Clouston syndrome (OMIM #129500), also known as hidrotic ectodermal dysplasia type 2, is a rare autosomal dominant skin disorder. To date, four mutations in the GJB6 gene, G11R, V37E, A88V, and D50N, have been confirmed to cause this condition. In previous studies, the focus has been mainly on gene sequencing, and there has been a lack of research on clinical manifestations and pathogenesis. To confirm the diagnosis of this pedigree at the molecular level and summarize and analyse the clinical phenotype of patients and to provide a basis for further study of the pathogenesis of the disease, we performed whole-exome and Sanger sequencing on a large Chinese Clouston syndrome pedigree. Detailed clinical examination included histopathology, hair microscopy, and scanning electron microscopy. We found a novel heterozygous missense variant (c.134G>C:p.G45A) for Clouston syndrome. We identified a new clinical phenotype involving all nail needling pain in all patients and found a special honeycomb hole structure in the patients' hair under scanning electron microscopy. Our data reveal that a novel variant (c.134G>C:p.G45A) plays a likely pathogenic role in this pedigree and highlight that genetic testing is necessary for the diagnosis of Clouston syndrome.
Humans ; Connexin 30/genetics* ; Connexins/genetics* ; East Asian People ; Ectodermal Dysplasia/pathology* ; Phenotype

Maintaining the stemness of the transplanted stem cell spheroids in an inflammatory microenvironment is challenging but important in regenerative medicine. Direct delivery of stem cells to repair periodontal defects may yield suboptimal effects due to the complexity of the periodontal inflammatory environment. Herein, stem cell spheroid is encapsulated by interfacial assembly of metal-phenolic network (MPN) nanofilm to form a stem cell microsphere capsule. Specifically, periodontal ligament stem cells (PDLSCs) spheroid was coated with Fe^III/tannic acid coordination network to obtain spheroid@[Fe^III-TA] microcapsules. The formed biodegradable MPN biointerface acted as a cytoprotective barrier and exhibited antioxidative, antibacterial and anti-inflammatory activities, effectively remodeling the inflammatory microenvironment and maintaining the stemness of PDLSCs. The stem cell microencapsulation proposed in this study can be applied to multiple stem cells with various functional metal ion/polyphenol coordination, providing a simple yet efficient delivery strategy for stem cell stemness maintenance in an inflammatory environment toward a better therapeutic outcome.
Anti-Bacterial Agents/pharmacology* ; Capsules/pharmacology* ; Cell Differentiation ; Cell Encapsulation ; Cells, Cultured ; Ferric Compounds/pharmacology* ; Osteogenesis/physiology* ; Periodontal Ligament ; Polyphenols/pharmacology* ; Stem Cells ; Tannins/pharmacology*

Objective: To compare the survival rates difference between diabetic kidney disease (DKD) and non-DKD maintenance hemodialysis patients. Methods: The eligible patients who started hemodialysis treatment in Dalian Municipal Central Hospital from January 1, 2010 to December 31, 2016 were enrolled. The endpoint was all-cause death. Patients were divided into two groups according to the primary disease: DKD group and non-DKD group. Survival between two groups was compared by Kaplan-Meier plots and log-rank test. Survival was timed from the start of dialysis until the date of death and was censored for the date of end of the study period (December 31, 2016). SPSS 13.0 software was used for statistical analysis. Univariate COX regression analysis was used for risk assessment. Independent analysis was performed by multivariate COX regression. P < 0.05 indicated that the difference was statistically significant. Results: A total of 769 patients were enrolled, including 305 patients with DKD (39.7%) and 464 patients with non-DKD (60.3%). There were 465 males, accounting for 60.5%, and 304 females, accounting for 39.5%. The mean age of starting dialysis was (56.2 ± 14.9) years. The median follow-up time was 21 months. One hundred and seventy patients died due to all causes, accounting for 21.7%. The 1-, 2-, 3-, 4-, 5-, 6- and 7-year survival rates in the diabetic kidney disease group were 94%, 77%, 68%, 56%, 44%, 31% and 26%. The 1-, 2-, 3-, 4-, 5-, 6- and 7-year survival rates in the non-diabetic kidney disease group were 94%, 87%, 81%, 77%, 69%, 65% and 60%. The survival rate of DKD group was significantly lower than that of non-DKD group (χ²=23.656, P < 0.01). Multivariate Cox regression analysis showed that age of onset of dialysis, primary disease, low density lipoprotein, serum potassium, ejection fraction (EF), coronary heart disease and stroke were independent risk factors of mortality (P < 0.05). Conclusions The survival rate of patients with diabetic kidney disease is significantly lower than that of patients with non-diabetic kidney disease in the maintenance hemodialysis patients in our center. Age, primary disease, low density lipoprotein, EF, coronary heart disease, and stroke are independent predictors of death.

