Multimodal data fusion based on IGERNNC algorithm for detecting pathogenic brain regions and genes in Alzheimer's disease.

At present, the study on the pathogenesis of Alzheimer's disease (AD) by multimodal data fusion analysis has been attracted wide attention. It often has the problems of small sample size and high dimension with the multimodal medical data. In view of the characteristics of multimodal medical data, the existing genetic evolution random neural network cluster (GERNNC) model combine genetic evolution algorithm and neural network for the classification of AD patients and the extraction of pathogenic factors. However, the model does not take into account the non-linear relationship between brain regions and genes and the problem that the genetic evolution algorithm can fall into local optimal solutions, which leads to the overall performance of the model is not satisfactory. In order to solve the above two problems, this paper made some improvements on the construction of fusion features and genetic evolution algorithm in GERNNC model, and proposed an improved genetic evolution random neural network cluster (IGERNNC) model. The IGERNNC model uses mutual information correlation analysis method to combine resting-state functional magnetic resonance imaging data with single nucleotide polymorphism data for the construction of fusion features. Based on the traditional genetic evolution algorithm, elite retention strategy and large variation genetic algorithm are added to avoid the model falling into the local optimal solution. Through multiple independent experimental comparisons, the IGERNNC model can more effectively identify AD patients and extract relevant pathogenic factors, which is expected to become an effective tool in the field of AD research.

[Expression and clinical significance of plasma exosomal miR-34-5p and miR-142-3p in systemic sclerosis].

OBJECTIVE: To detect the expression of plasma exosomal microRNA (miRNA) in systemic sclerosis (SSc), and to investigate its clinical significance. METHODS: A total of 20 patients who were initially diagnosed with SSc and did not receive medication in Department of Rheumatology and Immunology of Meizhou People' s Hospital from January 2020 to January 2022 were recruited, as well as 15 healthy individuals whose gender and age matched with those of the SSc patients. Plasma exosomes were isolated using ultracentrifugation method. The expression levels of exosomal miR-34-5p, miR-92-3p and miR-142-3p were detected by quantative real-time polymerase chain reaction (qRT-PCR). Correlations between the expression levels of exosomal miRNAs and clinical characteristic were analyzed by Spearman's rank correlation coefficient test. RESULTS: The mean age of 20 patients with SSc was (52.6±12.6) years, including 7 males and 13 females. Among the 20 SSc patients, 13 cases were diagnosed as limited cutaneous systemic sclerosis (lcSSc) and 7 cases were diagnosed as diffuse cutaneous systemic sclerosis (dcSSc) according to the extent of skin involvement. According to the findings of high resolution chest CT, 7 of 20 SSc patients were diagnosed with interstitial lung disease (ILD) and 13 SSc patients were diagnosed with non-ILD. The expression levels of exosomal miR-34-5p, miR-92-3p and miR-142-3p were significantly elevated in the SSc patients compared with those in the healthy controls group (P=0.003, P=0.000 1, and P=0.016, respectively). Compared with the SSc patients without ILD, the expression levels of miR-34-5p and miR-142-3p were significantly lower in the SSc patients with ILD (P=0.037 and P=0.015, respectively). The expression levels of exosomal miR-34-5p and miR-142-3p showed negative correlation with ILD (r=-0.48, P=0.031 and r=-0.55, P=0.011, respectively), and arthritis (r=-0.46, P=0.040 and r=-0.48, P=0.032, respectively). The expression levels of exosomal miR-142-3p showed a negative correlation with erythrocyte sedimentation rate (ESR) (r=-0.55, P=0.012). CONCLUSION: Plasma exosomal miR-34-5p, miR-92-3p and miR-142-3p were dysregulated in SSc. The dyregulation of exosomal miR-34-5p and miR-142-3p showed correlation with SSc associated ILD (SSc-ILD).

The Effects of Bone Cement Volume in Percutaneous Vertebroplasty for Thoracolumbar Junction Vertebral Compression Fractures: A Clinical Comparative Study.

