Clinical outcomes of negative pressure wound therapy with instillation vs standard negative pressure wound therapy for wounds: A meta-analysis of randomised controlled trials.

Negative pressure wound therapy (NPWT) with or without instillation has been extensively applied for patients with multiple wound types. Whether NPWT with instillation is superior to NPWT alone is not known. This study aims to compare the efficacy between negative pressure wound therapy with instillation (NPWTi) and standard negative pressure wound therapy for wounds. The authors searched for randomised controlled trials (RCTs) in PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials investigating clinical outcomes of negative pressure wound therapy with instillation vs standard negative pressure wound therapy for wounds. The registration number (protocol) on PROSPERO is CRD42022287178. Eight RCTs involved 564 patients met the inclusion criteria and were included finally. NPWTi showed a significant fewer surgeries and dressing changes (RR and 95% CI, -9.31 [-17.54, -1.08], P < 0.05), and smaller wound area after treatment (RR and 95% CI, -9.31 [-17.54, -1.08], P < 0.05) compared with NPWT. No significant difference was observed on healing rate, time to heal, length of stay, dehiscence, reinfection, reoperation and readmission between NPWTi and NPWT. The addition of instillation to NPWT could improve clinical outcomes regarding the number of surgeries and dressing changes, and wound area after treatment in patients with multiple wound types. However, because of the heterogeneity these conclusions still need to be further validated by more well-designed RCTs with large sample sizes.

Evaluating Screw Stability After Pedicle Screw Fixation With PEEK Rods.

STUDY DESIGN: Animal experiment. OBJECTIVE: To evaluate whether the use of polyetheretherketone (PEEK) rods for posterior spinal fixation can improve screw stability. METHODS: Sheep models of anterior-posterior cervical fusion were used in this study. Six sheep were randomly assigned to the PEEK rod group and titanium alloy group. A total of 8 screws and 2 fixing rods were implanted in each sheep. At 24 weeks postoperatively, a computed tomography (CT) evaluation, pull-out test, micro-CT evaluation and histological evaluation were conducted to evaluate screw stability in the harvested surgical segments. RESULT: According to the CT evaluation, there were no signs of screw loosening in either group. The pull-out force and energy of the PEEK rod group were significantly higher than those of the titanium alloy rod group. Denser and thicker trabecular bone around the screw was observed in the PEEK rod group according to the micro-CT reconstructed images, and quantitative analysis of the micro-CT data confirmed this finding. In the histological evaluation, more abundant and denser bone trabeculae were also observed in the PEEK rod group. However, there was no significant difference in the bone-screw interface between the 2 groups. CONCLUSION: Posterior spinal fixation with PEEK rods can increase screw stability by promoting bone growth around the screw but cannot promote bone integration at the bone-screw interface in an animal model study. This finding presents a new idea for clinical practices to reduce screw loosening rate.

Calcaneal fracture maps and their determinants.

BACKGROUND: Calcaneal fractures are associated with numerous complications and a poor prognosis with significant long-term quality-of-life issues, regardless of treatment. Therefore, in-depth research into the underlying mechanism of calcaneal fracture is still of great interest, with the goal of improving treatment for patients suffering from this condition. This study aimed to investigate the relationship between the distribution of calcaneal fracture lines and their determinants, especially those related to the internal structure of the calcaneus. This goal was achieved by fracture maps created by copying and stacking fracture lines as viewed from six surfaces of the calcaneus. METHODS: A total of 210 consecutive patients with 226 calcaneal fractures were retrospectively analyzed. Fracture lines were copied from a reduced 3D calcaneal fracture model and stacked on calcaneal templates to generate fracture maps. The stacked images of six calcaneus surfaces were also converted into spectrograms with MATLAB to highlight the fracture frequency at specific locations. RESULTS: There were four concentrated bands of fracture lines and two fracture hot spots on the superior surface. Three dense bands of fractures were observed on the medial surface, and four fracture bands were observed lateral to the calcaneus. Vertical fracture lines dominated the anterior calcaneal fracture map. On the posterior surface, the fracture lines appeared to be centered superiorly. All fracture locations coincided with the interfaces between the trabecular groups. CONCLUSIONS: The fracture maps showed fracture patterns and recurrent fracture zones on all calcaneal surfaces. The shape of the talus and calcaneus and the architecture within the calcaneus, especially the arrangement of the trabeculae, are essential factors for calcaneal fractures.

