.

The Effects of Safflower Yellow on Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Randomized, Controlled Clinical Trial.

OBJECTIVES: To evaluate the efficacy of safflower yellow in the acute exacerbation of chronic obstructive pulmonary disease (AECOPD). METHODS: In a prospective, randomized, controlled trial, 127 patients who met the inclusion criteria were enrolled and were randomly divided into two groups. The control group included 64 patients treated according to the global strategy for diagnosis, management, and prevention of COPD (www.goldcopd.org, updated 2011). The intervention group included 63 patients who received intravenous infusions of safflower yellow (100 mg of safflower yellow dissolved in 250 ml 0.9% saline) once daily for 14 consecutive days in addition to standard diagnosis and treatment. The difference in the average length of the hospital stay between the two groups of patients was determined. The follow-up period was 28 days; the differences in symptoms, clinical indicators, and 28-day mortality in the two groups were compared. Statistical analysis was conducted using SPSS 22.0 software to determine whether there were statistically significant differences (P <0.05) between groups. RESULTS: There were no statistically significant differences between the intervention group and the control group in changes in secondary indicators. There were no statistically significant differences in the 28-day mortality or in the survival curves of the two groups (P=0.496 and P=0.075, respectively). Safflower yellow treatment of AECOPD may relieve the patient's clinical symptoms, such as dyspnoea, shorten the average length of hospital stay (P=0.006, respectively), and decrease the duration of mechanical ventilation. CONCLUSION: Safflower yellow in the treatment of AECOPD has a degree of clinical value. This trial is registered under the identifier ChiCTR-IPR-17014176.

[Protective effect of pyrrolidine dithiocarbamate on erythrocytes during canine cardiopulmonary bypass].

OBJECTIVE: To investigate the protective effect of pyrrolidine dithiocarbamate (PDTC) on erythrocytes during canine cardiopulmonary bypass (CPB). METHODS: Twelve adult healthy dogs undergoing CPB were randomly divided into the control group (n = 6) and the PDTC group (n = 6). In the PDTC group, PDTC 30 mg/kg was administered intravenously before CPB. Dogs in the control group was intravenously administering with normal saline. The levels of interleukin (IL)-1beta, IL-8, malondiadehyde (MDA), free hemoglobin (F-HB) in plasma, erythrocyte adenosine triphosphate (E-ATP), and erythrocyte superoxide dismutase (E-SOD) were determined before CPB, 30 and 60 minutes after aortic cross-clamping (AC), and 30 and 60 minutes after declamping (DC). RESULTS: In the control group, plasma levels of IL-1beta and IL-8 significantly increased after CPB (P < 0.01). In the PDTC group, plasma levels of IL-1beta and IL-8 significantly increased after CPB (P < 0.05, P < 0.01). Plasma levels of MDA and F-HB significantly increased (P < 0.01) and the E-ATP level and E-SOD activity significantly decreased after CPB (P < 0.01) in both two groups. The E-ATP level and E-SOD activity in the PDTC group at 30 and 60 minutes after AC and 30 and 60 minutes after DC were significantly higher than those in control group (P < 0.01). However, the levels of IL-1beta, IL-8, MDA, and F-HB at 30 and 60 minutes after AC and 30 and 60 minutes after DC were significantly lower in the PDTC group than those in control group (P < 0.01). CONCLUSION: PDTC can protect erythrocytes by alleviating lipid peroxidation and inflammatory response during CPB.