Single-cell transcriptome analysis reveals heterogeneity of neutrophils in non-small cell lung cancer.

BACKGROUND: Lung cancer stands out as a highly perilous malignant tumor with severe implications for human health. There has been a growing interest in neutrophils as a result of their role in promoting cancer in recent years. Thus, the present study aimed to investigate the heterogeneity of neutrophils in non-small cell lung cancer (NSCLC). METHODS: Single-cell RNA sequencing of tumor-associated neutrophils (TANs) and polymorphonuclear neutrophils sourced from the Gene Expression Omnibus database was analyzed. Moreover, cell-cell communication, differentiation trajectories and transcription factor analyses were performed. RESULTS: Neutrophils were found to be closely associated with macrophages. Four major types of TANs were identified: a transitional subcluster that migrated from blood to tumor microenvironment (TAN-0), an inflammatory subcluster (TAN-1), a subpopulation that displayed a distinctive transcriptional signature (TAN-2) and a final differentiation state that promoted tumor formation (TAN-3). Meanwhile, TAN-3 displayed a marked increase in glycolytic activity. Finally, transcription factors were analyzed to uncover distinct TAN cluster-specific regulons. CONCLUSIONS: The discovery of the dynamic characteristics of TANs in the present study is anticipated to contribute to yielding a better understanding of the tumor microenvironment and advancing the treatment of NSCLC.

General anesthesia versus nongeneral anesthesia during endovascular therapy for acute ischemic stroke: A systematic review and meta-analysis.

OBJECTIVE: This study compares the safety and efficacy of general anesthesia (GA) and nongeneral anesthesia (non-GA) on functional outcomes in patients receiving endovascular therapy for ischemic stroke. METHODS: All available studies on the anesthetic management of patients with acute ischemic stroke in PubMed, the Cochrane Central Register of Controlled Trials, and Embase were included. We also compared the clinical outcomes in the studies with subgroup analyses of the occlusion site (anterior vs. posterior circulation) and preretriever group versus retriever group. Functional independence, mortality, successful recanalization, hemodynamic instability, intracerebral hemorrhage, and respiratory complications were considered primary or secondary outcomes. RESULTS: A total of 24,606 patients in 60 studies were included. GA had a lower risk of 90-day functional independence (OR = 0.67, 95% CI 0.58 to 0.77), higher risk of 90-day mortality (OR = 1.29; 95% CI 1.15 to 1.45), and successful reperfusion (OR = 1.18; 95% CI 1.94 to 6.82). However, there were no differences in functional independence and mortality between GA and non-GA at 90 days after the procedure. CONCLUSION: The study shows poorer results in the GA group, which may be due to the inclusion of nonrandomized studies. However, analysis of the RCTs suggested that the outcomes do not differ between the two groups (GA vs. non-GA). Thus, general anesthesia is as safe as nongeneral anesthesia under standardized management.

Advances in efficacy prediction and monitoring of neoadjuvant immunotherapy for non-small cell lung cancer.

The use of immune checkpoint inhibitors (ICIs) has become mainstream in the treatment of non-small cell lung cancer (NSCLC). The idea of harnessing the immune system to fight cancer is fast developing. Neoadjuvant treatment in NSCLC is undergoing unprecedented change. Chemo-immunotherapy combinations not only seem to achieve population-wide treating coverage irrespective of PD-L1 expression but also enable achieving a pathological complete response (pCR). Despite these recent advancements in neoadjuvant chemo-immunotherapy, not all patients respond favorably to treatment with ICIs plus chemo and may even suffer from severe immune-related adverse effects (irAEs). Similar to selection for target therapy, identifying patients most likely to benefit from chemo-immunotherapy may be valuable. Recently, several prognostic and predictive factors associated with the efficacy of neoadjuvant immunotherapy in NSCLC, such as tumor-intrinsic biomarkers, tumor microenvironment biomarkers, liquid biopsies, microbiota, metabolic profiles, and clinical characteristics, have been described. However, a specific and sensitive biomarker remains to be identified. Recently, the construction of prediction models for ICI therapy using novel tools, such as multi-omics factors, proteomic tests, host immune classifiers, and machine learning algorithms, has gained attention. In this review, we provide a comprehensive overview of the different positive prognostic and predictive factors in treating preoperative patients with ICIs, highlight the recent advances made in the efficacy prediction of neoadjuvant immunotherapy, and provide an outlook for joint predictors.

