ANGPTL2 deletion inhibits osteoclast generation by modulating NF-κB/MAPKs/Cyclin pathways.

Osteoclasts are multinucleated cells essential for bone-resorption. Successful repair of bone defciencies still remains a great challenge worldwide. The signaling factor angiopoietin-like protein 2 (ANGPTL2), one of eight ANGPTL proteins, functions in maintenance of tissue homeostasis partly through regulating inflammation. In the study, ANGPTL2 expression was promoted during osteoclast development and that suppressing ANGPTL2 alleviated osteoclast production regulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL). The results suggested that ANGPTL2 knockdown inhibited M-CSF-caused proliferation of osteoclast precursor cells. Further, ANGPTL2 silence reduced nuclear factor of activated T cell c 1 (NFATC1) and NFATC4 expressions in M-CSF-treated cells, along with decreased Runx2, OPN and Colla1. Moreover, silencing ANGPTL2 down-regulated M-CSF-promoted expressions of pro-inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1ß, IL-6, and chemoattractant protein-1 (CCL-2). Consistently, ANGPTL2 knockdown reduced M-CSF-enhanced activation of IKKα, IκBα and nuclear factor κB (NF-κB) and mitogen-activated protein kinases (MAPKs) (p38 MAPK, ERK1/2 MAPK and JNK MAPK). Additionally, knockdown of ANGPTL2 inhibited the induction of Cyclin D1, Cyclin D2 and Cyclin E1 due to M-CSF exposure. In vivo, we confirmed that ANGPTL2 knockout (KO) mice were protected against osteoporosis induced by ovariectomy (OVX), as proved by the improved bone loss and bone mineral density (BMD). Decreased expression of NFATCs was also observed in OVX-induced mice in the absence of ANGPTL2. Elevated release of pro-inflammatory cytokines was abrogated by ANGPTL2 knockout in femoral heads of mice with OVX operation, accompanied with a significant reduction of phosphorylated NF-κB and MAPKs signaling pathways. And down-regulated expression of Cyclin D1, Cyclin D2 and Cyclin E1 was observed in OVX-operated mice with ANGPTL2 knockout. Therefore, our study indicated that ANGPTL2 played an essential role in osteoclast generation through regulating the proliferation and inflammation of osteoclast lineage cells, providing new insights into the therapeutic strategy to alleviate bone loss.

Sarcolemma tissue of prepubertal concealed penis: pathological characterization and clinical implication / 中华男科学杂志

<p><b>OBJECTIVE</b>To evaluate the histopathological characteristics and clinical implication of sarcolemma tissue in prepubertal concealed penis.</p><p><b>METHODS</b>After measurement of the penile length, 10 prepubertal children with congenital concealed penis underwent modified Devine's operation (treatment group), and another 10 normal prepubertal children received circumcision (control group). The anatomic features of the penile sarcolemma tissue was observed intraoperatively, and its fibrosis was evaluated by Masson trichrome staining.</p><p><b>RESULTS</b>The penile length of the treatment group was significantly shorter than that of the control group preoperatively ([1.49 +/- 0.17 ] cm vs [4.26 +/- 0.23 ] cm, P < 0.01). The degree of penile concealment was correlated with the distal point of the attachment of its sarcolemma fibrous tissue: the closer the distal attachment point was to the coronary ditch, the more serious was penile concealment. The proportion of the area of collagen fibers in the penile sarcolemma tissue was significantly higher in the treatment group than in the control ([65.6 +/- 6.9]% vs [37.1 +/- 4.7]%, P < 0.01).</p><p><b>CONCLUSION</b>Sarcolemma fibrosis was obvious in congenital concealed penis, and the key to its management is drastic removal of all the fibrous sarcolemma tissue.</p>

Metformin versus metformin plus rosiglitazone in women with polycystic ovary syndrome.

