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

Objective:To investigate the relevant situation of the emergency departments (ED) of general hospitals at all levels in Zhejiang Province participating in the prevention and control of Corona Virus Disease 2019 (COVID-19), and to provide a reference for further improving the capacity of emergency services.Methods:A multi-center cross-sectional investigation study was jointly initiated by the Zhejiang Provincial Emergency Medicine Quality Control Center, the Emergency Medicine Branch of Zhejiang Medical Association, and the Emergency Physicians Branch of Zhejiang Medical Doctors Association. Before investigation, experts were organized to develop a special questionnaire. Then the ED of general people's hospitals or Chinese Medicine hospitals at the county/district-level or above were included and their participations in the prevention and control of COVID-19 epidemic between March 9, 2020 and March 15, 2020 were investigated. The collected information included: basic information of the hospitals; participation of ED in fever clinics; the number of COVID-19 patients admitted to ED; the situation of ED support to the anti-epidemic front-line; and the epidemic prevention facilities of ED, and the early supply of medical protective equipments.Results:A total of 181 hospitals from 11 prefectures and cities across the province were finally included, including 52 (28.7%) Grade-A tertiary hospitals, 45 (24.9%) Grade-B tertiary hospitals, 64(35.4%) Grade-A secondary hospitals, and 20 (11.0%) Grade-B secondary or lower hospitals. Among them, 93 (51.4%) were COVID-19 designated hospitals, and 49 (27.1%) had the ability to detect COVID-19 nucleic acid; 177 (97.8%) set up independent fever clinics and 33 (18.6%) were managed by ED alone or mainly. The medical staffs of 65 (36.7%) fever clinics were all or mainly from ED. A total of 213 cases of COVID-19 were received/treated in 40.3% ED, accounting for 17.3% of the total number of cases in Zhejiang Province. A total of 3 848 doctors and nurses supported the front-line of epidemic prevention, of them, 253 supported Hubei Province (accounting for 12.5% ??of the total number). There were 68.5% and 76.8% ED having spare separate clinic and ordinary rescue single room to deal with the COVID-19. In addition, at the early days of anti-epidemic, more than 50% ED were in short supply or even had no medical protective equipment.Conclusions:The ED of Zhejiang Province plays an important role and has made a great contribution to the prevention and control of the COVID-19 epidemic. It is necessary to improve the conditions of ED to effectively respond to the prevention and control of daily infectious diseases.

OBJECTIVE： To investigate the effects of tacrolimus combined with valsartan in immunosuppressive regimen on renal function， lipid metabolism and matrix metalloproteinase 2 （MMP-2）， MMP-9， tissue inhibitors of matrix metalloproteinases 2 （TIMP-2） and transforming growth factor-β （TGF-β） in patients with chronic allograft dysfunction （CAD）. METHODS： CAD patients admitted to nephrology department of our hospital from Mar. 2016 to Jun. 2018 were enrolled in group A， B， and C according to the random number table， 34 cases in each group. Group A was given cyclosporin A+Mycophenolate capsules+Prednisone acetate tablets； group B was treated with tacrolimus+Mycophenolate capsules+Prednisone acetate tablets； group C was treated with valsartan on the basis of group B； they were treated for continuous 3 months. Renal function indexes （24 h urinary protein， Scr）， lipid metabolism indicators （TC， TG， HDL， LDL） and the levels of MMP-2， MMP-9， TIMP-2 and TGF-β were compared among those groups. RESULTS： Before treatment， there was no statistical significance in above indexes among 3 groups （P＞0.05）. After treatment， 24 h urinary protein， Scr and TC levels of group A were still higher than normal level， while other lipid metabolism indexes were within normal range. 24 h urinary protein and TC level of group B were still higher than normal level， while Scr level was near the upper limit of the normal range， and other lipid metabolism indicators were within the normal range. Renal function indexes and lipid metabolism indexes of group C were within normal range， while renal function indexes levels of it were lower than those of group B （P＜0.05）； there was no statistical significance in lipid metabolism indexes， compared with group B （P＞0.05）. Compared with before treatment， TGF-β level of group A was significantly increased （P＜0.05）； there was no statistical significance in MMP-2， MMP-9 or TIMP-2 levels （P＞0.05）. TGF-β level of group B and group C was increased significantly （P＜0.05）， while the levels of MMP-2， MMP-9 and TIMP-2 were decreased significantly （P＜0.05）. CONCLUSIONS： Tacrolimus combined with valsartan can effectively delay renal dysfunction and improve lipid metabolism in CAD patients. The mechanism may be related to the inhibition of TIMP-2， MMP-2， MMP-9 and TGF-β expression.

