Objective To investigate the curative effect and safety of microinvasive percutaneous nephrolithotomy (MPCNL) and ureteroscope lithotripsy (URSL) in treatment of children′s (≤6 years old) middle and upper segment ureteral calculi. Methods Eighty children (≤6 years old) with middle and upper segment ureteral calculi were selected, and they were divided into observation group and control group according to random number table method with 40 cases each. The children of observation group were treated with MPCNL, and the children of control group were treated with URSL. The operation time, hospitalization time, calculi clearance rate of the first phase, decline situation of the postoperative hemoglobin and hematocrit and complication were compared between 2 groups. Results The operation time and hospitalization time in observation group were significantly shorter than those in control group:(45.43 ± 9.76) min vs. (68.32 ± 11.28) min and (8.12 ± 1.03) d vs. (13.45 ± 2.34) d, the calculi clearance rate of the first phase was significantly higher than that in control group: 100.0% (40/40) vs. 62.5%(25/40), the incidence of complication was significantly lower than that in control group:20.0%(8/40) vs. 60.0% (24/40), and there were statistical differences (P<0.05). There were no statistical differences in the decline situation of the postoperative hemoglobin and hematocrit between 2 groups (P>0.05). Conclusions The MPCNL in treatment of children′s middle and upper segment ureteral calculi has short operation time, high calculi clearance rate of the first phase, and low incidence of perioperative complication. Compared with URSL, the URSL is safe and efficient, and it is worthy of clinical application.

Objective To observe the microstructural changes in lesions of alopecia areata (AA) with dermoscopy and to evaluate their correlation with clinicopathological manifestations. Methods The area of alopecia of 62 patients with AA and 44 patients with other types of hair loss were observed by using a noncontact polarized dermoscope (Dermlite, USA). Clinical data on and laboratory findings from these patients were collected. Pathological examination was carried out with scalp biopsy specimens from the alopecia area of 15 AA patients. Results Characteristic dermoscopic signs of AA included yellow dots, black dots, broken hairs, exclamation mark hairs, short vellus hair and newly-grown short hairs. Among these signs, yellow dots showed the highest prevalence (83.9%). Exclamation mark hairs, black dots and broken hairs were rather specific signs for AA, and the prevalence of the three signs was positively correlated with disease activity and positivity rate of hair-pull test. A positive correlation was also noted between the prevalence of elevated thyroid peroxidase antibody levels and positivity rate of hair-pull test (r = 0.269, P ＜ 0.05 ) as well as prevalence of broken hairs (r = 0.445, P ＜ 0.05), and between the prevalence of yellow dots and that of keratinous plug in follicular orifice. There was a negative correlation between the prevalence of newly-grown short hairs and perifollicular mast cell infiltration and between the prevalence of black dots and the anagen/catagen ratio. Conclusions Yellow dots can serve as a preliminary screening marker for AA. Exclamation mark hairs, black dots and broken hairs are highly sensitive for the confirmation of diagnosis of AA, and often predict progressive AA.Dermoscopic signs are well correlated to the histopathology features of AA, and may be useful for the evaluation of disease severity and guidance on the treatment of AA.

Objective To detect the expressions of apoptosis-related factors and inflammatory cytokines in superficial and deep layers of as well as anagen hair follicles in lesions of early alopecia areata (AA).Methods Scalp biopsy samples were collected from 25 patients with early AA and 15 healthy human controls.Fluorescence-based quantitative PCR was performed to detect mRNA expressions of apoptosis-related genes p53,caspase 3,Fas,survivin and bcl-2,as well as those of inflammatory cytokines interleukin (IL)-4,IL-10,IL-12 and interferon (IFN)-γ.An immunohistochemical assay was conducted to measure the expression of p53 protein in anagen hair follicles.Results Compared with control skin samples,anagen hair follicles in AA lesions showed significantly increased mRNA expression levels (expressed as 2-△△Ct) of pro-apoptotic factors caspase 3,p53 and Fas (6.78,8.01,9.74,respectively,all P ＜ 0.05),but decreased mRNA expression levels of antiapoptotic factors bcl-2 and survivin (0.08 and 0.03 respectively,both P ＜ 0.01),and similar mRNA expression levels of inflammatory cytokines.There was a significant increase in mRNA expression levels of Th1 cytokines IFN-γ and IL-12 (2.75 vs.1.00,P ＜ 0.05; 85.67 vs.1.00,P ＜ 0.01),but a significant decrease in the expression level of the Th2 cytokine IL-10 (0.002 vs.1.000,P ＜ 0.01) in superficial layers of AA lesions compared with those of normal control skin.The degree of changes in mRNA expression levels of IL-10 and IL-12 was significantly higher in superficial layers than in deep layers of AA lesions (P＜0.01 and 0.05 respectively).The immunohistochemical assay showed that the number of p53-positive cells per 100 cells in anagen hair follicles of AA lesions was higher than that in those of control skin (t =23.79,P ＜ 0.01).Conclusions Anagen hair follicles in AA lesions exhibit high expressions of pro-apoptosis factors,but low expressions of antiapoptotic factors,suggesting that apoptotic factors play a role in the occurrence of AA.