Comprehensive analysis of lncRNA and miRNA expression profiles and ceRNA network construction in negative pressure wound therapy.

BACKGROUND: This study aims to explore the molecular mechanism of negative pressure wound therapy (NPWT) at the transcriptome level through whole transcriptome sequencing and biometric analysis. METHODS: A rat skin defect model was constructed and randomly divided into a NPWT group and a gauze group. The tissue in the center of the wound was used for whole transcriptome sequencing, and differentially expressed messenger RNAs (DEmRNAs), long noncoding RNAs (DElncRNAs), and microRNAs (DEmiRNAs) were identified between the two groups. Quantitative real time-polymerase chain reaction (qRT-PCR) analysis was used to verify the sequencing results. Functional enrichment analysis, pathway analysis, and protein-protein interaction (PPI) network analysis of DEmRNAs were conducted. Through bioinformatics analysis, a lncRNA-associated competing endogenous RNA (ceRNA) network was identified and constructed. RESULTS: We detected 896 DEmRNAs, 1,471 DElncRNAs, and 20 DEmiRNAs between the two groups. qRT-PCR verified the sequencing results. Functional analysis showed that DEmRNAs were mainly enriched in immune system processes and the Notch signaling pathway. Protein tyrosine phosphatase receptor type C (PTPRC) and signal transducer and activator of transcription 1 (STAT1) were the central hub nodes in the PPI analysis. The ceRNA network contained 11 mRNAs, 15 lncRNAs, and 4 miRNAs. CONCLUSIONS: We identified several DEmRNAs, DElncRNAs, and DEmiRNAs between the NPWT treatment group and the control group. These findings may provide new insights into the pathophysiological mechanism of NPWT and wound healing.

An intelligent vancomycin release system for preventing surgical site infections of bone tissues.

Preventing surgical site infections (SSIs) of implants has drawn significant attention in both basic and clinical research. Implants with convenient preparation methods and intelligent drug release capabilities are highly needed to resist bacterial infection. Herein, we designed an intelligent drug-release system, which can be instantly incorporated with implants during the surgical process. The drug-release system involves ß-glycerophosphate (ß-GP) and chitosan (CS) as a thermosensitive hydrogel for instant construction onto implants and hyaluronic acid (HA) as a trigger to release vancomycin hydrochloride (VH) on demand. Tertiary calcium phosphate (TCP) scaffolds (implants) are vacuum-adsorbed in a solution of the intelligent vancomycin-release system (VH-HA-CS/ß-GP), followed by heating for 40 min at 80 °C to form VH-HA-CS/ß-GP@TCP. The drug-release hydrogel intelligently releases vancomycin depending on the concentration of hyaluronidase, which is secreted by Staphylococcus aureus (S. aureus) in infection sites. Furthermore, VH-HA-CS/ß-GP@TCP showed effective antibacterial properties in vitro and in vivo. The VH-HA-CS/ß-GP drug-release system can be conveniently prepared during surgery for intelligently preventing SSIs in bone tissue.

Proinflammatory Effects of Ubiquitin-Specific Protease 5 (USP5) in Rheumatoid Arthritis Fibroblast-Like Synoviocytes.

Rheumatoid arthritis (RA) is a worldwide chronic autoimmune inflammatory disease which is affecting approximately 1% of the total population. It is characterized by abnormal proliferation of fibroblast-like synoviocytes (FLS) and increased production of proinflammatory cytokines. In the current study, we were aiming to investigate the role of ubiquitin-specific protease 5 (USP5) in the inflammatory process in RA-FLS. Expression of USP5 was found upregulated in RA-FLS compared with that in osteoarthritis- (OA-) FLS, and IL-1ß stimulation increased USP5 expression in a time-dependent manner. Furthermore, we found that USP5 overexpression significantly aggravated proinflammatory cytokine production and related nuclear factor κB (NF-κB) signaling activation. Consistently, silencing of USP5 decreased the release of cytokines and inhibited the activation of NF-κB. In addition, USP5 was found to interact with tumor necrosis factor receptor-associated factor 6 (TRAF6) and remove its K48-linked polyubiquitination chains therefore stabilizing TRAF6. Our data showed that a USP5-positive cell regulates inflammatory processes in RA-FLS and suggested USP5 as a potential target for RA treatment.