Early stellate ganglion block for improvement of postoperative cerebral blood flow velocity after aneurysmal subarachnoid hemorrhage: results of a pilot randomized controlled trial.

OBJECTIVE: Stellate ganglion block (SGB) is a commonly used sympathetic nerve block technique that may have benefits for patients with aneurysmal subarachnoid hemorrhage (aSAH) in the early stage. Cerebral vasospasm (CVS), one of the most common complications of aSAH, is accompanied by an abnormal increase in cerebral blood flow velocity (CBFV) and neurological dysfunction. In this pilot study the authors sought to determine the feasibility of early SGB for CVS in aSAH patients by observing the incidence of symptomatic CVS. METHODS: Prior to receiving surgical treatment, patients with aSAH were randomly assigned to the SGB group or the non-SGB group. The primary outcome was the incidence of symptomatic CVS within 14 ± 2 days after the onset of aSAH. As a higher CBFV is often associated with CVS and a poor prognosis, the mean CBFV of the middle cerebral artery was observed immediately after surgery and on postoperative days 1, 2, 3, 5, and 7. Other secondary outcomes included transcranial Doppler (TCD)/CTA-type CVS, delayed cerebral ischemia during hospitalization, new cerebral infarction within 3 months, adverse events (AEs), and clinical prognosis. RESULTS: Symptomatic CVS occurred in 40% of patients in the non-SGB group and in 20% in the SGB group (RR 0.50, 95% CI 0.22-1.16). Continuous TCD sonography revealed that the postoperative mean CBFV was lower in the SGB group than in the non-SGB group (F = 3.608, p = 0.02). In addition, the percentages of patients with CVS evaluated by TCD (TCD-CVS) and total new infarctions within 3 months were also significantly lower than those in patients with CVS (TCD-CVS 36.7% vs 70%, RR 0.52, 95% CI 0.31-0.89, and total new infarctions 26.7% vs 53.3%, RR 0.50, 95% CI 0.25-0.99). In terms of AEs and mortality, there were no significant differences between the two groups. CONCLUSIONS: This pilot study demonstrated for the first time, to the authors' knowledge, that early SGB is feasible and has the potential to reduce the risk of CVS and improve the prognosis of aSAH. This method may be a new treatment for patients with aSAH that may have more advantages than traditional therapeutic drugs and is worth further study. Clinical trial registration no.: NCT04691271 (ClinicalTrials.gov).

Esketamine combined with pregabalin on acute postoperative pain in patients undergoing resection of spinal neoplasms: study protocol for a randomized controlled trial.

BACKGROUND: Perioperative pain management is one of the most challenging issues for patients with spinal neoplasms. Inadequate postoperative analgesia usually leads to severe postsurgical pain, which could cause patients to suffer from many other related complications. Meanwhile, there is no appropriate analgesic strategy for patients with spinal neoplasms. METHODS/DESIGN: This is a protocol for a randomized double-blind controlled trial to evaluate the effect of esketamine combined with pregabalin on postsurgical pain in spinal surgery. Patients aged 18 to 65 years scheduled for spinal neoplasm resection will be randomly allocated into the combined and control groups in a 1:1 ratio. In the combined group, esketamine will be given during the during the surgery procedure until 48-h postoperative period, and pregabalin will be taken from 2 h before the surgery to 2 weeks postoperatively. The control group will receive normal saline and placebo capsules at the same time points. Both groups received a background analgesic regimen by using patient-controlled intravenous analgesia (containing 100 µg sufentanil and 16 mg ondansetron) until 2 days after surgery. To ensure the accuracy and reliability of this trial, all the researchers and patients will be blinded until the completion of this study. The primary outcome will be the proportion of patients with acute moderate-to-severe postsurgical pain (visual analog scale, VAS ≥ 40, range: 0-100, with 0, no pain; 100, the worst pain) during the 48-h postoperative period. The secondary outcomes will include the maximal VAS scores (when the patients felt the most intense pain over the last 24 h before being interviewed) at 0-2 h, 2-24 h, 24-48 h, and 48-72 h after leaving the operating room and 24 h before discharge; the incidence of acute moderate-to-severe postsurgical pain at each other time point; chronic postsurgical pain assessment; neuropathic pain assessment; and the incidence of drug-related adverse events and other postoperative complications, such as postoperative delirium and postoperative nausea and vomiting (PONV). DISCUSSION: The aim of this study was to evaluate the effect of esketamine combined with pregabalin on acute postsurgical pain in patients undergoing resection of spinal neoplasms. The safety of this perioperative pain management strategy will also be examined. TRIAL REGISTRATION: ClinicalTrials.gov NCT05096468. Registered on October 27, 2021.