We compared the outcomes of patients treated with different volumes of polymethyl methacrylate bone cement during percutaneous vertebroplasty (PVP) for thoracolumbar vertebral compression fractures. We performed a comparative, retrospective study of 316 patients who underwent PVP for a single-level thoracolumbar vertebral compression fracture. Patients were divided into two groups: group A (≤5 mL; n = 146) and group B (>5 mL; n = 170). The visual analogue scale (VAS) for pain and the Roland-Morris Disability Questionnaire (RDQ) scores were compared between the two groups at 1 week and at 1, 6, 12, and 24 months after PVP. The incidence of cement leakage into the intervertebral discs was evaluated by a postoperative lateral radiograph assessment. Patients were evaluated for new fractures 1 and 2 years after PVP or when new fractures were suspected. Among the 316 patients enrolled, 245 completed the clinical research. No difference between groups A and B in terms of the VAS, RDQ, and rate of complications at all time points after surgery was observed. The presence of intervertebral disc leakage was a relative risk (RR) for subsequent total vertebral fracture (RR, 6.42; 95% confidence interval (CI), 2.72-14.19; P < 0.0001) and adjacent vertebral fracture (RR, 8.03; 95% CI, 2.74-23.54; P = 0.0001). A high volume of bone cement may increase the rate of subsequent total and adjacent vertebral fractures. However, the occurrence of intervertebral disc leakage is the principal risk factor for these negative outcomes of PVP.

Role of Arterial Perfusion in Early Survival of Arterialized Venous Flaps: A Mechanism Study and Clinical Application.

BACKGROUND: The arterialized venous flap (AVF) is appropriate as a flap for hand and foot resurfacing meet the aesthetic demands in the same time. However, the inconsistency of survival rate limited its popularization in clinical settings. The purpose of this study was to investigate the role played by the caliber and location of the artery. METHODS: Arterialized venous flaps were designed on the abdomen of New Zealand rabbits, and the animals were randomized into 3 groups and 2 groups in experiment 1 and 2, respectively. In experiment 1, the artery flow was restricted with vascular staplers of different calibers. In experiment 2, the artery was anastomosed with the afferent vein in the center or at the margin of the flap. Blood perfusion state, water content, epidermal metabolite levels, and flap survival status were observed in both experiments. Furthermore, outcomes of 12 patients received AVF to resurface soft tissue defects in the digits, hands, and feet between January 2016 and February 2018 were analyzed. RESULTS: In experiment 1, compared with the control group, groups with restricted artery showed poor results regarding blood perfusion state, water content, epidermal metabolite levels, and flap survival status. In experiment 2, group with the afferent vein in the center of the flap showed better results mentioned previously. All the flaps survived uneventfully in this study. Two flaps partially failed (20% of the flap area) because of insufficient perfusion. Generally, larger caliber and center-located vein helped the survival of AVF. CONCLUSIONS: Experimental findings suggested that increased arterial perfusion and center-located vein are beneficial for the survival of AVF. Clinical series proved the findings previously. The problem of inconsistency of AVF can be partially solved by increasing arterial perfusion and dissecting afferent vein into the center of flap, and still, further studies are needed to shed light on the mechanism behind.

Superficial Peroneal Neurocutaneous Flap for Coverage of Donor Site Defect After the Combined Transfer of Toe and Dorsal Foot Flap.

