Tibial cortex transverse transport surgery improves wound healing in patients with severe type 2 DFUs by activating a systemic immune response: a cross-sectional study.

BACKGROUND: Tibial cortex transverse transport (TTT) surgery has become an ideal treatment for patients with type 2 severe diabetic foot ulcerations (DFUs) while conventional treatments are ineffective. Based on our clinical practice experience, the protective immune response from TTT surgery may play a role against infections to promote wound healing in patients with DFUs. Therefore, this research aimed to systematically study the specific clinical efficacy and the mechanism of TTT surgery. MATERIALS AND METHODS: Between June 2022 and September 2023, 68 patients with type 2 severe DFUs were enrolled and therapized by TTT surgery in this cross-sectional and experimental study. Major clinical outcomes including limb salvage rate and antibiotics usage rate were investigated. Ten clinical characteristics and laboratory features of glucose metabolism and kidney function were statistically analyzed. Blood samples from 6 key time points of TTT surgery were collected for label-free proteomics and clinical immune biomarker analysis. Besides, tissue samples from 3 key time points were for spatially resolved metabolomics and transcriptomics analysis, as well as applied to validate the key TTT-regulated molecules by RT-qPCR. RESULTS: Notably, 64.7% of patients did not use antibiotics during the entire TTT surgery. TTT surgery can achieve a high limb salvage rate of 92.6% in patients with unilateral or bilateral DFUs. Pathway analysis of a total of 252 differentially expressed proteins (DEPs) from the proteomic revealed that the immune response induced by TTT surgery at different stages was first comprehensively verified through multi-omics combined with immune biomarker analysis. The function of upward transport was activating the systemic immune response, and wound healing occurs with downward transport. The spatial metabolic characteristics of skin tissue from patients with DFUs indicated downregulated levels of stearoylcarnitine and the glycerophospholipid metabolism pathway in skin tissue from patients with severe DFUs. Finally, the expressions of PRNP (prion protein) to activate the immune response, PLCB3 (PLCB3, phospholipase C beta 3) and VE-cadherin to play roles in neovascularization, and PPDPF (pancreatic progenitor cell differentiation and proliferation factor), LAMC2 (laminin subunit gamma 2) and SPRR2G (small proline rich protein 2G) to facilitate the developmental process mainly keratinocyte differentiation were statistically significant in skin tissues through transcriptomic and RT-qPCR analysis. CONCLUSION: Tibial cortex transverse transport (TTT) surgery demonstrates favorable outcomes for patients with severe type 2 DFUs by activating a systemic immune response, contributing to anti-infection, ulcer recurrence, and the limb salvage rate for unilateral or bilateral DFUs. The specific clinical immune responses, candidate proteins, genes, and metabolic characteristics provide directions for in-depth mechanistic research on TTT surgery. Further research and public awareness are needed to optimize TTT surgery in patients with severe type 2 DFUs.

Scaling variation in the pinch-off of colloid-polymer mixtures.

HYPOTHESIS: The scaling laws of drop pinch-off are known to be affected by drop compositions including dissolved polymers and non-Brownian particles. When the size of the particles is comparable to the characteristic length scale of the polymer network, these particles may interact strongly with the polymer environment, leading to new types of scaling behaviors not reported before. EXPERIMENTS: Using high-speed imaging, we experimentally studied the time evolution of the neck diameter hmin of drops composed of silica nanoparticles dispersed in PEO solution when extruded from a nozzle. FINDINGS: After initial Newtonian necking with hmin âˆ¼ t2/3, the subsequent stage may exhibit scaling variation, characterized by either exponential or power-law decay, depending on the nanoparticle volume fraction ϕ. The exponential decay hmin âˆ¼ e-t/τ signifies the coil-stretch transition in typical viscoelastic suspensions. We conducted an analysis of the power-law scenario hmin âˆ¼ tα at high ϕ, categorizing the entire process into three distinct regimes based on the exponents α. The dependences of critical thicknesses at transition points and exponents on polymer concentration offer initial insights into the potential transition from heterogeneous to homogeneous thinning in the mixture. This novel scaling variation bears implications for accurately predicting and controlling droplet fragmentation in industrial applications.

ATP2C1 knockdown induces abnormal expressions of cytoskeletal and tight junction proteins mimicking Hailey-Hailey disease.