OBJECTIVE: To investigate the influence of oridonin on the killing activity of NK-92 MI cells targeting THP1 and the related mechanism. METHODS: The killing activity of NK-92 MI to THP1 before and after oridonin treatment was detected by LDH release assay; the expression of natural killer cell ligands activating receptor D (NKG2D, including MICA, MICB, ULBP1, ULBP2 and ULBP3) was detected by real-time quantitative polymerase chain reaction (qRT-PCR) and Western blot respectively; the expression of cytokine TNF-α, TNF-β and IFN-γ in the co-culture supernatant of NK-92 MI cells and THP1 cells were measured by ELISA. RESULTS: The killing efficiency after oridonin treatment at different effector-target ratio (1:1, 5:1, 10:1) was all significantly up-regulated in comparison with that before oridonin treatment (P＜0.05). QRT-PCR and Western blot showed that the expressions of mRNA and protein levels of MICB, ULBP1, ULBP2 increased to varying degree (P＜0.05), but the expression levels of MICA and ULBP3 were not statistically significant between experimental group and control group (P＞0.05). ELISA results indicated that IFN-γ and TNF-β release were significantly increased after oridonin treatment (P＜0.05), however, the TNF-α release was not statistically different in comparison with control group (P＞0.05). CONCLUSION Oridonin can significantly improve killing efficiency of NK-92 MI on THP1, that might be related with up-regulation of MICB, ULBP1 and ULBP2 expression and promotion of IFN-γ and TNF-β release.
Cell Line, Tumor ; Diterpenes, Kaurane ; pharmacology ; GPI-Linked Proteins ; Histocompatibility Antigens Class I ; Humans

Objective To understand the general self-efficacy level of patients with tuberculosis(TB patients) and its influencing factors, provide evidence for improving the general self-efficacy of TB patients.Methods All TB inpatients in a comprehensive pulmonary hospital were conducted face-to-face survey through a general questionnaire and general self-efficacy scale, self-efficacy level of TB patients and its influencing factors were analyzed.Results Mean scale of general self-efficacy of 402 TB patients was (20.4±4.2), of which only 14 cases(3.5%)showed a high level self-efficacy.163(40.5%), 225(56.0%), and 14(3.5%)patients were with low(10~),medium(20~), and high(30~) self-efficacy scale.The general self-efficacy level of TB patients was influenced by the course of disease(P<0.001), residence(P=0.012), whether or not attended the lecture on tuberculosis education(P=0.034), whether or not conducted physical exercise(P=0.053,stepwise multiple linear regression analysis: P=0.017), working status(P=0.027), No.of hospitalization due to TB(P=0.002), family economic situation(P=0.027), and education level(P=0.020).Conclusion TB patients' self-efficacy level is low, and the general self-efficacy level and its influencing factors should be assessed by health care workers during the follow-up for patients, individualized nursing intervention for improving the TB patients' self-efficacy level should be developed.

Objective:To compare expression levels of matrix Gla protein (MGP) and bone morphogenetic protein 2 (BMP-2) in Randall's plaque of renal papillary tissues in patients with calcium oxalate kidney stones and the underlying mechanism for stone formation.Methods:A total of 30 samples of Randall's plaque in renal papillary tissues from patients with calcium oxalate kidney stones were collected from the Department of Urology of Xiangya Hospital of Central South University from April,2015 to December,2015 and served as an experimental group.Ten samples of renal papillary tissues in patients undergone renal tumor nephrectomy were collected from the same hospital and served as a control group.The expressions of MGP and BMP-2 mRNA and protein were detected by quantitative real-time PCR and Western blot.Meanwhile,immunohistochemical technique was used to observe the expressions of MGP and BMP-2 in different parts of renal papillary tissues in the 2 groups.Results:1) The mRNA expression levels of MGP in the experimental group and the control group were 0.760±0.804 and 1.365±0.348,respectively,with significant difference between them (P＜0.05).Them RNA levels of BMP-2 in the experimental group and the control group were 2.500±0.725 and 1.485±0.870,respectively,with significant difference between them (P＜0.05).The expression levels of MGP protein in the experimental group and the control group were 0.130±0.424 and 0.202±0.704,respectively,with no significant difference between them (P＞0.05).The expression levels of BMP-2 protein in the experimental group and the control group were 0.885±0.220 and 0.682±0.272,respectively,with significant difference between them (P＜0.05).T-he immunohistochemistry showed that the protein expression of MGP in the experimental group was lower than that in the control group,while the protein expression of BMP-2 in the experimental group was higher than that in the control group (both P＜0.05).Conclusion:The BMP-2 expression is increased while MGP expression is decreased in renal papillary tissues in patients with calcium oxalate kidney stones,and the formation of calcium oxalate kidney stone might be a kind ofosteogenetic reaction or ectopic calcification.

OBJECTIVETo investigate the value of serum IgA/C3 ratio in the diagnosis of IgA nephropathy and explore its relationship with the clinicopathological features of the patients.