OBJECTIVETo investigate characteristics and the differences of the anatomical parameters of the proximal femur of the developmental dysplasia of the hip (DDH).

METHODSA total of 38 patients(47 hips) diagnosed as DDH with CT scan data and the pelvis radiograph from January 2012 to December 2014 in China-Japan Union Hospital of Jilin University were retrospectively analyzed. All the hips were divided into 3 groups according to Crowe classification method. Thirty normal hips were selected as controls who admitted at the same time. CT data of the patients were imported into Mimics 17.0. The three-dimensional models of the proximal femur were then reconstructed, and the following parameters were measured: neck-shaft angle, neck length, offset, height of the centre of femoral head, height of the isthmus, height of greater trochanter, the medullary canal diameter of isthmus (Di), the medullary canal diameter 10 mm above the apex of the lesser trochanter (DT+ 10), the medullary canal diameter 20 mm below the apex of the lesser trochanter (DT-20), and then DT+ 10/Di, DT-20/Di and DT+ 10/DT-20 were calculated.Variance discrepancy analysis was used to compare the difference among the four groups, and LSD method was used to compare the difference between either two groups.

RESULTSThe parameters of neck-shaft angle of DDH with Crowe I, Crowe II-III, Crowe IV and the control group were (131.8°±7.1°), (131.7°±6.5°), (122.8°±11.4°) and (131.8°±5.9°), respectively; the parameters of neck-shaft angle of DDH with Crowe IV was smaller than that of DDH with Crowe I, Crowe II-III and control group (all P<0.05). The parameters of the neck length of DDH with Crowe IV ((44.6±6.6) mm) was smaller than that of DDH with Crowe I ((48.6±6.7) mm), Crowe II-III ((50.4±4.7) mm) (all P<0.05). There is no statistic difference in the offset among the groups (F=2.392, P>0.05). The parameters of the height of greater trochanter of DDH with Crowe IV ((12.1±6.1) mm) was bigger than that of DDH with Crowe I ((8.9±7.2) mm), Crowe II-III ((7.5±3.3) mm) and control group ((6.1±3.9) mm) (all P<0.05). The parameters of the height of the centre of femoral head of DDH with Crowe I, Crowe II-III, Crowe IV were (39.6±6.5) mm, (39.1±4.2) mm, (38.8±8.6) mm, which were smaller than that of the control group ((46.5±6.2) mm) (all P<0.05). The parameters of Di of DDH with Crowe I, Crowe II-III, Crowe IV and the control group were (9.9±2.2) mm, (8.3±1.8) mm, (8.7±1.7) mm and (10.1±1.4) mm; the parameters of Di of DDH with Crowe II-III and Crowe IV were smaller than that of the control group (all P<0.05). The parameters of DT+ 10 ((17.2±5.3) mm) and DT-20 ((12.2±3.0) mm) of DDH with Crowe IV were smaller than that of DDH with Crowe I ((25.2±3.4) mm, (17.1±2.3) mm) and Crowe II-III ((21.9±4.2) mm, (16.3±3.2) mm) (all P<0.05). The parameter of the height of the isthmus of DDH with Crowe IV ((94.1±19.7) mm) was smaller than that of DDH with Crowe I ((106.2±13.8) mm), Crowe II-III ((108.8±10.5) mm) and control group ((116.5±10.6) mm), respectively (P=0.010, 0.008, 0.000). The parameters of DT+ 10/Di (2.0±0.4) and DT-20/Di (1.4±0.2) of DDH with Crowe IV were smaller than that of DDH with Crowe I (2.6±0.5, 1.8±0.3), Crowe II-III (2.7±0.60, 1.9±0.3) (all P<0.05).

CONCLUSIONSComparing to DDH with Crowe I-III and control group, DDH with Crowe IV has a dramatic change in the intramedullary and extramedullary parameters. The isthmus and the great trochanter are higher and there is apparent narrowing of the medullary canal around the level of the lesser trochanter.