Impact of negative-pressure wound therapy on bacterial behaviour and bioburden in a contaminated full-thickness wound.

The use of negative-pressure wound therapy (NPWT) has displayed significant clinical benefits in the healing of infected wounds. However, the effects of NPWT on bacterial colonisation and infection of traumatic wounds has been controversial. The aim of this study is to evaluate the impact of NPWT treatment in rabbits with a contaminated full-thickness wound on bacterial behaviour, including colony morphology, spatial distribution, fissional proliferation, and bacterial bioburden. Full-thickness wounds were created on the back of rabbits, and were inoculated with bioluminescent Staphylococcus aureus. The wounds were treated with sterile gauze dressings and NPWT with continuous negative pressure (-125 mm Hg). Wound samples were harvested on days 0 (6 hours after bacterial inoculation), 2, 4, 6, and 8 at the centre of wound beds before irrigation. Scanning electron microscopy and transmission electron microscopy (TEM) analyses were performed to determine the characteristic bacteriology. Laser scanning confocal microscopy was performed to obtain bioluminescent images, which were used to observe spatial distribution of the GFP-labelled S. aureus within the tissue and quantify the bacterial bioburden. NPWT resulted in sparse amounts of scattered bacteria on the wound surface or as sparsely spaced single colonies within the tissue. Wound bioburden on day 8 in the NPWT and gauze groups was 34.6 ± 5.5% and 141.9 ± 15.4% of the baseline values (N = 6), respectively (P < .0001). TEM showed a lack of S. aureus active fission within NPWT-treated tissue. NPWT can impact S. aureus colony morphology and spatial distribution both on the surface and within wound tissue, and reduce S. aureus as early as 48 hours after therapy initiation. Additionally, NPWT inhibits bacterial fissional proliferation in microcolonies.

Virulence analysis of Staphylococcus aureus in a rabbit model of infected full-thickness wound under negative pressure wound therapy.

The aim of this study was to evaluate the virulence of Staphylococcus aureus in a controlled animal study using the standard sterile gauze and negative pressure wound therapy (NPWT), including activation of agr, gene expression and production of virulence foctors and depth of bacterial invasion. The tissue specimens were harvested on days 0 (6 h after bacterial inoculation), 2, 4, 6, and 8 at the center of wound beds. Laser scanning confocal microscopy was performed to obtain bioluminescent images which were used to measure the depth of bacterial invasion. The agrA expression of S.aureus and the transcription and production of virulence factors including Eap, Spa and α-toxin were significantly different. The bacterial invasion depth was significantly less with effect of NPWT. The markedly different activation of quorum sensing systems that enable cell-to-cell communication and regulation of numerous colonization and virulence factors result in distinct gene expression and pathogenicity over time in different microenvironment. Thus, the agr system represents a fundamental regulatory paradigm that can encompass different adaptive strategies and accommodate horizontally acquired virulence determinants.

Association of tourniquet utilization with blood loss, rehabilitation, and complications in Chinese obese patients undergoing total knee arthroplasty: A retrospective study.

