Collagen type Ⅱ suppresses articular chondrocyte hypertrophy and osteoarthritis progression by promoting integrin β1-SMAD1 interaction

Hypertrophic differentiation is not only the terminal process of endochondral ossification in the growth plate but is also an important pathological change in osteoarthritic cartilage.Collagen type II(COL2A1)was previously considered to be only a structural component of the cartilage matrix,but recently,it has been revealed to be an extracellular signaling molecule that can significantly suppress chondrocyte hypertrophy.However,the mechanisms by which COL2A1 regulates hypertrophic differentiation remain unclear.In our study,a Col2a1 p.Gly1170Ser mutant mouse model was constructed,and Col2a1 loss was demonstrated in homozygotes.Loss of Col2a1 was found to accelerate chondrocyte hypertrophy through the bone morphogenetic protein(BMP)-SMAD1 pathway.Upon interacting with COL2A1,integrinβ1(ITGB1),the major receptor for COL2A1,competed with BMP receptors for binding to SMAD1 and then inhibited SMAD1 activation and nuclear import.COL2A1 could also activate ITGB1-induced ERK1/2 phosphorylation and,through ERK1/2-SMAD1 interaction,it further repressed SMAD1 activation,thus inhibiting BMP-SMAD1-mediated chondrocyte hypertrophy.Moreover,COL2A1 expression was downregulated,while chondrocyte hypertrophic markers and BMP-SMAD1 signaling activity were upregulated in degenerative human articular cartilage.Our study reveals novel mechanisms for the inhibition of chondrocyte hypertrophy by COL2A1 and suggests that the degradation and decrease in COL2A1 might initiate and promote osteoarthritis progression.

Clinical characteristics of malignant germ cell tumors in adolescents:A multicenter 10-year retrospective study in Beijing

Background:The aim of this study was to review clinical features of adolescent malignant germ cell tumors(MGCTs)in Beijing and analyze the peculiar characteristics of this age group.Methods:Clinical characteristics,pathological presentations,and survival outcomes of 34 patients were analyzed retrospectively.Results:Of 34 patients,12 girls and 22 boys,18(52.9%)had an extra-cranial tumor,including one testicular tumor,five ovarian tumors,one sacrococcygeal tumor,and 11 mediastinal tumors.Histologically,we found immature teratomas(n=6),yolk sac tumors(n=5),mixed malignant tumors(n=5),an embryonic carcinoma(n=1),and seminoma(n=1).Three-year event-free survival(EFS)and overall survival(OS)were 48.8%and 62.9%,respectively.Another 16(47.1%)patients had an intracranial tumor,including nine in the pineal region,five in the suprasellar region,one in basal ganglia,and one in cerebellopontine.All patients had localized disease and an excellent outcome with 3-year EFS and OS of 93.7%and 100%,respectively.Conclusions:Adolescent MGCTs are rare with a strong dependence on gender,and the mediastina and pineal region are the most common tumor locations.The prognosis is promising compared with that of other adolescent tumors and MGCTs in other age groups.MGCTs in mediastina have a tendency to companion with other hematological malignancies,and the prognosis is extremely poor in these patients.

Histone deacetylase inhibitors inhibit cervical cancer growth through Parkin acetylationmediated mitophagy

Parkin,an E3 ubiquitin ligase,plays a role in maintaining mitochondrial homeostasis through targeting damaged mitochondria for mitophagy.Accumulating evidence suggests that the acetylation modification of the key mitophagy machinery influences mitophagy level,but the underlying mechanism is poorly understood.Here,our study demonstrated that inhibition of histone deacetylase(HDAC)by treatment of HDACis activates mitophagy through mediating Parkin acetylation,leading to inhibition of cervical cancer cell proliferation.Bioinformatics analysis shows that Parkin expression is inversely correlated with HDAC2 expression in human cervical cancer,indicating the low acetylation level of Parkin.Using mass spectrometry,Parkin is identified to interact with two upstream molecules,acetylase acetyl-Co A acetyltransferase 1(ACAT1)and deacetylase HDAC2.Under treatment of suberoylanilide hydroxamic acid(SAHA),Parkin is acetylated at lysine residues 129,220 and 349,located in different domains of Parkin protein.In in vitro experiments,combined mutation of Parkin largely attenuate the interaction of Parkin with PTEN induced putative kinase 1(PINK1)and the function of Parkin in mitophagy induction and tumor suppression.In tumor xenografts,the expression of mutant Parkin impairs the tumor suppressive effect of Parkin and decreases the anticancer activity of SAHA.Our results reveal an acetylation-dependent regulatory mechanism governing Parkin in mitophagy and cervical carcinogenesis,which offers a new mitophagy modulation strategy for cancer therapy.

