The present study was designed to investigate the effect of late phase of whole body hypoxic preconditioning on endothelial-dependent vasorelaxation and cardioprotection from ischemia-reperfusion injury in spontaneously hypertensive rats (SHR). Hypoxic preconditioning was performed by subjecting rats to four episodes of alternate exposure to low O2 (8%) and normal air O2 of 10 min each. After 24 h, the mesenteric arteries and hearts were isolated to determine the vascular function and cardioprotection from ischemia-reperfusion (I/R) injury on the Langendorff apparatus. There was a significant impairment in acetylcholine-induced relaxation in norepinephrine precontracted arteries (endothelium-dependent function) and increase in I/R-induced myocardial injury in SHR in comparison to Wistar Kyoto rats (WKY). However, hypoxic preconditioning significantly restored endothelium-dependent relaxation in SHR and attenuated I/R injury in both SHR and WKY. Hypoxic preconditioning also led to an increase in the levels of endothelin-1 (not endothelin-2 or -3), vascular endothelial growth factor-A (VEGF-A) and HIF-1α levels. Pretreatment with bevacizumab (anti-VEGF-A) and bosentan (endothelin receptor blocker) significantly attenuated hypoxic preconditioning-induced restoration of endothelium-dependent relaxation and cardioprotection from I/R injury. These interventions also attenuated the levels of VEGF-A and HIF-1α without modulating the endothelin-1 levels. It may be concluded that an increase in the endothelin-1 levels with a subsequent increase in HIF-1α and VEGF expression may possibly contribute in improving endothelium-dependent vasorelaxation and protecting hearts from I/R injury in SHR during late phase of whole body hypoxic preconditioning.

AimsKeloid is a benign tumor that is characterized by the hyperproliferation of dermal fibroblasts and excessive deposition of extracellular matrix (ECM) especially the collagen. Aberrant activation of Wnt/β-catenin signaling is implicated in the pathogenesis of keloid. In this study, we investigated the effects of IWR-1, a small molecule inhibitor for Wnt/β-catenin signaling via the inhibition of tankyrase, on production of collagen and matrix metalloproteinase (MMP) in dermal fibroblasts.Main methodsWe cultured human normal skin- and keloid-derived fibroblasts, then treated with IWR-1. The effects of IWR-1 on collagen and MMP production were determined by Western blot, ELISA and zymography.Key findingsIWR-1 significantly suppressed the proliferation and migration of both the normal and keloid fibroblasts. IWR-1 also inhibited the production and secretion of type I collagen from the fibroblasts. In addition, IWR-1 significantly increased the expression of MMPs, such as MMP-1, MMP-3 and MMP-13, along with the increase of gelatinase activity. These results suggest that inhibitory effect of IWR-1 on collagen production may be related with the increased MMP activity.SignificanceThis study provides the possible action mechanism of IWR-1 on regulation of collagen expression, on which to base further investigation for preventing skin fibrotic diseases such as keloid.

AIMS:Keratinocytes are the predominant cells in the epidermis, exerting their primary role of physical barrier through sophisticated differentiation process. In addition, keratinocytes contribute to the activation of innate immunity, providing the surveillant role against external pathogens. It has been known that chronic skin inflammatory disease such as psoriasis can be provoked by viral pathogens including double-stranded RNA. In this study, we demonstrated that rosmarinic acid (RA) has an inhibitory potential on inflammatory reaction induced by double-stranded RNA mimic poly(I:C) in epidermal keratinocytes.MAIN METHODS:We cultured human epidermal keratinocytes and induced inflammatory reaction by poly(I:C) treatment. The effect of RA on inflammatory reaction of keratinocytes was determined by RT-PCR and Western blot.KEY FINDINGS:RA significantly inhibited poly(I:C)-induced expression of inflammatory cytokines including IL-1β, IL-6, IL-8, CCL20, and TNF-α, and downregulated NF-κB signaling pathway in human keratinocytes. In addition, RA significantly inhibited poly(I:C)-induced inflammasome activation, in terms of secretion of active form of IL-1β and caspase-1. Furthermore, RA markedly inhibited poly(I:C)-induced NLRP3 and ASC expression.SIGNIFICANCE:These results indicate that RA can inhibit poly(I:C)-induced inflammatory reaction of keratinocytes, and suggest that it may be a potential candidate for the treatment of psoriasis.

