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BackgroundA previous validation study showed a very low sensitivity and higher specificity associated with Hanifin and Rajka criteria (H&R) and the UK Working Party criteria (UKWP) in diagnosing AD vs. the Chinese criteria of atopic dermatitis (AD) for children (CCAD). However, their diagnostic efficacy in adult and elderly Chinese populations remains unknown.ObjectivesTo validate the diagnostic efficacy of three sets of AD criteria in adult and elderly Chinese populations in a hospital setting.MethodsA total of 1034 patients (aged 19–95 years) from five university hospital dermatological clinics were recruited. Medical history, dermatological examination, AD diagnosis and evaluation of AD severity were done by dermatologists. Each patient was investigated by two dermatologist panels, one to establish a clinical diagnosis, and the other to identify and record the major or minor signs of H&R criteria, UKWP criteria and CCAD. Taking clinical diagnosis as the reference, the diagnostic efficacy of three sets of diagnostic criteria was evaluated. The χ2 test or rank sum test were used for between-groups comparisons.ResultsCCAD had a higher sensitivity (84.0%), especially among mild and moderate cases of AD (72.7% and 90.3%, respectively), than the H&R (58.0%; P < 0.001) and UKWP criteria (56.0%; P < 0.001) in diagnosing AD. The specificity of CCAD (92.7%) was slightly lower than the H&R (97.3%; P < 0.001) or UKWP criteria (97.4%; P < 0.001). The CCAD had the highest Youden index (0.77), accuracy rate (0.90) and Kappa value (0.76) of the three sets of diagnostic criteria.ConclusionsConsistent with results in a population of Chinese children, although the H&R and UKWP criteria had a high specificity for diagnosing AD, their low sensitivity limited their use in adult and elderly Chinese patients. Based on the high sensitivity and favourable diagnostic efficacy, the CCAD is proposed for AD diagnosis in adult and elderly Chinese populations, especially for cases of mild and moderate AD.

Epidermolysis bullosa (EB) is a heterogeneous group of rare and incurable genetic blistering disorders.The objective was to analyse the genotype-phenotype correlation in EB among Chinese individuals.Next-generation sequencing and Sanger sequencing were performed to genetically confirm clinically diagnosed EB. Reverse transcription-PCR and splice-site analysis were used to evaluate the consequences of splicing mutations.A total of 441 cases (413 families) across 11 genes were included. EB simplex (EBS), junctional EB (JEB), dystrophic EB (DEB), Kindler EB, simplex and junctional compound EB accounted for 23.4%, 12.7%, 61.5%, 1.1% and 0.2%, respectively. In 16 probands with presumptive recessive EB, failed to find the second allele, COL7A1 (10), COL17A1 (4), LAMB3 (1) and ITGB4 (1). De novo mutations are common in dominant EB (63.8% in EBS, 27.5% in DEB) but extremely rare in recessive DEB (RDEB; 0.74%). Mosaicism is more common than presumed, with 5.4% of dominant EBS. In JEB, only 45.0% of patients with biallelic premature termination codon (PTC) mutations in laminin 332 genes died within 24 months, with a longer average survival age of 11.1 months. In JEB, unusual phenotypes are frequently observed, notably urinary tract involvement, duodenal atresia and EB nevi. In RDEB, 48.8% of cases with biallelic PTC mutations in COL7A1 exhibited a relatively mild phenotype; they are likely to develop a severe phenotype at 0-4 years old, and the PTC mutations position closer to the N-terminal, leading to earlier onset. Glycine substitution mutations in DEB have complex genotypic and phenotypic heterogeneity. The rare subtype, dominant and recessive compound DEB, consists of 1.8% of the total DEB.This study reveals the general rules governing genotype-phenotype correlations, rare phenotypes and complex genotypes. Collectively, mutation analysis in different forms of EB provides the basis for improved subclassification with accurate genetic counselling and for prenatal diagnosis.