Investigation of calcium phosphate (CaP) tribofilms from commercial automatic transmission fluids (ATFs) and their correlation with antishudder performance

The friction properties of wet clutches are highly dependent on the surface tribofilms formed by automatic transmission fluids (ATFs). Here, four commercial ATFs were evaluated with a disc-on-disc tribometer to study tribofilm formation on steel surfaces and the effects of tribofilms on the friction properties. The chemical composition, stoichiometry, structure, and thickness of the tribofilms were investigated by scanning electron microscopy (SEM), energy dispersive X-ray spectrometry (EDX), secondary ion mass spectrometry (SIMS), and X-ray photoelectron spectroscopy (XPS). Calcium phosphate (CaP) tribofilms form on the friction surface with all ATFs, which contributes to their antishudder characteristics. The thickness and surface coverage of CaP tribofilms are positively correlated with their antishudder properties.

Diagnosis and treatment of infantile malignant solid tumors in Beijing,China:A multicenter 10-year retrospective study

Importance:Cancer is the main cause of death by disease in children.Children experience the highest incidence of cancer in the first year of life.However,there is no comprehensive registration system for children with tumors in China.Objective:To summarize the diagnosis and treatment of infant cancer and analyze the status of standardized diagnosis and management among several treatment centers in Beijing,China,thereby providing evidence to guide further clinical research.Methods:From January 1,2010 to December 31,2019,patients with newly diagnosed infantile malignant solid tumors were admitted to six large tertiary pediatric solid tumor diagnosis and treatment centers in Beijing.The epidemiology,clinical features,and therapeutic effects of tumors in these patients were analyzed retrospectively.All patients were followed up until March 31,2020.Results:In total,938 patients were enrolled in this study.There were 530 boys(56.5%)and 408 girls(43.5%);the median age was 6.0 months(range,0-12.0 months).The three most common tumors were retinoblastoma in 366 patients(39.0%),neuroblastoma in 266 patients(28.4%),hepatoblastoma in 133 patients(14.2%),and central nervous system tumors in 52 patients(5.5%).The estimated 5-year overall survival rate was 81.3%±1.8%,and the 5-year event-free survival rate was 71.8%±2.9%.The 5-year overall survival rates of non-rhabdomyosarcoma soft tissue sarcoma,neuroblastoma,and retinoblastoma were 100%,88%±2.2%,and 86.9%±2.1%,respectively.The 5-year event-free survival rates were 81.1%±2.7%for neuroblastoma,81.6%±9.8%for non-rhabdomyosarcoma soft tissue sarcoma,and 72.7%±14.1%for extracranial malignant germ cell tumors.Interpretation:The three most common infantile malignant solid tumors were retinoblastoma,neuroblastoma,and hepatoblastoma.Multidisciplinary combined diagnosis and treatment is needed for infantile tumors.

肘关节外侧脱位入路临床研究及应用

目的探讨肘关节外侧脱位入路复位固定法治疗肱骨远端冠状面骨折的方法及临床疗效。方法2019年1月至2021年10月本院通过外侧切口脱位入路复位及内固定法治疗肱骨远端冠状面骨折患者12例,男4例、女8例,年龄23~80岁,平均年龄(51.67±4.90)岁。受伤原因为:摔伤6例、交通伤1例、运动损伤2例、高处坠落伤3例。根据Dubberley分型,2A型2例、2B型3例、3A型3例、3B型4例。合并外髁骨折10例。术中直视下进行关节面骨块复位,无头钉内固定,必要时附加后侧解剖钢板或铰链外架固定。术前、术后各应用抗生素1次,术后3 d开始主动功能锻炼,外固定支架固定6周门诊去除。观察术中显露范围、记录术后三维CT检查骨折复位、关节面平整性(分离或台阶<2 mm为优)、肱尺关节匹配情况、螺钉是否切割、术后3个月Mayo肘关节功能指数评分(Mayo elbow performance score,MEPS)及优良率、异位骨化及关节退变情况。结果术后随访3~16个月,平均7.9个月,术中所有病例均可完全显露肱骨远端关节面。术后三维CT证实所有患者关节面复位良好,分离或台阶<2 mm。无螺钉切割。1例术后出现尺神经牵拉症状,3周后恢复,所有患者无血管损伤等严重并发症。末次随访骨折愈合,未发现肱骨小头坏死,2例出现关节退变,无异位骨化。MEPS评分为(90.0±1.38)分,其中优9例、良3例,优良率100%。结论肘关节外侧脱位入路可以完全显露肱骨远端关节面,直视下解剖复位、精准固定,不影响肘关节稳定性,预后良好,值得推广。