Identification of compositional and structural changes in the nucleus pulposus of patients with cervical disc herniation by Raman spectroscopy.

Purpose: Cervical disc herniation (CDH) is one of the most common spinal diseases in modern society; intervertebral disc degeneration (IVDD) has long been considered as its primary cause. However, the mechanism of intervertebral disc degeneration is still unclear. The aim of the study is to examine the components and structures of proteoglycan and collagen in cervical disc herniated nucleus pulposus (NP) using a validated and convenient Raman spectra technique and histological methods to further elucidate the mechanism of IVDD at the microscopic level. Methods: Our study used a burgeoning technique of Raman spectroscopy combined with in vitro intervertebral disc NP to characterize the above mentioned research purposes. Firstly, we collected cervical disc NP samples and imaging data by certain inclusion and exclusion criteria. Then, we graded the NP of the responsible segment according to the patient's preoperative cervical magnetic resonance imaging (MRI) T2-weighted images by Pfirrmann grading criteria while measuring the T2 signal intensity value of NP. In addition, the structure of the NP samples was evaluated by histological staining (H&E staining and Safranin-O staining). Finally, the samples were scanned and analyzed by Raman spectroscopy. Results: A total of 28 NP tissues from 26 patients (two of these patients were cases that involved two segments) with CDH were included in this study. According to the Raman spectroscopy scan, the relative content of proteoglycans which is characterized by the ratio of the two peaks (I 1,064/ I 1,004) in the NP showed a significantly negative correlation with Pfirrmann grade (P < 0.001), while the collagen content and the NP intensity value showed a positive correlation (P < 0.001). For the microstructural characterization of collagen, we found that it may have an essential role in the degenerative process of the intervertebral disc. Moreover, histological staining (H&E staining and Safranin-O staining) showed the general structure of the NP and the distribution of macromolecules. Conclusion: The present study demonstrated the possibility of characterizing the macromolecular substances inside the cervical disc NP tissue by Raman spectroscopy. It also confirmed that macromolecular substances such as proteoglycans and collagen have some degree of alteration in content and structure during degeneration, which has a further positive significance for the elucidation of CDH's mechanism.

Study on the grain refinement mechanism of Mg-Al alloy based on carbon addition.

In this study, a comprehensive treatment process based on the rotary injection of Ar+CO2 Mg-Al alloy melt is proposed. The effect of carbon on the grain refinement of Mg-Al alloy is studied according to the proposed integrated treatment process. The regularity of carbon refinement in the Mg-Al alloy is examined by microstructural observation and theoretical calculation. The results show that carbon has no effect on the grain refinement of Mg-Al alloy when the Al content is less than 1wt.%. However, when the Al content reaches 2 wt.%, the refining effect is obvious, and the grain refinement efficiency is 62%. The refining effect increases with the increase in the Al content, and the refinement efficiency becomes 79% when the Al content reaches 9 wt.%. The size of Al-C-O in the matrix is approximately 5µm, which confirms the existence of Al4C3 phase exists as a heterogeneous nucleating agent. The theoretical calculations suggest that the Al4C3 heterogeneous nucleating agent cannot be formed when the Al content in the Mg alloy is less than 1.34%, so there is no thinning effect under such Al content. The crystallographic calculations reveal that the mismatch between the Al4C3 phase and Mg alloy matrix is only 4.05%, and Al4C3 can exist as a heterogeneous nucleating agent for α-Mg phase. Combining the measured solidification curves with the classical nucleation theory, the wetting angle of Mg-Al alloy on Al4C3 is calculated to be 24.3°.

Effectiveness of Preoperative Embolization in Patients with Spinal Metastases: A Systematic Review and Meta-Analysis.