Cutaneous warts caused by human papillomavirus are benign proliferative lesions that occur at any ages in human lives. Updated, comprehensive and systematic evidence-based guidelines to guide clinical practice are urgently needed.We collaborated with multidisciplinary experts to formulate this guideline based on evidences of already published literature, focusing on 13 clinical questions elected by a panel of experts. We adopted Grading of Recommendations Assessment, Development and Evaluation (GRADE) system to form classification of recommendations as well as the improved Delphi method to retain respective recommendations with a consensus degree of over 80%.Our guideline covered aspects of the diagnosis and treatment of cutaneous warts such as diagnostic gold standard, transmission routes, laboratory tests, treatment principle, clinical cure criterion, definitions, and treatments of common warts, flat warts, plantar warts, condyloma acuminatum, and epidermodysplasia verruciformis. Recommendations about special population such as children and pregnant women are also listed. In total, 49 recommendations have been obtained.It is a comprehensive and systematic evidence-based guideline and we hope this guideline could systematically and effectively guide the clinical practice of cutaneous warts and improve the overall levels of medical services.

Focal facial dermal dysplasias type III (FFDD III), commonly known as Setleis syndrome (SS; Online Mendelian Inheritance in Man #227260), is a type of focal facial dermal dysplasia, characterized by bitemporal atrophic skin lesion. The homozygous mutations in the TWIST2 gene and copy number variants (CNV) at chromosome 1p36.22p36.21 were reported as the pathogenic mechanism. In this study, we collected DNA samples from a large Chinese family affected by FFDD and found no mutation of TWSIT2. To determine the underlying genetic cause, we performed a multipoint parameter linkage analysis and haplotype analysis of the family 1 and mapped SS to a region Chr1:14.074-20.524cM (rs2401090-rs2294642). Copy number variant was identified by Sanger sequencing, which breakpoints were Chr1:11695972 and Chr1:11829858. The region contains eight genes, including FBXO2, FBXO44, FBXO6, MAD2L2, DRAXIN, AK125437, AGTRAP, and C1orf167. There were no candidate gene mutations of the second family with SS. Our study further reduced the size of CNV resulting in SS (Chr1:11696993-11829858) and focused on eight genes.

Cutaneous infection by Balamuthia mandrillaris is a rare condition that is sometimes complicated by life-threatening CNS involvement. It often evades timely diagnosis due to its rarity and non-specific clinical manifestations. Patients can be either immunocompetent or immunocompromised. It is probably transmitted via inhalation or inoculation through broken skin, and then spreads to the brain and other organs through haematogenous spread. It is important for clinicians to be aware of this disease because rapid diagnosis and subsequent therapy has, in some cases, been associated with survival. In this Grand Round, we report the case of a 7-year-old boy who presented with large, chronic plaques on his face. Several biopsies showed non-specific granulomatous inflammation. The patient deteriorated rapidly and died within 1 month of displaying abnormal symptoms in the CNS. Immunohistochemical staining of skin tissue identified B mandrillaris as the infectious agent. The diagnosis was confirmed with PCR, which detected B mandrillaris DNA in formalin-fixed skin tissue sections. B mandrillaris infection should be considered in the differential diagnosis of patients with chronic granulomatous lesions. We also reviewed the epidemiology, B mandrillaris in nature and in the laboratory, clinical manifestations, histopathology, diagnosis, and treatment of infection.

Palmoplantar keratoderma Bothnia type (PPKB) is caused by AQP5 pathogenic variants. The mechanisms of this disease and the genotype-phenotype correlation are still not fully understood. We report two pedigrees with PPKB caused by a recurrent variant c.367AT and a novel variant c.530TA in the AQP5 gene, respectively. We also summarize the cases with AQP5 variants identified, and found that there seemed to be no significant genotype-phenotype correlation of this disease. Moreover, we noticed that the epidermis of the patient had strong proliferation and immature differentiation potential as well as recognizing the possible important role of TRPV4 in the pathogenesis of PPKB.

