Pelvic bone tumor segmentation fusion algorithm based on fully convolutional neural network and conditional random field.

Background and objective: Pelvic bone tumors represent a harmful orthopedic condition, encompassing both benign and malignant forms. Addressing the issue of limited accuracy in current machine learning algorithms for bone tumor image segmentation, we have developed an enhanced bone tumor image segmentation algorithm. This algorithm is built upon an improved full convolutional neural network, incorporating both the fully convolutional neural network (FCNN-4s) and a conditional random field (CRF) to achieve more precise segmentation. Methodology: The enhanced fully convolutional neural network (FCNN-4s) was employed to conduct initial segmentation on preprocessed images. Following each convolutional layer, batch normalization layers were introduced to expedite network training convergence and enhance the accuracy of the trained model. Subsequently, a fully connected conditional random field (CRF) was integrated to fine-tune the segmentation results, refining the boundaries of pelvic bone tumors and achieving high-quality segmentation. Results: The experimental outcomes demonstrate a significant enhancement in segmentation accuracy and stability when compared to the conventional convolutional neural network bone tumor image segmentation algorithm. The algorithm achieves an average Dice coefficient of 93.31 %, indicating superior performance in real-time operations. Conclusion: In contrast to the conventional convolutional neural network segmentation algorithm, the algorithm presented in this paper boasts a more intricate structure, proficiently addressing issues of over-segmentation and under-segmentation in pelvic bone tumor segmentation. This segmentation model exhibits superior real-time performance, robust stability, and is capable of achieving heightened segmentation accuracy.

Dehydrocostus lactone (DHC) promotes osteoblastic differentiation and mineralization through p38/RUNX-2 signaling.

Dysregulation of osteoblastic differentiation is an important risk factor of osteoporosis, the therapy of which is challenging. Dehydrocostus lactone (DHC), a sesquiterpene isolated from medicinal plants, has displayed anti-inflammatory and antitumor properties. In this study, we investigated the effects of DHC on osteoblastic differentiation and mineralization of MC3T3-E1 cells. Interestingly, we found that DHC increased the expression of marker genes of osteoblastic differentiation, such as alkaline phosphatase (ALP), osteocalcin (OCN), and osteopontin (OPN). Additionally, DHC increased the expressions of collagen type I alpha 1 (Col1a1) and collagen type I alpha 2 (Col1a2). We also demonstrate that DHC increased ALP activity. Importantly, the Alizarin Red S staining assay revealed that DHC enhanced osteoblastic differentiation of MC3T3-E1 cells. Mechanistically, it is shown that DHC increased the expression of Runx-2, a central regulator of osteoblastic differentiation. Treatment with DHC also increased the levels of phosphorylated p38, and its blockage using its specific inhibitor SB203580 abolished the effects of DHC on runt-related transcription factor 2 (Runx-2) expression and osteoblastic differentiation, suggesting the involvement of p38. Based on these findings, we concluded that DHC might possess a capacity for the treatment of osteoporosis by promoting osteoblastic differentiation.

Bone tumor examination based on FCNN-4s and CRF fine segmentation fusion algorithm.

Background and objective: Bone tumor is a kind of harmful orthopedic disease, there are benign and malignant points. Aiming at the problem that the accuracy of the existing machine learning algorithm for bone tumor image segmentation is not high, a bone tumor image segmentation algorithm based on improved full convolutional neural network which consists fully convolutional neural network (FCNN-4s) and conditional random field (CRF). Methodology: The improved fully convolutional neural network (FCNN-4s) was used to perform coarse segmentation on preprocessed images. Batch normalization layers were added after each convolutional layer to accelerate the convergence speed of network training and improve the accuracy of the trained model. Then, a fully connected conditional random field (CRF) was fused to refine the bone tumor boundary in the coarse segmentation results, achieving the fine segmentation effect. Results: The experimental results show that compared with the traditional convolutional neural network bone tumor image segmentation algorithm, the algorithm has a great improvement in segmentation accuracy and stability, the average Dice can reach 91.56%, the real-time performance is better. Conclusion: Compared with the traditional convolutional neural network segmentation algorithm, the algorithm in this paper has a more refined structure, which can effectively solve the problem of over-segmentation and under-segmentation of bone tumors. The segmentation prediction has better real-time performance, strong stability, and can achieve higher segmentation accuracy.

