Targeting macrophagic SHP2 for ameliorating osteoarthritis via TLR signaling

Osteoarthritis (OA), in which M1 macrophage polarization in the synovium exacerbates disease progression, is a major cause of cartilage degeneration and functional disabilities. Therapeutic strategies of OA designed to interfere with the polarization of macrophages have rarely been reported. Here, we report that SHP099, as an allosteric inhibitor of src-homology 2-containing protein tyrosine phosphatase 2 (SHP2), attenuated osteoarthritis progression by inhibiting M1 macrophage polarization. We demonstrated that M1 macrophage polarization was accompanied by the overexpression of SHP2 in the synovial tissues of OA patients and OA model mice. Compared to wild-type (WT) mice, myeloid lineage conditional Shp2 knockout (cKO) mice showed decreased M1 macrophage polarization and attenuated severity of synovitis, an elevated expression of cartilage phenotype protein collagen II (COL2), and a decreased expression of cartilage degradation markers collagen X (COL10) and matrix metalloproteinase 3 (MMP3) in OA cartilage. Further mechanistic analysis showed thatSHP099 inhibited lipopolysaccharide (LPS)-induced Toll-like receptor (TLR) signaling mediated by nuclear factor kappa B (NF-κB) and PI3K-AKT signaling. Moreover, intra-articular injection of SHP099 also significantly attenuated OA progression, including joint synovitis and cartilage damage. These results indicated that allosteric inhibition of SHP2 might be a promising therapeutic strategy for the treatment of OA.

Cancer pain, a serious threat to patientsmemory / 生理学报

A large number of cancer patients suffer from pain. Growing evidence suggested that pain might be a serious risk factor for cancer patients. The shared modulators and modulation pathways between neural system and tumor cells, such as various neurotransmitters and neurogenic cytokines, provide essential basis for the effect of pain on tumor. In this article, we reviewed some possible mechanism of this process from two aspects: the systematic regulation of central nervous system on endocrine and immunity, and the regional regulation of peripheral nerves on tumor cells. The aim of this review is to provide more innovative knowledge about pain and cancer and to emphasize the importance of anti-pain in the therapy of cancer.

Revision surgery for malar reduction: causes and treatment strategies / 中华医学美学美容杂志

Objective To discuss the correlation between initial malar reduction procedures and the method of revision procedures and the personalized treatment strategies for the second deformity of postoperative prominent malar complex.Methods From January 2003 to December 2017,27 patients underwent personalized revision surgery of malar reduction according to the different second deformity of malar complex.The surgical technique included the double support malar reduction technique,orthotopic malar osteotomy technique,malar bone grinding surgery,and autogenous bone transplantation.Results A total of 27 patients subjected to revision surgery for malar reduction between November 2006 and December 2017 were retrospectively reviewed.22 patients were satisfied with aesthetic outcomes after the first revision procedure,while 5 patients were satisfied after 2 or 3 procedures follow-up for 10 to 12 months.Conclusions The incidence of complications after malar reduction is related to the first surgical method.According to the unsatisfactory results,it can be repaired individually to obtain a better clinical repair effect.

Double support technique in malar reduction surgery / 中华整形外科杂志

Objective@#To present a new method for correction of prominent malar complex via intraoral approach by double support technique osteotomy which can provide a stable support.@*Methods@#According to the anatomical characteristics of malar complex and relevant masseter muscle, we designed a malar reduction technique including anterior and posterior support. The reduction procedure entailed an L-shaped osteotomy ofthemalarbody and oblique osteotomy of malar arch. On the basis of prominence degree, bone fragment was moved inward and upward to form double support, which could reduce malar and zygomatic arch effectively.@*Results@#A total of 76 patients subjected to double support technique for malar reduction between January 2015 and January 2017 were retrospectively reviewed.The follow-up period ranged from 10 to 12 months. All patients were satisfied with aesthetic outcomes without major complications, such as facial nerve damage or bone ununion.@*Conclusions@#Double support technique is an effective method to correct malar prominence andreduce the zygomatic complex which can prevent saggy cheek and bony malunion.