BACKGROUND: Reconstruction of digital loss with soft tissue defects remains a tough challenge. Although a combined flap of toe and dorsal foot skin provides a good option for "like-for-like" hand reconstruction, the disappointed donor site morbidity prevents it from popularity. In this study, we presented experiences of the superficial peroneal neurocutaneous (SPNC) flap for donor site closure after the combined toe and dorsal foot flap transfer. METHODS: Superficial peroneal neurocutaneous flaps were used to cover foot donor site defects in 9 patients. The flaps harvested from feet including 3 cases of wrap-around flap with dorsal foot flap, 4 cases of 2nd toe flap with dorsal foot flap, 2 cases of 2nd and 3rd toe flap with dorsal foot flap. The flap size, operation time, and complications were documented, and the donor sites were evaluated by the subjective outcome measure, the foot evaluation questionnaire, and the Vancouver Scar Scale. RESULTS: All flaps but one survived completely without complications. Marginal necrosis occurred in the distal part of the flap in one case, which was treated by daily dressings. The skin grafts on the lower leg healed uneventfully. The average operation time of flap transfer was 40 minutes. Follow-up ranged from 9 to 16 months, and patients were content with the results of the foot donor site according to the outcome measures. All the patients were able to wear normal shoes walking and running with a normal gait, and none sustained complications of skin erosion or ulceration. Protective sensibility was obtained in all the flaps. Two patients complained of cold intolerance and 2 could not wear a thong sandal. The donor site scars on the lower leg were measured 3.2 on average on the Vancouver Scar Scale. CONCLUSIONS: The SPNC flap is a practical procedure for donor site closure on the foot, especially when extra dorsal foot skin is elevated with a toe flap for hand reconstruction.

Free extended posterior tibial artery perforator flap with the neurovascular plexus of a saphenous nerve branch for large soft tissue and sensory reconstruction: Anatomic study and clinical application.

BACKGROUND: The posterior tibial artery perforator (PTAP) flap is a useful tool for reconstruction of soft tissue defects in the leg. However, the size and reliability of the flap largely depends on the quality of the perforator by which the flap is supplied, and the sensory recovery of the flap is limited. In this study, the anatomy of the saphenous nerve branches and their accompanying vessels was investigated, and a free extended PTAP flap with the neurovascular plexus of a saphenous nerve branch was designed for large soft tissue and sensory reconstruction in a series of clinical cases. METHODS: Sixteen adult cadaveric legs perfused with red latex in the femoral artery were dissected. The number and location of the saphenous nerve branches and the features of their accompanying vessels were dissected and studied. From January 2016 to December 2017, six patients with soft tissue defects ranged from 8 × 2.5 cm to 21 × 4 cm were repaired by the free extended PTAP flap. The patients' average age was 48 years. The causes of the defects included machine injuries in three patients and traffic injuries in the other three. The defects located at the hand in three cases, foot in two cases, and ankle in one case. The flap was designed based on the perforators of the posterior tibial artery and included a branch of saphenous nerve. The perforator pedicle and the nerve branch were connected to the vessels and nerve in the recipient site, respectively. RESULTS: The saphenous nerve gave off 5.8 ± 1.1 branches, with a relatively constant one issuing 8.1 ± 0.7 cm distal to the medial femoral condyle. Every nerve branch had an accompanying vessel, which connected with the PTAPs and supplied the skin. The size of the flap ranged from 10 × 3.5 cm to 23 × 5 cm. All of the flaps survived completely without complications. Follow-up varied from 6 to 12 months. All the patients obtained cold/hot sensation and pain sensation. The results of Semmes-Weinstein monofilament test ranged from 4.31(2 g) to 5.46 (26 g), and the 2-point discrimination test varied from 20 to 35 mm. CONCLUSION: The free extended PTAP flap, containing the saphenous nerve branch and its accompanying vessels, may be an alternative for large soft tissue reconstruction with improved sensation recovery.

Non-Vitamin K Antagonist Oral Anticoagulants in Secondary Stroke Prevention in Atrial Fibrillation Patients: An Updated Analysis by Adding Observational Studies.

BACKGROUND: This meta-analysis aimed to evaluate the efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) versus vitamin K antagonists (VKAs) in secondary stroke prevention in atrial fibrillation (AF) patients. METHODS: PubMed and Embase electronic databases were systematically searched from January 2009 to July 2019 for relevant randomized clinical trials and observational studies. A random-effects model was applied in the pooled analysis. RESULTS: A total of 14 studies (4 randomized clinical trials and 10 observational studies) were included. Based on the randomized clinical trials, compared with VKA use, the use of NOACs was associated with decreased risk of stroke and systemic embolism, major bleeding, and intracranial bleeding. Based on the observational studies, compared with VKAs, the subgroup analysis showed that dabigatran and rivaroxaban were associated with a reduced risk of stroke or systemic embolism, whereas dabigatran and apixaban were associated with a decreased risk of major bleeding. CONCLUSION: Based on current data, the use of NOACs is at least non-inferior to the use of VKAs in AF patients for secondary stroke prevention irrespective of NOAC type.