Obesity not only gives rise to more blood loss volume but also correlates with postoperative rehabilitation and complications in surgical patients. It is not clear at present whether tourniquet utilization is associated with blood loss, rehabilitation, and complications, and it is imperative to ascertain the tactics of utilizing tourniquet in obese patients undergoing total knee arthroplasty (TKA). The present study was designed to explore the association of tourniquet utilization with blood loss, rehabilitation, and complications, and ascertain the tactics of utilizing tourniquet in obese patients undergoing TKA.A total of 130 patients from January 2014 to December 2014 were categorized into tourniquet group (n = 94) and non-tourniquet group (n = 36) based on whether the tourniquet was utilized or not during operation. Recorded data were as follows: total blood loss volume, intraoperative blood loss volume, hidden blood loss volume, blood transfusion volume, drainage volume, difference between hemoglobin value before operation and that on the fifth day after operation (5d Hb D-value), thigh swelling rate and visual analogue scale (VAS) score of motion pain, and Knee Society Score (KSS) score.Mean age was 65.27 ±â€Š7.43 (49-82) years, and 15 patients (11.5%) were men. No significant difference in total blood loss volume, drainage volume, blood transfusion volume, and 5d Hb D-value was noted between the 2 groups (P > .05 for all). Tourniquet group had significantly less intraoperative blood loss volume and significantly more hidden blood loss volume than the non-tourniquet group (P < .05 for all). Tourniquet group had significantly higher thigh swelling rate and VAS score of motion pain on the third day after operation, and significantly lower KSS function score in the third week after operation than non-tourniquet group (P < .05). No significant difference in KSS function score in the first year after operation was found between the 2 groups (P > .05). No difference in postoperative complications was observed between the groups (P > .05).The current study demonstrated that the tourniquet is not associated with reduced blood loss and increased postoperative complications in obese patients undergoing TKA. Step-down postoperative rehabilitation related to tourniquet is short-term rather than long-term in obese patients undergoing TKA.

Discovery of N-(benzyloxy)-1,3-diphenyl-1H-pyrazole-4-carboxamide derivatives as potential antiproliferative agents by inhibiting MEK.

Mitogen activated protein kinase (MAPK) signal transduction pathway has been proved to play an important role in tumorigenesis and cancer development. MEK inhibitor has been demonstrated significant clinical benefit for blocking MAPK pathway activation and possibly could block reactivation of the MAPK pathway at the time of BRAF inhibitor resistance. Twenty N-(benzyloxy)-1,3-diphenyl-1H-pyrazole-4-carboxamide derivatives have been designed and synthesized as MEK inhibitors, and their biological activities were evaluated. Among these compounds, compound 7b showed the most potent inhibitory activity with IC50 of 91nM for MEK1 and GI50 value of 0.26µM for A549 cells. The SAR analysis and docking simulation were performed to provide crucial pharmacophore clues that could be used in further structure optimization.

Effects of Cold Irrigation on Early Results after Total Knee Arthroplasty: A Randomized, Double-Blind, Controlled Study.

Several studies have indicated that pain peaks at 24 to 48 hours after total knee arthroplasty (TKA) surgery. TKA has been associated with disruption in normal sleep patterns, swelling knee, and significant blood loss. However, a satisfactory regime to resolve these mentioned problems has yet to be found.In this study, a total of 420 patients were randomly allocated into two groups and treated with continuous irrigation of either 4000 mL cold saline with 0.5% epinephrine or normal temperature solution. Clinical outcomes including pain scores at rest during postoperative three days, drainage output, analgesic consumption, decreased hemoglobin, sleep quality, and satisfaction rate were analyzed. Mean scores and postoperative change in scores were calculated.Visual analog scale (VAS) pain scores in the treatment group were significantly reduced from 4 hours (P = 0.0016) to 24 hours (P = 0.0004) after TKA. Additional benefits including reduced analgesic consumption, improved satisfaction rate, and sleep quality were observed. In addition, a significant reduction in blood loss reflected by decreased Hb and drainage was found.In this study, irrigation with a cold 0.5% epinephrine solution was a beneficial and cost-effective treatment that decreased acute postoperative VAS pain scores immediately after and 1 day after surgery. Patients reported postoperative improvement in sleep quality and overall satisfaction rate with a decrease in morphine usage. In addition, a reduction of intraoperative blood loss might decrease the blood transfusion rate and related costs. Collectively, irrigation with cold 0.5% epinephrine offers a safe, simple, and effective treatment that might improve recovery and enhance quality of life of patients undergoing TKA.

Early application of negative pressure wound therapy to acute wounds contaminated with Staphylococcus aureus: An effective approach to preventing biofilm formation.