Background Hailey-Hailey disease (HHD) is a rare, autosomal dominant, hereditary skin disorder characterised by epidermal acantholysis. The HHD-associated gene ATPase calcium-transporting type 2C member 1 (ATP2C1) encodes the protein secretory pathway Ca2+ ATPase1 (SPCA1), playing a critical role in HHD pathogenesis. Aims We aimed to investigate the effect of ATP2C1 knockdown on keratinocytes that mimicked acantholysis in HHD. Methods Immunohistochemistry (IHC) was employed to evaluate the levels of cytoskeletal and tight junction proteins such as SPCA1, P-cofilin, F-actin, claudins, occludin, and zonula occludens 1 in the skin biopsies of patients with HHD. Subsequently, the expression of these proteins in cultured ATP2C1 knockdown keratinocytes was analysed using Western blotting and immunofluorescence. Furthermore, we assessed the proliferation, apoptosis, and intracellular Ca2+ concentrations in the ATP2C1-knocked keratinocytes. Results The results showed decreased levels of these proteins (SPCA1, P-cofilin, F-actin, claudins, occluding, and zonula occludens 1) in HHD skin lesions. Moreover, their levels decreased in human keratinocytes transfected with ATP2C1 short hairpin RNA, accompanied by morphological acantholysis. Furthermore, the proliferation and apoptosis of the keratinocytes, as well as intracellular calcium concentrations in these cells, were not affected. Limitations The limitations of this study are the absence of animal experiments and the failure to explore the relationship between skeletal and tight junction proteins. Conclusion The present study indicated that ATP2C1 inhibition led to abnormal levels of the cytoskeletal and tight junction proteins in the keratinocytes. Therefore, keratinocytes can mimic HHD-like acantholysis and serve as an in vitro model, helping develop treatment strategies against HHD.

Increased Level of Serum Wingless-Type Mouse Mammary Tumor Virus Integration Site Family Member 5a in Patients with Cutaneous Lichen Planus.

PURPOSE: Cutaneous lichen planus (CLP) is an autoinflammatory skin disorder, and it is associated with metabolic syndrome. Wingless-type mouse mammary tumor virus integration site family member 5a (Wnt5a) is a potential factor in metabolic complications and it was shown to be upregulated in CLP lesions. Whether Wnt5a is altered in the circulation of patients with CLP is unclear. This study aimed to measure serum Wnt5a level in patients with CLP and to assess its relationship with body mass index (BMI). METHODS: We included 46 adult patients with CLP and 38 healthy adults as control. Serum Wnt5a was measured using enzyme-linked immunosorbent assay. RESULTS: The mean serum Wnt5a was significantly higher in patients than controls (all P-value <0.001). The mean serum Wnt5a levels in obese (BMI between 30 and 40) patients were significantly higher than lean (BMI between 20 and 25) patients (P-value <0.001). Compared to lean patients with CLP, the concentration of serum Wnt5a levels was increased gradually with BMI score (all P-value <0.05). CONCLUSION: Serum Wnt5a might be a potential biomarker for CLP and it was associated with BMI. An increase in serum Wnt5a may contribute to the development of metabolic comorbidity in CLP patients.

The LncRNA MIR155HG is Upregulated by SP1 in Melanoma Cells and Drives Melanoma Progression via Modulating the MiR-485-3p/PSIP1 Axis.

BACKGROUND: MIR155HG is a long non-coding RNA (lncRNA) that has been shown to be dysregulated in a range of tumor types, but the functions of this lncRNA in melanoma remain to be explored. OBJECTIVES: We explored the functions of lncRNA MIR155HG in melanoma progression. METHODS: The expression of miR155HG was analyzed in clinical melanoma. Bioinformatics analysis was performed to assess the potential tumor-related functions of miR155HG. The interaction of miR155HG and SP1 and the inhibition of PSIP1 by miR-485-3p were analyzed by ChIP, luciferase reporter experiments, and the biological effects in melanoma were explored by colony formation assays, EdU cell proliferation assays, Transwell analysis, and intracranial melanoma mouse model. RESULTS: Herein, we found that MIR155HG was markedly upregulated in melanoma cell lines and tissues. We further determined that the SP1 transcription factor was responsible for driving MIR155HG upregulation in melanoma. Elevated MIR155HG levels were linked to decreased overall survival (OS) in melanoma patients, and we further determined that MIR155HG expression was an independent predictor of melanoma patient prognosis. When MIR155HG was knocked down in melanoma cells, this impaired their proliferative, migratory, and invasive activity. By using predictive bioinformatics analyses, we identified miR-485-3p as a microRNA (miRNA) capable of binding to both MIR155HG and the 3' UTR of PSIP1. CONCLUSION: Together, these results suggest that MIR155HG is capable of promoting melanoma cell proliferation via the miR-485-3p/PSIP1 axis. These novel findings provide new insights into the development of melanoma, potentially highlighting future avenues for therapeutic intervention.