Non-Vitamin K Antagonist Oral Anticoagulants Versus Warfarin in Patients with Atrial Fibrillation and Peripheral Artery Disease: a Systematic Review and Meta-Analysis.

BACKGROUND: The efficacy and safety of non-vitamin K antagonist oral anticoagulants (NOACs) compared with warfarin in patients with atrial fibrillation (AF) and peripheral artery disease (PAD) remain largely unknown. Therefore, we conducted a meta-analysis to explore the effects of NOACs versus warfarin in this population. METHODS: We systematically searched the PubMed and Embase databases, with no linguistic restrictions, until December 2019 for relevant randomized controlled trials (RCTs) and observational studies. A random-effects model using an inverse variance method was selected to pool the risk ratios (RRs) and 95% confidence intervals (CIs). RESULTS: A total of six studies (three post hoc analyses of RCTs and three cohort studies) were included in this meta-analysis. Among AF patients treated with NOACs and warfarin, individuals with PAD had increased rates of all-cause death (RR = 1.26, 95% CI 1.07-1.48) and cardiovascular death (RR = 1.32, 95% CI 1.06-1.64) compared with those without PAD. In AF patients with PAD, we observed a similar risk of thromboembolic events, bleeding, and death with NOACs as with warfarin. In addition, there were no interactions between PAD and non-PAD subgroups regarding any of the reported outcomes of NOACs versus warfarin in AF patients (all Pinteraction > 0.05). CONCLUSIONS: Based on current evidence, AF patients with PAD are at a higher risk of death than those without PAD. Efficacy and safety outcomes with NOACs are comparable to those with warfarin, suggesting that the use of NOACs has effects similar to warfarin in AF patients with concomitant PAD.

Thumb reconstruction with combination of the wrap-around flap prefabricated by medialis pedis perforator flap with nail bed and phalanx banked from the amputated thumb: A case report.

Thumb reconstruction has been a very challenging issue for hand surgeons. In this report, we present a case of thumb reconstruction with combination of the wrap-around flap prefabricated by the medialis pedis perforator flap with phalanx and nail bed banked from the amputated thumb. A 22-year-old man suffered from the left thumb amputation as well as large soft tissue defect of hand and comminuted fracture in wrist due to a crush accident. The distal phalanx and nail bed of left thumb were exposed and no suitable vessels for microsurgical anastomosis could be found, resulting in the great difficulty of replantation. After debridement, nail bed of the amputated thumb was dissected and banked on the medial side of foot, while the distal phalanx was buried in the abdominal subcutaneous tissue. The fracture was fixed with an external fixation and the soft tissue defect was covered with a free anterolateral flap. Wound and bone healing was achieved 6 months after the initial treatment. Thumb was reconstructed with combination of the banked phalanx and a wrap-around flap prefabricated by the medialis pedis perforator flap and the banked nail bed. The postoperative course was uneventful with complications from both reconstruction and donor sites. The nail of the reconstructed thumb grew normally. Thumb oppositional function was rebuilt. The patient was satisfied with the aesthetic and functional outcome at 5-year postoperative follow-up. We propose that tissue banked from the nonreplantable amputated thumb could be used for secondary reconstruction with the technique of flap prefabrication.

Ferulic acid improves self-renewal and differentiation of human tendon-derived stem cells by upregulating early growth response 1 through hypoxia.