OBJECTIVE: Debate on the effectiveness of preoperative embolization for spinal metastatic lesions, especially for nonhypervascular tumors, has persisted. The present study aimed to identify the effectiveness of preoperative embolization in patients who had undergone surgery for spinal metastasis. METHODS: Two of us (Z.T. and Z.H.) independently searched the PubMed, Embase, and Cochrane Central Register of Controlled Trials databases to identify eligible clinical studies that had compared the outcomes of patients treated surgically for spinal metastatic disease with or without preoperative embolization. The primary outcomes included intraoperative blood loss, perioperative blood loss, and transfusion requirements. The secondary outcomes include the operative time, overall survival, and complication rates. Meta-analyses were performed for subgroups of hypervascular, nonhypervascular, and mixed tumors. A fixed effects model was applied when I2 was <50%, and a random effects model was applied when I2 was >50%. RESULTS: A total of 12 studies (1 randomized controlled trial and 11 retrospective case-control studies), with 744 patients, were included. Significantly less intraoperative blood loss (mean difference [MD], -1171.49 mL; 95% confidence interval [CI], -2283.10 to -59.88; P = 0.039), fewer blood transfusions (MD, -3.13 U; 95% CI, -4.86 to -1.39; P < 0.001), and shorter operative times (MD, -33.91 minutes; 95% CI, -59.65 to -8.17; P = 0.010) were identified for the embolization group in the hypervascular subgroup. In the nonhypervascular and mixed tumor subgroups, no differences in effectiveness were identified in blood loss, transfusion requirement, or operative time when stratified by the use of embolization. The overall survival and complication rates were similar between the embolization and nonembolization groups in each subgroup. CONCLUSIONS: The current data support the use of preoperative embolization for hypervascular metastatic tumors to the spine. However, little evidence is available to support the use of preoperative embolization for nonhypervascular metastatic tumors to the spine.

Establishment and validation of nomogram model for survival predicting in patients with spinal metastases secondary to lung cancer.

OBJECTIVES: To evaluate the prognostic effect of pre-treatment factors in patients with spinal metastases secondary to lung cancer, and establish a novel predicting nomogram for predicting the survival probability. METHODS: A total of 209 patients operated for spinal metastases from lung cancer were consecutively enrolled, and divided into the training and validation samples with a ratio of 7:3, for model establishing and validating, respectively. Basing on the training sample, univariate and multivariate COX proportional hazard models were used for identifying the prognostic effect of pre-treatment factors, following which significant prognostic factors would be listed as items in nomogram to calculate the survival probabilities at 3, 6, 12 and 18 months. Then, the C-indexes and the calibration curves would be figured out to evaluate the discrimination ability and accuracy of the model both for the training and validation samples. RESULTS: In the multivariate COX analysis, the gender, smoking history, location of spinal metastasis, visceral metastasis, Karnofsky performance status (KPS), adjuvant therapy, lymphocyte percentage and globulin were found to be significantly associated with the overall survival, and a novel nomogram was generated basing on these independent predictors. The C-indexes for the training and validation samples were 0.761 and 0.732, respectively. Favorable consistencies between the predicted and actual survival rates were demonstrated both in the internal and external validations. DISCUSSION: Pre-treatment characteristics, including gender, smoking history, location of spinal metastasis, visceral metastasis, KPS, adjuvant therapy, percentage of lymphocyte, and serum globulin level, were identified to be significantly associated with overall survival of patients living with spinal metastases derived from lung cancer, and a user-friendly nomogram was established using these independent predictors.

Prognostic factors for overall survival in patients with spinal metastasis secondary to prostate cancer: a systematic review and meta-analysis.

