Identification of histone deacetylase inhibitors as neutrophil recruitment modulators in zebrafish using a chemical library screen.

Tissue injury-induced neutrophil recruitment is a prerequisite for the initiation and amplification of inflammatory responses. Although multiple proteases and enzymes involved in post-translational modification (PTM) of proteins regulate leukocyte recruitment, an unbiased functional screen of enzymes regulating inflammatory leukocyte recruitment has yet to be undertaken. Here, using a zebrafish tail fin amputation (TFA) model to screen a chemical library consisting of 295 compounds that target proteases and PTM enzymes, we identified multiple histone deacetylase (HDAC) inhibitors that modulate inflammatory neutrophil recruitment. AR-42, a pan-HDAC inhibitor, was shown to inhibit neutrophil recruitment in three different zebrafish sterile tissue injury models: a TFA model, a copper-induced neuromast damage and mechanical otic vesicle injury (MOVI) model, and a sterile murine peritonitis model. RNA sequencing analysis of AR-42-treated fish embryos revealed downregulation of neutrophil-associated cytokines/chemokines, and exogenous supplementation with recombinant human IL-1ß and CXCL8 partially restored the defective neutrophil recruitment in AR-42-treated MOVI model fish embryos. We thus demonstrate that AR-42 non-cell-autonomously modulates neutrophil recruitment by suppressing transcriptional expression of cytokines/chemokines, thereby identifying AR-42 as a promising anti-inflammatory drug for treating sterile tissue injury-associated diseases.

Diagnostic Value of Circular RNA hsa_circ_0002874 Expression in Peripheral Blood of Patients with Gastric Cancer.

The purpose of this study was to determine whether circular RNA hsa_circ_0002874 could serve as a novel biomarker for the diagnosis of gastric cancer (GC). The expression level of hsa_circ_0002874 mean (interquartile range [IQR]) in the plasma of patients with GC, patients with benign gastric lesions, and healthy individuals was 3.482 (IQR, 1.524-9.048), 1.261 (IQR, 0.817-2.000), and 1.00 (IQR, 0.726-1.382), respectively, whereas there was no significant difference between the latter 2 groups. The plasma expression level of hsa_circ_0002874 was significantly correlated with tumor stage (U = 234.0; P < .001) and lymph node metastasis (U = 240.0; P < .001). The receiver operating characteristic (ROC) curve showed that the sensitivity of the combined determination of hsa_circ_0002874 and the serum markers CEA and CA19-9 was 95.8% in patients with GC compared with that of the healthy group and 93.0% compared with that of patients with benign gastric tumor lesions. The specificity of hsa_circ_0002874 in differentiating GC from benign lesions was 98.3%. The results showed that plasma hsa_circ_0002874 may prove to be a useful biomarker for auxiliary diagnosis, the grading of malignant neoplasms, and the prognostic prediction of GC.

Closed-circuit anesthesia prolongs the neuromuscular blockade of rocuronium.

BACKGROUND: Volatile anesthetics are known to potentiate the neuromuscular blocking effect of nondepolarizing muscle relaxants. The influences of anesthetic techniques, closed-circuit anesthesia (CCA) and high flow semi-closed anesthesia (SCA), on the neuromuscular blockade of rocuronium has not yet been studied in detail. This study was purposed to compare the effects of isoflurane conveyed in minimal flow (CCA) and in high flow (SCA) on the neuromuscular blockade of rocuronium. METHODS: Fifty females scheduled for elective laparoscopic gynecological surgery were enrolled for study and randomly assigned to receive either CCA (n = 25) or SCA (n = 25). Anesthesia was induced with fentanyl 2 micrograms/kg, thiopental 5 mg/kg and rocuronium 0.6 mg/kg. Two percent isoflurane in high O2 flow (3 l/min) was given for 10 min to all patients initially to wash isoflurane in the functional residual capacity of both lungs and the breathing circuit. After the wash in, for CCA group, the O2 flow was reduced to 300 ml/min with isoflurane vaporizer setting adjusted to 3-5% for anesthesia maintenance, while for SCA group, anesthesia was maintained with 1.5-2% isoflurane in 3 l/min O2 flow throughout the surgery. Electromyogram was used to determine neuromuscular blockade. Rocuronium (0.15 mg/kg) was given to maintain muscle relaxation when T1 reached 25% of control. We maintained the anesthetic depth until the recordings of T1 twitch response which reached 75% was completed. Onset time, duration, recovery index and intubating conditions were recorded. The hemodynamic parameters and the inhaled/exhaled concentrations were also measured every 15 min after skin incision in both groups. RESULTS: The onset time and intubating conditions were similar in both groups. In comparison with SCA group, longer clinical durations (54.1 +/- 14.4 vs. 45.4 +/- 9.2 min, P < 0.05), longer durations of maintained dose (41.1 +/- 11.1 vs. 30.2 +/- 8.6 min, P < 0.01) and longer recovery index (34.2 +/- 10.7 vs. 20.9 +/- 5.4 min, P < 0.0001) were observed in CCA group. CONCLUSIONS: We conclude that CCA may further prolong the neuromuscular blocking effect of rocuronium than SCA.

Intracranial subdural hematoma after unintended durotomy during spine surgery.

PURPOSE: To report a case of intracranial subdural hematoma occurring after a spinal dural tear that was made unintentionally during the course of a posterior laminectomy and spinal fusion at the L(5)-S(1) level. The possible physiopathological mechanisms are discussed. CLINICAL FEATURES: On the fourth postoperative day, a 59-yr-old woman displayed persistent headache following unintended durotomy during spine implant revision. Perioperative blood loss was 2840 mL and intravascular replacement was about 3000 mL. She was hydrated with iv fluids and treated with non-steroidal anti-inflammatory drugs. The symptoms improved but persisted. With the aggravation of the headache complicated with unconsciousness and the appearance of focal neurological signs on the eighth day, a computed tomography was obtained and revealed a right subdural hematoma. Following surgical drainage, the patient made an uneventful recovery. CONCLUSION: This case reminds us that subdural hematoma formation can complicate durotomy during spine surgery. Neurological deterioration in the postoperative period should prompt clinicians to rule out the diagnosis and intervene rapidly as appropriate.