Ilizarov technology in China: a historic review of thirty-one years.

PURPOSE: To summarize the evolution of Ilizarov technology in China, highlight important milestones, introduce the atmosphere of the era concerning the first uses and development of this technology, and share Chinese modification and experience in this field. METHOD: A thorough interview with senior ASAMI members of China and literature search and physical books in libraries was undertaken to summarize the history of Ilizarov technology in China. RESULTS: The formal development of Ilizarov technology began when professor Ilizarov himself came to Beijing (1991) and gave a speech. In the following 31 years, his technology was rapidly developed through China, with many symposiums held and associations established including ASAMI China (2003) and ILLRS China (2015). Today, Ilizarov technology has become the main treatment of complex fractures, defects, nonunion, infections, deformities, and chronic ischemic ulcers of the limbs. In those years, Chinese scholars also developed some special treatment methods and made many modifications to Ilizarov external fixators. CONCLUSION: Ilizarov technology has developed in China for 31 years. It revolutionized the treatment of complex limb traumas, deformities, and diseases. In the treatment of millions of patients, Chinese scholars had many unique experiences and made modifications to this technology which is worthy to share with the world.

The Levels of Wnt5a and Its Receptors Frizzled5 and Frizzled2 as Immunohistochemical Biomarkers of Severity of Psoriasis.

PURPOSE: Psoriasis is a systemic, chronic and inflammatory condition. The exact pathogenesis is unclear. The abnormal expression of Wnt5a pathway in psoriasis vulgaris has been confirmed. Whether it is related to the severity of psoriasis is unclear. METHODS: Thirty-eight skin lesions from psoriasis vulgaris patients and 22 healthy adult skin tissues were taken. The semi-quantitative immunohistochemistry score of Wnt5a, Frizzled5 and Frizzled2 was evaluated under a microscope by two independent dermatologists. Psoriasis area and severity index (PASI) score system was used to evaluate the disease severity. RESULTS: The average PASI score of the patients was 16.25 ± 7.8, and the average duration of disease was 19.6 ± 10.4 months. Wnt5a, Frizzled5 and Frizzled2 were highly expressed in psoriasis lesions. The semi-quantitative immunohistochemistry scores of Wnt5a, Frizzled5 and Frizzled2 were positively correlated with PASI scores (r = 0.71, r = 0.46, r = 0.65, respectively, all P-value < 0.01), but not correlated with duration of disease (r = 0.11, r = 0.17, r = 0.29, respectively, all P-value > 0.05). There were significant positive correlations between Wnt5a and Frizzled5 (r = 0.57, P-value < 0.01), as well as Wnt5a and Frizzled2 (r = 0.59, P-value < 0.01). CONCLUSION: Wnt5a and its receptors play an important role in pathogenesis of psoriasis vulgaris and are positively correlated with the severity of psoriasis, and may be one of the immunohistochemical predictors of the severity of the disease.

Novel missense mutations of MVK and FDPS gene in Chinese patients with disseminated superficial actinic porokeratosis.

BACKGROUND AND AIMS: Porokeratosis (PK) is a heterogeneous group of cutaneous keratinization disorders and has five clinical subtypes. DSAP is the most common clinical subtype and is characterized by multiple small, annular, anhidrotic, keratotic lesions predominantly on sun-exposed areas of the skin. It is an autosomal dominantly inherited epidermal keratinization disorder. However, studies on its molecular basis is limited. MATERIALS AND METHODS: We performed mutation analysis of genes in four pedigrees and three sporadic cases of DSAP in the Chinese population. Genomic DNA was extracted from blood samples obtained from patients, unaffected family members, and 100 unrelated individuals. All exons and flanking intron sequences of the mevalonate kinase (MVK) and farnesyl diphosphate synthase (FDPS) genes were amplified. RESULTS: One missense mutation in exon 7 (C.G677A) of the MVK gene was identified in pedigree 3, and one missense mutation in exon 5 (C.C535T) of the FDPS gene was identified in sporadic case 3. No mutation was detected in the MVK and FDPS genes in the remaining three pedigrees and two sporadic cases with DSAP. CONCLUSION: Our results may be useful for genetic counseling and prenatal diagnosis of affected families and for expanding the repertoire of MVK and FDPS mutations underlying DSAP.

