Osteoarthritis is mainly caused by the degenerative changes of cartilage and cartilage extracellular matrix,while Aggrecanases degradate Proteoglycans which are the major components of cartilage.This review includes three aspects:(1) We have concluded the major enzymes(ADAMTS-4 and ADAMTS-5) which regulate the metabolism of cartilage extracellular matrix.Meanwhile,we have summarized the structure of aggrecanases(ADAMTS-4 and ADAMTS-5) and introduced the function of each regional structure;(2) We have concluded the way cytokines and glycosaminoglycans regulate the metabolism of aggrecanases,and discussed the regulation and control principle of cytokines and glycosaminoglycan;(3) We have summarized the majority of inhibitors to the aggrecanases,introduced the endogenic inhibitors,and put our emphasis on the extrinsic inhibitors(chelating agents,polypeptides and so on).Through deeper research on the enzymes,it will help us further understand the pathogenesis of osteoarthritis,and open up new avenues to clinical treatment.Abstract:SUMM ARY Osteoarthritis is mainly caused by the degenerative changes of cartilage and cartilage extra-cellular matrix,while Aggrecanases degradate Proteoglycanswhich are the major components of cartilage.This review includes three aspects:(1) W e have concluded the major enzymes(ADAMTS-4 and ADAMTS-5) which regulate the metabolism of cartilage extracellular matrix.Meanwhile,we have sum-marized the structure of aggrecanases(ADAMTS-4 and ADAMTS-5) and introduced the function of each regional structure;(2) W e have concluded the way cytokines and glycosam inoglycans regulate the metab-olism of aggrecanases,and d iscussed the regulation and control principle of cytokines and glycosam inogly-can;(3) W e have summarized the majority of inhibitors to the aggrecanases,introduced the endogenic inhibitors,and put our emphasis on the extrinsic inhibitors(chelating agents,polypeptides and so on).Through deeper research on the enzymes,it will help us further understand the pathogenesis of osteoar-thritis,and open up new avenues to clinical treatment.

Objective: To evaluate the impacts of the prognostic factors of T2N0M0 upper tract urothelial carcinoma (UTUC) for Chinese patients.Methods: A retrospective study was conducted including 235 patients who were diagnosed with T2N0M0 UTUC in our hospital and received radical nephroureterectomy (RNU) or partial ureterectomy during January 2000 and December 2013.The 3 and 5-year can-cer-specific survival rates and bladder recurrence-free survival rates of all the patients were valued using Kaplan-Meier method, and the survival curves with statistical significance between the two were compared using the Log-rank test.Variables with significant differences in the univariate analysis were subjected to the multivariate analysis by Cox regression model.Results: A total of 235 patients were included in this study, including 95 (40.4%) male patients and 140 (59.6%) female patients.The mean age was 66.73±10.49 years.The median follow-up time was 53 (rang: 3-142) months, and during the follow-up, 74 (31.5%) patients died of UTUC after a median of 35 months,and 96 (40.9%) patients developed intravesical recurrence after a median of 19.5 months.The 3 and 5-year cancer-specific survival rates of all the patients were 89.1% and 85.9%, respectively;the bladder recurrence-free survival rates were 85.5% and 80.2%, respectively.The independent prognostic factors of cancer-specific mortality were tumor age elder than 55 years (HR=3.138, 95%CI: 1.348-7.306, P=0.008) and diameter larger than 5 cm (HR=3.320, 95%CI: 1.882-5.857, P<0.001).The independent prognostic factors of bladder recurrence-free survival were ureter tumor (HR=1.757, 95%CI: 1.159-2.664, P=0.008) and lower tumor grade (HR=1.760, 95% CI: 1.151-2.692, P=0.009).Conclusion: T2N0M0 UTUC has a better cancer-specific survival.The intravesical recurrence was equivalent to non-muscle invasive UTUC but earlier.The tumor diameter larger than 5 cm and the patient age elder than 55 years were independently associated with cancer-specific mortality;the primary tumor located in ureter and lower tumor grade were more likely to develop intravesical recurrence.

Objective Toinvestigatetheriskfactorsforleukoaraiosis(LA)inpatientswithlarge arteryatherosclerosis(LAA).Methods Theclinicaldata(age,sex,hypertension,diabetes,smoking, serum lipid level,hyperhomocysteinemia,and numbers of stenosis or occluded cerebral arteries)of 312 patients with LAA classified by the modified stop stroke study trial of Org 10172 in acute stroke treatment (SSS-TOAST ) were analyzed retrospectively. The age-related white matter changes (age related white matter changes,ARWMC)scale was used to evaluate LA. All the 312 patients were divided into non-LA group(n=72)and LA group(n=240)according the T2 weighted magnetic resonance imaging (MRI) and fluid attenuated inversion recovery(FLAIR)sequence,and 3 groups according to the (age-related white matter changes,ARWMC)scores:mild LA,moderate LA,and severe LA groups. The patients with multiple risk factors were analyzed by the univariate and multivariate Logistic regression analyses. Results (1)Of the 312 patients with LA,227 were males (72. 8%). Their average age was 64 ± 11 years,and 240 of them (76. 9%)had LA. Multivariate Logistic regression analysis showed that age (OR,2. 911,95%CI 1. 647-5.146,P=0. 000),hypertension (OR,2. 583,95%CI 1. 373-4.857,P<0. 01),diabetes (OR,1. 882, 95%CI 1. 058-3. 348,P <0. 05),the numbers of stenosis or occlusion arteries (OR,1. 851,95%CI 1.018-3. 367,P<0. 05),and lacunar infarction (LI)(OR,1.493,95%CI 1. 202-1. 853,P<0. 01)were the risk factors for LA. (2)The comparison of the clinical data in patients with different severity in the LA group found that there were significant differences in age,hypertension,diabetes,the numbers of stenosis or occlusionarteries,andLIamongthe3groups(allP<0.05).Conclusion Age,hypertension,diabetes, the numbers of stenosis or occlusion arteries,and LI are the independent risk factors for patients with LAA,and it is associated with the severity of LA.