BACKGROUND: Hyperinsulinemia and insulin resistance are present in the majority of women with polycystic ovary syndrome (PCOS). Both metformin and rosiglitazone can improve the ovulation and endocrine disorders of the patients. How about the combination of the two? It is rarely reported. This study aimed to compare the therapeutic efficacy of metformin versus metformin plus rosiglitazone in patients with PCOS. METHODS: Fifty-eight women with PCOS were randomly assigned to two groups. Metformin group (29) was treated with metformin mono-therapy and metformin plus rosiglitazone group (29) was treated with metformin plus rosiglitazone for 6 months. Treatment was discontinued once pregnancy was diagnosed. RESULTS: Fasting insulin, postprandial insulin, the homeostatic model assessment of insulin resistance (HOMA-IR), luteinizing hormone (LH), triglyceride, lower density cholesterol and testosterone level decreased significantly in both groups (P < 0.05). Metformin plus rosiglitazone had a better effect than metformin mono-therapy. Body mass index decreased by 7.8% in metformin group while no significant change in metformin plus rosiglitazone group. There were eight pregnancies, six in metformin plus rosiglitazone group (one abortion) and two in metformin group. There was no congenital anomaly at birth and seven infants developed well at one year's follow-up. CONCLUSIONS: Metformin can improve insulin resistance and imbalance of endocrine hormones. Metformin plus rosiglitazone has a more pronounced therapeutic effect and achieved more pregnancies than mono-therapy with metformin. The use of metformin and rosiglitazone before pregnancy has no obvious side effect on the development of the infants. Our study might suggest that metformin is the better choice in PCOS patients with serious obese and rosiglitazone plus metformin would be more effective in patients with severe insulin resistance or those do not respond to metformin.

Surgical intervention and radiotherapy outcome of solitary plasmacytoma of cervical spine / 中华外科杂志

<p><b>OBJECTIVE</b>To study the clinical features, treatment methods and outcome of solitary plasmacytoma of cervical spine.</p><p><b>METHODS</b>From January 1995 to December 2007, the data of 23 cases with solitary plasmacytoma of cervical spine was analyzed. There were 16 males and 7 females (mean age 56 years, range: 32 - 76 years). Two cases underwent radiotherapy alone and 21 patients received surgery. According to WBB staging system, surgical procedures were defined as total or subtotal resection (6 cases), appendix resection (4 cases), sagittal resection (3 cases) and total spondylectomy (8 cases). All surgical cases were managed using an anterior approach, posterior approach or combined anterior and posterior approach. The cervical spinal reconstruction was achieved through anterior cervical titanium plate and titanium mesh cage filled with auto iliac graft or bone cement, or anterior and posterior combined instrumented fusion. All patients received radiotherapy as adjunctive therapy.</p><p><b>RESULTS</b>Follow-up of the 23 cases lasted 24.0 - 143.0 months (mean: 64.7 months). Neck pains obviously improved, and nerve compression symptoms disappeared or improved after surgery. Neurological function improved by 1 - 2 grades based on Frankel grading system. All the internal fixations were fused well and stability of the cervical spine was fine and no spine instability could be seen in our series. The bone graft fusion rate was 100%. During the follow-up period, 6 surgical cases had local recurrence and finally progressed to multiple myeloma (MM) and 3 died. Two cases without surgical treatment progressed to MM in 1 year and 1.5 years after confirmed diagnosis. They were given systemic chemotherapy. The other 15 patients had disease-free survival and after surgery and adjunctive radiotherapy. Obvious abnormity were not found in such examinations as M protein, bone marrow aspiration and emission computed tomography or PET-CT examinations.</p><p><b>CONCLUSIONS</b>Solitary plasmacytoma of cervical spine is rarely seen clinically. Surgery is recommended as the primary management for patients with overt bone destruction and spinal instability or neurological dysfunction. Tumor excision with adjunctive radiotherapy can obviously reduce local recurrences and lower the possibility of progression to MM. The patients with progression to MM should receive chemotherapy according to chemotherapy protocol while the prognosis is comparatively worse.</p>