A Comparison of the Safety, Efficacy, and Accuracy of Frame-Based versus Remebot Robot-Assisted Stereotactic Systems for Biopsy of Brainstem Tumors.

BACKGROUND: Brainstem tumors are rare and extremely heterogeneous and present significant challenges in surgical treatment. Thus, biopsies often set the foundation for the diagnosis of brainstem tumors. Multimodal, image-guided, robot-assisted frameless stereotactic biopsies are increasingly popular in neurosurgery centers. This study aimed to compare the safety, efficacy, and duration of the Remebot robot-assisted (Remebot) frameless brainstem tumor biopsy versus those of frame-based stereotactic biopsy. METHOD: A retrospective analysis of 33 patients with brainstem tumors who underwent stereotactic brainstem biopsies in the department of neurosurgery from January 2016 to January 2021 was conducted. The patients were divided into two groups: the Remebot group (n = 22) and the frame-based group (n = 11). The clinical characteristics, trajectory strategy, duration of procedure, diagnostic yielding, histopathological diagnosis, and postoperative complications were retrospectively analyzed and compared between the groups. RESULTS: More pediatric patients performed Remebot frameless brainstem tumor biopsy than frame-based biopsy, with a mean age of 17.3 ± 18.7 vs. 32.8 ± 17.1 (p = 0.027). The diagnostic yield had no significant difference in the two groups, with the diagnostic yield of frame-based biopsy and Remebot frameless brain biopsy being 90.9% and 95.5%, respectively. The time of the total process was 124.5 min for the frame-based biopsy and 84.7 min for the Remebot frameless brain biopsy (p < 0.001). There were no significant differences with respect to the occurrence of complication or the duration of the operation between the two groups. CONCLUSION: Remebot frameless stereotactic brainstem biopsy is as safe and efficacious as frame-based stereotactic biopsy. However, Remebot frameless biopsy can reduce the total duration of the procedure and has better application in young pediatric patients. Remebot frameless stereotactic biopsies can be a better option towards the safe and efficient treatment of brainstem tumors.

Geographical pattern of minerals and its association with health disparities in the USA.

This study aimed to determine the common latent patterns of geographical distribution of health-related minerals across the USA and to evaluate the real-world cumulative effects of these patterns on overall population health. It was an ecological study using county-level data (3080 contiguous counties) on the concentrations of 14 minerals (i.e., aluminum, arsenic, calcium, copper, iron, lead, magnesium, manganese, mercury, phosphorus, selenium, sodium, titanium, zinc) in stream sediments (or surface soils), and the measurements of overall health including life expectancy at birth, age-specific mortality risks and cause-specific (summarized by 21 mutually exclusive groups) mortality rates. Latent class analysis (LCA) was employed to identify the common clusters of life expectancy-related minerals based on their concentration characteristics. Multivariate linear regression analyses were then conducted to examine the relationship between the LCA-derived clusters and the health measurements, with adjustment for potential confounding factors. Five minerals (i.e., arsenic, calcium, selenium, sodium and zinc) were associated with life expectancy and were analyzed in LCA. Three clusters were determined across the USA, the 'common' (n = 2056, 66.8%), 'infertile' (n = 739, 24.0%) and 'plentiful' (n = 285, 9.3%) clusters. Residents in counties with the 'infertile' profile were associated with the shortest life expectancy, highest mortality risks at all ages, and highest mortality rates for many reasons including the top five leading causes of death: cardiovascular diseases, neoplasms, neurological disorders, chronic respiratory conditions, and diabetes, urogenital, blood and endocrine diseases. Results remained statistically significant after confounding adjustment. Our study brings novel perspectives regarding environmental geochemistry to explain health disparities in the USA.

