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To compare clinical efficacy of scarf osteotomy and double metatarsal osteotomy(DMO) in treating moderate to severe hallux valgus.Fifty patients (81 feet) with moderate to severe hallux valgus deformity were treated from January 2017 to December 2019, and were divided into Scarf osteotomy (SO) group or DMO group according to different osteotomy methods. There were 26 patients (44 feet) in SO group, including 1 male and 25 females, aged from 48 to 65 years old with an average of (55.5±4.67) years old;18 patients (30 feet) with moderate and 8 patients (14 feet) with severe. There were 24 patients(37 feet) in DMO group, including 1 male and 23 females, aged from 45 to 62 years old with an average of (52.1±6.8) years old;there were 14 patients (24 feet) with moderate and 10 patients (13 feet) with severe. Hallux valgus angle (HVA), intermetatarsal angle (IMA), distal metatarsal articular angle (DMAA) and relative length of the first metatarsal(RLFM) on weight-bearing anteroposterior radiographs before and after operation were compared. American Orthopaedic Foot and Ankle Society (AOFAS) hallux, metatarsal, and interphalangeal joint scores was used for evaluate clinical effects. Weight bearing time and complications were observed.Fivty patients were followed up. The follow-up time in SO group ranged from 12 to 36 months with an average of(20.50±6.22) months and from 16 to 28 months with an avaerge of(19.80±2.44) months in DMO group while there was no significant difference between two groups(Both of Scarf osteotomy and the first metatarsal biplane osteotomy could effectively treat moderate to severe hallux valgus deformity, with similar imaging and clinical evaluation. However, the relative length of the first metatarsal bone in SO group was longer than that in DMO group after operation, and the time of weight bearing in Scarf osteotomy is earlier than that of double metatarsal osteotomy of the first metatarsal.

Methylglyoxal (MGO), an endogenous reactive carbonyl compound, plays a key role in the pathogenesis of diabetic neuropathy. The aim of this study is to investigate the role of MGO in diabetic itch and hypoalgesia, two common symptoms associated with diabetic neuropathy. Methods: Scratching behavior, mechanical itch (alloknesis), and thermal hypoalgesia were quantified after intradermal (i.d.) injection of MGO in naive mice or in diabetic mice induced by intraperitoneal (i.p.) injection of streptozotocin (STZ). Behavioral testing, patch-clamp recording, transgenic mice, and gene expression analysis were used to investigate the mechanisms underlying diabetic itch and hypoalgesia in mice. Results: I.d. injection of MGO evoked dose-dependent scratching in normal mice. Addition of MGO directly activated transient receptor potential ankyrin 1 (TRPA1) to induce inward currents and calcium influx in dorsal root ganglia (DRG) neurons or in TRPA1-expressing HEK293 cells. Mechanical itch, but not spontaneous itch was developed in STZ-induced diabetic mice. Genetic ablation of Trpa1 (Trpa1-/- ), pharmacological blockade of TRPA1 and Nav1.7, antioxidants, and mitogen-activated protein kinase kinase enzyme (MEK) inhibitor U0126 abrogated itch induced by MGO or in STZ-induced diabetic mice. Thermal hypoalgesia was induced by intrathecal (i.t.) injection of MGO or in STZ-induced diabetic mice, which was abolished by MGO scavengers, intrathecal injection of TRPA1 blockers, and in Trpa1-/- mice. Conclusion: This study revealed that Nav1.7 and MGO-mediated activation of TRPA1 play key roles in itch and hypoalgesia in a murine model of type 1 diabetes. Thereby, we provide a novel potential therapeutic strategy for the treatment of itch and hypoalgesia induced by diabetic neuropathy.

To explore the clinical effect of vacuum sealing drainage (VSD) technique andFrom November 2017 to April 2019, 21 patients (21 feet) with foot skin defect were treated with VSD technique andAll the 21 patients were followed up for 7 to 17 (10.8±2.7) months. There was no infection or nonunion in all patients. At the final follow-up, the skin margin of the healing site grew tightly, the skin was elastic, the texture was tough, the appearance was no obvious carbuncle. The time of wound healing was for 18 to 63 (41.2±13.3) days. Eight patients underwent stageⅡfixation or/and fusion, and all incisions healed by stageⅠ. According to Maryland's foot scoring, 9 cases got excellent results, 11 good, and 1 middle.VSD can effectively remove the necrotic tissue of the wound, provide a smooth drainage of the wound, combine with

Autosomal-recessive nonsyndromic hearing loss (ARNSHL) features a high degree of genetic heterogeneity. Many genes responsible for ARNSHL have been identified or mapped. We previously mapped an ARNSHL locus at 17q12, herein designated DFNB99, in a consanguineous Chinese family. In this study, whole-exome sequencing revealed a homozygous missense mutation (c.1259G>A, p.Arg420Gln) in the gene-encoding transmembrane protein 132E (TMEM132E) as the causative variant. Immunofluorescence staining of the Organ of Corti showed Tmem132e highly expressed in murine inner hair cells. Furthermore, knockdown of the tmem132e ortholog in zebrafish affected the mechanotransduction of hair cells. Finally, wild-type human TMEM132E mRNA, but not the mRNA carrying the c.1259G>A mutation rescued the Tmem132e knockdown phenotype. We conclude that the variant in TMEM132E is the most likely cause of DFNB99.