Background:The musk glands of adult male Chinese forest musk deer(Moschus berezovskii Flerov,1929)(FMD),which are considered as special skin glands,secrete a mixture of sebum,lipids,and proteins into the musk pod.Together,these components form musk,which plays an important role in attracting females during the breeding season.However,the relationship between the musk glands and skin of Chinese FMD remains undiscovered.Here,the musk gland and skin of Chinese FMD were examined using histological analysis and RNA sequencing(RNA-seq),and the expression of key regulatory genes was evaluated to determine whether the musk gland is derived from the skin.Methods:A comparative analysis of musk gland anatomy between juvenile and adult Chinese FMD was conducted.Then,based on the anatomical structure of the musk gland,skin tissues from the abdomen and back as well as musk gland tissues were obtained from three juvenile FMD.These tissues were used for RNA-seq,hematoxylin-eosin(HE)staining,immunohistochemistry(IHC),western blot(WB),and quantitative real-time polymerase chain reaction(qRT-PCR)experiments.Results:Anatomical analysis showed that only adult male FMD had a complete glandular organ and musk pod,while juvenile FMD did not have any well-developed musk pods.Transcriptomic data revealed that 88.24%of genes were co-expressed in the skin and musk gland tissues.Kyoto Encyclopedia of Genes and Genomes(KEGG)signaling pathway analysis found that the genes co-expressed in the abdomen skin,back skin,and musk gland were enriched in biological development,endocrine system,lipid metabolism,and other pathways.Gene Ontology(GO)enrichment analysis indicated that the genes expressed in these tissues were enriched in biological processes such as multicellular development and cell division.Moreover,the Metascape predictive analysis tool demonstrated that genes expressed in musk glands were skin tissue-specific.qRT-PCR and WB revealed that sex-determining region Y-box protein 9(Sox9),Caveolin-1(Cav-1),and androgen receptor(AR)were expressed in all three tissues,although the expression levels differed among the tissues.According to the IHC results,Sox9 and AR were expressed in the nuclei of sebaceous gland,hair follicle,and musk gland cells,whereas Cav-1 was expressed in the cell membrane.Conclusions:The musk gland of Chinese FMD may be a derivative of skin tissue,and Sox9,Cav-1,and AR may play significant roles in musk gland development.

Objective To evaluate the risk factors and prognosis of high risk bladder recurrence developing after radical nephroureterectomy(RNU) for upper tract urothelial carcinoma (UTUC).Methods The data of 148 UTUC patients who developed bladder tumor after RNU between January 2000 and December 2013 was retrospectively studied.There were 69 males and 79 females,aged from 34 to 82 years old (average 68 years old).83 patients were accompanied with hydronephrosis.80 patients were renal pelvic carcinoma.32 patients had the history of smoking.24 patients had the history of ureteroscope.68 patients had the tumor larger than 3 cm.Logistic regression model was used to analyze the risk factors of muscle invasive and high grade bladder recurrence lesions.We compared the clinocopathologic characteristics between primary UTUC and bladder cancer recurrence by using Fisher' s exact test.Cancer specific survival was analyzed using the Kaplan-Meier method,with the log-rank test used to assess significance.A Cox proportional hazard model was used for multivariate analysis.Results Of the 148 patients,non-muscle invasive (Tis、Ta and T1) tumors of primary UTUC and bladder recurrence were 51 (34.5％) and 119 (80.4％),respectively.High grade (G3) tumors of primary UTUC and bladder recurrence were 41 (27.7％) and 53(35.8％),respectively.During follow-up,94 (63.5％) experienced bladder recurrence once and 54 (36.5％) experienced multiple bladder recurrence.The median follow-up time was 59.5 (rang 8-142) months,48 (32.4％) patients died of UTUC.The grade of bladder cancer recurrence correlated with the grade (P =0.046),muscle-invasion (P =0.002) and tumor architecture (P =0.034) of the primary UTUC;muscle-invasive bladder cancer recurrence associated with that of the primary UTUC (P =0.009);bladder multiple recurrence related to gender (P =0.007).On multivariate logistic regression analysis,the muscle-invasion of primary UTUC was an independent risk factor for muscle-invasive (HR =5.512,95％ CI 1.654-18.37,P =0.004) and high grade (HR =3.948,95％ CI 1.589-9.813,P =0.004) bladder recurrence tumor.The muscle invasion of primary UTUC (HR =3.498,95％ CI 1.569-7.803,P =0.002) was a prognostic factor for cancer specific survival on multivariate Cox regression analysis.Conclusions Muscle-invasive UTUC tend to predict high risk bladder recurrence tumor,and the female could be more likely to appear multiple recurrence tumor.The muscle invasion of primary UTUC could be an independent prognostic factor for cancer specific survival.