HnRNP K regulates inflammatory gene expression by mediating splicing pattern of transcriptional factors.

HnRNP K is a heterogeneous nuclear ribonucleoprotein and has been identified as an oncogene in most solid tumors via regulating gene expression or alternative splicing of genes by binding both DNA and pre-mRNA. However, how hnRNP K affects tumorigenesis and regulates the gene expression in cervical cancer (CESC) remains to be elucidated. In these data, higher expression of hnRNP K was observed in CESC and was negatively correlated with the patient survival time. We then overexpressed hnRNP K (hnRNP K-OE) and found that its overexpression promoted cell proliferation in HeLa cells (P = 0.0052). Next, global transcriptome sequencing (RNA-seq) experiments were conducted to explore gene expression and alternative splicing profiles regulated by hnRNP K. It is shown that upregulated genes by hnRNP K-OE were associated with inflammatory response and an apoptotic process of neuron cells, which involves in cancer. In addition, the alternative splicing of those genes regulated by hnRNP K-OE was associated with transcriptional regulation. Analysis of the binding features of dysregulated transcription factors (TFs) in the promoter region of the inflammatory response genes regulated by hnRNP K revealed that hnRNP K may modulate the expression level of genes related to inflammatory response by influencing the alternative splicing of TFs. Among these hnRNP K-TFs-inflammatory gene regulatory networks, quantitative reverse transcription polymerase chain reaction (RT-qPCR) experiments and gene silencing were conducted to verify the hnRNP K-IRF1-CCL5 axis. In conclusion, the hnRNP K-TFs-inflammatory gene regulatory axis provides a novel molecular mechanism for hnRNP K in promoting CESC and offers a new therapeutic target.

Screening and identification of osteoarthritis related differential genes and construction of a risk prognosis model based on bioinformatics analysis.

Background: Searching for the production mechanism of synovial lesions helps to find precise therapeutic targets and improve prognosis. The previous identification and screening of differential genes in osteoarthritis (OA) pathogenesis were well combined to further build a risk prognosis model of OA, which is beneficial to the diagnosis and treatment of patients with OA. Methods: The synovia-related chip data sets GSE82107, GSE12021, GSE55457, and GSE55235 were downloaded from the public database of Gene Expression Omnibus (GEO), and 40 cases of synovial tissues of OA and 36 cases of normal synovial tissues were included. R software was used to screen differentially expressed genes (DEGs), Gene Ontology (GO) functional enrichment, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis. The STRING online analysis tool and Cytoscape software were used to further screen key genes, and a prognostic model of OA susceptibility risk was constructed. Results: The results showed 1,921 differential genes, including 762 upregulated genes and 1,159 downregulated genes, which were mainly involved cell growth, cell adhesion, skeletal muscle growth, iron ion binding, ubiquitin protein ligase binding, and hormone receptor binding. Co-acquisition based on 10 key target genes of the protein interaction network, containing CTNNB1, GSK3B, STAT1, RHOC, HDAC9, PSEN1, KDM5C, BACE1, JAK3, and CUL1. The area under the concentration-time curve (AUC) was used to evaluate the prognostic model of OA risk, and the curve results showed that the prognostic model had high accuracy and validity (AUC =0.690). Conclusions: Bioinformatics analysis was applied to screen out the DEG profiles of OA. This may provide functional predictions to provide new ideas for treatment of the disease and may be a biological marker for its diagnosis and a potential target for treatment. The construction of the risk and prognosis model is beneficial to the risk assessment of rehabilitation function recovery of patients with OA, the evaluation of the severity of the disease and the subsequent treatment guidance.

Reconstruction of a Distal Foot Skin Defect Using an Intermediate Dorsal Neurocutaneous Flap.

OBJECTIVE: To present the use of an intermediate dorsal neurocutaneous flap for the reconstruction of defects on the distal foot. METHODS: From September 2016 to October 2018, five patients (mean age at operation 33.8 years; range, 7-70 years; female/male = 2/3) with skin defects on one of their feet caused by road-traffic accidents, electrical injury, and syndactyly correction were retrospectively reviewed. The size of the defects ranged from 2.0 cm × 1.0 cm to 5.0 cm × 3.5 cm. All patients had undergone a reconstruction surgery using intermediate dorsal neurocutaneous flap. One patient underwent a syndactyly correction, and four patients first experienced aggressive debridement. The sizes of the flaps were between 5.0 cm × 2.0 cm and 6.0 cm × 4.0 cm. The function, appearance, and pain of the injured foot were assessed using the Chinese Manchester Foot Pain and Disability Index and visual analogue scale. RESULTS: These five patients were systematically followed up for a mean of 15.8 months (range, 12-20 months). The donor sites were closed primarily in two cases, and skin grafts were performed in three cases. All the flaps survived with a success rate of 100%; the wounds healed well, and the color matches were excellent. Partial superficial flap necrosis occurred in one of five flaps, which was treated by dressing change using a hypertonic saline gauze. No significant problems were found at the donor site in any patient immediately afterwards or at follow-up. There were no problems in any patients associated with wearing shoes. Based on the Chinese Manchester Foot Pain and Disability Index, four patients were strongly satisfied and one was satisfied with the recovery of physical function; all the patients were strongly satisfied with the appearance of the injured foot; all five patients had an excellent score of pain intensity subscale. Except for one patient who reported mild pain, all the other patients reported no pain based on the visual analogue scale. Two typical cases are presented in this paper. CONCLUSIONS: The intermediate dorsal neurocutaneous flap is an alternative and effective technique that can reliably cover minor- to medium-sized defects on the distal foot, toes, and web spaces. This surgical method leads to satisfactory functional recovery with minimal donor site morbidity, and no major vessels need to be sacrificed. This procedure offers an advisable option for orthopaedic surgeons to treat defects on the distal foot.