General Anesthesia Versus Nongeneral Anesthesia for Patients With Acute Posterior Circulation Stroke Undergoing Endovascular Therapy: A Systematic Review and Meta-analysis.

There is continued controversy regarding the optimal anesthetic technique for endovascular therapy in patients with acute posterior circulation ischemic stroke. To compare the clinical outcomes general anesthesia (GA) and non-GA, we performed a systematic review and meta-analysis of randomized controlled trials and observational studies focused on the anesthetic management for endovascular therapy in patients with acute posterior circulation stroke, without language restriction. In addition, we compared clinical outcomes among the studies with different non-GA types (conscious sedation or local anesthesia). Outcome variables were functional independence, excellent outcomes, favorable outcomes, mortality, successful recanalization, hemodynamic instability, intracerebral hemorrhage, and respiratory or vascular complications. Eight studies including 1777 patients were identified. Although GA was associated with a lower odds of functional independence at 90 days (odds ratio [OR]: 0.55; 95% confidence interval [CI] 0.38 to 0.81; P =0.009), substantial heterogeneity was noted ( I2 =65%). Subgroup analysis showed that GA was associated with higher odds of mortality than conscious sedation (OR: 1.83; 95% CI, 1.30 to 2.57; I2 =0%), but there was no difference between GA and local anesthesia ( I2 =0%). Interestingly, subgroup analysis did not identify a relationship between functional independence and GA compared with local anesthesia (OR: 0.90; 95% CI, 0.64 to 1.25; P =0.919; I2 =0%). This meta-analysis demonstrates that GA is associated with worse outcomes in patients with acute posterior circulation stroke undergoing endovascular therapy based on current studies.

Effect of early stellate ganglion block in cerebral vasospasm after aneurysmal subarachnoid hemorrhage (BLOCK-CVS): study protocol for a randomized controlled trial.

INTRODUCTION: Stellate ganglion block has been reported to expand cerebral vessels and alleviate vasospasm after aneurysmal subarachnoid hemorrhage. However, the causal relationship between early stellate ganglion block and cerebral vasospasm prevention has not yet been established. The purpose of this study was to explore the effectiveness and safety of early stellate ganglion block as a preventive treatment for cerebral vasospasm and delayed cerebral ischemia. METHODS/DESIGN: This is a single-center, prospective, randomized, controlled, blinded endpoint assessment superiority trial. A total of 228 patients will be randomized within 48 h of aneurysmal subarachnoid hemorrhage onset in a 1:1 ratio into two groups, one group receiving an additional e-SGB and the other group receiving only a camouflaging action before anesthesia induction in the operating room. The primary outcome is the incidence of symptomatic vasospasm within 14 days after aSAH. Further safety and efficacy parameters include the incidence of radiographic vasospasm, new cerebral infarction, postoperative delirium, and complications up to 90 days after surgery; postoperative cerebral hemodynamics; Mini-Mental State Examination score; modified Rankin scale score; and all-cause mortality up to 90 days after surgery. DISCUSSION: This is a randomized controlled trial to explore the effectiveness and safety of early stellate ganglion block as a preventive treatment to reduce cerebral vasospasm in patients with aneurysmal subarachnoid hemorrhage. If the results are positive, it may provide a new direction for the prevention and treatment of cerebral vasospasm and delayed cerebral ischemia. TRIAL REGISTRATION: The study was registered on Clincaltrials.gov on December 13, 2020 (NCT04691271).

MiR-210-3p targets CELF2 to facilitate progression of lung squamous carcinoma through PI3K/AKT pathway.