Background This study aimed to investigate the bone morphogenetic protein-2 (BMP-2) levels in serum and synovial fluid (SF) of patients with primary knee osteoarthritis (OA) and to exam its correlation with radiographic and symptomatic severity of the disease. Material/Methods A total of 37 knee OA patients and 20 healthy controls were enrolled in this study. Knee OA radiographic grading was performed according to the Kellgren-Lawrence (KL) grading system by evaluating X-ray changes observed in anteroposterior knee radiography. Symptomatic severity of the disease was evaluated according to the Western Ontario McMaster University Osteoarthritis Index (WOMAC) scores. BMP-2 levels in serum and SF were determined using enzyme-linked immunosorbent assay. Results Serum BMP-2 level in patients with knee OA was higher than that in healthy controls. Knee OA patients with KL grade 4 showed significantly elevated BMP-2 levels in the serum and SF compared with those with KL grade 2 and 3. Knee OA patients with KL grade 3 had significant higher SF levels of BMP-2 than those with KL grade 2. BMP-2 levels in the serum and SF of knee OA patients were both positively correlated with KL grades and WOMAC scores. Conclusions BMP2 levels in serum and SF were closely related to the radiographic and symptomatic severity of knee OA and may serve as an alternative biochemical parameter to determine disease severity of primary knee OA.

The aim of this research was to investigate the impact of calcium channel blockers (verapamil) on the formation of scars in the sciatic nerve anastomosis after peripheral nerve injury. One hundred twenty healthy, male Sprague-Dawley rats were selected and prepared with right sciatic nerve injury for this study. Samples were selected at the fourth and 12th weeks, respectively, after treatment and observations were made on the nerve anastomosis healing and diameter. Image analysis and statistical processing were carried out relating to the results of the study. The diameter of the anastomosis of the treatment group at weeks 4 and 12 was noticeably smaller than the control group (P < 0.05). In the treatment group at week 4, there were many vesicles observed in the fibroblasts' cytosol and in the control group, the fibroblasts exhibited high number of rough endoplasmic reticulum. The collagen content of the nerve scarring at week 12 in the treatment group was apparently less than the control group (P < 0.01). The calcium channel blocker (verapamil) reduced the axon resistance through the anastomosis during nerve regeneration. It can effectively inhibit the formation of scarring from nerve injury. It also provided an excellent microenvironment for the regeneration of nerve fibers.

Our study aimed to identify candidate genes associated with Dupuytren’s contracture (DC) and elucidate their roles in DC development. The microarray data of GSE21221 were downloaded from Gene Expression Omnibus database, including six samples from carpal tunnel-derived fibroblasts and six samples from DC-derived fibroblasts. The differentially expressed genes (DEGs) in DC samples were screened using limma package. GO annotation and KEGG pathway analyses were performed by DAVID online tool. Protein–protein interaction network and expression correlation network were constructed to identify crucial relationships between DEGs. Finally, candidate DC-associated genes were predicted based on comparative toxicogenomics database. A total of 529 DEGs (138 up- and 391 down-regulated) in DC-derived fibroblasts were screened and compared with carpal tunnel-derived fibroblasts. Only ten DC-associated genes, such as neurotrophin 3 (NTF3) and protein kinase C, epsilon (PRKCE), were further screened. In addition, NTF3 was significantly enriched in MAPK signaling pathway, in which other DEGs, such as nuclear receptor subfamily 4, group A, member 1 (NR4A1), fibroblast growth factor 22 (FGF22) and BDNF, were enriched. Besides, NTF3 could co-express with fibrillin 2 (FBN2), and PRKCE could co-express with zinc finger protein 516 (ZNF516), solute carrier organic anion transporter family, member 2A1 (SLCO2A1), chromosome 10 open reading frame 10 (C10orf10) and Kelch domain containing 7A (KLHDC7A). Our study indicates that these DEGs, including NTF3, FBN2, NR4A1, FGF22, BDNF, PRKCE, ZNF516, SLCO2A1, C10orf10 and KLHDC7A, may play important roles in DC development and serve as candidate molecular targets for treating DC.

Glycyrrhizin has a role in immune regulation in the central nervous system, but its impact on sciatic nerve injury had not previously been reported. In this study, a BALB/c mouse model of sciatic nerve injury was used to explore the role of glycyrrhizin in sciatic nerve repair and its underlying mechanism. Glycyrrhizin with intragastric gavage of 10 and 20 mg/kg weight per day (mid- and high-dose, respectively) inhibited p75 neurotrophin receptor (p75NTR) expression at the protein and mRNA levels versus the 5 mg/kg (low-dose) group and control (0.9% NaCl solution) at one, two, four and eight weeks following sciatic nerve injury, and simultaneously improved the action potential amplitude and motor nerve conductive velocity. Combined Mars land, Glees and Erikson's silver stain and Luxol fast blue staining results indicated that high- and mid-dose glycyrrhizin promoted improved sciatic nerve myelination compared with the low-dose or control groups eight weeks after injury. Immunofluorescence staining demonstrated that glycyrrhizin had an inhibitory effect to a certain degree on local hypertrophic scar and inflammatory responses in the mouse model. In conclusion, glycyrrhizin can promote sciatic nerve regeneration and functional repair, in which doses of 10 and 20 mg/kg per day are more effective than lower doses, and such regeneration is associated with the down regulation of p75NTR.