Although 5-HT has been implicated in cholestatic itch and antinociception, two common phenomena in patients with cholestatic disease, the roles of 5-HT receptor subtypes are unclear. Herein, we investigated the roles of 5-HT receptors in itch and antinociception associated with cholestasis, which was induced by common bile duct ligation (BDL) in rats. 5-HT-induced enhanced scratching and antinociception to mechanical and heat stimuli were demonstrated in BDL rats. 5-HT level in the skin and spinal cord was significantly increased in BDL rats. Quantitative RT-PCR analysis showed 5-HT1B, 5-HT1D, 5-HT2A, 5-HT3A, 5-HT5B, 5-HT6, and 5-HT7 were up-regulated in peripheral nervous system and 5-HT1A, 5-HT1F, 5-HT2B, and 5-HT3A were down-regulated in the spinal cord of BDL rats. Intradermal 5-HT2, 5-HT3, and 5-HT7 receptor agonists induced scratching in BDL rats, whereas 5-HT3 agonist did not induce scratching in sham rats. 5-HT1A, 5-HT2, 5-HT3, and 5-HT7 agonists or antagonists suppressed itch in BDL rats. 5-HT1A agonist attenuated, but 5-HT1A antagonist enhanced antinociception in BDL rats. 5-HT2 and 5-HT3 agonists or antagonists attenuated antinociception in BDL rats. Our data suggested peripheral and central 5-HT system dynamically participated in itch and antinociception under cholestasis condition and targeting 5-HT receptors may be an effective treatment for cholestatic itch.

Itch (pruritus) is one of the most disabling syndromes in patients suffering from skin, liver, or kidney diseases. Our previous study highlighted a key role of oxidative stress in acute itch. Here, we evaluated the effects of antioxidants in mouse models of acute and chronic itch and explored the potential mechanisms. The effects of systemic administration of the antioxidants N-acetyl-L-cysteine (NAC) and N-tert-butyl-α-phenylnitrone (PBN) were determined by behavioral tests in mouse models of acute itch induced by compound 48/80 or chloroquine, and chronic itch by treatment with a mixture of acetone-diethyl-ether-water. We found that systemic administration of NAC or PBN significantly alleviated compound 48/80- and chloroquine-induced acute itch in a dose-dependent manner, attenuated dry skin-induced chronic itch, and suppressed oxidative stress in the affected skin. Antioxidants significantly decreased the accumulation of intracellular reactive oxygen species directly induced by compound 48/80 and chloroquine in the cultured dorsal root ganglia-derived cell line ND7-23. Finally, the antioxidants remarkably inhibited the compound 48/80-induced phosphorylation of extracellular signal-regulated kinase in the spinal cord. These results indicated that oxidative stress plays a critical role in acute and chronic itch in the periphery and spinal cord and antioxidant treatment may be a promising strategy for anti-itch therapy.

In the present study, we investigated whether restoring descending noradrenergic inhibitory tone can attenuate pain in a PD rat model, which was established by stereotaxic infusion of 6-hydroxydopamine (6-OHDA) into the bilateral striatum (CPu). PD rats developed thermal and mechanical hypersensitivity at the 4th week after surgery. HPLC analysis showed that NE content, but not dopamine or 5-HT, significantly decreased in lumbar spinal cord in PD rats. Additional noradrenergic depletion by injection of N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4) aggravated pain hypersensitivity in PD rats. At the 5th week after injection of 6-OHDA, systemic treatment with pharmacological norepinephrine (NE) precursor droxidopa (L-DOPS) orα2 adrenoceptor agonist clonidine significantly attenuated thermal and mechanical pain hypersensitivity in PD rats. Furthermore, application of norepinephrine (NE) and 5-hydroxytryptamine (5-HT) reuptake inhibitors duloxetine, but not 5-HT selective reuptake inhibitors sertraline, significantly inhibited thermal and mechanical pain hypersensitivity in PD rats. Systemic administration of Madopar (L-DOPA) or the D2/D3 agonist pramipexole slightly inhibited the thermal, but not mechanical, hypersensitivity in PD rats. Thus, our study revealed that impairment of descending noradrenergic system may play a key role in PD-associated pain and restoring spinal noradrenergic inhibitory tone may serve as a novel strategy to manage PD-associated pain.