This study examined the internal mechanism of miR-210-3p/CELF2 in LUSC. Expression data of mRNAs and miRNAs in LUSC were acquired from TCGA and subjected to differential expression analysis. qRT-PCR was applied to examine miR-210-3p and CELF2 expression. Besides, western blot was utilized to evaluate protein expression of CELF2 and PI3K/AKT pathway-related proteins. Dual-luciferase reporter analysis was conducted to validate targeting relationship between miR-210-3p and CELF2. Additionally, CCK-8, colony formation, transwell and flow cytometry were employed to respectively test proliferation, migration, invasion abilities and cell cycle distribution. Xenograft tumor models were used to evaluate the influence of miR-210-3p and CELF2 on tumor growth. MiR-210-3p was highly expressed, while CELF2 was less expressed in LUSC cells. Besides, miR-210-3p could downregulate CELF2 expression. Cell functional assay verified that miR-210-3p accelerated aggressive behaviors of LUSC cells. Additionally, rescue assay suggested that miR-210-3p downregulated CELF2 level to stimulate LUSC cell phenotypes and cell cycle progression through PI3K/AKT pathway. Moreover, miR-210-3p/CELF2 stimulated the tumor growth in vivo. To sum up, miR-210-3p modulated CELF2 expression, thus affecting cell phenotypes and cell cycle distribution in LUSC through PI3K/AKT pathway.

Primary pulmonary extranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissue type: a case report and literature review.

Primary pulmonary mucosa-associated lymphoid tissue (MALT)-derived lymphoma is a low-grade B-cell non-Hodgkin's lymphoma. It is rare with unclear clinical and imaging findings, requiring biopsy or surgery for diagnosis. Here, we provide a new case to learn the symptoms, diagnosis and treatment of primary pulmonary MALT lymphoma. The patient was a 51-year-old male. During the annual physical examination in 2019, a shadow in the lower lobe of the right lung was accidentally found in his chest computed tomography image. In 2020, the size and density of the shadows increased, which was suspected to be lung adenocarcinoma. The patient underwent video-assisted thoracoscopic surgery and segmental resection. Pathological examination showed residual germinal centers around the tumor cells, and many inflammatory cells had diffusely infiltrated, mainly monocyte-like B cells. Immunohistochemical analysis showed that CD3, CD20, Bcl-2, CD43, CK-pan and CD23 were positive, while BCL-6, CD5, CD10, c-myc and cyclin D1 were negative. The patient was diagnosed with MALT extranodal marginal zone B-cell lymphoma. The patient did not receive chemotherapy or radiotherapy after the operation but was still under close observation. Primary pulmonary MALT develops slowly and tends to be inert and spontaneous. Due to the lack of specific clinical symptoms and imaging findings, it can easily be misdiagnosed as tuberculosis, lung cancer, or infection. Thoracoscopic resection may be a good choice for the diagnosis and treatment.

Factors impacting cumulative dissipated energy levels and postoperative visual acuity outcome in cataract surgery.

PURPOSE: To determine factors impacting cumulative dissipated energy (CDE) and postoperative best-corrected visual acuity (BCVA) in phacoemulsification. DESIGN: Review of 1102 cases at University of California, San Francisco (UCSF) and at Zhongshan Ophthalmic Center (ZOC), China. SUBJECTS: Patients who underwent cataract surgery at UCSF 03/2014-03/2019 and at ZOC 10/2018-05/2019. METHODS: Patient demographics, medical history, routine ocular examination, and surgical information, including disassembly method, complications, and surgeon training level were recorded. Univariable and multivariable regression models were used to determine factors associated with CDE and good postoperative BCVA (20/40 or better) at 1 month. OUTCOME MEASURES: CDE, postoperative BCVA. RESULTS: In multivariable analysis, patient age at time of surgery, diabetes, degree of nuclear sclerosis (NS), white-to-white corneal diameter, disassembly method, preoperative BCVA, surgeon training level, and surgical center were significantly associated with CDE. Log10CDE increased by 0.20-0.31 for patient age ≥ 70 years, by 0.07 if the patient had diabetes, by 0.12-0.41 for NS grade ≥ 2, by 0.48 per 10 mm increase in white-to-white corneal diameter, by 0.34-0.47 for disassembly method other than non-stop chop, by 0.16 per unit increase in preoperative logMAR BCVA, and by > 0.09 when phacoemulsification was performed by residents early in their training. Log10CDE was 0.33 higher at UCSF than ZOC. In multivariable analysis, worse baseline visual acuity and age above 90 years at time of surgery decreased the odds of good BCVA (OR = 0.26 per unit increase in preoperative logMAR BCVA; OR = 0.12 for age > 90); comorbid retinal issues decreased the odds of good postoperative BCVA (OR = 0.13-0.39); greater anterior chamber depth (ACD) or shorter axial length (AL), increased the odds of good postoperative outcome (OR = 2.64 per 1 mm increase ACD, OR = 0.84 per 1 mm increase AL). CONCLUSIONS: Cataract grade determined by slit lamp exam and, for the first time, older patient age, were noted to be important predictors of high CDE. CDE was not a risk factor for postoperative BCVA measured at postoperative 1 month. When surgery was performed by trainees under supervision, lower training level was associated with higher CDE, but not with worse postoperative BCVA.