Negative pressure wound therapy (NPWT) has been demonstrated to be effective at preventing biofilm-associated infections; however, its role in biofilm prevention is unknown. The present study evaluated the effect of NPWT on biofilm prevention when rapidly initiated following wound contamination. Full-thickness dermal wounds (8 mm) were created in rabbit ears and inoculated with green fluorescent protein-labeled Staphylococcus aureus (S. aureus). At 6 h following inoculation, continuous NPWT at -125 mmHg was initiated, with the wounds on the contralateral ear left untreated in order to serve as self-controls. S. aureus rapidly formed mature biofilms in the wound beds post-inoculation, with a persistent bacterial burden of ~105-107 colony-forming units (CFUs)/wound and impaired wound healing. Compared with the untreated group, NPWT resulted in a significant reduction in biofilm matrix, which was verified by scanning electron microscopy and epifluorescence. A reduction in bacterial counts followed (P<0.05) with ~103 CFUs/wound on postoperative day 13 and improvement in all healing parameters (P<0.05) relative to control wounds. The results of the present investigation suggest that NPWT is an effective strategy to impeding the formation of S. aureus wound biofilms when initiated rapidly following bacterial contamination. The early application of NPWT, aimed at biofilm prevention, may improve wound care.

Percutaneous Anterior Column Fixation for Acetabulum Fractures, Does It Have to Be Difficult?-The New Axial Pedicle View of the Anterior Column for Percutaneous Fixation.

Anterior column percutaneous screw fixation can be challenging. The purpose of this new technique is to offer a rapid, simple, and safe method to place an anterior screw. The authors used a 3-dimensional reconstruction simulation, cadaver study, and a clinical case series to demonstrate this new alternative to standard previously described techniques.

Synergistic Effects of BMP9 and miR-548d-5p on Promoting Osteogenic Differentiation of Mesenchymal Stem Cells.

Various stimulators have been reported to promote MSC osteogenic differentiation via different pathways such as bone morphogenetic protein 9 (BMP9) through influencing COX-2 and miR-548d-5p through targeting peroxisome proliferator-activated receptor-γ (PPARγ). Whether synergistic effects between BMP9 and miR-548d-5p existed in promoting osteogenesis from MSCs was unclear. In the study, the potential synergistic effects of BMP9 and miR-548d-5p on human MSC differentiation were investigated. Osteogenic differentiation of MSCs treated with BMP9 or miR-548d-5p was detected with multimodality of methods. The results demonstrated that BMP9 and miR-548d-5p significantly influenced COX-2 and PPARγ, respectively. BMP9 also influenced the expression of PPARγ, but no significant effect of miR-548d-5p on COX-2 was observed. When BMP9 and miR-548d-5p were combined, more potent effects on both COX-2 and PPARγ were observed than BMP9 or miR-548d-5p alone. Consistently, osteogenic analysis at different timepoints demonstrated that osteogenic genes, ALP activity, calcium deposition, OPN protein, and matrix mineralization were remarkably upregulated by BMP9/miR-548d-5p compared with BMP9 or miR-548d-5p alone, indicating the synergetic effects of BMP9 and miR-548d-5p on osteogenic differentiation of MSCs. Our study demonstrated that regulating different osteogenic regulators may be an effective strategy to promote bone tissue regeneration for bone defects.

Advancing computer-assisted orthopaedic surgery using a hexapod device for closed diaphyseal fracture reduction.

BACKGROUND: Surgical complications such as healing problems, in fractures treated using the Arbeitsgemeinschaft für Osteosynthesefragen (AO) technique, present functional and economic challenges to patients and treatment dilemmas for surgeons. Computer-assisted orthopaedic surgery using minimally invasive techniques focused on biological osteosynthesis is a novel direction for fracture treatment. METHOD: We modified the hexapod computer-assisted fracture reduction system by introducing a new reduction strategy, building a new system configuration and upgrading the corresponding software. We then validated the entire system, using a fracture model of bovine femur. RESULTS: Precision tests were performed seven times on a bovine femur with a transverse fracture. Residual deviation was 1.23 ± 0.60 mm in axial deflection, 1.04 ± 0.47 mm in translation, 2.34 ± 1.79° in angulation and 2.83 ± 0.96° in rotation. CONCLUSION: Our new reduction system described here is detachable, flexible and more precise in coordinate transformations. The detachable, modular design will allow for more analogous applications in the future. Copyright © 2014 John Wiley & Sons, Ltd.

Isolation and purification of psoralen and isopsoralen and their efficacy and safety in the treatment of osteosarcoma in nude rats.