[Analysis of complications in diabetic foot treated with tibial transverse transport].

OBJECTIVE: To explore the causes and management of the complications in diabetic foot treated with tibial transverse transport (TTT). METHODS: Between September 2015 and September 2019, 196 patients with diabetic foot were treated with TTT. There were 109 males and 87 females, with an average age of 67.6 years (range, 45-86 years). According to Wagner's classification, there were 124 cases of grade 3, 62 cases of grade 4, and 10 cases of grade 5; the course of disease was 1-12 months, with an average of 2.6 months. All patients underwent the minimally invasive tibial osteotomy. The osteotomy site was the middle and lower tibia in 62 cases and the middle and upper tibia in 134 cases. The area of osteotomy was 20 cm 2 in 83 cases and 7.5 cm 2 in 113 cases. The osteotomy block was moved back and forth once in 92 cases and twice in 104 cases. The complications were recorded, including secondary fracture at tibial osteotomy, skin necrosis in osteotomy area, and pin tract infection. RESULTS: Among 196 patients, 41 cases (20.9%) had complications. Nine cases (4.6%) had secondary fracture at tibial osteotomy, among which 6 cases (9.6%) of middle and lower segment osteotomies and 3 cases (2.2%) of middle and upper segment osteotomies. The incidence between the patients with different osteotomy sites was significant ( χ 2=5.354, P=0.021). The area of osteotomy was 20 cm 2 in 5 cases (6.0%) and 7.5 cm 2 in 4 cases (3.5%). There was no significant difference in the incidence between patients with different areas ( χ 2=0.457, P=0.499). Skin necrosis occurred in the osteotomy area in 12 cases (6.1%), all of which were moved back and forth once. There was a significant difference in the incidence between patients who were treated with transport once and twice ( P=0.001). There were 18 cases (9.1%) with pin tract infection, including 12 cases (6.1%) with mild infection and 6 cases (3.0%) with severe infection. There was no significant difference in the incidence between the patients with mild and severe infections ( P=0.107). CONCLUSION: TTT is an effective method to treat diabetic foot, but there are complications such as secondary fracture at tibial osteotomy, skin necrosis in osteotomy area, and pin tract infection during transport. Preoperative evaluation of indication, standardization of osteotomy mode, size and position of osteotomy block, establishment of individualized removal plan, and strengthening of pin track nursing after operation can effectively reduce complications.

Identification of ATP2C1 mutations in the patients of Hailey-Hailey disease.

BACKGROUND: Familial benign chronic pemphigus, also known as Hailey-Hailey disease (HHD), is a clinically rare bullous Dermatosis. However the mechanism has not been clarified. The study aim to detect novel mutations in exons of ATP2C1 gene in HHD patients; to explore the possible mechnism of HHD pathogenesis by examining the expression profile of hSPCA1, miR-203, p63, Notch1 and HKII proteins in the skin lesions of HHD patients. METHODS: Genomic DNA was extracted from peripheral blood of HHD patients. All exons of ATP2C1 gene in HHD patients were amplified by PCR and the products were purified and sequenced. All related signaling proteins of interest were stained by using skin lesion tissues from HHD patients and miR-203 levels were also determined. RESULTS: One synonymous mutation c.G2598A (in exon 26), one nonsense mutation c.C635A and two missense mutations c.C1286A (p.A429D) and c. A1931G (p. D644G) were identified. The nonsense mutation changed codon UCG to stop codon UAG, causing a premature polypeptide chain of the functional region A. The two missense mutations were located in the region P (phosphorylation region) and the Mn binding site of hSPCA1. The level of hSPCA1 was significantly decreased in HHD patients compared to the normal human controls, accompanied by an increase of miR-203 level and a decrease of p63 and HKII levels. CONCLUSION: In our study, we found four mutations in HHD. Meanwhile we found increase of miR-203 level and a decrease of p63 and HKII levels. In addition, Notch1, which was negatively regulated p63, is downregulated. These factors may be involved in the signaling pathways of HHD pathogenesis. Our data showed that both p63 and miR-203 may have significant regulatory effects on Notch1 in the skin.