Role of exercise and rapamycin on the expression of energy metabolism genes in liver tissues of rats fed a high­fat diet.

The mTOR pathway serves an important role in the development of insulin resistance induced by obesity. Exercise improves obesity­associated insulin resistance and hepatic energy metabolism; however, the precise mechanism of this process remains unknown. Therefore, the present study investigated the role of rapamycin, an inhibitor of mTOR, on exercise­induced expression of hepatic energy metabolism genes in rats fed a high­fat diet (HFD). A total of 30 male rats were divided into the following groups: Normal group (n=6) fed chow diets and HFD group (n=24) fed an HFD for 6 weeks. The HFD rats performed exercise adaptation for 1 week and were randomly divided into the four following groups (each containing six rats): i) Group of HFD rats with sedentary (H group); ii) group of HFD rats with exercise (HE group); iii) group of HFD rats with rapamycin (HR group); and iv) group of HFD rats with exercise and rapamycin (HER group). Both HE and HER rats were placed on incremental treadmill training for 4 weeks (from week 8­11). Both HR and HER rats were injected with rapamycin intraperitoneally at the dose of 2 mg/kg once a day for 2 weeks (from week 10­11). All rats were sacrificed following a 12­16 h fasting period at the end of week 11. The levels of mitochondrial and oxidative enzyme activities, as well as of the expression of genes involved in energy metabolism were assessed in liver tissues. Biochemical assays and oil red staining were used to assess the content of hepatic triglycerides (TGs). The results indicated that exercise, but not rapamycin, reduced TG content in the liver of HFD rats. Further analysis indicated that rapamycin reduced the activity of cytochrome c oxidase, but not the activities of succinate dehydrogenase and ß­hydroxyacyl­CoA dehydrogenase in the liver of HFD rats. Exercise significantly upregulated the mRNA expression of peroxisome proliferator­activated receptor γ coactivator 1 ß, while rapamycin exhibited no effect on the mRNA expression levels of hepatic transcription factors associated with energy metabolism enzymes in the liver of HFD rats. Collectively, the results indicated that exercise reduced TG content and upregulated mitochondrial metabolic gene expression in the liver of HFD rats. Moreover, this mechanism may not involve the mTOR pathway.

Clinical analysis of minimally invasive McKeown esophagectomy in a single center by a single medical group.

OBJECTIVE: McKeown esophagectomy followed by cervical and abdominal procedures has been commonly used for invasive esophageal carcinoma. This minimally-invasive operative procedure in the lateral prone position has been considered to be the most appropriate method. We describe our experiences in minimally invasive McKeown esophagectomy (MIME) for esophageal cancer. METHODS: Between March 2016 and February 2018, a total of 82 patients underwent MIME by a single group in our department (a single center). All procedure, operation, oncology, and complication data were reviewed. RESULTS: All MIME procedures were completed successfully, with no conversions to open surgery. The median operative time was 260 min, and median blood loss was 100 ml. The average number of total harvested lymph nodes was 20.1 in the chest and 13.5 in the abdomen. There were no deaths within 30 postoperative days. Twenty cases (24.4%) developed postoperative complications, including anastomotic leak in 4 (4.9%), single lateral recurrent nerve palsy in 4 (4.9%), bilateral recurrent nerve palsy in 1 (1.2%), pulmonary problems in 3 (3.7%), chyle leak in 1 (1.2%), and other complications in 7 (including pleural effusions in 4, incomplete ileus in 2, and neck incision infection in 1; 8.54%). Average postoperative hospitalization time was 12 d. Blood loss, operation time, morbidity rate, and the number of harvested lymph nodes were analyzed by evaluating learning curves in different periods. Significant differences were found in operative time (P=0.006), postoperative hospitalization days (P=0.015), total harvested lymph nodes (P=0.003), harvested thoracic lymph nodes (P=0.006), and harvested abdominal lymph nodes (P=0.022) among different periods. CONCLUSIONS: Surgical outcomes following MIME for esophageal cancer are safe and acceptable. The MIME procedure for stages I and II could be performed proficiently and reached an experience plateau after approximately 25 cases.

