Quercetin as a promising intervention for rat osteoarthritis by decreasing M1-polarized macrophages via blocking the TRPV1-mediated P2X7/NLRP3 signaling pathway.

Osteoarthritis (OA) is characterized by an imbalance between M1 and M2 polarized synovial macrophages. Quercetin has shown protective effects against OA by altering M1/M2-polarized macrophages, but the underlying mechanisms remain unclear. In this study, rat chondrocytes were treated with 10 ng/mL of IL-1ß. To create M1-polarized macrophages in vitro, rat bone marrow-derived macrophages (rBMDMs) were treated with 100 ng/mL LPS. To mimic OA conditions observed in vivo, a co-culture system of chondrocytes and macrophages was established. ATP release assays, immunofluorescence assays, Fluo-4 AM staining, Transwell assays, ELISA assays, and flow cytometry were performed. Male adult Sprague-Dawley (SD) rats were used to create an OA model. Histological analyses, including H&E, and safranin O-fast green staining were performed. Our data showed a quercetin-mediated suppression of calcium ion influx and ATP release, with concurrent downregulation of TRPV1 and P2X7 in the chondrocytes treated with IL-1ß. Activation of TRPV1 abolished the quercetin-mediated effects on calcium ion influx and ATP release in chondrocytes treated with IL-1ß. In the co-culture system, overexpression of P2X7 in macrophages attenuated the quercetin-mediated effects on M1 polarization, migration, and inflammation. Either P2X7 or NLRP3 knockdown attenuated IL-1ß-induced M1/M2 polarization, migration, and inflammation. Moreover, overexpression of TRPV1 reduced the quercetin-mediated suppressive effects on OA by promoting M1/M2-polarized macrophages in vivo. Collectively, our data showed that quercetin-induced suppression of TRPV1 leads to a delay in OA progression by shifting the macrophage polarization from M1 to M2 subtypes via modulation of the P2X7/NLRP3 pathway.

Nimotuzumab in combination with chemotherapy for patients with malignant gliomas / 中华肿瘤杂志

<p><b>OBJECTIVE</b>Nimotuzumab is a humanized monoclonal antibody targeted against epidermal growth factor receptor (EGFR). Recent clinical studies show that patients with malignant gliomas could benefit from nimotuzumab treatment. The aim of the present study was to evaluate the efficacy and side effects of nimotuzumab in combination with chemotherapy for patients with malignant gliomas.</p><p><b>METHODS</b>The patients received 200 mg of nimotuzumab infusion intravenously over 60 minutes once weekly for the first eight weeks and then once every two weeks until unacceptable toxicity or tumor progression occurred. Individualized chemotherapy was administered based on O(6)-methylguanine-DNA methyltransferase (MGMT) expression and previous chemotherapy responses in combined with nimotuzumab.</p><p><b>RESULTS</b>Fourteen patients received a total of 122 times of nimotuzumab ranging from 2 to 20 (median 7.5 times). Combined chemotherapy regimens included: continuous 21-day temozolomide (10 cases), standard 5-day temozolomide (2 cases), teniposide plus cisplatin (1 case), and teniposide plus nimustine (1 case). Partial response (PR) and stable disease (SD) were found in 3 patients (21.4%)and 6 patients (42.9%), respectively. Disease control rate (PR + SD) was 64.3%. The median progression-free survival (PFS) was 4 months (95%CI: 0.7 - 7.3) and PFS at 6 months was 30.6%. The most common toxicities include grade I-II neutropenia (2 cases), thrombocytopenia (2 cases), lymphopenia (1 case), nausea and vomitting (3 case) and asymptomatic transaminase increase (1 case). One patient developed grade IV neutropenia and thrombocytopenia. One patient developed nimotuzumab-related acneiform rash.</p><p><b>CONCLUSIONS</b>Nimotuzumab in combination with chemotherapy has moderate activity in patients with malignant gliomas and the toxicities are well tolerable, therefore, worth further investigation.</p>

Clinical features and differential diagnosis in 18 cases of lepromatous type brain abscess / 中华神经医学杂志

Objective To investigate the clinical features and differential diagnosis of lepromatous type brain abscess. Methods A total of 18 cases with brain abscess admitted to Department of Neurosurgery, Cancer Center, Sun Yat-sen University during October 2000 to February 2007 were retrospectively analyzed with regard to their clinical data and prognosis during follow-up.Results 11 cases had been diagnosed with gliomas and 7 cases had been diagnosed with metastatic tumors in other hospitals. Among the 18 cases, 16 patients took the onset in winter and spring. All of the 18 cases had not found the primary focus of infection. Two cases among them had got a fever 1 month prior to hospitalization. Among the 18 cases, 7 cases had higher total white blood cells (10.1×109/L-13.7×109/L), and 6 cases had higher neutrophil rate (80.8%-90.5%). And the other 11 cases had normal blood routine. After hospitalization, all of the patients received MRI. 14 cases of them were diagnosed with brain abscess, 2 cases with metastatic tumor, 1 case with glioma, and 1 case with parasite. All of the patients got bacterial culture, and showed asepsis in 9 cases, Gram-positive bacteria in 4 cases, streptococci in 3 cases,Staphylococcus epidermidis in 1 case, and Klebsiella pneumoniae in 1 case. Twelve cases underwent resection, and 6 cases received puncture and drainage. During the follow-up ranging 1-6 years, 17 cases healed well, and 1 case get better. Conclusion Lepromatous type brain abscess commonly occurs in winter and spring. The clinical manifestations are untypical. MRI is the most valuable auxiliary examination, and the magnetic resonance spectroscopy and diffusion weighted imaging takes an important role in differential diagnosis between brain abscess and cystic brain tumor with necroses.

Postoperative diabetes insipidus after transsphenoidal resection of pituitary tumor / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To study the prevention and treatment of postoperative diabetes insipidus after removal of pituitary tumor through transsphenoidal operation, to decrease the incidence of postoperative complications and improve the treatment of pituitary tumor.</p><p><b>METHODS</b>The clinical data of 86 cases of transsphenoidal resection of pituitary tumor in recent 8 years were retrospectively reviewed, including 35 endoscopic operation and 51 microscopic operation. The incidence, prevention and treatment of diabetes insipidus were statistically analysed.</p><p><b>RESULTS</b>There were 18 cases of postoperative diabetes insipidus in total of 86 operations, including 15 acute cases, 3 delayed cases. Twelve were temporary , which recovered within 1 week. After prompt treatment, 14 recovered within 1 week, 4 recovered within 2 weeks. No persistent diabetes insipidus was found.</p><p><b>CONCLUSIONS</b>The key points to prevent postoperative diabetes insipidus lay in the improvement of operative skills, careful protection during operation and avoidance of unnecessary injury. In case of diabetes insipidus occurred, rational use of antidiuretics and correction of electrolyte balance were effective in the treatment of postoperative diabetes insipidus.</p>