Research advancement of tissue engineering in urology / 中国组织工程研究

BACKGROUND: Tissue engineering provides a new way for the repair of urinary tissue and organ defects.Urinary tissue engineering has shown a bright prospect.OBJECTIVE: To review the latest research on urinary tissue engineering at national and international level.METHODS: With the keywords of tissue engineering, urology, scaffold, vascularization in Chinese and in English,respectively, a computer-based search for articles published from January 2000 to January 2016 was performed in CNKI and PubMed databases. The articles addressing urology tissue engineering, scaffolds and vascularization were collected,summarized and analyzed.RESULTS AND CONCLUSION: The selection and cultivation of seed cells, scaffold material performance, tissue construction in vitro, and degree of vascularization all make an important influence on the repair of urinary injuries. As different seed cells hold different biological characteristics, we should make full consideration prior to choosing an appropriate seed cell, so as to pave a good foundation for urinary tissue engineering. Scaffolds with good three-dimensional structure can promote the cell growth and proliferation, tissue in-growth and vascularization.Tissue-engineered materials are superior to traditional repair materials, but still on initial stage, and further large scale trials will be necessary. Moreover, some problems needed to be solved, such as the regenerated tissue with incomplete function different from natural tissues, and regeneration failure caused by biological stent rejection.

The clinical characteristic and prognostic analysis of 23 cases of anti-N-methyl-D-aspartate receptor encephalitis / 临床神经病学杂志

Objective To investigate the clinical characteristics and prognosis of anti-N-methyl-D-aspartate receptor ( NMDAR) encephalitis .Methods The clinical data of 23 anti-NMDAR encephalitis patients , including 9 cases of severe patients were retrospectively analyzed .Results There were 9 cases of severe patients ( including 2 males and 7 females ) admitted to ICU for the treatment , and 14 patients ( including 3 males and 11 females ) admitted to the neurology department for the treatment .The age of the patients was (32.6 ±14.6) years , the course of disease was (26.7 ±36.9) d, and the length of stay was (34.2 ±27.5) days.In critically ill patients, the average length of stay was (22.2 ±13.7) d.The main clinical manifestations included 21 patients with mental and behavioral abnormalities , 13 patients with fever , 19 patients with epilepsy , 15 patients with conscious disturbance , 2 patients with motor dysfunction , 13 patients with dysautonomia , and 5 patients with hypoventilation . There was 1 case of patients with teratoma .The anti-NMDAR antibodies of CFS were positive in all patients , of which 18 cases of serum anti-NMDAR antibody were positive .Five patients of head MRI showed the abnormal signal of the temporal lobe , hippocampus or frontal lobe .The EEG of 19 patients showed abnormal slow wave .23 patients received the glucocorticoid , the gamma globulin , the plasma exchange and other immunomodulatory treatment .Six patients were completely cured , and 17 patients were improved but with residual symptoms .Conclusions The patients with Anti-NMDAR encephalitis usually manifest such as the rapid changes in mental behavior , the epilepsy and other symptoms , as well as the disturbance of consciousness , the movement disorders , the autonomic dysfunction , but of which combined tumors are rare .The prognosis of patients with anti NMDAR encephalitis is better, who received positive immunotherapy .