[Endoscopic trans-fistula drainage for gastroesophageal anastomotic fistula with para-fistula abscess after esophagectomy].

Objective: To evaluate the efficiency and safety of endoscopic trans-fistula drainage (ETFD) for gastroesophageal anastomotic fistula with para-fistula abscess after esophagectomy. Methods: Among 456 esophageal cancer patients receiving esophagectomy between February 2012 and February 2017 in Sir Run Run Shaw Hospital, 15 cases were diagnosed as gastroesophageal anastomotic fistula with para-fistula abscess after surgery. Seven cases received ETFD treatment (ETFD group), and 8 cases received conventional treatment (control group). Recovery of inflammatory markers and fistula, length of hospital stay after esophagectomy and total medical expenses were compared between ETFD group and control group. Results: All patients recovered in ETFD group. Time of white cell count returning to normal and decline of C-reactive protein, time of fistula healing and length of hospital stay after esophagectomy in ETFD group were significantly shorter than those of control group (all P<0.05). And medical expenses in ETFD group was also lower (P<0.05). Conclusion: ETFD is effective and safe for gastroesophageal anastomotic fistula with para-fistula abscess after esophagectomy.

Broadband near-infrared spectroscopy can detect cyanide-induced cytochrome aa3 inhibition in rats: a proof of concept study.

PURPOSE: Clinically available near-infrared spectroscopy (NIRS) devices use two to five wavelengths of light to measure the relative amounts of oxyhemoglobin and deoxyhemoglobin in tissue to determine tissue hemoglobin oxygen saturation (StO2). In addition to StO2, broadband NIRS devices (using hundreds of wavelengths of light) may be able to measure the oxidation state of mitochondrial cytochrome aa3 (Cytox) which reflects the subcellular energetic state. We hypothesize that broadband NIRS devices can measure Cytox independent of changes in hemoglobin saturation. METHODS: In this prospective non-randomized study, 20 male Sprague-Dawley rats (300 g) were anesthetized with isoflurane, tracheally intubated, and ventilated with 100% O2 containing 2% isoflurane. They were subsequently instrumented with a broadband NIRS device that used a halogen light source coupled to an emitting fibreoptic cable. Three receiving fibreoptic cables were utilized; one analyzed the light source and the other two were directed at the base of the skull. Each receiving fibre was connected to a spectrometer to measure light intensity. Sodium cyanide (NaCN) 5 mg·kg-1 iv was injected in order to produce cytochrome aa3 reduction. Two to three minutes after injection, oxygen was eliminated and 100% nitrogen (i.e., anoxia) was used for ventilation in order to induce a reduction in both cytochrome aa3 and hemoglobin desaturation. Changes in the cytochrome oxidation state and hemoglobin oxygenation were calculated using a broadband algorithm and compared before and after both the NaCN and anoxia interventions. RESULTS: The NaCN injection resulted in a decrease in median [interquartile range (IQR)] deoxyhemoglobin (-0.014 [-0.29 to -0.005] arbitrary units [AU]; P < 0.001), an increase in oxyhemoglobin (0.013 [-0.011 to 0.031] AU; P < 0.001), and a reduction in cytochrome aa3 (-0.015 [-0.020 to -0.011] AU; P < 0.001). Anoxia resulted in an increase in median [IQR] deoxyhemoglobin (0.13 [0.11 to 0.18] AU; P < 0.001), a decrease in oxyhemoglobin (-0.17 [-0.22 to -0.15] AU; P < 0.001), and a reduction in cytochrome aa3 (-0.04 [-0.06 to -0.03] AU; P < 0.001). CONCLUSION: Broadband NIRS can effectively measure the directionality of changes in both Cytox and StO2 by uncoupling the cytochrome and hemoglobin signals through inhibition of the electron transport chain and anoxia.

Dexmedetomidine-induced neuroprotection: is it translational?

Dexmedetomidine is often used in anesthesia and critical care medicine practice to sedate patients. Its neuroprotective effects have been shown in various ischemic and hemorrhagic brain injury models of animals. Randomized clinical trials have indicated that dexmedetomidine can improve outcome of patients under intensive care. Clinical trials are needed to determine whether dexmedetomidine can provide neuroprotection against ischemic and hemorrhagic stroke.