ObjectiveTo assess the relationship of filaggrin expression with atopic diathesis and disease severity in patients with alopecia areata (AA).MethodsThirty-seven patients with AA aged (26.3 ± 10.6) years were enrolled in this study.Atopic diseases were noted in 8 of these patients.Clinical data and laboratory test resuhs were reviewed.Immunohistochemical staining was performed to quantify the expression of filaggrin protein in scalp biopsy specimens from all of the 37 patients with AA and from 10 human controls,and fluorescence-based semiquantitative reverse transcription-PCR to detect the expression of filaggrin mRNA in scalp biopsy specimens from 22 patients with AA and 13 healthy controls.Data were statistically analyzed by Mann Whitney U test,chi-square test,and Spearman's rank correlation test.ResultsThe expressions of filaggrin protein and mRNA were significantly lower in patients with AA than in the controls(P ＜ 0.05 or 0.01 ),and the decrease seemed more obvious in patients with large areas of lesions,long duration of disease,and nail abnormalities,but the degree of decrease was unrelated to the complication with atopic diseases.No significant differences were observed in sex ratio,age at onset,disease duration,area of hair loss,the prevalence of family history or incidence of nail abnormalities and increase in serum IgE and eosinophils,between patients with atopic diseases and those without.ConclusionsThe expressions of filaggrin protein and mRNA are decreased in patients with AA,suggesting that filaggrin may participate in the development of AA and is correlated with the severity of AA.

The BCCIP (BRCA2- and CDKN1A-interacting protein) is an important cofactor for BRCA2 in tumor suppression. Although the low expression of BCCIP is observed in multiple clinically diagnosed primary tumor tissues such as ovarian cancer, renal cell carcinoma and colorectal carcinoma, the mechanism of how BCCIP is regulated in cells is still unclear. The human INO80/YY1 chromatin remodeling complex composed of 15 subunits catalyzes ATP-dependent sliding of nucleosomes along DNA. Here, we first report that BCCIP is a novel target gene of the INO80/YY1 complex by presenting a series of experimental evidence. Gene expression studies combined with siRNA knockdown data locked candidate genes including BCCIP of the INO80/YY1 complex. Silencing or over-expressing the subunits of the INO80/YY1 complex regulates the expression level of BCCIP both in mRNA and proteins in cells. Also, the functions of INO80/YY1 complex in regulating the transactivation of BCCIP were confirmed by luciferase reporter assays. Chromatin immunoprecipitation (ChIP) experiments clarify the enrichment of INO80 and YY1 at +0.17 kb downstream of the BCCIP transcriptional start site. However, this enrichment is significantly inhibited by either knocking down INO80 or YY1, suggesting the existence of both INO80 and YY1 is required for recruiting the INO80/YY1 complex to BCCIP promoter region. Our findings strongly indicate that BCCIP is a potential target gene of the INO80/YY1 complex.
Calcium-Binding Proteins ; genetics ; metabolism ; Cell Cycle Proteins ; genetics ; metabolism ; Chromatin Assembly and Disassembly ; physiology ; DNA Helicases ; genetics ; metabolism ; HeLa Cells ; Humans ; Multiprotein Complexes ; genetics ; metabolism ; Nuclear Proteins ; genetics ; metabolism ; Promoter Regions, Genetic ; physiology ; Transcription, Genetic ; physiology ; YY1 Transcription Factor ; genetics ; metabolism

Although the mTOR-4E-BP1 signaling pathway is implicated in aging and aging-related disorders, the role of 4E-BP1 in regulating human stem cell homeostasis remains largely unknown. Here, we report that the expression of 4E-BP1 decreases along with the senescence of human mesenchymal stem cells (hMSCs). Genetic inactivation of 4E-BP1 in hMSCs compromises mitochondrial respiration, increases mitochondrial reactive oxygen species (ROS) production, and accelerates cellular senescence. Mechanistically, the absence of 4E-BP1 destabilizes proteins in mitochondrial respiration complexes, especially several key subunits of complex III including UQCRC2. Ectopic expression of 4E-BP1 attenuates mitochondrial abnormalities and alleviates cellular senescence in 4E-BP1-deficient hMSCs as well as in physiologically aged hMSCs. These f indings together demonstrate that 4E-BP1 functions as a geroprotector to mitigate human stem cell senescence and maintain mitochondrial homeostasis, particularly for the mitochondrial respiration complex III, thus providing a new potential target to counteract human stem cell senescence.
Mesenchymal Stem Cells/physiology* ; Cellular Senescence ; Homeostasis ; Cell Cycle Proteins/metabolism* ; Adaptor Proteins, Signal Transducing/metabolism* ; Mitochondria/metabolism* ; Electron Transport Complex III/metabolism* ; Humans ; Cells, Cultured

Animals ; Antlers ; Exosomes ; Mesenchymal Stem Cells ; Osteoarthritis/therapy*

Humans ; Mechanistic Target of Rapamycin Complex 2/metabolism* ; Multiprotein Complexes/metabolism* ; Neural Stem Cells/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rapamycin-Insensitive Companion of mTOR Protein/metabolism* ; TOR Serine-Threonine Kinases/metabolism*