BACKGROUND: Modern studies have shown that psoralen has a significant inhibitory effect on tumor growth in a variety of animals and humans. OBJECTIVE: To obtain coumarin compounds - psoralen and isopsoralen - from traditional Chinese medicine Psoralea corylifolia L. using chromatographic techniques and isolation and purification methods, and to observe the transplanted tumor growth inhibitory effects and adverse reactions of psoralen and isopsoralen in nude rats with osteosarcoma. METHODS: Dried ripe fruits of Psoralea corylifolia L. were taken as the raw material to prepare crude extract of Psoralea corylifolia L. by ethanol reflux method. Column chromatography was used to isolate the crude extract; compounds were structurally identified based on (1)H-NMR, (13)C-NMR spectra, the two compounds were identified as psoralen andisopsoralen, and their contents were 99.7% and 99.6, respectively. Nude rat model of osteosarcoma was established; the rats were randomized into: normal saline group, psoralen low- and high-dose groups, isopsoralen low- and high-dose groups, and cisplatin group. Osteosarcoma volume and weight inhibition rates in nude rats in each group were observed; radioimmunoassay was used to determine the serum alkaline phosphatase activity; peripheral blood cell and bone marrow nucleated cell counts were determined; light microscopy was used to observe heart, liver, spleen, lung, kidney, and tumor histopathology; and electron microscopy was used to observe the fine structure of tumor cells. RESULTS: Tumor volume inhibition rates were 43.75% and 40.18%, respectively, in the psoralen and isopsoralen low-dose groups, and tumor weight inhibition rates were 38.83% and 37.77%. Tumor volume inhibition rates were 67.86% and 66.96%, respectively, in the psoralen and isopsoralen high-dose groups, and tumor weight inhibition rates were 49.47% and 47.87%. Psoralen and ispsoralen markedly lowered serum AKP level. Psoralen and isopsoralen induced apoptosis or necrosis of osteosarcoma. After administration of high doses of psoralen and isopsoralen, toxic reactions such as writhing, lassitude, and hypoactivity were seen. Kidney histopathology showed tubulointerstitial dilatation and congestion, and inflammatory cell aggregation in the renal intercellular space. Psoralen and isopsoralen did not cause any significant toxic side effects to the bone marrow, or other organs such as heart, lung, liver, and spleen. CONCLUSION: Psoralen and isopsoralen have growth inhibitory effects on transplanted tumor in nude rats with osteosarcoma, and can induce tumor cell apoptosis or necrosis, without significant toxic effects.

Operative versus nonoperative treatment in complex proximal humeral fractures.

This updated meta-analysis investigated whether operative treatment is superior to nonoperative treatment in complex proximal humeral fractures. The authors searched the Cochrane Central Register of Controlled Trials, PubMed, and EMBASE. Randomized controlled trials that evaluated operative vs nonoperative treatment for exclusively 3- or 4-part proximal humeral fractures were considered. Six studies with a total of 287 patients who had proximal humeral fractures were included. According to the meta-analysis, no statistically significant differences were found between operative and nonoperative treatment in Constant-Murley shoulder scores (Constant scores); Disabilities of the Arm, Shoulder, and Hand scores; total complication events; mortality; infection; nonunion; avascular necrosis; osteoarthritis; redisplacement of fractures; or dislocation or resorption of tuberosity. For health-related quality of life, EuroQol-5D (EQ-5D) favored operative treatment, but 15D scores showed no significant difference. Compared with nonoperative treatment, open reduction and internal fixation required significantly more additional surgeries (risk ratio, 6.50; 95% confidence interval, 1.54-27.50; P=.01), and more penetrations into joint space occurred (risk ratio, 9.56; 95% confidence interval, 2.27-40.13; P=.002). The limited evidence suggests that no convincing findings support the use of either open reduction and internal fixation or hemiarthroplasty for the treatment of complex proximal humeral fractures. The findings of the current study should be interpreted cautiously because of the modest sample size and the short follow-up period.

Acute spinal cord injury in rats induces autophagy activation.