Adult ; Analysis of Variance ; Case-Control Studies ; Femur ; abnormalities ; diagnostic imaging ; Hip Dislocation, Congenital ; classification ; diagnostic imaging ; Hip Joint ; diagnostic imaging ; Humans ; Retrospective Studies ; Tomography, X-Ray Computed

Abnormal activation of Notch1 plays pivotal roles in the molecular pathogenesis of human T-cell acutelymphoblastic leukemia (T-ALL). Activating Notch1 mutations present in over 60% of the T-ALL patients. However, so far,there is no therapy with little side effects that specifically targets the abnormally activated Notch1 pathway-induced T-ALL. Thepresent study briefly reviewed the effects of abnormal activation of Notch1 in the pathogenesis of T-ALL, as well as the currentapproaches targeting Notch1 and its limitations, thus providing some guidance for the research and development of clinicaltherapies targeting T-ALL.

ObjectiveTo clarify the characteristics and clinical signiifcance of the NOTCH1 mutations in childhood T-cell acute lymphoblastic leukemia (T-ALL).MethodsAmplify and sequence the heterodimerization (HD) domain and the pro-line-glutamicacid-serine-threonine (PEST) domain of theNOTCH1 gene in 28 T-ALL children, in order to explore the frequency, position and type of the mutations as well as their reletions with prognosis.ResultsIn 28 children with T-ALL, 15 cases (51.57%) had been identiifed theNOTCH1 mutations, all of which were heterozygous mutations. The lymphoblast counts in peripher-al blood and bone marrow in theNOTCH1 mutant group at admission were signiifcantly higher than in the non-mutant group (P<0.05). The 1-year remission rate in the 28 children with T-ALL was 75% (21/28), including 80% (12/15) in mutant group in which 3 patients relapsed and all of them died (1-year mortality 20%) and 69.20% (9/13) in non-mutant group in which 4 patients relapsed but all survived (1-year mortality 0%).ConclusionsThe children with T-ALL had a high incidence of NOTCH1 mu-tations at various sites. In addition, the patients withNOTCH1 mutations had more severe disease at diagnosis, better short-term prognosis and poor outcome with salvage therapy after relapse.

BACKGROUND:Over the past 10 years, scholars have proposed the tubular stomach as an alternative to the whole stomach for digestive tract reconstruction; however, its occurrence rate of postoperative complications has been controversial. OBJECTIVE:To evaluate the clinical efficacy of tubular stomach versus whole stomach for digestive tract reconstruction in the resection of esophageal carcinoma. METHODS: The randomized controled trials about tubular stomach for digestive tract reconstruction in the resection of esophageal carcinoma were searched from PubMed, OVID, CNKI, EBSCO, Science online, Wangfang, Super Star Digital Library, CMB, Baidu and Google search engines. Two searchers screened studies based on the included criteria strictly. Literature quality and bias risk were assessed according to the criteria of Cochrane Colaboration, GRADEprofiler3.6.1 software was used for evaluation of the quality grade, and Revman5.3 for data management and statistical analysis. RESULTS AND CONCLUSION:Totaly 12 randomized controled trials including 4 137 patients were enroled. Compared with the whole stomach group, in the tubular stomach group, the incidences of reflux esophagitis and thoracic stomach syndrome were significantly lower, but there was no difference in the incidences of anastomotic leakage and anastomotic stenosis between the two groups. These findings indicate that the tubular stomach as a substitute of the whole stomach for digestive tract reconstruction in the resection of esophageal carcinoma is a safe and effective. However, the literatures included are only in English and Chinese, and there is publication bias and smal sample size. Therefore, the large-sample high-quality clinical randomized controled trials are stil needed for further confirmation.