Role of focal adhesion kinase in adhesion and migration of Hep G2 cells / 生物医学工程学杂志

Focal adhesion kinase (FAK) plays a critical role in the process of cell adhesion and migration by regulating the expression of downstream small G proteins. A kind of focal adhesion kinase (FAK) inhibitor was used to inhibit the phosphorylation of Y397 site of FAK, and scratch wound migration assay was used to examine the effect of FAK inhibitor with different concentrations (0-250 nmol/mL) on the migration of hepatomal cells (Hep G2 cells) at 0, 2, 4, 8 and 24h. Immunofluorescence analysis and Western blot analysis were performed to detect the expression of F-actin and small G proteins Rac1, RhoA and Cdc42 in Hep G2 cells treated with FAK inhibitor for 120 min. The results indicated that the FAK inhibitor can inhibit the migration of Hep G2 cells with a dose- and time-dependent manner. F-actin was down-regulated in Hep G2 cells treated with FAK inhibitor for 120 min, and expression of small G proteins were inhibited at different durations. The inhibition of FAK phosphorylation could inhibit cell adhesion and migration by down-regulating small G proteins. These results suggested that FAK inhibitor can inhibit the migration of tumor cells by blocking FAK phosphorylation. This means that FAK inhibitor can block the metastasis of tumor cells to surrounding tissues. It may be a potential application in the prevention and treatment of cancer.

Study on FAK regulation of migration of vascular endothelial cells depending upon focal adhesion proteins / 生物医学工程学杂志

Tumor angiogenesis induced by vascular endothelial cells (VECs) migration is a necessary condition for tumor growth and metastasis. The purpose of this study is to investigate the effect of focal adhesion kinase (FAK) inhibitor (50nmol/mL) on the adhesion and migration of endothelial cells(ECs) and the expression of focal adhesion proteins vinculin, talin and paxillin. Scratch wound migration assay was performed to examine the effect of FAK inhibitor with 50nmol/mL on ECs migration at 0, 5, 10, 30, 60 and 120min, respectively. And immunofluorescence analysis was performed to detect the expression of F-actin in ECs treated with FAK inhibitor within 2h. Western blot was carried out to determine the effect of FAK inhibitor on expression of vinculin, talin and paxillin proteins. The results showed that the migration distance and the expression of F-actin in ECs treated with FAK inhibitor decreased significantly compared with that of the controls, and the level of vinculin showed no significant difference with increasing of treated time of FAK inhibitor. However, the talin and paxillin showed an identical decreasing tendency in 5-10min, but slowly going up in 30min and then after subsequently decreasing. The results of this study proved that blocking phosphorylation of FAK could inhibit VECs adhesion and migration by downregulating focal adhesion proteins so that it may inhibit tumor angiogenesis. This may provide a new approach for tumor therapy.

Influence of titanium particles loading on releases of cytokines of osteoblasts / 生物医学工程学杂志

Aseptic loosening is mainly mediated by bone resorption cytokines in the surrounding area of orthopaedic implants. Our previous investigation demonstrtated that different-sized titanium particles loading can inbibit the osteoblastic differentiation and mineraliztion. In order to investigate the hypothesis that particulate wear debris derived from prosthetic biomaterials affects the release of bone resorption related cytokines, we studied the influence of different-sized titanium particles loading on the osteoblastic cytokines by assaying the secretion of IL-6, IL-10 with use of ABC-quantitative sandwich enzyme-linked immunosorbent assay, and on the expression of osteoclast differentiation factors (ODF) by RT-PCR. The results showed that the 0.9 microm titanium particles promoted osteoblasts producing bone resorption cytokines (IL-6, ODF), and simultaneously secreted bone absorption restraining factor (IL-10) quickly and transitorily. In comparison, the 2.7 microm and 6.9 microm titanium particles,especially the latter primarily promoted osteoblasts secreting bone absorption promoting factors powerfully and slowly. The results suggested that there was a biphasic response appearing in titanium particles loaded-osteoblastic cultures, the level of which varied according to the different size and the loading time of titanium particles. This in vitro experimental result showed that attentaion to the inhibition of bone resorption cytokines stimulated by wear debris and to the screen potential favourable biomaterials for implants must be taken.