AIM: Autophagy is an important process that balances cellular protein synthesis and degradation and is involved in many physiological and pathological conditions. However, the precise role of autophagy has not yet been defined in the model of spinal cord injury (SCI). MATERIAL AND METHODS: Here, we utilized a hemisection model of acute SCI to elucidate the role of autophagy in the pathological processes underlying SCI. RESULTS: LC3B-II, a well-known marker of autophagy, was immunohistochemically detected 4H after SCI, peaked at 3D, and decreased at 21D. Hematoxylin-eosin (HE) staining confirmed accurate spinal cord hemisection, which was accompanied by both neuronal swelling and shrunken neurons with darkly stained, condensed nuclei. These findings suggest that the process of autophagy is related with pathological changes following SCI. CONCLUSION: Our results indicate autophagy is involved in the pathological changes after SCI, and potential therapies to promote neuronal regeneration following SCI should target the mechanism of autophagy.

Negative-pressure wound therapy enhances local inflammatory responses in acute infected soft-tissue wound.

Clinical studies found that negative-pressure wound therapy (NPWT) displayed significant clinical benefits in the healing of infected wounds. However, the effect of NPWT on local inflammatory responses in acute infected soft-tissue wound has not been investigated thoroughly. The purpose of this study was to test the impact of NPWT on local expression of proinflammatory cytokines, amount of neutrophils, and bacterial bioburden in wound from acute infected soft-tissue wounds. Full-thickness wounds were created on the back of rabbits, and were inoculated with Staphylococcus aureus strain ATCC29213. The wounds were treated with sterile saline-moistened gauze dressings and NPWT with continuous negative pressure (-125 mmHg). Wound samples were harvested on days 0 (6 h after bacterial inoculation), 2, 4, 6, and 8 at the center of wound beds before irrigation for real-time PCR analysis of gene expression of IL-1ß, IL-8, and TNF-α. Wound biopsies were examined histologically for neutrophil quantification in different layers of tissue. Quantitative bacterial cultures at the same time point were analyzed for bacterial clearance. Application of NPWT to acute infected wounds in rabbits was compared with treatment with sterile saline-moistened gauze, over an 8-day period. NPWT-treated wounds exhibited earlier and greater peaking of IL-1ß and IL-8 expression and decrease in TNF-α expression over the early 4 days (P < 0.05). Furthermore, histologic examination revealed that significantly increased neutrophil count was observed in the shallow layer in wound biopsies of NPWT treatment at day 2 (P < 0.001). In addition, there was a statistically significant decrease of bacteria load from baseline (day 0) at days 2 and 8 in NPWT group (P < 0.05). In conclusion, this study demonstrates that NPWT of acute infected soft-tissue wounds leads to increased local IL-1ß and IL-8 expression in early phase of inflammation, which may trigger accumulation of neutrophils and thus accelerate bacterial clearance. Meanwhile, the success of NPWT in the treatment of acute wounds can attenuate the expression of TNF-α, and the result may partly explain how NPWT can avoid significantly impairing wound healing.

Autophagy reduces neuronal damage and promotes locomotor recovery via inhibition of apoptosis after spinal cord injury in rats.

Autophagy is an intracellular catabolic mechanism that maintains the balance of proteins, lipids and aging organelles. 3-Methyladenine (3-MA) is a selective inhibitor of autophagy, whereas rapamycin, an antifungal agent, is a specific inducer of autophagy, inhibiting the protein mammalian target of rapamycin. In the present study, we examined the role of autophagy, inhibited by 3-MA and enhanced by rapamycin, in a model of acute spinal cord injury in rats. We found that rapamycin could significantly increase the expression of microtubule-associated protein 1 light chain 3 (LC3) and Beclin1 at the injury site. At the same time, the number of neurons and astrocytes with LC3 positive in the spinal cord was upregulated with time. In addition, administration of rapamycin produced an increase in the Basso, Beattie and Bresnahan scores of injured rats, indicating high recovery of locomotor function. Furthermore, expression of the proteins Bcl-2 and Bax was upregulated and downregulated, respectively. By contrast, the results for rats treated with 3-MA, which inhibits autophagy, were the opposite of those seen with the rapamycin-treated rats. These results show that induction of autophagy can produce neuroprotective effects in acute spinal cord injury in rats via inhibition of apoptosis.