Passivating contacts based on poly-Si have enabled record-high c-Si solar cell efficiencies due to their excellent surface passivation quality and carrier selectivity. The eventual existence of pinholes within the ultra-thin SiOx layer is one of the key factors for carrier collection, beside the tunneling mechanism. However, pinholes are usually believed to have negative impact on the passivation quality of poly-Si passivating contacts. This work studied the influence of the pinhole density on the passivation quality of ion-implanted poly-Si passivating contacts by decoupling the pinhole generation from the dopants diffusion process by means of two annealing steps: (1) a pre-annealing step at high temperature after the intrinsic poly-Si deposition to visualize the formation of pinholes and (2) a post-annealing step for dopants activation/diffusion after ion-implantation. The pinhole density is quantified in the range of 1✕106 to 3✕108 cm2 by the TMAH selective etching approach. The passivation quality is discussed with respect to the pinhole density and the post-annealing thermal budget (TB) for dopants diffusion. The study shows that a moderate pinhole density does not induce doping profile variations that can be detectable by the coarse spatial resolution of ECV measurements. It is surprising that the existence of pinholes in a moderate density within our thickness fixed SiOx layer can effectively enhance the passivation qualities for both n+ and p+ poly-Si passivating contacts. We speculate the reason is due to the enhanced field-effect passivation at the pinhole surrounding. In fact, the variation of the passivation quality depends on the balance between a strengthened field-effect passivation and an excessive local Auger recombination, being both effects induced by the higher and deeper level of dopants diffused into the c-Si surface through the pinholes.

An innovative dopant-free ZnS/p-Si heterojunction solar cell features hole selective WO3 contact were fabricated by thermal evaporation at room temperature. Light soaking effect was observed in the ZnS/p-Si heterojunction solar cells for the first time. The device performance is found to increase with the increasing light soaking times and finally reaches saturation. Besides, when the illumination stops, the power conversion efficiency (PCE) would decrease slightly. Device performance under different light soaking time and preservation time in the dark were investigated. Moreover, different monochromatic illuminations were conducted to further specify the active layer that is responsible for the light soaking effect. The result shows the ZnS layer and the short-wavelength light absorbed in ZnS layer are supposed to be the main reason for the effect. Based on these results, a model was proposed from the point of view of defect states variation in the energy band of ZnS to explain the effect. At last, Deep Level Transient Spectroscopy (DLTS) measurements with different monochromatic illumination were conducted to further verify the proposed model.

Holocarboxylase synthetase deficiency (HSD) is a rare autosomal recessive disorder of biotin metabolism. Typical manifestations include irreversible metabolic disorders and erythroderma-like dermatitis. Most patients respond well to biotin supplementation. Psoriasis-like phenotype associated with this disease has been rarely reported in the literature and experiences with the use of biologics in patients with HSD are still lacking. We reported a rare case of recurrent psoriasis-like skin lesions in a 6-year-old child with HSD. The patient did not respond to initial therapy with high-dose oral biotin. Immunofluorescence staining showed an increased number of interleukin (IL)-17A+ cells in his skin lesions. Based on this finding, the patient was successfully treated with human anti-IL-17A monoclonal antibody (secukinumab). He did not report any side effects and remained healthy during the 2-year follow-up. We provide a comprehensive review of the reported cases of HSD with psoriasis-like dermatitis to date. The psoriasis-like phenotype of HSD is controversial in treatment and IL-17A inhibitor is an alternative therapeutic option.

This study aimed to investigate the relationship between centrifugal lipodystrophy (CLD) and lupus erythematosus panniculitis (LEP), and the efficacy and safety of hydroxychloroquine (HCQ) for treating CLD in children. A total of 29 cases clinically diagnosed as CLD (n = 24) and CLD/LEP overlap (n = 5) were enrolled and all were confirmed by skin biopsies of CLD and LEP. The clinicopathological findings, clinical outcomes, and prognosis with the treatment of HCQ between CLD and LEP were compared. All 29 cases (male: female = 1:1.6; median age at onset: 3 years) had cutaneous lesions of centrifugally expanding lipoatrophy, of which five cases overlapped with LEP lesions presented as erythematous indurated plaque (n = 2), subcutaneous nodules (n = 2) and alopecia along Blaschko's lines (n = 1). Antinuclear antibodies were found in six (25.0%) CLD and two (40.0%) overlapped patients (p = 0.597). Histopathologically, of the 24 cases of CLD, 14 (58.5%) exhibited subcutis loss or mild lobular inflammation. Ten (41.7%) cases displayed lobular panniculitis with moderate to dense lymphohistiocytic infiltrate and plasma cells, similar to the five cases of overlap. Small clusters of CD123 positive plasmacytoid dendritic cells were found in 62.5% (5/8) of CLD and 66.7% (2/3) of overlap cases (p 0.99). HCQ (5 mg/kg/d) treatment showed improvement in 91.3% (21/23) of CLD and all overlap cases, including four cases unresponsive to previous oral glucocorticosteroid treatment. Our findings suggested that CLD and LEP represent a spectrum within the same disease. HCQ (5 mg/kg/d) was effective and safe for treating CLD (age 1.5 years), and early treatment and a regular long-term follow-up are essential.