Activation of HDAC8 Can Suppress the Proliferation of Osteosarcoma Cells via TP53 and STAT3/ERK Signaling Pathways.

OBJECTIVE: Osteosarcoma is the most common malignant bone cancer and is typically associated with poor prognosis. Histone deacetylase 8 (HDAC8) presents as an effective target in anti-tumor treatment in various tumors. As the functions of HDAC8 in osteosarcoma have not been studied thoroughly, our study aims to explore the effects of HDAC8 in osteosarcoma proliferation. METHODS: HDAC8 expression was analyzed in The Cancer Genome Atlas (TCGA)-pan-cancer dataset. The expression of HDAC8 in osteosarcoma cell lines was detected by western blot. TM-2-51, an activator of HDAC8, was taken to promote HDAC8 expression in osteosarcoma cells. Cell Counting Kit-8 (CCK-8) assay was applied to analyze cell viability changes and colony formation while 5-ethynyl-29-deoxyuridine (EdU) assays were used to evaluate cell proliferation. The migration and invasion abilities were analyzed by transwell assay, the distributions of cell cycle were analyzed by flow cytometry, and xenograft models were used to study the effect of HDAC8 activation in vivo. Furthermore, the mechanism underlying HDAC8's influence in osteosarcoma was analyzed by western blot assay. RESULTS: Our study demonstrated that activation of HDAC8 in osteosarcoma cells can suppress cell viability, proliferation, migration, invasion, and arrest cell cycle of the osteosarcoma cells via TP53 and STAT3/ERK signaling pathway. Xenograft models confirmed that HDAC8 activation can reduce tumor growth in vivo. CONCLUSION: The activation of HDCA8 could contribute negatively to osteosarcoma proliferation, and HDAC8 may represent a valuable therapeutic target in osteosarcoma therapy.

The GBM Tumor Microenvironment as a Modulator of Therapy Response: ADAM8 Causes Tumor Infiltration of Tams through HB-EGF/EGFR-Mediated CCL2 Expression and Overcomes TMZ Chemosensitization in Glioblastoma.

Standard chemotherapy of Glioblastoma multiforme (GBM) using temozolomide (TMZ) frequently fails due to acquired chemoresistance. Tumor-associated macrophages and microglia (TAMs) as major immune cell population in the tumor microenvironment are potential modulators of TMZ response. However; little is known about how TAMs participate in TMZ induced chemoresistance. Members of the metzincin superfamily such as Matrix Metalloproteases (MMPs) and A Disintegrin and Metalloprotease (ADAM) proteases are important mediators of cellular communication in the tumor microenvironment. A qPCR screening was performed to identify potential targets within the ADAM and MMP family members in GBM cells. In co-culture with macrophages ADAM8 was the only signature gene up-regulated in GBM cells induced by macrophages under TMZ treatment. The relationship between ADAM8 expression and TAM infiltration in GBM was determined in a patient cohort by qPCR; IF; and IHC staining and TCGA data analysis. Moreover; RNA-seq was carried out to identify the potential targets regulated by ADAM8. CCL2 expression levels were determined by qPCR; Western blot; IF; and ELISA. Utilizing qPCR; IF; and IHC staining; we observed a positive relationship between ADAM8 expression and TAMs infiltration level in GBM patient tissues. Furthermore; ADAM8 induced TAMs recruitment in vitro and in vivo. Mechanistically; we revealed that ADAM8 activated HB-EGF/EGFR signaling and subsequently up-regulated production of CCL2 in GBM cells in the presence of TMZ treatment; promoting TAMs recruitment; which further induced ADAM8 expression in GBM cells to mediate TMZ chemoresistance. Thus; we revealed an ADAM8 dependent positive feedback loop between TAMs and GBM cells under TMZ treatment which involves CCL2 and EGFR signaling to cause TMZ resistance in GBM.