Previous research on categorical perception of pitch contours has mainly considered the contrast between tone language and non-tone language listeners. This study investigates not only the influence of tone language vs. non-tone language experience (German vs. Chinese), but also the influence of different tone inventories (Mandarin tones vs. Cantonese tones), on the categorical perception of pitch contours. The results show that the positions of the identification boundaries do not differ significantly across the 3 groups of listeners, i.e., Mandarin, Cantonese, and German, but that the boundary widths do differ significantly between tone language (Mandarin and Cantonese) listeners and non-tone language (German) listeners, with broader boundary widths for non-tone language listeners. In the discrimination tasks, the German listeners exhibit only psychophysical boundaries, whereas Chinese listeners exhibit linguistic boundaries, and these linguistic boundaries are further shaped by the different tone inventories.

Endo-1,4-β-glucanase (EGase, EC 3.2.1.4) is proposed to be involved in the control of cell wall modification. However, the relationship between EGase and longan fruit growth remains obscure. In the present work, the expression profiles of three Dl-EGase genes in pericarp and aril tissues of longan fruit during growth and development were characterized; moreover, the effects of plant growth substances, naphthalene acetic acid (NAA) and thidiazuron (TDZ) on their expressions of fruits at two different developmental stages were also investigated. The results showed that high levels of EGase activities in aril were in accordance with rapid aril growth, and three Dl-EGase genes exhibited different expression patterns in pericarp and aril during fruit growth and development. Dl-EGase1 and Dl-EGase3 seemed to be associated with the growth of both pericarp and aril, while Dl-EGase2 was closely related to pericarp growth. In addition, treatment of NAA and TDZ at the stage of pericarp growth increased the EGase activities and induced the expressions of all the three Dl-EGases. However, when NAA or TDZ was applied at the rapid aril growth stage, the accumulations of Dl-EGase1 and Dl-EGase2 in the pericarp, and the accumulations of Dl-EGase1 and Dl-EGase3 in the aril were induced. Furthermore, the expression patterns of the three Dl-EGases showed different tissue specificity. It is thus speculated that Dl-EGase genes played a different role in longan fruit growth and were developmentally regulated, and more importantly, the responses of Dl-EGases to plant growth substances were different and dependent on fruit development stage and fruit tissue.

BACKGROUND: The aim of the present study was to investigate the expression profiles of three endo-1,4-β-glucanase (EGase, EC 3.2.1.4) genes during aril breakdown of longan fruit stored at room temperature (25 °C), low temperature (10 °C) or on transferring fruit stored at 10 °C for 20 days to 25 °C. RESULTS: Three longan full-length cDNAs, designated Dl-EGase1, Dl-EGase2 and Dl-EGase3, were isolated and characterized. EGase activity in aril tissues of longan fruit increased with the appearance of aril breakdown symptoms, while RNA gel blot analysis revealed that the accumulations of three Dl-EGase genes exhibited differential characteristics with the occurrence of aril breakdown. Dl-EGase2 may be involved in the aril breakdown in longan fruit at the later stage of storage at room temperature. Conversely, expression of Dl-EGase3 could be mainly involved in aril breakdown of fruit stored at 10 °C. In addition, Dl-EGase3 and Dl-Egase2 were related to the aril breakdown of fruit transferred from low temperature to room temperature. CONCLUSION: The results obtained in this study indicate that Dl-EGase genes are involved in the aril breakdown of longan fruit and that considerable variation exists between expression patterns of individual members of the EGase gene family. Copyright © 2009 Society of Chemical Industry

SummaryA full-length phenylalanine ammonia-lyase gene (PAL) cDNA, named DlPAL1, was isolated and characterised from harvested longan fruit. The expression pattern of DlPAL1 and PAL activities in relation to aril breakdown in longan fruit stored at different temperatures were investigated. The results showed that both PAL activity and the accumulation of DlPAL1 mRNA increased during storage at 25oC and at 10oC, which coincided with an increase in the aril breakdown index (ABI). The increase in PAL activity or in the accumulation of DlPAL1 mRNA coincided with the increase in ABI in fruit stored at 4oC for 40 d, then transferred to 25oC for 2 d. No accumulation of DlPAL1 mRNA throughout storage at 4oC could be detected, although the increase in PAL activity was in accordance with the increase in ABI. Furthermore, changes in DlPAL1 mRNA accumulation were not fully in accordance with the changes observed in PAL activity, and a rapid increase in PAL activity in arils was observed as aril breakdown occurred rapi...

