Mutation p.Arg127Pro in the 1A Domain of KRT16 Causes Pachyonychia Congenita in Chinese Patient: A Case Report of PC Associated with Acral Melanoma.

Pachyonychia congenita (PC) is a group of rare hereditary disorders, characterised by hypertrophic nails and palmoplantar keratoderma (PPK), particularly localised to the pressure areas of the feet. At a molecular level, it is caused by mutations in genes encoding KRT6A, KRT6B, KRT6C, KRT16, or KRT17. To identify the underlying gene mutation in a Chinese family with PC presenting with disabling palmoplantar keratoderma and subsequent associated acral melanoma. Genomic DNA was extracted from peripheral blood samples of three available individuals in the Chinese family, which included the patient and his two unaffected sisters. The index patient presented with severe palmoplantar keratoderma as well as a newly diagnosed acral malignant melanoma (MM). Whole-exome sequencing (WES) was carried out with amplification of exon 1 of KRT16 by polymerase chain reaction (PCR). PCR products were then sequenced to identify potential mutations. We identified the proline substitution mutation p.Arg127Pro (c.380G>C) in our patient's 1A domain of KRT16. The same mutation was not found in his sisters or unrelated healthy controls. The mutation (p.Arg127Pro (c.380G>C)) in KRT16 has been reported in Dutch patients with PC. However, it is the first such report of a patient with a PC of Chinese origin. In addition, the acral MM occurred under the background of genetic PPK caused by KRT16 mutation in this patient.

[Intra-annual radial growth of Abies georgei and Larix potaninii and its responses to environmental factors in the Baima Snow Mountain, Northwest Yunnan, China.] / æ»‡è¥¿åŒ—ç™½é©¬é›ªå±±é•¿è‹žå†·æ‰å’Œå¤§æžœçº¢æ‰å¹´å† å¾„å‘ç”Ÿé•¿åŠ¨æ€åŠå ¶å¯¹çŽ¯å¢ƒå› å­çš„å“åº”.

Using high-resolution dendrometers, we monitored the intra-annual stem radial variations of Abies georgei and Larix potaninii in the subalpine coniferous forest in Baima Snow Mountain, Northwest Yunnan Province. The seasonal dynamics of stem radial growth of both species and their responses to environmental factors were analyzed. The results showed that the stem radial growth of A. georgei and L. potaninii mainly occurred during April to August, with the maximum growth rate in June. Compared with A. georgei, L. potaninii showed an earlier start but later cessation of stem radial growth, resulting in longer growth duration. Annual radial growth and maximum radial growth rates of L. potaninii were slightly higher than those of A. georgei. Daily growth rate of A. georgei was positively correlated with precipitation, but negatively correlated with vapor pressure deficit and air temperature. Daily growth rate of L. potaninii was positively correlated with precipitation, but negatively correlated with soil volume water content and vapor pressure deficit. Radial growth of A. georgei and L. potaninii was limited by water availability, with L. potaninii being more sensitive to moisture. Under the background of global warming, the increase of plant transpiration and soil evaporation might further aggravate soil water loss and reduce water availability for plants, which would make A. georgei and L. potaninii more vulnerable to drought stress.

G59S mutation in the GJB2 gene in a Chinese family with classic Vohwinkel syndrome.

Vohwinkel syndrome (VS) is a rare autosomal dominant condition, also known as mutilating palmoplantar keratoderma accompanied by sensorineural deafness. The LOR and GJB2 genes are reported to be responsible for VS. The GJB2 gene encodes connexin 26, a component of intercellular gap junctions expressed in various tissues. We report the case of a 31-year-old Chinese woman with classic VS characterized by sensorineural deafness and mutilating palmoplantar keratoderma. Further genetic studies demonstrated a nucleotide change (c.175G>A) in the GJB2 gene, leading to an amino acid alteration (G59S). This identical missense mutation (G59S) has also been reported in a patient with Bart-Pumphrey syndrome. Together with our findings and previous studies, we conclude that the identical mutation (G59S) in the GJB2 gene contributes to various manifestations.

The role of Sprouty1 in the proliferation, differentiation and apoptosis of epidermal keratinocytes.