Recent advances in cell-based and cell-free therapeutic approaches for sarcopenia.

Sarcopenia is a progressive loss of muscle mass and function that is connected with increased hospital expenditures, falls, fractures, and mortality. Although muscle loss has been related to aging, injury, hormonal imbalances, and diseases such as malignancies, chronic obstructive pulmonary disease, heart failure, and kidney failure, the underlying pathogenic mechanisms of sarcopenia are unclear. Exercise-based interventions and multimodal strategies are currently being considered as potential therapeutic approaches to prevent or treat these diseases. Although drug therapy research is ongoing, no drug has yet been proven to have a substantial safety and clinical value to be the first drug therapy to be licensed for sarcopenia. To better understand the molecular alterations underlying sarcopenia and effective treatments, we review leading research and available findings from the systemic change to the muscle-specific microenvironment. Furthermore, we explore possible mechanisms of sarcopenia and provide new knowledge for the development of novel cell-free and cell-based therapeutics. This review will assist researchers in developing better therapies to improve muscle health in the elderly.

Long non-coding RNA plasmacytoma variant translocation 1 and growth arrest specific 5 regulate each other in osteoarthritis to regulate the apoptosis of chondrocytes.

Long non-coding RNA (lncRNA) plasmacytoma variant translocation 1 (PVT1) and growth arrest specific 5 (GAS5) have opposite functions in the apoptosis of chondrocytes, which are involved in the pathogenesis of osteoarthritis (OA). The opposite roles of PVT1 and GAS5 in OA may indicate the existence of crosstalk between them in OA. This study aimed to explore the possible interaction between PVT1 and GAS5 in OA. Accumulation of PVT1 and GAS5 in OA and control synovial fluid samples was measured by RT-qPCR. The interaction between PVT1 and GAS5 in chondrocytes was explored by overexpression experiments. Dual-luciferase reporter assay was performed to analyze the binding of PVT1 and GAS5 to each other's promoter regions. Regulatory roles of PVT1 and GAS5 in the apoptosis of chondrocytes were studied with cell apoptosis assay. PVT1 was upregulated in OA, and GAS5 was downregulated in OA. An inverse correlation between PVT1 and GAS5 was observed across OA samples. Under lipopolysaccharides (LPS) treatment, PVT1 was upregulated and GAS5 was downregulated. Interestingly, PVT1 and GAS5 overexpression downregulated each other in chondrocytes. Cell apoptosis analysis showed that PVT1 overexpression promoted cell apoptosis, while GAS5 overexpression suppressed cell apoptosis induced by LPS. Co-transfection of PVT1 and GAS5 failed to significantly affect cell apoptosis. PVT1 and GAS5 directly bound to each other's promoter regions. Our study characterized the interaction between PVT1 and GAS5 in OA. Their interaction regulated the apoptosis of chondrocytes, which play a critical role in OA. PVT1 and GAS5 may form a negative feedback loop in OA.

MicroRNA-455-3p regulates proliferation and osteoclast differentiation of RAW264.7 cells by targeting PTEN.

BACKGROUND: Macrophages are one of the important cells in immune system. In this article, we aim to explore the regulatory role of miR-455-3p on proliferation and osteoblast differentiation of RAW264.7 cells. METHODS: Expression levels of genes and proteins in cells were tested via qRT-PCR and western blot. The targeted correlation between miR-455-3p and PTEN was identified by luciferase analysis. MTT assay and flow cytometry were applied to detect the proliferation and apoptosis of cells. Osteoclastogenesis was completed by stimulating RAW 264.7 cells with RANKL. Tartrate-resistant acid phosphatase (TRAP) activity in different groups of cells were assessed. RESULTS: Firstly, we determined that up-regulation of miR-455-3p promoted the proliferation and inhibited apoptosis of RAW 264.7 cells. MiR-455-3p deficiency played opposite effect in RAW 264.7 cells. Additionally, osteoclastogenesis-related factors (TRAP, CTSK and NFATc1) expression levels were remarkably up-regulated in miR-455-3p-mimic group of RAW264.7 cells treated with RANKL, but decreased in inhibitor group. Luciferase assay proved that miR-455-3p targeted PTEN. We took a further step and found overexpression of PTEN significantly inhibited the increased proliferation and osteoblast differentiation of RAW264.7 cells induced by miR-455-3p. CONCLUSIONS: Our findings supported basic to explore the molecular mechanism of proliferation and osteoblast differentiation of RAW264.7 cells.