Fresh fruit of longan (Dimocarpus longan Lour.) are susceptible to pericarp browning and aril breakdown. Aril breakdown in longan fruit is regarded as one of the most important factors reducing quality and shortening storage life of the fruit. To better understand the molecular mechanism of aril breakdown, the expression patterns of three expansin (EXP) and three xyloglucan endotransglucosylase (XET) genes in relation to the aril breakdown of longan fruit stored at room temperature (25 °C) or low temperature (4 °C) were investigated. The results showed that aril breakdown index increased progressively during storage at 25 and at 4 °C. Northern blotting analysis revealed that the accumulations of three EXP and three XET genes exhibited differential characteristics with the occurrence of aril breakdown. During storage at 25 °C, the accumulations of Dl-XET3 increased after 1 day, suggesting that Dl-XET3 correlated well with the early aril breakdown, while Dl-EXP3 together with Dl-XET1 and Dl-XET2 was involved in later aril breakdown. However, expression of Dl-XET1 and Dl-XET2 could be mainly involved in aril breakdown of longan fruit stored at 4 °C. In addition, Dl-EXP2, whose accumulation increased sharply when longan fruit were transferred from low temperature to room temperature within 12 hours, was related to the aril breakdown in this storage period. These data indicated that Dl-EXPs and Dl-XETs were closely related to aril breakdown in longan fruit.

Osteopetrosis is a rare genetically heterogeneous disorder of bone metabolism characterized by increased skeleton density. In the past, standard methods for genetic diagnosis of osteopetrosis have primarily been performed by candidate gene screening and positional cloning. However, these methods are time and labor consumptive; and the genetic basis of approximately 30% of the cases is yet to be elucidated. Here, we employed whole exome sequencing of two affected individuals from an osteopetrosis family to identify a candidate mutation in CLCN7 (Y99C). It was identified from a total of 1757 and 1728 genetic variations found in either patient, which were then distilled using filtering strategies and confirmed using Sanger sequencing. We identified this mutation in six family members, while not in population matched controls. This mutation was previously found in osteopetrosis patients by other researchers. Our evolutionary analysis also indicated that it is under extremely high selective pressure, and is likely to be critical for the correct function of ClC-7, and thus is likely to be the responsible cause of disease. Collectively, our data further indicated that mutation (Y99C) may be a cause of osteopetrosis, and highlights the use of whole exome sequencing as a valuable approach to identifying disease mutations in a cost and time efficient manner.

Background Punctate palmoplantar keratoderma (PPPK) is a rare autosomal dominant skin disorder characterised by numerous hyperkeratotic papules irregularly distributed on the palms and soles. To date, no causal gene for this disease has been identified. Methods We performed exome sequencing analysis of four affected individuals and two unaffected controls from one Chinese PPPK family where disease locus was mapped at 8q24.13-8q24.21 by our previous linkage analysis. Results We identified a novel heterozygous mutation in COL14A1 gene (c.4505C→T (p.Pro1502Leu)), which located within the linkage region that we previously identified for PPPK. The mutation was shared by the four affected individuals, but not for the two controls of the family. Sanger sequencing confirmed this mutation in another four cases from this family. This mutation was invisible in the normal controls of this family as well as the additional 676 unrelated normal controls and 781 patients with other disease. The shared COL14A1 mutation, p.Pro1502Leu, is a missense substitution at a highly conserved amino acid residue across multiple species. Conclusions The power of combining exome sequencing and linkage information in the study of genetics of autosomal dominant disorders, even in simplex cases, has been demonstrated. Our results suggested that COL14A1 would be a casual gene for PPPK, which was helpful for advancing us on understanding of the pathogenesis of PPPK.

Pure hair and nail ectodermal dysplasia (PHNED) is a congenital condition characterized by hypotrichosis and nail dystrophy. Autosomal-recessive PHNED has previously been mapped to chromosomal region 12q12-q14.1, which contains the type II hair keratin and HOXC clusters. Hoxc13-null mice are known to develop hair and nail defects very similar to those seen in human PHNED. We performed whole-exome sequencing in a consanguineous Chinese family affected by PHNED and identified a homozygous nonsense mutation (c.390CA [p.Tyr130(∗)]) in HOXC13 in all affected individuals. In an additional affected female from a consanguineous Afghan family, we found a 27.6 kb homozygous microdeletion involving the first exon of HOXC13. We examined HOXC13 expression in scalp specimen obtained from the index individual of the Chinese family and detected dramatically reduced mRNA levels in skin tissue and nearly absent protein staining in hair follicles, suggesting a mechanism of nonsense-mediated mRNA decay. We also observed markedly decreased expression of four HOXC13 target genes in the specimen. Taken together, our results demonstrate that loss-of-function mutations in HOXC13 cause autosomal-recessive PHNED and further highlight the importance of HOXC13 in hair and nail development.