Spermidine activates RIP1 deubiquitination to inhibit TNF-α-induced NF-κB/p65 signaling pathway in osteoarthritis.

Spermidine has been known to inhibit the production of pro-inflammatory cytokines. However, there are no reports about anti-inflammatory effects of spermidine on osteoarthritis (OA). Herein, we examined whether OA progression could be delayed by intraperitoneal injection (i.p.) of spermidine in the anterior cruciate ligament transection (ACLT) and TNF-α induced arthritis (TIA) mouse models. During the process, human FLS cells (H-FLS) were used to investigate the potential ubiquitination mechanism of spermidine-mediated RIP1 in TNF-α-induced NF-κB/p65 signaling. We found that spermidine attenuated synovitis, cartilage degeneration and osteophyte formation, resulting in substantially lower OARSI scores and TNF-α scores in spermidine-treated ACLT and TIA mice. In terms of the mechanism, 9 µM spermidine did not affect the viability, proliferation, cell cycle and apoptosis of H-FLS, and exerted inhibitory effects by activating CYLD-mediated RIP1 deubiquitination on TNF-α-induced NF-κB/p65 signaling in H-FLS. From these data, we can conclude that spermidine attenuates OA progression by the inhibition of TNF-α-induced NF-κB pathway via the deubiquitination of RIP1 in FLS. Therefore, intake of spermidine could be a potential therapy for preventing OA.

Endoscopic Endonasal Surgery Treatment Strategies for Invasive Pituitary Adenoma: Analysis of Four Approaches.

OBJECTIVE: To explore the surgical methods and clinical effect of endoscopic endonasal approaches for the treatment of invasive pituitary adenomas (IPAs). METHODS: A retrospective analysis was made of the clinical data of 74 patients (75 procedures) with IPAs treated by different endoscopic endonasal approaches at the Department of Neurosurgery, The First Affiliated Hospital of Shenzhen University from May 2014 to August 2017. The data include clinical manifestation, imaging features, surgical methods and complications, resection rate, cure rate, prognosis, and complications in different Knosp classifications and Hardy stages. The transcavernous approach was used in 47 patients, the lateral-cavernous approach was used in 14 patients, the tuberculum sella planum approach was used in 8 patients, and the diaphragma sellae open or dorsum sellae cut approach was used in 6 patients. RESULTS: The gross total resection (GTR) rate was 70.7% (53 patients) and tumor residue rate was 29.3% (22 patients). GTR rate for pituitary adenoma according to Knosp classification was 89.3% in grade 3 and 28.6% in grade 4. The biology cure rate was 75.0% and 23.8%, respectively. There was significance between them (P < 0.05). In addition, the GTR rate of Hardy stage was 90.5% in stage C, 90.0% in stage D, 26.1% in stage E, and the biology cure rate was 80.1%, 75.0%, and 13.0%, respectively. There was significance among them (P < 0.05) Postoperative severe complications included 9 patients (12.0%) with cerebrospinal fluid leaks, 26 patients (34.7%)with electrolyte imbalance, 36 patients (48.0%) with transient diabetes insipidus, 22 patients (29.3%) with hypopituitarism, 2 patients (2.7%) with permanent hypopituitarism, and 2 patients (2.7%)with epistaxis. The follow-up lasted 2-41 months (average, 19.3 months). No patient experienced recurrence after GTR, 1 patient undergoing subtotal experienced recurrence and underwent reoperation, 3 patients underwent postoperative Gamma Knife treatment, and 2 patients with refractory IPA were given temozolomide and metformin chemotherapy. CONCLUSIONS: According to the invasiveness of IPA, choosing the appropriate endoscopic surgical approach is helpful in removing tumors and reducing complications.

Endoscopic Versus Microscopic Transsphenoidal Surgery for Pituitary Tumors.

BACKGROUND: To compare the clinical outcomes and complications of 247 pituitary tumor patients managed by endoscopic and microscopic approaches in our hospital. METHODS: The authors performed a retrospective review of 100 pituitary tumor patients treated by endoscopic endonasal transsphenoidal surgery (ETS) and 147 patients treated by microscopic transsphenoidal surgery (MTS) at our center from January 2007 to July 2014. The tumors were stratified by Knosp classification and modified Hardy classification, and tumor gross total resection (GTR)/remission rate, visual improvement rate, complications, operation time, intraoperative bleeding and length of hospital stay were compared between ETS and MTS. RESULTS: The GTR rate decreased with increasing Knosp grades for both ETS and MTS, with the rates of 93.3%, 87.5%, 71.4%, 58.8% for ETS and 82.8%, 92.0%, 70.7%, 36.0% for MTS in resecting Knosp grades 0, I, II, and III tumors, respectively. The visual improvement rates increased with increasing Hardy grades, which was 66.7% and 45.5% for Hardy grade B lesion, 72.2% and 71.4% for grade C lesion, and 88.9% and 78.9% for grade D lesion treated by ETS and MTS, respectively. No significant differences were observed for GTR rate, visual outcome and complication rate between ETS and MTS, while ETS resulted in more intraoperative blood loss, longer operative time, and shorter hospital stay than MTS. CONCLUSIONS: These data conclude that, compared with MTS, ETS needs longer operation time and results in more intraoperative blood loss, but appears to achieve higher GTR rate for Knosp grade III pituitary tumors.

Violent head trauma in China: report of 2254 cases.

BACKGROUND: The occurrence of violent trauma has recently increased, and it has become both a social and medical problem in China. We are the first to explore violent head trauma in China. METHODS: Patients with violent head trauma were taken from all hospitalized patients with head trauma from January 2001 to December 2006 admitted to 11 hospitals in China. The rate, causes, age, sex, injury severity (GCS score), CT findings, management, outcome, and complications of patients with violent head trauma were retrospectively analyzed. RESULTS: Two thousand two hundred fifty-four (9.46%) patients with violent head trauma were found among a total of 23816 hospitalized patients with head trauma at 11 hospitals. Violent head trauma was caused by blunt objects (n = 1260, 55.90%), sharp/cutting instruments (n = 271, 12.02%), gunshots (n = 10, 0.44%), and others (n = 713, 31.63%). Violent head trauma was more likely to be found men (n = 1890, 83.85%) and in persons aged 21 to 40 years (n = 1216, 53.95%). In 2254 patients with violent head trauma, scalpel injury was seen in 1277 cases, skull fracture in 786 cases, cerebral contusion in 285 cases, and intracranial hematomas in 898 cases. Five hundred eighty-nine (26.13%) patients had body violent trauma besides violent head trauma. A GCS score of 13 to 15 was found in 1869 (82.92%) patients, 9 to 12 in 166 (7.36%), and 8 or less in 219 (9.72%). One thousand forty-two patients got surgical treatment, and another 1212 received medical management. One thousand nine hundred thirty-one (85.67%) patients had good recovery, 141 (6.47%) had moderate deficits, 36 (1.65%) had severe deficits, 7 (0.32%) had PVS, 63 (2.89%) died, and for the other 76, records were lost. CONCLUSIONS: Violent head trauma is certainly both a social and medical problem now, which indicates that violence should be controlled and that the human right of social safety needs to be improved in China.