LncRNA-Fendrr protects against the ubiquitination and degradation of NLRC4 protein through HERC2 to regulate the pyroptosis of microglia.

OBJECTIVES: Targeted inhibition of inflammatory response can reduce diabetic cerebral ischemia-reperfusion (I/R) injure. Pyroptosis is characterized by caspase-1 dependence and the release of a large number of pro-inflammatory factors. LncRNA-Fendrr is associated with a variety of diseases, but Fendrr has not been studied in diabetic cerebral I/R. NLR-family CARD-containing protein 4 (NLRC4) regulate the pyroptosis of microglia cells. This study was designed to investigate whether Fendrr is involved in the effects of diabetic cerebral I/R injury. METHODS: The diabetic brain I/R model in mice was constructed. Mouse microglia cell line BV-2 cells were exposed to high glucose followed by hypoxia/reoxygenation (H/R). Fendrr and some pyroptosis-associated proteins were detected by qRT-PCR, western blot or ELISA. HE staining was used to detect pathological changes. Microglia pyroptosis was detected by TUNEL staining. RNA pull-down and RNA Immunoprecipitation were used to detect binding of Fendrr to HERC2 (E3 ubiquitin ligase), and CO-IP detected binding of HERC2 to NLRC4. The ubiquitination of NLRC4 was detected by ubiquitination experiments. RESULTS: Fendrr was significantly increased in the diabetic cerebral I/R model, and NLRC4 inflammatory complex and pyroptosis mediated inflammatory factors were increased. NLRC4 and inflammatory cytokines associated with pyroptosis were decreased in the high glucose-treated hypoxia/reoxygenation (H/R)-induced microglia after Fendrr knockdown. Fendrr bound to HERC2 protein, and HERC2 bound to NLRC4. Meanwhile, Fendrr could inhibit the ubiquitination of NLRC4, HERC2 promoted the ubiquitination of NLRC4 protein. Moreover, the effect of Fendrr overexpression in the diabetic cerebral I/R model of microglia can be reversed by HERC2 overexpression. CONCLUSION: Fendrr can protect against the ubiquitination and degradation of NLRC4 protein through E3 ubiquitin ligase HERC2, thereby accelerating the pyroptosis of microglia.

Relationship between genetic variation in the α2A-adrenergic receptor and the cardiovascular effects of dexmedetomidine in the Chinese Han population.

There are differences in individual cardiovascular responses to the administration of dexmedetomidine, a highly selective α2A-adrenergic receptor (ADRA2A) agonist. The aim of this study was to investigate ADRA2A gene polymorphisms in the Chinese Han population and their association with the cardiovascular response to intravenous dexmedetomidine infusion. Sixty elective surgery patients of Chinese Han nationality were administered 1 µg/kg dexmedetomidine intravenously over 10 min as a premedication. ADRA2A C-1291G and A1780G polymorphism status was determined in these patients, and their relationships to changes in blood pressure and heart rate after dexmedetomidine administration were analyzed. There were neither significant differences in systolic or diastolic blood pressure changes in individuals with different A1780G and C-1291G genotypes after dexmedetomidine administration, nor in heart rates among the different A1780G genotypes. However, there were significant differences in changes in heart rates in patients with different C-1291G genotypes. There were no significant differences in the sedative effects of dexmedetomidine among different A1780G and C-1291G genotypes. Logistic regression revealed that the C-1291G polymorphism was associated with differential decreases in heart rate after intravenous infusion of dexmedetomidine. These findings indicate that the ADRA2A C-1291G polymorphism can affect heart rate changes in patients after intravenous infusion of dexmedetomidine.

In vivo evaluation of bronchial injury of irreversible electroporation in a porcine lung ablation model by using laboratory, pathological, and CT findings.

Irreversible electroporation (IRE) creates permanent pores in the cell membrane, leading to irreversible cell death. In this study, the impact of IRE on bronchial injury was comprehensively examined in a timed series study. Altogether, 8 Bama miniature pigs were included in this study and were randomly assigned to experimental and control groups. The experimental group underwent IRE that was guided and monitored by spiral computed tomography (CT). The monopole probe of the IRE was positioned at the right pulmonary hilum. Specimens were collected at 0 h, 2 h, 2 d, 7 d, and 14 d after the IRE procedure for a pathological examination. A small amount of needle-tract bleeding occurred in two animals, and mild pneumothorax occurred in another. IRE can elicit acute bronchial inflammation, bleeding, and mucosal injury, but severe complications were not found. Pathological examinations and transmission electron microscopy (TEM) showed dead vascular epithelium cells in the region of the ablation, while the bronchioli and the vascular extracellular matrix were preserved. At 2 hours post-IRE, there were marked increases in bronchoalveolar macrophages (P<0.001), but the inflammation could recover after 14 days and showed no statistical significance when compared with the control group at the same time. In conclusion, CT-guided IRE ablation can elicit acute but recoverable bronchial inflammation, bleeding, and mucosal injury in porcine lung tissues. However, longer follow-up is still required to establish an evaluation of the long-term safety.

Can Dexmedetomidine Improve Arterial Oxygenation and Intrapulmonary Shunt during One-lung Ventilation in Adults Undergoing Thoracic Surgery? A Meta-analysis of Randomized, Placebo-controlled Trials.

