关节镜下行外侧韧带修复术治疗慢性踝关节外侧不稳症

目的探讨关节镜下带线锚钉缝合修复距腓前韧带治疗慢性踝关节外侧不稳症的临床疗效。方法2017年1月—2018年6月,对20例慢性踝关节外侧不稳症患者在保守治疗效果不佳后,行关节镜下带线锚钉缝合修复距腓前韧带,手术前后根据症状、体征、MRI和应力位片、AOFAS评分、Cumberland踝关节不稳定评分问卷对手术疗效进行评价。结果20例均获得12~18个月随访,平均(12.5±3.5)个月。术后1个月,所有患者踝关节不稳感完全消失,5例患者缝合区稍有压痛感,轻微肿胀,支具保护下正常行走,2例患者有局部皮肤麻木感。术后1年内,所有患者踝关节疼痛、不稳感、肿胀均消失,行走正常,关节活动度良好,前抽屉试验(-),内翻试验(-),1例患者局部皮肤仍有麻木感,1例明显好转,末次随访时AOFAS评分为(92.0±5.6)分,较术前明显提高,差异有统计学意义(P<0.001)。术前Cumberland评分13分,术后30分。结论关节镜下带线锚钉加强缝合修复距腓前韧带治疗慢性踝关节外侧不稳症可以更好地恢复踝关节的稳定性,手术创伤较小,操作简便,术后并发症少,并且能取得良好疗效。     

Muir-Torre综合征的研究进展

Muir-Torre综合征是一种罕见的常染色体显性遗传病,是Lynch综合征（又称遗传性非息肉性大肠癌）的一个亚型,临床特征为皮脂腺肿瘤或角化棘皮瘤至少合并一种内脏恶性肿瘤,种系DNA错配修复基因突变是本病的遗传学特征。本文对近年来Muir-Torre综合征的流行病学、基因研究、临床特征和预防治疗等方面进展加以综述,以提高对Muir-Torre综合征的认识。     

Basal cell carcinoma—Primary closure of moderate defect of mid forehead

This is a case presentation of successful defect repair after radical surgical excision of a moderately large basal cell carcinoma by a simple procedure taking advantage of a patient's individual face features.     

Relationship between MLH1, PMS2, MSH2 and MSH6 gene-specific alterations and tumor mutational burden in 1057 microsatellite instability-high solid tumors

Microsatellite instability-high (MSI-H) and tumor mutational burden (TMB) are predictive biomarkers for immune-checkpoint inhibitors (ICIs). Still, the relationship between the underlying cause(s) of MSI and TMB in tumors remains poorly defined. We investigated associations of TMB to mismatch repair (MMR) protein expression patterns by immunohistochemistry (IHC) and MMR mutations in a diverse sample of tumors. Hypothesized differences were identified by the protein/gene affected/mutated and the tumor histology/primary site. Overall, 1057 MSI-H tumors were identified from the 32 932 tested. MSI was examined by NGS using 7000+ target microsatellite loci. TMB was calculated using only nonsynonymous missense mutations sequenced with a 592-gene panel; a subset of MSI-H tumors also had MMR IHC performed. Analyses examined TMB by MMR protein heterodimer impacted (loss of MLH1/PMS2 vs. MSH2/MSH6 expression) and gene-specific mutations. The sample was 54.6% female; mean age was 63.5 years. Among IHC tested tumors, loss of co-expression of MLH1/PMS2 was more common (n = 544/705, 77.2%) than loss of MSH2/MSH6 (n = 81/705, 11.5%; P < .0001), and was associated with lower mean TMB (MLH1/PMS2: 25.03 mut/Mb vs MSH2/MSH6 46.83 mut/Mb; P < .0001). TMB also varied by tumor histology: colorectal cancers demonstrating MLH1/PMS2 loss had higher TMBs (33.14 mut/Mb) than endometrial cancers (20.60 mut/Mb) and other tumors (25.59 mut/Mb; P < .0001). MMR gene mutations were detected in 42.0% of tumors; among these, MSH6 mutations were most common (25.7%). MSH6 mutation patterns showed variability by tumor histology and TMB. TMB varies by underlying cause(s) of MSI and tumor histology; this heterogeneity may contribute to differences in response to ICI.     

Inhibitory milieu at the multiple sclerosis lesion site and the challenges for remyelination

Regeneration of myelin, following injury, can occur within the central nervous system to reinstate proper axonal conductance and provide trophic support. Failure to do so renders the axons vulnerable, leading to eventual degeneration, and neuronal loss. Thus, it is essential to understand the mechanisms by which remyelination or failure to remyelinate occur, particularly in the context of demyelinating and neurodegenerative disorders. In multiple sclerosis, oligodendrocyte progenitor cells (OPCs) migrate to lesion sites to repair myelin. However, during disease progression, the ability of OPCs to participate in remyelination diminishes coincident with worsening of the symptoms. Remyelination is affected by a broad range of cues from intrinsic programming of OPCs and extrinsic local factors to the immune system and other systemic elements including diet and exercise. Here we review the literature on these diverse inhibitory factors and the challenges they pose to remyelination. Results spanning several disciplines from fundamental preclinical studies to knowledge gained in the clinic will be discussed.     

Protective role of histone deacetylase 4 from ultraviolet radiation-induced DNA lesions

Ultraviolet B (UVB) exposure is a core factor that leads to skin disease or carcinogenesis through the insufficient repair of DNA lesions. UVB-induced DNA lesions are mainly removed by the nucleotide excision repair (NER) mechanism. The expression of histone deacetylase 4 (HDAC4) is altered in the skin upon UVB exposure, indicating its possible implication in UVB-induced DNA lesions repair. Here, we investigated the role of HDAC4 in the NER removal of the main classes of UVB-induced DNA lesions consisting of cyclobutane pyrimidine dimers and pyrimidine (6-4) pyrimidone photoproducts (6-4PPs). We found that UVB irradiation increased HDAC4 expression at both the mRNA and protein levels. HDAC4 interacted with NER factor XPC, which played an important role in effectively removing the UVB-induced DNA lesions. This study provides an understanding of the HDAC4 function in DNA repair, which will allow the development of efficient strategies to protect the skin from UVR-induced diseases.