OBJECTIVES: Sprouty (SPRY) 1 is one of the SPRY proteins that inhibits signalling from various growth factors pathways and has also been known as a tumour suppressor in various malignancies. However, no study elucidates the role of SPRY1 in the skin. Our study was conducted to determine the function of SPRY1 in human keratinocytes and the epidermis. MATERIALS AND METHODS: In vitro primary cultured epidermal keratinocytes were used to investigate the proliferation, differentiation and apoptosis of these cells. We also established overexpression of SPRY1 in vitro and K14-SPRY1 transgenic mice. RESULTS: SPRY1 was mainly located in the cytoplasm of the epidermal keratinocytes from the granular epidermal layer of the skin and cultured cells. Overexpressed SPRY1 in keratinocytes resulted in up-regulation of P21, P27 and down-regulation of cyclin B1; decrease in MMP3 and integrin α6. SPRY1-overexpressed primary keratinocytes exhibited a lower proliferation and migration capability and higher rates of apoptosis. Epidermis of SPRY1-TG mice represented delayed wound healing. Proteomics analysis and GO enrichment showed DEPs of SPRY1 TG mice epidermis is significantly enriched in immune- and inflammatory-associated biological process. CONCLUSIONS: In summary, SPRY1 expression was inversely correlated with cell proliferation, migration and promote cell apoptosis of keratinocytes. SPRY1 maybe a negative feedback regulator in normal human epidermal keratinocytes and cutaneous inflammatory responses. Our study raised the possibility that enhancing expression of SPRY1 may have the potential to promote anti-inflammatory effects.

Inhibition of the hedgehog pathway leads to antifibrotic effects in dermal fibrosis.

Dermal fibrosis is characterized by the activation of the matrix-producing 'positive' myofibroblasts, and the relentless production and deposition of extracellular matrix. The hedgehog pathway has recently been demonstrated to work in a pro-fibrotic manner in systemic sclerosis (SSc). A negative regulator of the hedgehog pathway (Hh), the suppressor of fused (Sufu), was shown to be involved in the activation of fibrotic diseases. However, the exact role of Sufu in fibrosis has not been investigated so far. In our study, we aimed to define the role of sufu in the process of fibrosis using dermal fibroblasts of healthy donors that were cultured in vitro. Cyclopamine, a Smo antagonist, and Sufu lentivector were used to treat or transfect cells. The expression of fibrosis markers and ERK1/2, Smad2, and GSK3ß at the protein level was determined by Western blot. Fibroblast migration was measured by in vitro wound healing assay. Bleomycin-induced dermal fibrosis mouse model was introduced to assess the effect of cyclopamine on dermal fibrosis in vivo. We found that cyclopamine significantly upregulated the expression of Sufu. Both cyclopamine and Sufu lentivector reduced migration and myofibroblast differentiation of human dermal fibroblasts at a statistically significant level. Furthermore, cyclopamine reversed dermal fibrosis induced by TGF-ß1. Cyclopamine and the overexpression of Sufu inhibited the phosphorylation of GSK-3ß and restrained the migration of fibroblasts. Dermal fibrosis was inhibited by intraperitoneal injection of cyclopamine in a mouse model of scleroderma. Our findings suggest that cyclopamine and Sufu-overexpression may effectively inhibit the endogenous as well as the TGF-ß1-induced activation of fibroblasts through subsequent activation of GSK-3ß. Sufu agonists may be a promising approach in the development of antifibrotic medications for dermal fibrosis and systemic sclerosis.

[Coupling effect of water and nitrogen on mechanically harvested cotton with drip irrigation under plastic film in arid area of western Inner Mongolia, China.] / å† è’™å¤è¥¿éƒ¨æ—±åŒºæœºé‡‡æ£‰è†œä¸‹æ»´çŒæ°´æ°®è€¦åˆæ•ˆåº”.