Surgical treatment and prognosis of aneurysmal bone cyst in mobile spine / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the effects of surgical treatment and prognosis of aneurysmal bone cyst (ABC) in mobile spine.</p><p><b>METHODS</b>A total of 12 patients with ABC were operated on from 1996 to 2006, and the clinical data were retrospectively reviewed. The patients included 7 male and 5 female, aged from 16 to 52 years (mean, 29 years). Surgical interventions were selected according to WBB criteria. Seven patients underwent total spondylectomy, four underwent resection of posterior arch, one patient received sagittal resection only. Anti-poster or post-lateral approach reconstruction with bone-graft or bone cement and transpedicular screws fixation were performed in the cases. Eight cases received radiotherapy after the operation.</p><p><b>RESULTS</b>The mean operation blood lose was 3210 ml. The patients were followed-up for 10 to 116 months (mean, 41.8 months). Seven patients got complete recover of spinal cord function, 4 patients experienced local recurrence in 1-2 years post operation. One patient died of multiple metastasis of chondrosarcoma after radiotherapy.</p><p><b>CONCLUSIONS</b>ABC in spine is an aggressive disease with high local recurrence rate. Enbloc if possible provides the best result, with excellent prognosis. Radiotherapy should be selected carefully.</p>

The study of total spondylectomy in the treatment of cervical spinal tumors / 中华外科杂志

<p><b>OBJECTIVE</b>To study the surgical indications, approaches and the clinical results of the total spondylectomy and instrumentation reconstruction in the treatment of cervical spinal tumor.</p><p><b>METHODS</b>From October 1998 to October 2003, 39 patients with lower cervical bone tumors, including 34 cases with primary tumor and 5 cases with metastatic tumor, were admitted and operated on with total spondylectomy. The patients underwent anteroposterior total spondylectomy including anterior cervical plating, titanium mesh reconstruction and posterior instrumentation based on the location of tumor lesions in the lower cervical spine. One vertebral level total spondylectomy was performed in 29 cases, two level in 7 cases and three level in 3 cases.</p><p><b>RESULTS</b>The postoperative follow-up ranged from 6 months to 4 years. A majority of patients achieved good results postoperatively. Nineteen cases had complete relief of neurological status. One patient died of multiple metastases and systemic failure 24 months later. One case with malignant neurilemmoma developed local recurrence one year postoperatively.</p><p><b>CONCLUSION</b>Anteroposterior total spondylectomy and reconstruction can reduce local recurrence, improve neurological function and increase operation therapeutic effect. Meanwhile, the technique of cervical total spondylectomy carries relatively greater risks and should be more attention to the operation indication.</p>

Investigation of resection and reconstruction procedure of high-sacrum tumors / 中华外科杂志

<p><b>OBJECTIVE</b>To investigate the way of resection of high-sacrum tumors and the way and duration of the spinal-pelvic TSRH or ISOLA internal fixation.</p><p><b>METHOD</b>From October 1998 through April 2002, 35 patients with sacral tumor were enrolled in our hospital, including 4 cases in L(5)-S(1), 2 in L(5)-S(2), 4 in S(1), 8 in S(1 - 2), 6 in S(1 - 3), 6 in S(1 - 4), 5 in S(1 - 5). 35 patients were followed by lumbo-pelvic TSRH or ISOLA internal fixation and corresponding chemotherapy and radiotherapy.</p><p><b>RESULTS</b>In the follow-up period of 6 - 42 months, the short-term results were satisfactory with the lumbosacral pain reduced and the neurological function improved in different degrees, however dysuria occurred in 1 case and skin necrobiosis at coccygeal incision occurred in 1 case; two cases experienced cerebrospinal fluid leakage and 1 case experienced postoperative infection and delayed healing, 1 case with chordoma and 2 cases with malignant fibrous histiocytoma recurred 1 year after postoperation, one of these 2 cases with malignant fibrous histiocytoma suffered from lung metastasis and died of system failure 19 months after postoperation. No fractured rod occurred.</p><p><b>CONCLUSION</b>Surgical procedure and postoperative comprehensive treatment have important effects on the prognosis. High-sacral tumor resection and reconstruction are effective means of achieving stabilization, providing significant pain relief and preserving ambulatory capacity.</p>