We aimed to investigate the potential beneficial effect of ferulic acid (FA) on stemness of human tendon-derived stem cells (hTSCs) in vitro and to elucidate the underlying molecular mechanism. The self-renewal ability of hTSCs was evaluated by colony formation and cell proliferation was determined by CCK-8 kit. Adipogenesis, osteogenesis, and chondrogenesis were determined by Oil Red O, Alizarin Red, and Alcian Blue stainings, respectively. Relative mRNA levels of PPARγ, Col2A1, Acan, Runx2, HIF1α, and EGR1 were measured with real-time PCR. Protein levels of HIF1α and EGR1 were detected by western blot. Direct binding of HIF1α with EGR1 promoter was analyzed by ChIP assay. Hypoxia-induced expression of EGR1 was interrogated by luciferase reporter assay. We demonstrated that FA treatment improved both self-renewal ability and multi-differentiation potential of hTSCs. FA induced hypoxia which in turn upregulated EGR1 expression via direct association with its hypoxia response element consensus sequence. Furthermore, we showed that both HIF1α and EGR1 were required for the enhancing effects of FA on hTSC self-renewal and differentiation. We hereby characterize the beneficial effect of FA on the stemness of hTSCs and highlight the critical role of HIF1α-EGR1 axis in this process.

All-Trans Retinoic Acid Promotes Osteogenic Differentiation and Bone Consolidation in a Rat Distraction Osteogenesis Model.

Distraction osteogenesis (DO) is used to treat specific disorders associated with growth abnormalities and/or loss of bone stock secondary to trauma or disease. However, a high rate of complications and discomfort hamper its further application in clinical practice. Here, we investigated the effects of all-trans retinoic acid (ATRA) on osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBMSCs) and bone consolidation in a rat DO model. Different doses of ATRA were used to treat rBMSCs. Cell viability and osteogenic differentiation were assessed using CCK-8 and alkaline phosphatase staining, respectively. The mRNA expression of osteogenic differentiation-genes (including ALP, Runx2, OCN, OPN, OSX, and BMP2) and angiogenic genes (including VEGF, HIF-1, FLK-2, ANG-2, and ANG-4) were determined by quantitative real-time PCR analysis. Further, we locally injected ATRA or PBS into the gap in the rat DO model every 3 days until termination. X-rays, micro-computed tomography (Micro-CT), mechanical testing, and immunohistochemistry stains were used to evaluate the quality of the regenerates. ATRA promoted osteogenic differentiation of rBMSCs. Moreover, ATRA elevated the mRNA expression levels of osteogenic differentiation-genes and angiogenic genes. In the rat model, new bone properties of bone volume/total tissue volume and mechanical strength were significantly higher in the ATRA-treatment group. Micro-CT examination showed more mineralized bone after the ATRA-treatment, and immunohistochemistry demonstrated more new bone formation after ATRA-treatment than that in the PBS group. In conclusion, as a readily available and very cost effective bio-source, ATRA may be a novel therapeutic method to enhance bone consolidation in the clinical setting.

The Microsurgical Calcaneus Osteocutaneous Fillet Flap After Traumatic Amputation in Lower Extremities: Flap Design and Harvest Technique.

BACKGROUND: Attempts to salvage upper and lower extremities have performed more frequently in recent decades, although there are clear cases that cannot be salvaged. The purpose of this retrospective study was to present our experience in using free calcaneus osteocutaneous fillet flap for preserving below-knee amputation stump after traumatic amputations or functional preserving after nonsalvageable lower extremities. METHODS: Between January 2012 and May 2017, 11 free calcaneus osteocutaneous fillet flap were used to preserving or lengthening below-knee amputation stump secondary to amputation on 8 males and 3 females. Patients' information and postoperative data were collected, including age of patient, sex, amputation site, flap survival, sensation recovery, and number of complications. RESULT: All amputations were trauma related and secondary to motor vehicle accidents (n = 8) and industrial accidents (n = 3). The age of the patients ranged from 16 to 59 years, with a mean of 34.4 years. Free calcaneus osteocutaneous fillet flap were designed and harvested from all patients. All flaps survived and 2 complications developed in 2 patients. Nine of 11 patients obtained protective sensory recovery during the period of follow-up. CONCLUSIONS: The free calcaneus osteocutaneous fillet flap harvested from the amputated limb provides reliable and robust tissue for reconstruction of large defects of the residual limb without additional donor-site morbidity.

DownRegulated SOX4 Expression Suppresses Cell Proliferation, Migration, and Induces Apoptosis in Osteosarcoma In Vitro and In Vivo.