The energy conversion efficiency (η) of silicon heterojunction (SHJ) solar cells is limited by the current losses in the layer stack on the illuminated side. To reduce these losses, hydrogenated nanocrystalline silicon oxide (nc-SiOx:H) was implemented as a window layer in SHJ solar cells. However, the integration of nc-SiOx:H in devices without degradation of fill factor (FF) is still a challenge. To optimize the electron performance of devices, the optoelectronic properties and microstructure of nc-SiOx:H were characterized and analyzed systematically. It was found that the PH3 gas fraction (fPH3) plays a big role on the microstructure, oxygen content, and phosphorus (P) doping efficiency of the films. The highest conductivity, 2.84 × 10–1 S/cm, is obtained at a moderate fPH3 with an optical band gap of 2.26 eV. A ternary model was creatively used to show the variation in the composition of nc-SiOx:H as tuning fPH3. The growth of crystalline phase was accelerated by the P dopants when fPH3 is low, but further increasing fPH3 leads to excessive P inactive dopants, causing a phase transition from nanocrystalline silicon to amorphous silicon in nc-SiOx:H. In this work, the best solar cell with an nc-SiOx:H window layer achieves an FF of 81.4%, a short current density (Jsc) of 39.8 mA/cm2, an open-circuit voltage (Voc) of 731 mV, and an η of 23.7% at the moderate fPH3. A decrease in FF and Jsc is shown with higher fPH3, which is the consequence of the increased front contact resistivity and decreased optical band gap of nc-SiOx:H window layer.

Children with severe atopic dermatitis (AD) can benefit from intravenous immunoglobulin (IVIG) therapy. This study aimed to identify the efficacy and safety of IVIG therapy in children with severe AD. Twenty pediatric AD patients were enrolled in this study. Patients with an Investigator's Global Assessment score of 0 or 1 or a reduction of 2 points after treatment were defined as high-responders (HRs), otherwise, they were defined as low-responders (LRs). Twelve patients (60%) achieved an excellent treatment response after 2 months, while eight (40%) had a low response. The Scoring Atopic Dermatitis index had improved significantly at 2 months post-treatment compared with baseline (p 0.001). Baseline total serum IgE levels and eosinophil counts were elevated in all subjects and decreased significantly at 2 months post-treatment (p = 0.004 and 0.021, respectively). Baseline IgE levels were significantly higher in the HR group compared with the LR group (p = 0.020). The treatment was well tolerated. Fever was the most common adverse event and occurred in five patients (25%). In conclusion, IVIG could be a safe and effective therapy for children with severe AD and may be more effective in patients with higher IgE levels. Further studies are needed to investigate the different therapeutic responses in patients with different AD phenotypes.

Objective:. Biallelic mutations in the RecQ like helicase (RECQL) 4 gene, a guardian of the genome, cause Rothmund–Thomson syndrome type II (RTS-II). Two Chinese girls with mild-phenotype RTS-II mainly restricted to their skin are herein described. Methods:. Blood specimens from two families with mild-phenotype RTS-II were collected. DNA isolation, RNA isolation and complementary DNA synthesis, and next-generation sequencing using a multi-gene panel were applied to verify the underlying pathogenic variants in the causative RECQL4 gene. Results:. We analyzed two patients with mild phenotypes. One patient had an unreported paternal c.2885+1G>A alteration in intervening sequence 16 and the previously reported maternal exon 14 c.2272C>T (p.R758X), both resulting in premature termination codons. The other patient carried two novel alterations, c.2886-1G>A and c.2752G>T (p.E918X). Complementary DNA sequencing showed that different splice-site mutations within the same intron could lead to completely different splicing modes. Conclusion:. We identified three novel pathogenic RECQL4 variants in two patients with RTS, thus expanding the mutational spectrum of RTS-II. We also explored their pathogenic effect by transcripts analysis to address genotype–phenotype correlations.