Repression of miR-142-3p alleviates psoriasis-like inflammation by repressing proliferation and promoting apoptosis of keratinocytes via targeting Sema3A.

Psoriasis is a multifactorial, recurring, and chronic inflammatory skin disease characterized by hyperproliferation of keratinocytes. Evidence is rapidly accumulating for the role of microRNAs in psoriasis. The object of the study was to explore the functions and precise mechanism of miR-142-3p in human keratinocyte HaCaT cells in the presence of M5. Here, the results showed that miR-142-3p expression was heightened in HaCaT cells induced by M5. In addition, inhibition of miR-142-3p dramatically restricted cell proliferation and enhanced apoptosis in HaCaT cells exposed to M5, as exemplified by a decrease in the antiapoptotic Bcl-2 protein, concomitant with an increase in the proapoptotic proteins Bax. Moreover, depleting miR-142-3p effectively ameliorated M5-induced inflammation response, as reflected by the attenuation of multiple inflammatory factors. Importantly, Sema3A was identified as an authentic target of miR-142-3p, and indeed regulated by miR-142-3p. Mechanistically, silencing of Sema3A effectively abolished the anti-proliferative, apoptosis-promoting, and anti-inflammatory effects of miR-142-3p inhibition in keratinocytes. Taken together, these data elucidated that repression of miR-142-3p protect HaCaT cells against M5-induced hyper-proliferation and inflammatory injury by suppressing its target Sema3A, implying that the miR-142-3p/Sema3A axis may be a new target for preventing keratinocyte injury process. These findings provide a new and better understanding of the mediating role of miR-142-3p in psoriasis.

[Effects of chemerin/chemR23 axis on Th9/Treg in patients with psoriasis].

OBJECTIVE: To investigate the effects of chemerin on helper T cells 9 (Th9)/regulatory T cells (Treg) in patients with psoriasis and the potential molecular mechanisms.
 Methods: Twenty-five patients with psoriasis and twenty healthy volunteers were selected for this study. CD4+ T cells were isolated from peripheral blood of samples by magnetic bead separation. The levels of chemerin and its receptor chemR23 were detected by real-time RT-PCR and ELISA. CD4+ T cells isolated from the healthy volunteers were treated with different concentrations of chemerin (50, 100, 150, 200 ng/mL), then cell viability was detected by MTT assay. The expression of inflammatory molecules and Th9/Treg were detected by ELISA and flow cytometry, respectively.
 Results: The expressions of chemerin and chemR23 in peripheral blood from patients with psoriasis were higher than those in healthy control (both P<0.05). The Th9/Treg was higher in patients with psoriasis than that in healthy control (P<0.05). After treating CD4+ T cells with 150 ng/mL of chemerin, the levels of IL-6, IL-9 and IL-17 were increased significantly (all P<0.05). Additionally, Th9/Treg was increased (P<0.05) and the cell balance was disrupt. However, the effects of chemerin on CD4+ T cells were reversed by silencing of chemR23 (all P<0.05).
 Conclusion: Chemerin may regulate the immune balance for Th9/Treg in CD4+ T cells from patients of psoriasis.

A unified mitochondria mechanistic target of rapamycin acyl-coenzyme A dehydrogenase 10 signal relay modulation for metformin growth inhibition in human immortalized keratinocytes cells.

Metformin exhibits antiproliferative and proapoptotic effects in a variety of diseases, characterized by malignant and nonmalignant hyperplastic cells; however, the underlying molecular mechanism of metformin in psoriasis has not been elucidated. In the current study, we found that after metformin treatment the proliferation of human immortalized keratinocytes (HaCaT) was significantly inhibited, while cell apoptosis was increased in a dose-dependent manner, accompanied with enhanced protein expression of acyl-coenzyme A dehydrogenase 10 (ACAD10). Furthermore, mechanism analysis revealed that ACAD10 expression is induced by downregulated activities of mechanistic target of rapamycin 1 (mTORC1) signaling rather than AMP-activated protein kinase signaling. The inactivation of mTORC1 by rapamycin pretreatment or rotenone-induced mitochondrial complex inhibition showed a similar effect because of the metformin treatment on the proliferation and apoptosis of HaCaT keratinocytes. Overexpression of mTORC1 almost reversed the antiproliferation and proapoptosis effects induced by metformin. This study showed that the metformin treatment inhibited HaCaT cells proliferation and promoted apoptosis by affecting the mitochondrial-mTORC1 signaling and elevated the ACAD10 expression. Hence, metformin can be used as a potential therapeutic agent for psoriasis.