The SOX4 transcription factor is involved in various cellular processes, such as embryonic development and differentiation. Deregulated expression of Sox4 in several human cancers has been reported to date, but its biological functions in the progression of osteosarcoma remain unclear. In this study, we found that the expression levels of SOX4 protein were significantly higher in high-grade osteosarcoma tissues and metastatic osteosarcoma tissues. Its overexpression was associated with poor prognosis in osteosarcoma. Knockdown of the SOX4 gene in the osteosarcoma cell lines resulted in decreased cell proliferation, migration, invasion, and induced apoptosis. After SOX4 gene silencing, the protein expression levels of Bax, Caspase-3, and P53 in osteosarcoma cells were significantly elevated, while the protein expression levels of Bcl-2, MMP2, and MMP9 were obviously decreased. In vivo analysis in nude mice further confirmed that knockdown of SOX4 suppressed tumor growth. In conclusion, SOX4 appears to be an important tumor oncogene in the regulation of osteosarcoma cell proliferation, apoptosis, and invasion, and it may be a potential target for effective osteosarcoma therapy.

Medial Plantar Venous Flap: Classic Donor Site Modification for Hand Defects.

BACKGROUND: Destruction of digits from trauma results in a much more significant influence on patients' mental state and quality of life than do injuries to other parts. The purpose of this study was to describe a novel modification of medial plantar venous flap for soft tissue defects in the hands and digits. METHODS: Nine patients received medial plantar venous flap to resurface soft tissue defects in the hands or digits between January 2015 and February 2017. This flap can be used either in a free-island pattern or in a flow-through pattern through the medial branch of the great saphenous vein. All patient data including preoperative statues and follow-up examinations (flap survival rates, complication rates, total active motion, static 2-point discrimination, and Semme-Weinstein test score) were analyzed. RESULTS: We included 6 men and 3 women, with a mean age of 34.2 years. The medial plantar venous flaps were used for vascularization in 5 patients because of segmental defects of bilateral digit arteries. Eight flaps survived uneventfully in this study. One flap partially failed (20% of the flap area) because of venous congestion. The functional outcomes and sensory restoration were satisfied for all 9 flaps. CONCLUSIONS: Compared with the traditional medial plantar flap, the medial plantar venous flap involves a simpler surgical procedure and allows for revascularization of distal areas using the flow-through technique. Furthermore, the medial plantar area presents a sensitive, glabrous skin with proper bulkiness and allows for movement of the underlying structure.

Reconstruction of complex tissue defect of forearm with a chimeric flap composed of a sural neurocutaneous flap and a vascularized fibular graft: A case report.

One-stage reconstruction of composite bone and soft-tissue defects in the forearm remains a tough challenge. Here, we present a case of reconstruction of complex tissue defect at forearm with a chimeric flap consisting of a sural neurocutaneous flap and a fibular graft. A 61-year-old man suffered from a machine crush injury in his left forearm, resulting in a complex tissue defect including extensive dorsomedial soft-tissue, digit extensor muscles of 2-4 fingers, the muscle flexor carpi ulnaris, the ulna bone with 5.5 cm in length, segmental injuries of ulna nerve and vessels, and the radius fracture. The defects were reconstructed by a modified chimeric flap, in which the sural neurocutaneous flap supplied by a peroneal perforator was used to repair the soft-tissue defect and the vascularized fibular graft was used to repair the ulna defect. The two components were supplied by the peroneal vessels. The ulnar nerve defect was bridged by a sural nerve graft. The venous congestion caused by thrombosis was observed at 24 hours postoperatively. After the venous anastomosis was reperformed, the flap survived completely without other complications. Bone healing was achieved at the 7-month follow-up. The index and middle fingers reached nearly full range of motion, while the ranges of motion of metacarpophalangeal joint of the ring and little fingers were less than 60 degrees. The results showed that the modified chimeric flap may be an option for reconstruction of complex tissue defect in the forearm.

Fingertip Replantation With Palmar Venous Anastomoses in Children.