BACKGROUND: One-lung ventilation (OLV) is a common ventilation technology during thoracic surgery that can cause serious clinical problems. We aimed to conduct a meta-analysis to compare oxygenation and intrapulmonary shunt during OLV in adults undergoing thoracic surgery with dexmedetomidine (Dex) versus placebo to assess the influence and safety of using Dex. METHODS: Randomized controlled trials comparing lung protection in patients who underwent thoracic surgery with Dex or a placebo were retrieved from PubMed, EMBASE, MEDLINE, Cochrane Library, and China CNKI database. The following information was extracted from the paper: arterial oxygen partial pressure (PaO2), PaO2/inspired oxygen concentration (PaO2/FiO2, oxygenation index [OI]), intrapulmonary shunt (calculated as Qs/Qt), mean arterial pressure (MAP), heart rate (HR), tumor necrosis factor-α (TNF-α), interleukin (IL)-6, superoxide dismutase (SOD), and malondialdehyde (MDA). RESULTS: Fourteen randomized controlled trials were included containing a total of 625 patients. Compared with placebo group, Dex significantly increased PaO2/FiO2(standard mean difference [SMD] = 0.98, 95% confidence interval [CI] [0.72, 1.23], P < 0.00001). Besides, Qs/Qt (SMD= -1.22, 95% CI [-2.20, -0.23], P = 0.020), HR (SMD= -0.69, 95% CI [-1.20, 0.17], P = 0.009), MAP (SMD= -0.44, 95% CI [-0.84, 0.04], P = 0.030), the concentrations of TNF-α (SMD = -1.55, 95% CI [-2.16, -0.95], P <0.001), and IL-6 (SMD = -1.53, 95% CI [-2.37, -0.70], P = 0.0003) were decreased in the treated group, when compared to placebo group. No significant difference was found in MDA (SMD = -1.14, 95% CI [-3.48, 1.20], P = 0.340) and SOD (SMD = 0.41, 95% CI [-0.29, 1.10], P = 0.250) between the Dex group and the placebo group. Funnel plots did not detect any significant publication bias. CONCLUSIONS: Dex may improve OI and reduce intrapulmonary shunt during OLV in adults undergoing thoracic surgery. However, this conclusion might be weakened by the limited number of pooled studies and patients.

Metastatic squamous cell carcinoma of the gingiva appearing as a solitary branchial cyst carcinoma: diagnostic role of PET/CT.

We herein present a case of a left cervical cystic mass, for which the initial pathological diagnosis was branchial cleft cyst carcinoma (following complete mass excision). Thorough postoperative examinations, including with FDG positron emission tomography/computed tomography (PET/CT), revealed a primary tumor in the retromolar region of the left mandible. A 52-year-old female presented with a 2-month history of a painless, progressively enlarged left-sided neck mass. Fine-needle aspiration biopsy suggested a branchial cleft cyst. Physical examination revealed a 3 × 3-cm smooth, tender mass in the upper-left neck and anterior border of the sternocleidomastoid muscle. Examination using nasendoscopy and a strobolaryngoscope revealed no abnormalities of the nasal cavity, nasopharynx, oropharynx, hypopharynx or larynx. MRI of the neck revealed a solitary, round, cystic mass under the left parotid gland. The mass was excised completely. Pathologic results indicated a branchial cleft cyst carcinoma. According to the diagnostic criteria for a branchial cleft cystic carcinoma, PET/CT was performed to detect the occult primary site. PET/CT revealed high FDG uptake in the tooth root of the left mandible. Frozen sections of the mass were indicative of moderate, differentiated squamous cell carcinoma. The carcinoma in the retromolar region of the left mandible was locally excised under general anesthesia. A partial left maxillectomy, partial mandibulectomy, and left radical neck dissection were performed. The patient received postoperative concurrent chemoradiotherapy, and was disease-free at the 8-month follow-up. True branchial cleft cyst carcinoma is rare: once diagnosed, it should be distinguished from metastatic cystic cervical lymph and occult primary carcinoma. FDG PET/CT is useful in the identification of occult primary tumor.

[Anesthetic management of Stanford type A aortic dissection operation].

OBJECTIVE: To explore the anesthetic management experiences of patients with Stanford A aortic dissection undergoing surgical treatment through moderate or deep hypothermia circulatory arrest (DHCA). METHODS: From June 2008 to December 2011, a total of 77 patients undergoing surgical treatment of Stanford A aortic dissection was recruited. RESULTS: Cardiopulmonary bypass (CPB) was established under general anesthesia in all patients. The procedures included moderate hypothermia (n = 51) and DHCA (n = 26). The total surgical duration was 152 - 600 (292 ± 91) min, CPB time 38 - 310 (128 ± 43) min and aortic cross-clamp time 31 - 169 (87 ± 26) min. The time of circulatory arrest under deep hypothermia was 20 - 113 (41 ± 19) min in 26 patients. Among 77 patients, there were 5 intraoperative and 7 postoperative fatalities. The remained 65 patients were discharged postoperatively and received a regular outpatient follow-up. None of them died or required reoperation. CONCLUSION: Surgical treatment is appropriate and efficient for the patients with Stanford A aortic dissection. During surgery, the keys of preventing neurological complications are blood volume monitoring and blood protection.