Chemerin/ChemR23 axis triggers an inflammatory response in keratinocytes through ROS-sirt1-NF-κB signaling.

Psoriasis is a chronic disease which carries the emotional and social burden, promotes joint disability and raises comorbidity possibility in patients. Obesity is closely correlated with the occurrence of psoriasis and adipokines produced by adipose tissues were found to be critical culprits. Chemerin is one of them and its expression was increased in patients with psoriatic arthritis. In our hypothesis, chemerin might act on keratinocytes and promote an inflammatory response, which plays an essential role in psoriatic epidermis. To validate our hypothesis, HaCaT cells and primary human keratinocytes were treated with chemerin (5, 10, and 20 ng/mL for 24 hours). Enzyme-linked immunosorbent assay (ELISA) was used to determine the secretion of inflammatory factors. Nuclear factor-κB (NF-κB) activation and p65 acetylation were evaluated by Western blot analysis. The expression and activity of sirtuin 1 (sirt1), a deacetylase act on p65, were also analyzed. The results showed that chemerin prompted inflammatory factors secretion, NF-κB activation and p65 acetylation through chemerin receptor 23 receptor. Chemerin constrained the expression and deacetylase activity of sirt1 through augment of reactive oxygen species (ROS) production. Additionally, chemerin exacerbated psoriasiform dermatitis in imiquimod-treated mice model. In conclusion, chemerin can seduce inflammatory response and promote NF-κB activation through inhibition of sirt1 activity by ROS production.

Altered levels of focal adhesion and extracellular matrix-receptor interacting proteins were identified in Hailey-Hailey disease by quantitative iTRAQ proteome analysis.

Benign chronic familial pemphigus or Hailey-Hailey disease (HHD, OMIM 169600) is a rare, autosomal dominant blistering skin disorder characterized by suprabasal cell separation (acantholysis) of the epidermis. To date, the proteomic changes in skin lesions from HHD patients has not been reported yet. In this study, a sample of skin lesions from HHD patients was collected for isobaric tags for relative and absolute quantitation to analyze proteome changes compared with unaffected individuals. The 134 differentially expressed proteins were assigned to at least one Gene Ontology term, and 123 annotated proteins with significant matches were assigned to 187 known metabolic or signaling pathways listed in the Kyoto Encyclopedia of Genes and Genomes. Most of the altered proteins in skin lesions of HHD patients were enriched in pathways involved in the PI3K-Akt signaling, focal adhesion, extracellular matrix (ECM)-receptor interaction, and protein digestion and absorption, such as collagen family members, microfibril-associated glycoprotein 4 and plakophilin. The changes of proteins related to cell adhesion, ECM-receptor interaction, and protein folding and glycosylation suggested that strategy targeted to alter cell junction and extracellular microenvironment might provide a potential treatment for HHD.

MicroRNA-485-5p represses melanoma cell invasion and proliferation by suppressing Frizzled7.

MicroRNAs (miRNAs) have emerged as critical regulators for malignant melanoma development. miR-485-5p has been suggested as a tumor-suppressive miRNA in many types of human malignancies. However, the role of miR-485-5p in melanoma remains unknown. In this study, we aimed to explore the potential role and underlying mechanism of miR-485-5p in the regulation of melanoma development. Here, we showed that miR-485-5p was significantly decreased in melanoma tissues and cell lines compared with their corresponding controls. Transwell invasion assay showed that miR-485-5p overexpression markedly inhibited melanoma cell invasion. WST-1 and cell cycle assays exhibited that miR-485-5p overexpression significantly suppressed melanoma cell proliferation. By contrast, miR-485-5p suppression promoted the invasion and proliferation of melanoma cells. Using bioinformatics analysis, we observed that miR-485-5p potentially targets the 3'-untranslated region (3'-UTR) of Frizzled7 (FZD7). Dual-luciferase assay confirmed the direct binding between miR-485-5p and FZD7 3'-UTR. Meanwhile, real-time quantitative polymerase chain reaction and Western blot analysis showed that miR-485-5p overexpression suppressed FZD7 expression, whereas miR-485-5p suppression resulted in the opposite effect. Moreover, miR-485-5p expression was observed to be inversely correlated with FZD7 mRNA expression in melanoma tissues. Further experiments showed that miR-485-5p regulated Wnt signaling. The restoration of FZD7 expression markedly reversed the antitumor effects induced by miR-485-5p overexpression in melanoma cells. Taken together, our study suggests that miR-485-5p represses melanoma cell invasion and proliferation by suppressing FZD7, indicating a new tumor-suppressive role for miR-485-5p in melanoma. The miR-485-5p/FZD7 axis may provide novel insights into understanding the molecular pathogenesis of melanoma and may be a promising therapeutic target for melanoma.