METHODSSixty-six patients with IgA nephropathy, 111 with other glomerular diseases, and 40 healthy control subjects without kidney disease were tested for serum IgA and C3 levels using CRM470 adjusted standardized immune turbidimetric method, and the IgA/C3 ratio was calculated. According to Oxford and Lee's classification criteria, we analyzed the pathological grades of the renal biopsy samples from patients with IgA nephropathy. The ROC curve was used to assess the value of serum IgA and IgA/C3 ratio in predicting IgA nephropathy.

RESULTSPatients with IgA nephropathy had an elevated serum IgA/C3 ratio than those with other glomerular diseases and the control subjects, with an area under the ROC curve of 0.776. An elevated serum IgA/C3 ratio was not found to significantly correlate with the pathological grade of renal biopsy samples in patients with IgA nephropathy.

CONCLUSIONIn the absence of renal biopsy findings, serum IgA/C3 ratio can help in the diagnosis of IgA nephropathy.

Biopsy ; Case-Control Studies ; Complement C3 ; analysis ; Glomerulonephritis, IGA ; blood ; diagnosis ; Humans ; Immunoglobulin A ; blood ; Kidney ; pathology

OBJECTIVETo analyze the quantity and size distribution of 24-hour urinary extracellular vesicles (uEVs) from healthy adults.

METHODSThe 24-hour uEVs from 9 healthy adults were isolated by hydrostatic filtration dialysis (HFD). The effectiveness of uEVs enrichment was evaluated using Western blotting and transmission electron microscopy (TEM). The quantity and size distribution of the uEVs was analyzed with BCA protein quantification, TEM, and nanoparticle tracking analysis (NTA).

RESULTSuEVs with different sizes and morphologies were observed under TEM. Western blotting confirmed the expression of TSG101 in all the uEV fractions from the 9 donors, ranging from 132.50 to 760.70 ng/mL. NTA results showed that the number of 24-hour uEVs amount ranged from 3.56 × 10¹² particles to 5.12 × 10¹² particles, with a CV of 14.23%. The proportion of the vesicles with a diameter <40 nm was 0.04%-0.69% with a number range of (1.80-26.49)× 10⁹ particles; the proportion of vesicles with a diameter of 40-100 nm (which is consistent with the size of exosomes)was 22.07%-42.08% with a number range of (1.00-1.77)× 10¹² particles. The proportion of vesicles with a diameter of 100-1000 nm (consistent with the size of microvesicles) was 57.88%-77.85% with a number range of (2.09-3.86)× 10¹² particles.

CONCLUSIONThe established HFD method allows efficient and convenient isolation of uEVs from a large amount of urine samples. The 24-hour uEVs from healthy adults show narrow differences between individuals and thus can be an ideal source of samples for relevant studies.

Adult ; Blotting, Western ; Cell-Derived Microparticles ; Exosomes ; Extracellular Vesicles ; Humans ; Microscopy, Electron, Transmission ; Nanoparticles ; Urine

Objective To investigate the value of serum IgA/C3 ratio in the diagnosis of IgA nephropathy and explore its relationship with the clinicopathological features of the patients. Methods Sixty-six patients with IgA nephropathy, 111 with other glomerular diseases, and 40 healthy control subjects without kidney disease were tested for serum IgA and C3 levels using CRM470 adjusted standardized immune turbidimetric method, and the IgA/C3 ratio was calculated. According to Oxford and Lee's classification criteria, we analyzed the pathological grades of the renal biopsy samples from patients with IgA nephropathy. The ROC curve was used to assess the value of serum IgA and IgA/C3 ratio in predicting IgA nephropathy. Results Patients with IgA nephropathy had an elevated serum IgA/C3 ratio than those with other glomerular diseases and the control subjects, with an area under the ROC curve of 0.776. An elevated serum IgA/C3 ratio was not found to significantly correlate with the pathological grade of renal biopsy samples in patients with IgA nephropathy. Conclusion In the absence of renal biopsy findings, serum IgA/C3 ratio can help in the diagnosis of IgA nephropathy.

Objective To investigate the value of serum IgA/C3 ratio in the diagnosis of IgA nephropathy and explore its relationship with the clinicopathological features of the patients. Methods Sixty-six patients with IgA nephropathy, 111 with other glomerular diseases, and 40 healthy control subjects without kidney disease were tested for serum IgA and C3 levels using CRM470 adjusted standardized immune turbidimetric method, and the IgA/C3 ratio was calculated. According to Oxford and Lee's classification criteria, we analyzed the pathological grades of the renal biopsy samples from patients with IgA nephropathy. The ROC curve was used to assess the value of serum IgA and IgA/C3 ratio in predicting IgA nephropathy. Results Patients with IgA nephropathy had an elevated serum IgA/C3 ratio than those with other glomerular diseases and the control subjects, with an area under the ROC curve of 0.776. An elevated serum IgA/C3 ratio was not found to significantly correlate with the pathological grade of renal biopsy samples in patients with IgA nephropathy. Conclusion In the absence of renal biopsy findings, serum IgA/C3 ratio can help in the diagnosis of IgA nephropathy.