In order to understand the main and interactive effects of water and nitrogen on crop growth and development, yield, fiber quality, and water-nitrogen use efficiency of mechanically harvested cotton with drip irrigation under plastic film in arid area of western Inner Mongolia, a two-factorial experiment with irrigation water amount and nitrogen dosage in completely randomized block design was conducted in Alxa Left Banner of Alxa League in Inner Mongolia. The levels of water irrigation were 216 mm (W1), 288 mm (W2) and 360 mm (W3), and the nitrogen dosages were 127.5 kg·hm-2(N1), 195 kg·hm-2(N2) and 262.5 kg·hm-2(N3). The results showed that water was the decisive factor for cotton growth, and plant height and dry matter accumulation increased rapidly with increasing the water irrigation level, but the ratio of reproductive organs to shoot biomass decreased. Compared with the treatments W1 and W2, the average boll number per plant in W3 was increased by 25.4% and 17.5%, the seed cotton yield was improved by 18.1% and 11.9%, but the single boll mass was decreased by 5.8% and 4.6%, respectively. It indicated that an increase in boll number per plant was the determining factor in achieving high seed cotton yield. Moreover, there was also a significant interactive effect between water and nitrogen affecting the seed cotton yield. Under the condition with low-level irrigation (W1 and W2), the highest seed cotton yield was measured in N1; while for the condition in W3, the seed cotton yield in N2 was greater than that in N1 and N3 by 8.5% and 31.9%, respectively. In general, the regulation of water and nitrogen had no significant effect on fiber quality. Water use efficiencyin W1N1 was 1.37 kg·m-3, which was not significantly different with the value in W3N2, and the nitrogen partial factor productivityin W3N1 was the maximum (51.35 kg·kg-1). Therefore, irrigation had a significant effect on yield increasing, but nitrogen application promoted the seed cotton yield only under well-watered conditions. The treatment with irrigation amount of 360 mm and nitrogen fertilizer of 195 kg·hm-2 could promote the shoot biomass accumulation significantly and achieve the highest seed cotton yield, and its water use efficiency and nitrogen partial factor productivity were 1.37 kg·m-3 and 36.41 kg·kg-1, respectively, indicating the potential of water-saving and yield increasing. Therefore, it was recommended as a suitable water and nitrogen management for the mechanically harvested cotton in arid area of western Inner Mongolia.

Multiple facial basal cell carcinomas in xeroderma pigmentosum treated with topical imiquimod 5% cream.

Xeroderma pigmentosum (XP) is an autosomal recessive disease characterized by solar sensitivity, photophobia, early onset of freckling, and solar-induced cutaneous neoplastic changes. Management of patients with XP is a therapeutic challenge as they usually develop multiple cutaneous malignancies, making surgical therapy difficult, and continue to form skin malignancies at a high rate. We describe a 30-year-old Chinese man with XP who had been previously treated with excision and dermatoplasty. Upon recurrence of multiple superficial, ulcerative, and pigmented lesions, imiquimod 5% cream was recommended for 4 months. His multiple facial lesions demonstrated an excellent response to topical imiquimod 5% cream with minor side effects. This favorable response indicates that topical application of imiquimod 5% cream is an effective means of treating multiple basal cell carcinomas in XP.

Genome-wide association study in a Chinese Han population identifies nine new susceptibility loci for systemic lupus erythematosus.

We performed a genome-wide association study (GWAS) of systemic lupus erythematosus (SLE) in a Chinese Han population by genotyping 1,047 cases and 1,205 controls using Illumina Human610-Quad BeadChips and replicating 78 SNPs in two additional cohorts (3,152 cases and 7,050 controls). We identified nine new susceptibility loci (ETS1, IKZF1, RASGRP3, SLC15A4, TNIP1, 7q11.23, 10q11.22, 11q23.3 and 16p11.2; 1.77 x 10(-25) < or = P(combined) < or = 2.77 x 10(-8)) and confirmed seven previously reported loci (BLK, IRF5, STAT4, TNFAIP3, TNFSF4, 6q21 and 22q11.21; 5.17 x 10(-42) < or = P(combined) < or = 5.18 x 10(-12)). Comparison with previous GWAS findings highlighted the genetic heterogeneity of SLE susceptibility between Chinese Han and European populations. This study not only advances our understanding of the genetic basis of SLE but also highlights the value of performing GWAS in diverse ancestral populations.