Background Severe dermatitis, multiple allergies and metabolic wasting (SAM) syndrome comprise a rare genodermatosis associated with biallelic (homozygous or compound heterozygous) mutations in the DSG1 (desmoglein-1) gene, or heterozygous mutations in the DSP (desmoplakin) gene. To date, while many patients with SAM syndrome have been described, the number of cases with SAM syndrome with deep-intronic variants, together its genetic aetiology, remain limited. Objectives We report the case of a five-year-old Chinese boy with atypical SAM syndrome. Materials & methods Relevant blood specimens from the family were collected. DNA isolation, RNA isolation and cDNA synthesis, and next-generation sequencing using a multi-gene panel were applied to verify the pathogenic gene. To test the functional consequences and pathogenic mechanism of the deep-intronic mutation in vitro, a mini gene strategy was constructed. Results A heterozygous DSG1 deletion (c.2437_2450delACCTATCCCTCGGG: p.Tyr814Trpfs*6) and a deep-intronic (c.1688-30A > T) variant were identified. The identified intronic variant was shown to create an alternative splice site, leading to nonsense-mediated mRNA decay of the aberrant transcript. Conclusion This is the first study to demonstrate a causal role for a deep-intronic DSG1 mutation in a patient with SAM syndrome. Our findings underline the need to analyse the intronic regions of DSG1 in patients with SAM syndrome. Improved diagnosis and a better understanding of prognosis will lead to clearer a picture of the concept of atypical SAM syndrome.

Diffuse plane xanthomas (DPX) is a rare, chronic, metabolic skin disease which can seriously affect the appearance of the patients and result in psychological problems. Existing treatments are seriously limited. Our objective was to assess the efficacy of and tolerance to simvastatin ointment for the treatment of skin lesions in seven DPX patients. In this study, patients were treated twice daily on the right side of the lesions for 10 months with the 1% or 5% simvastatin ointment. Meanwhile, the left body was untreated as a contralateral controlled side. Efficacy was assessed via the change of rash and was further confirmed by histological study. For all seven participants, both the 1% and 5% simvastatin ointments were effective. The histological change in DPX showed significant decrease of foam cells in skin lesions. The immunohistochemical staining of CD68, macrophage scavenger receptor type 1, oxidized low-density lipoprotein receptor 1 and Oil Red O became obviously reduced after treatment. The test medicines were safe with only some skin-related side-effects. This is the first research reported on simvastatin ointment treatment in DPX. Our results are the first to suggest that simvastatin ointment is effective in improving skin lesions of DPX clinically and histopathologically.

Dopant-free carrier-selective contacts have gained attention for application in silicon solar cells because of their simpler preparation process and low-temperature fabrication. However, there were few reports on efficient p-Si solar cells having dopant-free electron contacts. In this study, indium sulfide (In2S3) thin films were successfully deposited by simple thermal evaporation at room temperature and used as dopant-free electron-selective contacts on the front side of p-Si heterojunction solar cells. The changes in crystal structures, optical properties, compositions, and energy-band structures of the In2S3 thin films due to different annealing temperatures were investigated. The champion conversion efficiency of 10.72% was achieved with lightly doped, textured front Czochralski (Cz) p-Si wafers, and a low thermal energy cost. This study demonstrates that In2S3 film is an effective electron-selective contact for silicon solar cells, providing an alternative simple process to the fabrication of dopant-free optoelectronic devices.

Background Psoriasis is an immune-mediated, chronic inflammatory disease with diverse phenotypes. However, its biological diversity has not been well-characterized in Chinese psoriasis population. Objectives To characterize psoriasis biological heterogenicity using gene expression profiles of lesional skin biopsy specimens in a Chinese psoriasis population. Methods Lesional tissues and blood samples from Chinese psoriasis patients (n = 40), atopic dermatitis (AD) patients (n = 25) and age-matched healthy controls (n = 19) were investigated by using real-time PCR array, histological evaluation and flow cytometry. Unsupervised hierarchical clustering was performed using gene expression profiles of patients with psoriasis. Results Two distinct psoriasis clusters were identified. Both clusters indicated high TH 17 activation. One cluster (n = 6 of 40 consecutive psoriasis patients) indicated a strong TH 2 component in skin lesions, with early onset and low peripheral blood eosinophil level. Significantly higher IL-4, IL-13, IL-25, IL-31 and TSLP gene induction typified this cluster of psoriasis patients, even compared with AD patients. Both psoriasis clusters were characterized by neutrophilic microabscess formation. Histologically, the TH 2 high psoriasis cluster indicated a low percentage of perivascular eosinophils. Conclusions Two distinct psoriasis clusters were identified. One presented early onset and a low eosinophil level, indicating TH 17 polarization and a strong TH 2 component. These results laid the foundation for further demonstrating the pathogenesis of psoriasis in Chinese population.