BACKGROUND: Fingertip amputation in children is difficult to manage using microsurgical replantation techniques and many salvage procedures have failed owing to the nonavailability of suitable veins for anastomosis in the fingertip. This study reviewed our experience of pediatric fingertip replantation involving palmar venous anastomoses and evaluated the clinical outcomes. METHODS: From October 2008 to May 2013, 21 pediatric fingertips that had been completely amputated at or distal to the distal interphalangeal joint of the finger, or at or distal to the interphalangeal joint of the thumb were managed using complete replantation. One artery was anastomosed for revascularization with or without nerve repair, and a palmar venous anastomosis was performed to reestablish the outflow system. RESULTS: Twenty (95.2%) of the 21 fingertips survived. One replant involving an avulsion amputation of the left little finger failed, and the patient underwent stump cap-plasty. Excellent restoration of finger motion, pinch strength, and appearance was observed during the mean 39.9-month (range, 18-65 months) follow-up. The mean regained static 2-point discrimination sensation was 3.8 mm (range, 3.2-4.2 mm). All of the children and their families were satisfied with the surgical outcomes. CONCLUSIONS: Successful palmar venous anastomosis appears to promote the survival of replanted fingertips in children. Given that the procedure may simplify postoperative care, minimize complications, and achieve a high survival rate, it should be attempted if the technical expertise is available.

The Combined Use of a Neurocutaneous Flap and the Ilizarov Technique for Reconstruction of Large Soft Tissue Defects and Bone Loss in the Tibia.

BACKGROUND: Management of posttraumatic large soft tissue defects and bone loss remains a therapeutic and surgical challenge for orthopedic surgeons. We assessed the use of a neurocutaneous flap and the Ilizarov technique in the reconstruction of severe composite defects in the tibia. METHODS: We retrospectively reviewed 18 consecutive patients with trauma-related soft tissue defects and bone loss. The size of the soft tissue defect ranges from 8 × 9 cm to 14 × 18 cm. The mean size of bone loss was 4.5 cm. A great saphenous neurocutaneous flap or sural neurocutaneous flap was created to reconstruct the soft tissue defect. The Ilizarov external fixator was applied to reconstruct bony loss by means of distraction osteogenesis. RESULTS: The mean follow-up period was 38.8 months. All transferred flaps survived completely. The area covered ranged from 9 × 10 cm to 15 × 20 cm. The mean distraction length and duration of use of the external fixator were 6 cm and 11.4 months, respectively. All patients achieved final union. Complications of superficial pin-tract infections and mild Achilles tendon contracture were observed, but these were resolved over time. All patients were satisfied with the outcome of the surgery. CONCLUSIONS: A well-vascularized neurocutaneous flap is a safe and effective option in lower extremity reconstruction under a stable mechanical environment, which can be created using the Ilizarov technique. It is a good option for reconstructing severe complex defects in the lower limb.

Protective effects of paeonol on inflammatory response in IL-1ß-induced human fibroblast-like synoviocytes and rheumatoid arthritis progression via modulating NF-κB pathway.

Various investigations have demonstrated that human fibroblast-like synoviocytes rheumatoid arthritis (HFLS-RA) take part in the chronic inflammatory responses and RA progression. Inhibition of synovium activation and inflammatory processes may represent a therapeutic target to alleviate RA. Paeonol, a major natural product, has many biological and pharmacological activities. However, its protective effects against RA considering HFLS-RA have not been explored. In this study, anti-inflammatory effects of paeonol were detected in interleukin-1ß (IL-1ß)-treated HFLS-RA. Our results demonstrated that paeonol had no effect on cell survival and IL-1ß-induced proliferation in HFLS-RA. Pretreatment with paeonol significantly suppressed the production of pro-inflammatory TNF-α, IL-6 and IL-1ß, and the expressions of matrix metalloproteinase-1/-3 in vitro and in vivo. Mice treated with paeonol (10 mg/kg) remarkablely attenuated arthritic symptoms based on clinical arthritis scores and histopathology in collagen-induced arthritis mice. Furthermore, the TLR4 expression and NF-κB p65 activation were inhibited by paeonol in vitro and in vivo. Our findings illustrated that paeonol had significantly suppressed inflammation effects in synovial tissues and RA progression. The potential mechanism might be based on the attenuation TLR4-NF-κB activation. These collective results indicated that paeonol might be a promising therapeutic agent for alleviating RA progress through inhibiting inflammations and NF-κB signalling pathway.