The role of surgical resection in primary central nervous system lymphoma: a single-center retrospective analysis of 70 patients.

BACKGROUND: The aim of this study was to evaluate the effect of surgical resection and stereotactic biopsy on the complication rate, progression-free survival (PFS) and overall survival (OS) of 70 patients diagnosed at a single institution with primary central nervous system lymphoma (PCNSL) and to explore the predictors of selection for resection and the prognostic factors of PCNSL. METHODS: A retrospective analysis was performed of 70 patients with PCNSL that was diagnosed by surgical resection or stereotactic brain biopsy in our department from January 2013 to May 2019. We divided the patients into two groups: a resection group (n = 28) and a stereotactic biopsy group (n = 42). Data on clinical characteristics, imaging findings, complication rates, PFS and OS were retrospectively reviewed and compared between these two groups. We also analysed the predictors of selection for resection and prognostic factors of PCNSL by multivariate analysis. RESULTS: The median age was 53.3 ± 14.3 years, and there was a male predominance with a sex ratio of 1.33:1. The most common clinical manifestation was a headache. The complication rate in the resection group was 10.7% versus 7.1% in the stereotactic biopsy group, and there was no statistically significant difference. The rate of improvement in symptoms of the resection group was significantly higher than that of the stereotactic biopsy group. Multivariable analysis identified a single tumour and not involving deep structures as predictors of selection for resection. With a median follow-up of 30 months (range 1-110), the mean OS and PFS of all patients were 16.1 months and 6.2 months, respectively. Patients who underwent surgical resection had a mean OS of 23.4 months and PFS of 8.6 months versus 11.2 months and 4.6 months for those who had a brain biopsy performed. In addition, multivariable analysis showed that not involving deep structures and resection were favourable prognostic factors for PCNSL. CONCLUSIONS: The outcomes of patients with PCNSL treated in our cohort are still poor. In our series, surgical resection might play a role in significantly improving OS and PFS compared with stereotactic biopsy in a subset of patients. The type of surgery and tumour location are prognostic factors for PCNSL.

Teres minor muscle hypertrophy is a negative predictor of outcomes after reverse total shoulder arthroplasty: an evaluation of preoperative magnetic resonance imaging and postoperative implant position.

BACKGROUND: Predictors of outcomes after reverse total shoulder arthroplasty (rTSA) remain unclear. The purpose of this study was to analyze the impact of preoperative muscle quality and postoperative implant positioning on patient-reported outcomes following rTSA. METHODS: We evaluated 88 shoulders treated with rTSA in which preoperative magnetic resonance imaging was available. Preoperative muscle quality was evaluated, including fatty infiltration, rotator cuff muscle volume, and total tear size. Postoperative implant position was determined radiographically. The correlation between imaging parameters and the 2-year postoperative American Shoulder and Elbow Surgeons (ASES) score was examined. Multivariate analyses were performed to adjust for confounding factors including patient demographic characteristics and implant position. RESULTS: Univariate analysis showed that the ASES score was significantly lower in patients with teres minor muscle hypertrophy relative to those with normal muscle (73.3 ± 22.8 vs. 84.2 ± 16.9, P = .02). The functional subscore was significantly lower in patients with grade 2 fatty infiltration of the deltoid muscle relative to those with grade 0 fatty infiltration (26.1 ± 14.6 vs. 34.8 ± 11.6, P = .03). Older age was associated with a higher pain subscore (ρ = 0.32, P = .002). Multivariate analysis demonstrated that teres minor muscle hypertrophy remained a significant independent predictor of the ASES score (ß coefficient = 91.3, P = .03). CONCLUSION: Teres minor muscle hypertrophy is an independent negative predictor of patient-reported outcomes after rTSA.

