180例性分化异常患者的临床和细胞遗传学分析

筛选性分化异常患者180例行细胞遗传学检查。结果检出：性腺发育不全64例；性染色体异常55例（检出率31％）。其中表型与核型不一致24例，包括睾丸女性化17例，性反转综合征7例；男性性染色体数目异常31例，包括先天性小睾丸征30例，XYY综合征1例；女性假两性畸形28例，尿道下裂22例，包括男性19例，女性3例。文章就各类型性分化异常的临床特征，性腺功能及细胞遗传学进行了讨论。     

CD46 accelerates macrophage‐mediated host susceptibility to meningococcal sepsis in a murine model

CD46, a membrane cofactor expressed on all nucleated human cells, plays an essential role in suppressing autoimmune reactions and protecting host cells from complement‐mediated attack. Human transgenic CD46 homozygous mice (CD46^+/+) are prone to lethal sepsis upon infection with Neisseria meningitidis (N. meningitidis). However, the underlying mechanisms are poorly understood. Here, we determined thatCD46^+/+ mice produce large numbers of M1 type macrophages with enhanced surface expression of MHC II and production of pro‐inflammatory mediators such as IL‐6, TNF, IL‐12, and IL‐1β In the presence of M‐CSF or GM‐CSF, CD46 signaling enhances monocyte‐macrophage differentiation. Additionally, CD46^+/+ macrophages rapidly undergo apoptosis upon LPS challenge or meningococcal infection, which could contribute to uncontrolled bacterial dissemination in vivo. Adoptive transfer of CD46^+/+ peritoneal macrophages aggravated septic responses in wild‐type mice, but the depletion of macrophages partially alleviated septic reactions in CD46^+/+ mice after N. meningitidis infection. Our findings reveal a novel role of CD46 in accelerating inflammatory responses upon meningococcal infection or LPS stimulation by regulating the functional polarization and survival of macrophages.     

F12‐46C/T polymorphism as modifier of the clinical phenotype of hereditary angioedema

The factors influencing the heterogeneous clinical manifestation of hereditary angioedema due to C1‐INH deficiency (C1‐INH‐HAE) represent one of the oldest unsolved problems of the disease. Considering that factor XII (FXII) levels may affect bradykinin production, we investigated the contribution of the functional promoter polymorphism F12‐46C/T in disease phenotype. We studied 258 C1‐INH‐HAE patients from 113 European families, and we explored possible associations of F12‐46C/T with clinical features and the SERPING1 mutational status. Given that our cohort consisted of related subjects, we implemented generalized estimating equations (GEEs), an extension of the generalized linear model accounting for the within‐subject correlation. F12‐46C/T carriers exhibited a significantly delayed disease onset (P < 0.001) and did not need long‐term treatment (P = 0.02). In a GEE linear regression model, the presence of F12‐46C/T was significantly associated with a 7‐year delay in disease onset (P < 0.0001) regardless of SERPING1 mutational status. It is concluded that F12‐46C/T carriage acts as an independent modifier of C1‐INH‐HAE severity.     

miR-27a acts as an oncogene to regulate endometrial cancer progression by targeting USP46

Endometrial cancer (EC) ranks as the fourth most common diagnosed cancer type in females worldwide. MicroRNAs (miRNAs) are important regulators with crucial roles in regulating diverse biologic processes, including tumor initiation and progression. Previous studies have demonstrated that miR-27a was correlated with the tumorigenesis of various cancers. However, its expression and biologic role in EC remain to be determined. This study aimed to clarify whether miR-27a acts as an oncogene in endometrial cancer (EC) by downregulating ubiquitin specific peptidase 46 (USP46). Expression of miR-27a was measured by qRT-PCR, and the results demonstrated that miR-27a was upregulated in EC cell lines compared to normal cell lines. Cell counting kit-8 (CCK-8) and wound-healing assays demonstrated that overexpression of miR-27a significantly promoted cell proliferation and migration. Online prediction algorithm and dual luciferase activity reporter assay revealed that USP46 acts as a direct target of miR-27a. USP46 expression was downregulated in EC cell lines during miR-27a overexpression. Collectively, our results indicated that miR-27a targets USP46 to promote EC cell proliferation and migration, suggesting an oncogene role of miR-27a in EC.     

4例SRY阳性的46，XX男性综合征患者临床及细胞分子遗传学研究

目的：探讨SRY阳性的46，XX男性综合征患者的临床及细胞分子遗传学特征。方法：分析4例SRY阳性的46，XX男性综合征患者的临床特点，并进行染色体核型分析、荧光原位杂交（FISH）、SRY基因检测、Y染色体微缺失等细胞和分子遗传学检测。结果：4例患者社会性别均为男性，身材低于正常男性均值。均因不育就诊，双侧睾丸体积小、质地软，精液检查均为无精子症。阴茎发育正常。性激素检查示高促性腺激素性性腺功能不全。染色体核型均为46，XX，Y染色体微缺失检测示AZFa，b，C区域均缺失。SRY基因均存在，FISH结果3例患者显示SRY基因易位于X染色体短臂。结论：SRY阳性的46，XX男性综合征患者常为男性表型，但睾丸发育不良，多伴有身材矮小和不育。患者的男性表型是由于基因组中存在SRY基因。无精子表型是由于缺失AZF。Y染色体长臂上可能存在与身高相关的基因。深入进行细胞、分子遗传学研究有助于揭示46，XX男性综合征基因型-表型的关系。