Efficacy of home-based exercise programme on physical function after hip fracture: a systematic review and meta-analysis of randomised controlled trials.

We performed a meta-analysis to evaluate the effect of home exercise programmes on body function after hip fractures. A computerised literature search was performed for published trials in PubMed, EMBASE, CENTRAL, and Cochrane Database of Systematic Reviews. Randomised trials were selected investigating home-based exercise programmes vs usual care without home-based exercise in hip fracture patients. Physical health (measured by Short Form 36), normal gait speed, fast gait speed, balance, instrumental activities of daily living (IADL), activities of daily living (ADL), lower extremity strength, leg strength in fractured leg, leg strength in non-fractured leg, and Six-Minute Walk Test (6MWT) per randomised patient were measured as outcomes. Eleven randomised controlled trials of 1068 subjects were included, 533 in the home-based exercise group and 535 in the control group. The results of this meta-analysis showed that the home-based exercise programmes were not significantly associated with physical health, normal gait speed, fast gait speed, balance, IADL, ADL, and lower extremity strength but were significantly associated with leg strength in the fractured leg, leg strength in the non-fractured leg, and 6MWT. The home-based exercise programme had a positive, although not significant, effect on physical function after hip fracture. Low-intensity training and poor patient compliance are unavoidable problems in home-based exercise rehabilitation. A more task-oriented rehabilitation programme might possibly yield more benefits for disability outcomes.

Long-term follow-up of fibular graft for the reconstruction of bone defects.

The use of fibular graft for the reconstruction of bone defects has been demonstrated to be a reliable method. The aim of this study was to assess the clinical outcome of graft union, functional outcome (hypertrophy of the graft bones) and complications of both non-vascularized and vascularized grafts.From 1981 to 2015, 10 patients were treated using non-vascularized fibular graft or free vascularized fibular graft. The outcomes were bony union time, graft hypertrophy and complications based on radiograph and functional outcomes according to the Musculoskeletal Tumor Society (MSTS) score. Mobility of the ankle at the donor site was evaluated using the Kofoed ankle score system.This study included 10 patients with an average follow-up of 6.8 years. The union rate for all patients was 100%. The mean union time was 21.3 weeks for vascularized fibular grafts and 30.5 weeks for non-vascularized fibular grafts (P = .310). There was a significant difference between the upper limbs and the lower limbs regarding hypertrophy of the grafts in 5 patients (P = .003). The mean MSTS score in 10 patients was 84% (range 53%-97%). Stress fracture of the graft occurred in 1 patient. Donor site complications, including valgus deformity and length discrepancy, between 2 legs occurred in 2 patients who were under 18 years of age at the time of operation (P = .114). The mean Kofoed score was 96.8 (range 88-100).A greater increase in hypertrophy of grafts was observed with reconstruction in the lower limbs. There was no difference in MSTS score between these 2 types of grafts. Children were more likely to experience the valgus deformity at the donor site after harvesting the fibula. Keeping at least the distal 1/4 of the fibula intact during the surgery is a valid means of ensuring ankle stability at the donor site, and children should be considered for prophylactic distal tibiofibular synostosis creation to prevent the valgus deformity of the ankle at the donor site.

[Relations between nonalcoholic fatty liver disease and metabolic syndrome].

OBJECTIVE: To analyze the relation between nonalcoholic fatty liver disease (NAFLD) and metabolic syndrome (MS) among adults from the Functional University Society (FUS). METHODS: This survey was conducted among the staff of Wuhan University who underwent physical check-ups from 2010 to 2011 at the Affiliated Hospital of Wuhan University. The participants had records related to medical history, clinical examination, anthropometry, laboratory tests and routine liver ultrasonography. According to the diagnostic criteria of NAFLD, the cases were divided into two groups-with NAFLD or without. MS and its relevant risk factors of the two groups were compared. RESULTS: 1) The prevalence rates of nonalcoholic fatty liver disease and MS were 20.7%, and 13.3%, respectively. People with nonalcoholic fatty liver disease had higher levels of BMI, SBP, DBP, TG, FPG and lower level of HDL-C than those who did not have the problem. 2) The risks of NAFLD group in developing MS, obesity, hypertension and dyslipidemia were higher than the non-group (P < 0.001). 3) The NAFLD group had 1.66, 4.22, 8.72 and 25.62 times chances of having 1 to 4 risk factors on MS than those without NAFLD. CONCLUSION: NAFLD was closely associated with MS and its relevant risk factors.

Repair of severe composite tissue defects in the lower leg using two different cross-leg free composite tissue flaps.

This article reports 2 cross-leg free composite tissue flaps for repairing the severe composite tissue defects in lower leg without suitable adjacent recipient vasculature for microvascular anastomosis. The osseous myocutaneous flap of ilium and tensor fascia lata pedicled with ascending branch of lateral femoral circumflex vessels and the osseous muscle flap of scapula and latissimus dorsi pedicled with subscapular vessels were performed, respectively, to reconstruct the bone and soft-tissue defects in the lower leg of 2 patients. Both donor vessels were the posterior tibial artery and great saphenous vein from the contralateral lower leg. The legs and the bone flaps were immobilized by an external fixator. The periods of pedicle division were 43 and 67 days, respectively, after transplantation. Both flaps survived after pedicle division and the patients regained the ability to walk. There were no such complications as joint stiffness or donor site morbidity except for a linear scar. The 2 cross-leg free composite tissue flaps were optional methods for salvaging limbs that were otherwise nonreconstructable. But the indication for cross-leg free-tissue flap should be limited strictly.