Catalog of insect type specimens preserved at the Kunming Institute of Zoology, Chinese Academy of Science with corrections of some specimens.

This article presents a list of insect types preserved in Kunming Natural History Museum of Zoology (KNHMZ). As of March, 2015, 3 412 type specimens belonging to 266 species/subspecies of 37 families in 9 orders (Odonata, Isoptera, Mantodea, Orthoptera, Hemiptera, Coleoptera, Diptera, Hymenoptera and Lepidoptera) are included. Information corrections of some specimens are provided in this article.

Transfusion of Old RBCs Induces Neuroinflammation and Cognitive Impairment.

OBJECTIVES: Transfusing RBCs stored for longer than 14 days (old RBC) in humans is common. This transfusion can injure organs, such as lungs and kidneys. We determined whether transfusion with old RBC injured brain. DESIGN: Prospective, controlled animal study. SETTING: University research laboratory. SUBJECTS: Adult male Sprague-Dawley rats. INTERVENTIONS: Six-month-old Sprague-Dawley rats lost 20% total blood volume and then received RBC prepared from equal volume of the lost blood. RBC was stored for 1 day (fresh RBC) or 7 days (old RBC, storage lesions similar to those of human RBC stored for 28 d). Some rats received IV cell-free hemoglobin. These rats were not subjected to hemorrhage and RBC transfusion. MEASUREMENTS AND MAIN RESULTS: Rats were subjected to Barnes maze and fear conditioning tests from 1 week after blood transfusion. Rats transfused with old RBC but not fresh RBC took a longer time to identify the target hole in the Barnes maze and had less context-related fear conditioning behavior than control rats. Old RBC significantly increased interleukin 6 and ionized calcium-binding adapter molecule 1 in the hippocampus at 24 hours after the transfusion. These effects were attenuated by sulforaphane and minocycline, an antibiotic with anti-inflammatory property. Old RBC solution had a higher concentration of cell-free hemoglobin. Sulforaphane increased haptoglobin, a chelator of cell-free hemoglobin. Rats that received cell-free hemoglobin had a pattern of neuroinflammation and impairment of learning and memory similar to that of rats that received old RBC. CONCLUSIONS: These results provide initial evidence to suggest that transfusion of old RBC induces neuroinflammation and impairment of learning and memory. These effects may be mediated by cell-free hemoglobin.

Propofol ameliorates calpain-induced collapsin response mediator protein-2 proteolysis in traumatic brain injury in rats.

BACKGROUND: Collapsin response mediator protein-2 (CRMP2), a multifunctional cytosolic protein highly expressed in the brain, is degraded by calpain following traumatic brain injury (TBI), possibly inhibiting posttraumatic neurite regeneration. Lipid peroxidation (LP) is involved in triggering postinjury CRMP2 proteolysis. We examined the hypothesis that propofol could attenuate LP, calpain-induced CRMP2 degradation, and brain injury after TBI. METHODS: A unilateral moderate controlled cortical impact injury was induced in adult male Sprague-Dawley rats. The animals were randomly divided into seven groups: Sham control group, TBI group, TBI + propofol groups (including propofol 1 h, 2 h, and 4 h groups), TBI + U83836E group and TBI + fat emulsion group. The LP inhibitor U83836E was used as a control to identify that antioxidation partially accounts for the potential neuroprotective effects of propofol. The solvent of propofol, fat emulsion, was used as the vehicle control. Ipsilateral cortex tissues were harvested at 24 h post-TBI. Immunofluorescent staining, Western blot analysis, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling were used to evaluate LP, calpain activity, CRMP2 proteolysis and programmed cell death. The data were statistically analyzed using one-way analysis of variance and a paired t-test. RESULTS: Propofol and U83836E significantly ameliorated the CRMP2 proteolysis. In addition, both propofol and U83836E significantly decreased the ratio of 145-kDa αII-spectrin breakdown products to intact 270-kDa spectrin, the 4-hydroxynonenal expression and programmed cell death in the pericontusional cortex at 24 h after TBI. There was no difference between the TBI group and the fat emulsion group. CONCLUSIONS: These results demonstrate that propofol postconditioning alleviates calpain-mediated CRMP2 proteolysis and provides neuroprotective effects following moderate TBI potentially by counteracting LP and reducing calpain activation.