A comparison of the efficacy, safety, and duration of frame-based and Remebot robot-assisted frameless stereotactic biopsy.

OBJECTIVE: The aim of this study was to compare the efficacy, safety, and duration of Remebot robot-assisted frameless brain biopsy with those of standard frame-based stereotactic biopsy. PATIENTS AND METHODS: A retrospective analysis of 66 patients undergoing stereotactic brain biopsy in our department from January 2015 to January 2019 was performed. We divided the patients into two groups: the frame-based group (n = 35) and the Remebot robot group (n = 31). Data on clinical characteristics, total procedure length, overall discomfort, diagnostic yield, complications, and postoperative length of hospital stay were retrospectively reviewed and compared between these two groups. RESULTS: No significant difference in diagnostic yield was detected in the two groups, with frame-based biopsy having a diagnostic yield of 91.4% and Remebot robot-assisted frameless brain biopsy having a diagnostic yield of 93.5%. The duration of the total procedure was 116.5 min for the frame-based biopsy and 80.1 min for the Remebot robot-assisted frameless brain biopsy (p < 0.001). There were no statistically significant differences in complication rate or postoperative duration of hospitalization between the two groups. The overall patient discomfort in the frame-based group was significantly greater than that in the Remebot robot group (visual analog scale score 2.7 ± 1.2 versus 1.5 ± 0.7, p = 0.001). CONCLUSIONS: Remebot robot-assisted frameless brain biopsy was as efficacious and safe as standard stereotactic frame-based biopsy. However, frameless biopsy can alleviate the suffering of the patient and reduce the total duration of the procedure. Remebot robot-assisted frameless brain biopsy is easy to use and better accepted by patients than frame-based biopsy.

Glutamine synthetase gene glnA plays a vital role in curdlan biosynthesis of Agrobacterium sp. CGMCC 11546.

Curdlan is a neutral linear exopolysaccharide produced by Agrobacterium spp. under nitrogen-limiting conditions. In this study, we explored the role of glnA in curdlan biosynthesis in Agrobacterium sp. CGMCC 11546. The curdlan production of the ΔglnA strain was impaired, decreasing by 93% compared with that of the wild-type strain after 96 h fermentation. Analysis of fermentation profiles revealed that cell growth and utilization of carbon and nitrogen sources were impaired in the ΔglnA strain. Transcriptome analysis indicated that various of genes involved in curdlan biosynthesis were downregulated after 24 h fermentation in the ΔglnA strain, particularly genes involved in heme synthesis and the electron transport chain, which are essential for energy generation. Metabolomics analysis revealed flavin adenine dinucleotide (FAD) and adenosine diphosphate (ADP) accumulation in the ΔglnA strain, suggesting insufficient energy supply. Furthermore, glnA overexpression led to an 18% increase in the curdlan yield of the ΔglnA mutant compared with that of the wild-type strain after 96 h fermentation. Taken together, the findings demonstrate that glnA plays a vital role in curdlan biosynthesis by supplying ATP via regulating the expression of genes involved in heme synthesis and the electron transport chain.

[Effectiveness analysis of modified tarsal sinus approach for Sanders â ¡- â ¢type calcaneal fractures].