残指的残端痛在临床上比较常见,大部分是由残端神经瘤引起.残指的神经瘤性残端痛的治疗比较困难,且复发率较高.临床上治疗上臂残端及手指残端神经瘤性残端痛,常采用的手术方法为神经瘤骨骼肌内植入法、神经外膜包埋法、神经瘤骨内植入法、神经残端与肌腱残端吻合法、静脉桥接法、两神经残端直接缝合法[1]等方法,但其疗效各异.2010年10月我们采取小间隙静脉桥接神经吻合重建残端神经连续性的方法治疗12例指神经瘤性残端痛患者,取得了满意的疗效,现将临床观察报告如下.

BALB/c mice were intraperitoneally injected with 10, 5 or 2.5 mg/kg Brazil for 14 days after sciatic nerve injury. Results demonstrate that the spleen T/B lymphocyte stimulation index and serum circulating immune complex concentration were significantly reduced, and the morphology of the soleus muscle was restored in mice with sciatic nerve injury. These effects of Brazil were dose-dependent. Our experimental findings indicate that Brazil can regulate immune responses after nerve injury and promote sciatic nerve repair.

Objective To investigate the effectiveness of in situ osteotomy for correction of rotational deformity of the proximal phalanx. Methods Six cases of proximal phalanx rotational deformity resulted from fracture malunion were treated.Ostectomy was done at the site of the fracture via a dorsal approach.After correction of the rotation a contoured plate and screws were used for fixation. Results All patients were followup for 6 to 22 months.There was no infection or skin necrosis.Bone healing occurred in 6 to 9 weeks.There were no delayed union,nonunion or malunion. Conclusion In situ correction ostectomy can not only provide more accurate correction to restore finger function and appearance,but also addresses secondary tendon adhesion and decreases soft tissue damage.

正>本文对坐骨神经损伤BALB/c小鼠应用苦参碱,通过对坐骨神经相应脊髓节段S100蛋白表达的测定和神经电生理指标的观察,探讨苦参碱对周围神经损伤后的恢复作用。1材料与方法1.1实验动物和分组健康成年雄性BALB/c小鼠160只（体重25±2g,由吉林大学基础医学院实验动物中心提供）,单

Objective To compare the clinical results of arthrodesis of the proximal interphalangeal joints by miniplates and Kirschner wires respectively.Methods Fifty-nine cases with 85 intra-articular fractures and bone defects of the proximal interphalangeal joints were treated with arthrodesis by miniplate fixation (Group A,55 lesions in 38 cases) and by K-wire fixation (Group B,30 lesions in 21 cases).The functional outcomes were evaluated using the TAF criteria.Results Postoperative follow-up ranged from 4 to 39 months.There was no infection in group A,while 4 cases in group B had infection.The average duration of bone union was 7.2 weeks (range,6 to8 weeks) for group A and 11.4 weeks (range,7 to 16 weeks) for group B.The time for return to work was 13.1 weeks for group A and 17.9 weeks for group B.Excellent and good rate of 85.5％ (47/55) was achieved in group A,while in group B the excellent and good rate was 66.7％ (20/30).Conclusion Fixation by miniplates is more favorable in treating hand fractures than by using K-wires.

目的 探讨桡动脉穿支皮瓣修复手及腕部皮肤缺损的临床疗效.方法 应用前臂桡动脉穿支皮瓣修复手及腕部创面17例.结果 14例皮瓣全部成活,3例皮瓣远端坏死,经植皮后愈合.术后随访3～14个月,皮瓣血运、质地、感觉良好,手功能及皮瓣外形恢复满意.结论 应用桡动脉穿支皮瓣修复手部创面,血管解剖恒定,切取容易,值得临床推广应用.