Objective To explore the association of galactose-deifcient IgA1 levels with clinical features, and further to provide guidance for individualized treatment of HSP. Methods According to the clinical symptoms and curative effect, 57 children with HSP were divided into four groups:non-HSPN group (n=26), HSPN group (n=7), refractory HSP group (n=7) and remission group (n=17). In non-HSPN group, 12 cases received glucorticoid therapy and 14 cases did not. Serum galactose-de-ifcient IgA1 (Gd-IgA1) concentrations were detected using a Helix aspersa-lectin-based enzyme-linked immunosorbent assay (ELISA), and the total IgA1 levels were measured by ELISA. Results The serum Gd-IgA1 level was signiifcantly higher in 40 HSP children who were not cured than that in remission group and control group (P<0.05). However, there was no difference in Gd-IgA1 level between remission group and control group (P>0.05). Compared with the control group, the serum Gd-IgA1 level was signiifcantly higher in HSPN group, non-HSPN group and refractory HSP, and children with refractory HSP had signiifcantly higher Gd-IgA1 level than children in non-HSPN group (P<0.05). No signiifcant difference in Gd-IgA1 level was found either between HSPN group and refractory HSP group or between HSPN group and non-HSPN group (P>0.05). Furthermore, in non-HSPN group, the serum Gd-IgA1 level in HSP children who were not treated with glucorticoid was signiifcantly higher than that in HSP children treated with glucorticoid (P<0.05). Conclusions The serum Gd-IgA1 level is associated with the disease activ-ity and curative effect of HSP, especially in children with refractory HSP, and it is thus likely to be a new non-invasive disease activity marker for guiding the proper usage of glucocorticoid and immunosuppressants in HSP children.

Objective To explore whether the change of S phase kinase-associated protein 2 (Skp2) expression could regulate mesangial cell proliferation. Methods Skp2 siRNA and control siRNA, pIRES-GFP-Skp2 plasmid and pIRES-GFP plasmid were designed and synthesized. Cell transfection was performed by Lipofectamine 2000. Skp2 mRNA and protein levels were detected by semiquantitative PCR and Western blotting respectively. Primary culture rat mesangial cells were divided into 6 groups: 0%FCS, 20%FCS, 10%FCS+pIRES-GFP plasmid, 10%FCS+pIRES-GFP-Skp2 plasmid, 20%FCS+control siRNA, 20%FCS+Skp2 siRNA. Cell number was detected by MTT. S phase entry was measured by BrdU labeling. Cell cycle profile was determined by flow cytometric analysis. Results Skp2 mRNA level was significantly down-regulated by Skp2 siRNA compared to control siRNA. Skp2 protein level increased after pIRES-GFP-Skp2plasmid transfection compared to pIRES-GFP plasmid. MTT, BrdU labeling and cell cycle profile demonstrated that cell number (A: 0.419±0.088 vs 0.305±0.036, P＜0.01) and S-phase cells (BrdU labeling positive cell: 0.21±0.04 vs 0.15±0.03, P＜0.01;S-phase cell number:20.18±0.64vs 14.33±0.37, P＜0.01) obviously increased after Skp2 plasmid transfection, while decreased after Skp2 siRNA transfection compared to control groups (A: 0.328±0.069 vs 0.482±0.133, P＜0.01;BrdU labeling positive cell: 0.17±0.01 vs 0.24±0.00, P＜0.01; S-phase cell number: 16.52±0.75vs 23.81 ±1.25, P＜0.01). Conclusion Over-expression of Skp2 stimulates mesangial cell proliferation while down-regulated expression of Skp2 inhibits mesangial cell proliferation.

Objective To evaluate the relationship between endoscopic rectal aberrant crypt foci (ACF) and colon neoplasm, including lesions with high risk of aggressive progression (adenoma with diameter ≥ 1cm, villus adenoma, tubular-villus adenoma, adenoma of high grade dysplasia, or cancer). Methods The rectum of 212 patients who underwent colonoscopy was stained by 0. 4% indigo armine, and the patient was classified into different grade according to the number of rectal ACF, namely Grade 0 as no ACF, Grade Ⅰ as 1-4, Grade Ⅱ as 5-9 and Grade Ⅲ as more than 10. The correlation between rectal ACF grade and colon lesions was analyzed. Results Of 212 patients, 72 were classified as Grade 0, 48 as Grade Ⅰ , 41 as Grade Ⅱ, and 51 as Grade Ⅲ. The detection rate of colon neoplasm and lesions with high risk of aggressive progression in patients with rectal ACF were significantly higher than that in patients without rectal ACF (OR at 95% CI was 22. 352 (6. 716 -74. 395) and 7. 982 ( 1. 838-34. 672), respcetively). Conclusion Rectal ACF may predict the detection of colon lesions, including those with high risk of aggressive progression.