OBJECTIVE: To investigate the short-term effectiveness of modified tarsal sinus approach and traditional tarsal sinus approach in the treatment of Sanders Ⅱ-Ⅲ type calcaneal fractures. METHODS: Between January 2015 and August 2017, 53 patients with Sanders Ⅱ-Ⅲ type calcaneal fractures were selected and divided into observation group (21 cases, using modified tarsal sinus approach for fracture reduction after exposure of the subtalar joint below the long and short fibular tendon) and control group (32 cases, using traditional tarsal sinus approach) by random number method. There was no significant difference between the two groups in terms of gender, age, side, cause of injury, fracture type, injury to operation time, and preoperative Böhler angle, Gissane angle, visual analogue scale (VAS) core ( P>0.05), which were comparable. The operation time, postoperative drainage volume, postoperative Böhler angle, Gissane angle, and postoperative angle improvement values of the two groups were recorded and compared. VAS score, American Orthopaedic Foot and Ankle Society (AOFAS) score, and short-form 36 health survey scale (SF-36) score were used to evaluate the effectiveness. RESULTS: All the 53 patients successfully completed the operation without serious complications such as vascular and nerve injury and perioperative death. There was no significant difference in operation time and postoperative drainage volume between the two groups ( P>0.05). Patients in both groups were followed up 12-36 months (mean, 17 months). No infection, fracture displacement, failure of internal fixation, and malunion of fracture occurred after operation. None of the patients underwent secondary joint fusion. There was no significant difference in fracture healing time between the two groups ( t=0.30, P=0.77). The postoperative Böhler angle and Gissane angle at 2 days in the two groups were significantly improved when compared with those before operation ( P<0.05); however, there was no significant difference in Böhler angle, Gissane angle, and improvement value between the observation group and the control group at 2 days after operation ( P>0.05). VAS scores at 24 hours and 1 year after operation were significantly improved when compared with that before operation in both groups ( P<0.05). There was no significant difference in VAS scores between the two groups at 24 hours and 1 year after operation ( P>0.05). There was no significant difference in AOFAS scores between the two groups at 1 year after operation ( t=1.46, P=0.15). However, the SF-36 scale score at 1 year after operation was significantly higher than that of the control group ( t=2.08, P=0.04). At last follow-up, 2 patients in the observation group and 8 patients in the control group presented subtalar joint stiffness or pain, and there was no significant difference in the incidence between the two groups ( χ 2=1.98, P=0.16). CONCLUSION: The modified tarsal sinus approach for the treatment of Sanders Ⅱ-Ⅲ type calcaneal fractures has the advantages of minimal invasion, clear reduction under direct vision, reliable reduction and fixation, and low incision complications.

[Clinical comparative study of thoracoscopic assisted reduction and traditional manual reduction with percutaneous intramedullary nail internal fixation for mid-clavicular fractures].

Objective: To compare the effectiveness of thoracoscopic assisted reduction and traditional manual reduction with percutaneous intramedullary nail internal fixation in the treatment of mid-clavicular fractures. Methods: A prospective randomized controlled trial was conducted. Twenty-two patients with mid-clavicular fractures who met the selection criteria between March 2012 and March 2017 were recruited and randomly divided into trial group (7 cases, thoracoscopic assisted reduction and percutaneous intramedullary nail fixation) and control group (15 cases, traditional manual reduction and percutaneous intramedullary nail fixation). There was no significant difference in gender, age, side, cause of injury, fracture classification, interval between injury and operation between the two groups ( P>0.05). The operation time and fracture healing time were recorded and compared between the two groups. The effectiveness was evaluated by Constant-Murley scale at 6 months after operation, which included subjective evaluation indexes (functional activity and pain) and objective evaluation indexes (range of motion of shoulder joint and muscle strength). Results: The operation time of the trial group was significantly longer than that of the control group ( t=5.881, P=0.000). Patients in both groups were followed up 7-20 months, with an average of 11 months. Satisfactory anatomical reduction achieved in all patients, and all incisions healed by first intension. In the control group, 1 patient had difficulty in removing the intramedullary nail, and 1 patient had fracture nonunion. No fracture nonunion or intramedullary nail rupture in the other patients of two groups. There was no significant difference in fracture healing time between the two groups ( t=0.764, P=0.453). At 6 months after operation, there was no significant difference in Constant-Murley scale between the two groups ( P>0.05). Conclusion: The treatment of the mid-clavicular fracture by using thoracoscopic assisted reduction with intramedullary nail internal fixation requires longer operation time, but does not require fluoroscopy. The effectiveness is comparable to that of traditional surgery.