Epidermolysis bullosa (EB) is a heritable blistering disorder. We performed a next-generation sequencing-based multigene panel test and successfully predicted 100% of the EB types, including, 36 EB simplex (EBS), 13 junctional EB (JEB), 86 dystrophic EB (DEB), and 3 Kindler EB. Chinese JEB and recessive DEB (RDEB) patients have relatively mild phenotypes; for severe type separately accounts for 45.5% and 23.8%, respectively. We identified 96 novel and 49 recurrent pathogenic variants in 11 genes, although we failed to detect the second mutation in one JEB and five RDEB patients. We identified one novel p.E475K mosaic mutation in the clinically normal mother of one out of 13 EBS patients with KRT5 mutations, one recurrent p.G2034R mosaic mutation, and one novel p.G2043R mosaic mutation in the clinically normal relatives of two out of 19 dominant DEB patients. This study shows that next-generation technology could be an effective tool in diagnosing EB.

In this study, two (18.2%) clinically unaffected parents from 11 trios were identified with mosaic KRT14 variants.To our knowledge, this is the first report to study the proportion of low-level mosaicism in the clinically unaffected parents whose children were previously regarded as sporadic EBS cases.

Thin films of transition metal oxides such as molybdenum oxide (MoOx) are attractive for application in silicon heterojunction solar cells for their potential to yield large short-circuit current density. However, full control of electrical properties of thin MoOx layers must be mastered to obtain an efficient hole collector. Here, we show that the key to control the MoOx layer quality is the interface between the MoOx and the hydrogenated intrinsic amorphous silicon passivation layer underneath. By means of ab initio modelling, we demonstrate a dipole at such interface and study its minimization in terms of work function variation to enable high performance hole transport. We apply this knowledge to experimentally tailor the oxygen content in MoOx by plasma treatments (PTs). PTs act as a barrier to oxygen diffusion/reaction and result in optimal electrical properties of the MoOx hole collector. With this approach, we can thin down the MoOx thickness to 1.7 nm and demonstrate short-circuit current density well above 40 mA/cm2 and a champion device exhibiting 23.83% conversion efficiency.

Excellent surface passivation induced by (i)a-Si:H is critical to achieve high-efficiency silicon heterojunction (SHJ) solar cells. This is key for conventional single-junction cell applications but also for bottom cell application in tandem devices. In this study, we investigated the effects of (i)a-Si:H deposition temperature on passivation quality and SHJ solar cell performance. At the lower end of temperatures ranging from 140°C to 200°C, it was observed with Fourier-transform infrared spectroscopy (FTIR) that (i)a-Si:H films are less dense, thus hindering their surface passivation capabilities. However, with additional hydrogen plasma treatments (HPTs), those (i)a-Si:H layers deposited at lower temperatures exhibited significant improvements and better passivation qualities than their counterparts deposited at higher temperatures. On the other hand, even though we observed the highest VOCs for cells with (i)a-Si:H deposited at the lowest temperature (140°C), the related FFs are poorer as compared to their higher temperature counterparts. The optimum trade-off between VOC and FF for the SHJ cells was found with temperatures ranging from 160°C to 180°C, which delivered independently certified efficiencies of 23.71%. With a further improved p-layer that enables a FF of 83.3%, an efficiency of 24.18% was achieved. Thus, our study reveals two critical requirements for optimizing the (i)a-Si:H layers in high-efficiency SHJ solar cells: (i) excellent surface passivation quality to reduce losses induced by interface recombination and simultaneously (ii) less-defective (i)a-Si:H bulk to not disrupt the charge carrier collections.