Protective effect of Rabdosia amethystoides (Benth) Hara extract on acute liver injury induced by Concanavalin A in mice through inhibition of TLR4-NF-κB signaling pathway.

Extract of Rabdosia amethystoides (Benth) Hara (ERA), a traditional Chinese medicine has antibacterial, antiviral, anti-tumor, anti-hepatitis and anti-inflammatory properties. However, the hepatoprotective effects and molecular mechanisms of ERA on acute liver injury have not been fully elucidated. This study aims to investigate the anti-inflammatory effect and liver protection of ERA against the acute liver injury induced by Concanavalin A (Con A) and its underlying molecular mechanisms in mice. Mice received ERA (50, 100, 150 mg/kg body weight) by gavage before Con A intravenous administration. We found that ERA pretreatment was able to significantly reduce the elevated serum alanine and aspartate aminotransferase levels and liver necrosis in Con A-induced hepatitis. In addition, ERA treatment significantly decreased the myeloperoxidase, malondialdehyde levels and augmented superoxide dismutase level in the liver tissue, and also suppressed the secretion of proinflammatory cytokines in the serum, compared with Con A group by enzyme linked immunosorbent assay. Furthermore, we observed that ERA pretreatment can significantly decrease the expression level of Toll-like receptor (TLR) 4 mRNA or protein in liver tissues. Further results showed that ERA pretreatment was capable of attenuating the activation of the NF-κB pathway by inhibiting IκBα kinase and p65 phosphorylation in Con A-induced liver injury. Our results demonstrate that ERA pretreatment has hepatoprotective property against Con A-induced liver injury through inhibition of inflammatory mediators in mice. The beneficial effect of ERA may be mediated by the downregulation of TLR4 expression and the inhibition of NF-κB activation.

Versatility of the reversed superficial peroneal neurocutaneous island flap in the coverage of ankle and foot.

BACKGROUND: In the last decades, the skin island flap supplied by the vascular axis of sensitive superficial nerves, like the sural and saphenous nerves, has emerged as one of the most ideal reconstructive options for soft tissue coverage of lower limbs. The nutrient vessels of reversed superficial peroneal neurocutaneous island flap have been well described; however, it is still not commonly clinically applied. The aim of this study was to evaluate the efficacy of reversed superficial peroneal neurocutaneous island flap for coverage of ankle and foot. STUDY DESIGN: This is a retrospective and descriptive study of reversed superficial peroneal neurocutaneous island flap which was carried out for reconstruction of ankle and foot. PLACE AND DURATION OF STUDY: This study was conducted at the Department of Repair and Reconstructive Surgery, the 6th People's Hospital affiliated to Shanghai Jiaotong University, during a period of 51 months from July 2008 to October 2012. PATIENTS AND METHODS: A total of 12 patients with soft tissue defect of ankle and foot were included in the series; reversed superficial peroneal neurocutaneous island flap was performed on each case if relevant indications permitted. Preoperative and postoperative data of each patient, including etiology, size of defect, dimension of flap, complications, and functional and aesthetic results were noted. RESULTS: Among the 12 patients, there were 8 men and 4 women with an average age of 40.7 years (22-65 years) and with a mean follow-up time of 17.3 months (10-23 months). Most patients (11 patients) were posttraumatic. The size of the flap ranged from 48 to 108 cm2. Postoperatively, 11 flaps survived uneventfully, whereas marginal venous congestion was seen in the remaining patient, and secondary healing was achieved by conservative treatment. CONCLUSIONS: The reversed superficial peroneal neurocutaneous island flap could be an excellent alternative to other neurocutaneous perforator flap in the soft tissue reconstruction of foot and ankle.