Heme oxygenase-1 protects spinal cord neurons from hydrogen peroxide-induced apoptosis via suppression of Cdc42/MLK3/MKK7/JNK3 signaling.

The mechanisms by which oxidative stress induces spinal cord neuron death has not been completely understood. Investigation on the molecular signal pathways involved in oxidative stress-mediated neuronal death is important for development of new therapeutics for oxidative stress-associated spinal cord disorders. In current study we examined the role of heme oxygenase-1 (HO-1) in the modulation of MLK3/MKK7/JNK3 signaling, which is a pro-apoptotic pathway, after treating primary spinal cord neurons with H2O2. We found that MLK3/MKK7/JNK3 signaling was substantially activated by H2O2 in a time-dependent manner, demonstrated by increase of activating phosphorylation of MLK3, MKK7 and JNK3. H2O2 also induced expression of HO-1. Transduction of neurons with HO-1-expressing adeno-associated virus before H2O2 treatment introduced expression of exogenous HO-1 in neurons. Exogenous HO-1 reduced phosphorylation of MLK3, MKK7 and JNK3. Consistent with its inhibitory effect on MLK3/MKK7/JNK3 signaling, exogenous HO-1 decreased H2O2-induced neuronal apoptosis and necrosis. Furthermore, we found that exogenous HO-1 inhibited expression of Cdc42, which is crucial for MLK3 activation. In addition, HO-1-induced down-regulation of MLK3/MKK7/JNK3 signaling might be related to up-regulation of microRNA-137 (mir-137). A mir-137 inhibitor alleviated the inhibitory effect of HO-1 on JNK3 activation. This inhibitor also increased neuronal death even when exogenous HO-1 was expressed. Therefore, our study suggests a novel mechanism by which HO-1 exerted its neuroprotective efficacy on oxidative stress.

Heme Oxygenase-1 Inhibits Neuronal Apoptosis in Spinal Cord Injury through Down-Regulation of Cdc42-MLK3-MKK7-JNK3 Axis.

The mechanism by which spinal cord injury (SCI) induces neuronal death has not been thoroughly understood. Investigation on the molecular signal pathways involved in SCI-mediated neuronal apoptosis is important for development of new therapeutics for SCI. In the current study, we explore the role of heme oxygenase-1 (HO-1) in the modulation of mixed lineage kinase 3/mitogen-activated protein kinase kinase/cJUN N-terminal kinase 3 (MLK3/MKK7/JNK3) signaling, which is a pro-apoptotic pathway, after SCI. We found that MLK3/MKK7/JNK3 signaling was activated by SCI in a time-dependent manner, demonstrated by increase in activating phosphorylation of MLK3, MKK7, and JNK3. SCI also induced HO-1 expression. Administration of HO-1-expressing adeno-associated virus before SCI introduced expression of exogenous HO-1 in injured spinal cords. Exogenous HO-1 reduced phosphorylation of MLK3, MKK7, and JNK3. Consistent with its inhibitory effect on MLK3/MKK7/JNK3 signaling, exogenous HO-1 decreased SCI-induced neuronal apoptosis and improved neurological score. Further, we found that exogenous HO-1 inhibited expression of cell division cycle 42 (Cdc42), which is crucial for MLK3 activation. In vitro experiments indicated that Cdc42 was essential for neuronal apoptosis, while transduction of neurons with HO-1-expressing adeno-associated virus significantly reduced neuronal apoptosis to enhance neuronal survival. Therefore, our study disclosed a novel mechanism by which HO-1 exerted its neuroprotective efficacy. Our discovery might be valuable for developing a new therapeutic approach for SCI.