The acitretin and methotrexate combination therapy for psoriasis vulgaris achieves higher effectiveness and less liver fibrosis.

Both acitretin and methotrexate are effective in ameliorating psoriatic lesion. However, their combination has been seldom reported in the treatment of psoriasis because of the warning regarding the potential hepatotoxicity of the drug interactions. This study was designed to investigate the effectiveness of such combination therapy for psoriasis vulgaris, and the potential benefit as well as side effect during the treatment. Thirty-nine patients with psoriasis vulgaris were treated with acitretin, methotrexate or their combination or as control. Similarly, K14-VEGF transgenic psoriasis-like mice were treated with these drugs. Human primary keratinocytes and hepatic stellate cells were used for analyzing their effect in vitro. The results showed that the combination therapy exhibited higher effectiveness in remitting skin lesion, but did not significantly affect the liver function of both patients and mice. Moreover, the combination groups showed less elevation of profibrotic factors in sera when compared with methotrexate alone groups accordingly. Furthermore, primary keratinocytes expressed more involucrin as well as loricrin and proliferated more slowly on the combined stimulation. Interestingly, such combination treatment induced lower expression of profibrotic factors in hepatic stellate cells. In conclusion, the acitretin-methotrexate combination therapy for psoriasis vulgaris can achieve higher effectiveness and result in less liver fibrosis.

[Treatment of traumatic ulnar styloid impaction syndrome by Sauvé-Kapandji procedure].

Objective: To evaluate the effectiveness of Sauvé-Kapandji procedure in the treatment of traumatic ulnar styloid impaction syndrome. Methods: Between June 2010 and January 2013, 12 patients with traumatic ulnar styloid impaction syndrome were treated by Sauvé-Kapandji procedure. There were 4 men and 8 women, with an average age of 58.9 years (range, 50-69 years). The disease was caused by traffic accident in 1 case, and by falling from height in 11 cases. All patients had dislocation of the distal radioulnar joint, and 7 patients also had old fractures of the distal radius. The main clinical symptoms were pain and limited activity of the wrist joint, and the disease duration was 2-4 months (mean, 3.5 months). The visual analogue scale (VAS) was 6.2±1.4. The clinical outcomes were assessed by VAS, range of motion (ROM) of the wrist, grip strength, Evans score, and X-ray film of wrist joint during follow-up. Results: All patients obtained healing of incision by first intention and were followed up 37-73 months (mean, 58.4 months); no complication of infection, blood vessel injury, or nerves injury occurred. VAS was 1.2±1.0 at the final follow-up, showing significant difference when compared with preoperative one ( t=9.950, P=0.000). The ROM of the affected wrist joint in flexion, extension, ulnar deviation, forearm pronation and supination were improved, but the ROM of the affected side were significantly less than those of normal side ( P<0.05). No significant difference was found in the grip strength and Evans score between the affected side and normal side ( t=-0.885, P=0.386; t=-1.969, P=0.062). According to Evans scores, the results were excellent in 8 cases, good in 3 cases, and fair in 1 case, with an excellent and good rate of 91.7%. Postoperative radiographs showed bony healing in all patients, with the average healing time of 3.5 months (range, 3-6 months). The instability of proximal ulna occurred in 3 cases. Conclusion: Sauvé-Kapandji procedure is a reliable remedy method for traumatic ulnar styloid impaction syndrome, with favorable improvement in wrist pain and forearm rotation. However, the surgical indications for Sauvé-Kapandji procedure should be strictly controlled.