拇指功能极为重要,占手功能的36％[1].只有最大限度地保留拇指的长度,才能正常发挥手部的功能.外伤后拇指皮肤缺损常伴有指骨、肌腱的外露,若处理不当,严重影响手部的功能,基本的治疗原则为最大限度保留拇指的长度[2].目前临床上修复拇指皮肤缺损的方法较多,有传统皮瓣、示指背侧岛状皮瓣、中指侧方岛状皮瓣、第二足趾趾腹皮瓣等各有其优点,但也不同程度的存在诸如治疗周期长、副损伤大、外观欠佳等缺点[3-5].2008年1月至2011年3月,我们采用虎口背侧逆行岛状皮瓣修复拇指皮肤缺损13例,术后受区外形及拇指的功能满意,报道如下。

Objective To investigate the BALB / c mice after sciatic nerve injury in the sciatic nerve after application of matrine corresponding spinal segment in the expression of gap-43.Methods Healthy adult BALB / c mice 320,consistent with unilateral sciatic nerve cut,the randomized dose,at different times for L4-6 spinal segment,using Real time-PCR detection of the corresponding spinal segment of sciatic nerve gap-43 expression changes,while the LFB myelin staining of sciatic nerve recovery.Results Realtime-PCR results indicate that high-dose and medium-dose group 12h,24h 3d 5d 1w,2w,4w,gap-43 expression was significantly higher than low-dose group and blank control group,8w no significant difference between the groups.LFB staining showed that the recovery of the sciatic nerve high-dose group was significantly better than low-dose group and control group.Conclusion application of sciatic nerve injury in the spinal cord of matrine on the corresponding segments of sciatic nerve cells in the activation of gap-43 play a catalytic role in reducing the infiltration of inflammatory cells to achieve the purpose of promoting nerve regeneration.

目的对应用拇指背侧皮瓣修复拇指远节软组织缺损的病例进行回顾性研究,探讨其应用方法、注意事项,评价其临床疗效。方法 2005年3月至2011年1月,应用包括拇指尺背侧和桡背侧皮瓣两种拇指背侧皮瓣,修复拇指远节皮肤软组织缺损共33例,其中应用拇指桡背侧皮瓣修复9例,拇指尺背侧皮瓣24例,皮瓣大小为1.0cm×2.0cm～2.5cm×3.0cm。结果术后4例发生静脉回流障碍,经对应处理2例部分坏死,1例完全坏死,其余30例皮瓣完全成活。随访3个月～2年,皮瓣质地优良,外形满意,拇指掌指关节及指间关节屈伸活动正常,外展与健侧无明显差异。结论两种拇指背侧皮瓣是修复拇指远节软组织缺损简单、实用的方法之一。

Objective Investigate anatomy basis of musculocutaneous nerve easy compression factor.Methods Dissect and observe both upper extremitries of four adults (eight sides),observe anatomy of the musculocutaneous nerve easy entrapment point.The effect of body position change to measure length,t-test analysis of measurement data.Results Point of afferens muscles of musculocutaneous nerve to coracobrachialis muscle and nerve piercing point at elbow of cutaneous antebrachii lateralis nerve facility formed stamped.When upper endoduction and upper abduction,the distance of point of afferens coracobrachialis muscles to coronoid process are:( 8.74 ± 1.24) cm,( 10.49 ± 1.29) cm.Distance change are statistically significant from the data ( t =2.765,P ＜ 0.05 ).The distance of point of efferens coracobrachialis muscles to coronoid process are:( 10.74 ± 1.23) cm,( 12.52 ± 1.32) cm,distance change are statistically significant from the data (t =2.786,P ＜ 0.05 ).Conclusion Facility formed stamped place of musculocutaneous nerve are point of afferens coracobrachialis muscles and nerve piercing point at elbow of cutaneous antebrachii lateralis nerve.The change of body position of upper is one of the factors of musculocutaneous nerve facility formed stamped.

目的 介绍应用(踇)趾及第二趾微型皮瓣游离移植修复手指掌侧软组织缺损的临床疗效.方法 2007年8月至2010年7月,对31例手指掌侧软组织缺损患者,其中拇指15例,示指7例,中指6例,示指及环指近节掌侧软组织伴动脉缺损3例.根据清创后创面情况,应用(踇)趾及第二趾微型皮瓣游离移植修复,其中(踇)趾腓侧皮瓣15例,第二趾胫侧皮瓣13例,第二趾C型皮瓣3例.皮瓣切取面积为1.5 cm× 1.5 cm～ 3.0 cm× 3.5 cm.结果 术后皮瓣存活良好,31例获得随访时间为6～ 12个月,皮瓣质地、弹性良好,指腹饱满,外形满意,皮瓣两点分辨觉达6～9mm.足趾供区创面均Ⅰ期愈合,不影响穿鞋和行走.结论 应用(踇)趾及第二趾微型皮瓣游离移植手术是修复手指掌侧软组织小面积缺损的理想治疗方法.

正>尽管外周神经修复技术日益提高,但临床上,神经的恢复疗效仍不令人满意[1]。尤其是臂丛神经的根性撕脱伤,可供移位的近端动力源神经很少,如何用细小的神经完成与粗大神经之间有效的神经传导