Prognostic factors of stage IB and IIA carcinoma of the cervix treated by surgery / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate prognostic factors in patients with stage IB-IIA of cervical carcinoma treated by surgery.</p><p><b>METHODS</b>Between December 1992 and December 2001, 111 patients with stage IB-IIA cervical cancer surgically treated were analyzed. Median age 40 years. According to 1994 FIGO Staging System: IB 80 (IB1 40, IB2 40) and IIA 31. There were 93 cases of squamous cell carcinoma (83.5%), 17 cases of adenocarcinoma (15.3%) and one case of small cell carcinoma. All patients were treated by radical hysterectomy and pelvic lymphadenectomy, 74 patients had preoperative adjuvant radiotherapy, 24 patients had postoperative adjuvant treatment. Kaplan-Meier method was used to evaluate the survival, the related prognostic factors were assessed by Cox regression and chi(2) test.</p><p><b>RESULTS</b>The overall 5-year survival rate was 85.9%, being 89.1%, 90.7% and 78.4% for stage IB1, IB2 and IIA, respectively. Univariate analysis showed that tumor size (hazards ratio [HR] = 1.479, P = 0.152), tumor type (HR = 1.440, P = 0.264), clinical stage (HR = 1.380, P = 0.354), adjuvant treatment (HR = 1.210, P = 0.450), lymph node metastasis (HR = 1.432, P = 0.540), endocervical involvement (HR = 2.244, P = 0.036), depth of myometrial invasion (HR = 3.295, P = 0.06) and multiple sexual partners during pregnancy (HR = 10.172, P = 0.000) were of prognostic significance. The latter two were the most important factors indicative of poor prognosis.</p><p><b>CONCLUSION</b>The depth of myometrial invasion and multi-partners combined with pregnancy are closely related to the prognosis while the pre- and/or postoperative adjuvant therapy should be considered for stage IB-IIA cervical cancer with deep myometrial invasion and in pregnant patients with multiple sexual partners.</p>

Telomerase activity in cervical intraepithelial neoplasia / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>It was reported that telomerase expression is closely associated with cellular immortality and cancer. This study was designed to investigate the relationship between telomerase expression and the carcinogenesis of cervical cancer, the possible use of telomerase as a marker of cervical intraepithelial neoplasia (CIN) progression or regression, and the natural history of CIN.</p><p><b>METHODS</b>Telomeric repeat amplification protocol (TRAP) assay was used to measure telomerase activity in cervical scrapings and biopsy samples obtained from 105 cases affected with various cervical conditions, including chronic cervicitis (n = 20), CIN (n = 64, 16 cases of CIN I, 20 cases of CIN II, and 28 cases of CIN III), and invasive squamous cell carcinoma (n = 21).</p><p><b>RESULTS</b>In exfoliated cell samples, telomerase activity was detected in 5 of 20 (25.0%) cases of cervicitis, 10 of 16 (62.5%) cases of CIN I, 11 of 20 (55.0%) cases of CIN II, 23 of 28 (82.1%) cases of CIN III, and 13 of 21 (61.9%) cases of carcinoma. In cervical biopsy samples, telomerase activity was detected in 6 of 20 (30.0%) cases of cervicitis, 8 of 16 (50.0%) cases of CIN I, 9 of 20 (45.0%) cases of CIN II, 27 of 28 (96.4%) cases of CIN III, and 20 of 21 (95.2%) cases of carcinoma. Telomerase activation was significantly higher in CIN samples than in cervicitis samples. Telomerase activity was detected at similar frequency in samples from cervical scrapings and cervical biopsies.</p><p><b>CONCLUSION</b>These results seem to suggest that telomerase expression may be associated with carcinogenesis of the cervix. TRAP assay of cervical scraping samples could be used to monitor and predict the development of CIN in clinical practice.</p>

Present status of radiotherapy in the treatment of gynecological malignancy / 中国医学科学院学报

This paper introduces radiation in the treatment of gynecological malignancy, including its importance, methods, curative effects, and some critical issues nowadays.