BACKGROUND: To guide the selection of treatments for spinal metastases, the expected survival time is one of the most important determinants. Few scoring systems are fully applicable for spinal metastasis secondary to prostate cancer (PCa). This study aimed to identify the independent factors to predict the overall survival (OS) of patients with spinal metastases from PCa. METHODS: The PubMed, Embase and CENTRAL were retrieved by two reviewers independently, to identify studies analyzed the prognostic effect of different factors in spinal metastasis from PCa. A systematic review and quantitative meta-analysis was conducted with hazard ratio (HR) and 95% confidence interval (95%CI) as the effect size. RESULTS: A total of 12 retrospective cohort studies (1566 patients) were eligible for qualitative synthesis and 10 for quantitative meta-analyses. The OS was significantly influenced by performance status, visceral metastasis, ambulatory status and time from PCa diagnosis in more than half of the available studies. The meta-analyses demonstrated that OS was significantly influenced by visceral metastasis (HR = 2.24, 95%CI:1.53-3.27, p < 0.001), pre-treatment ambulatory status (HR = 2.64, 95%CI:1.82-3.83, p < 0.001), KPS (HR = 4.45, 95%CI:2.01-9.85, p < 0.001), ECOG (HR = 2.96, 95%CI:2.02-4.35, p < 0.001), extraspinal bone metastasis (HR = 2.04, 95%CI:1.13-3.68, p = 0.018), time developing motor deficit (HR = 1.57, 95%CI:1.30-1.88, p < 0.001) and time from PCa diagnosis (HR = 1.37, 95%CI:1.17-1.59, p < 0.001). CONCLUSIONS: Visceral metastasis, ambulatory status, extraspinal bone metastasis, performance status, time developing motor deficit and time interval from primary tumor diagnosis were significantly associated with the OS for spinal metastasis from PCa. When selecting the treatment modality, clinicians should fully consider the patients' systematic status based on all potential prognostic factors. LEVEL OF EVIDENCE: I Meta-analysis.

Does Percutaneous Vertebroplasty or Balloon Kyphoplasty for Osteoporotic Vertebral Compression Fractures Increase the Incidence of New Vertebral Fractures? A Meta-Analysis.

BACKGROUND: Because of an aging population,osteoporotic vertebral fractures are becoming more frequent.Conservative therapy was considered the gold standard for treating osteoporotic vertebral compression fractures (OVCFs) in the past. Percutaneous vertebroplasty (PVP) or balloon kyphoplasty (BKP) as minimally invasive techniques are new treatments that are widely used for painful OVCFs. However, an increase in new vertebral compression fractures at non-treated levels following augmentation is of concern. There is no convincing evidence that new fractures are inevitable after augmentation compared to after conservative treatment, and it is still unclear whether further fractures are the consequence of augmentation or a result of the natural progression of osteoporosis. OBJECTIVE: The objective of this study was to evaluate the new-level fracture risk after PVP or BKP compared with conservative (non-operative) treatment and to determine the dominant risk factor associated with new OVCFs. STUDY DESIGN: A meta-analysis of comparative studies was performed to evaluate the incidence of new vertebral fractures between vertebral augmentation, such as vertebroplasty and kyphoplasty, and no operation. SETTING: The PubMed, ISI Web of Science, ELSEVIER ScienceDirect, and Cochrane Library databases and abstracts published in annual proceedings were systematically searched.In addition, we also retrieved data from references when titles met our inclusion criteria. METHODS: Detailed searches of a number of online databases comparing operative and non-operative groups were performed. We included randomized controlled trials,clinical controlled trials,and prospective clinical studies to provide available data. All studies were reviewed by two reviewers independently, and all the references that met our inclusion criteria were searched for additional trials, using the guidelines set by the QUOROM (Quality of Reporting of Meta-analysis) statement. RESULTS: We evaluated 12 studies encompassing 1,328 patients in total, including 768 who underwent operation with polymethylmethacrylateand 560 who received non-operative treatments. For new-level vertebral fractures, our meta-analysis found no significant difference between the 2 methods, including total new fractures (P = 0.55) and adjacent fractures (P = 0.5). For pre-existing vertebral fractures, there was no significant difference between the 2 groups (operative and non-operative groups) (P = 0.24). Additionally,there was no significant difference in bone mineral density, both in the lumbar (P = 0 .13) and femoral neck regions (P = 0.37), between the 2 interventions. LIMITATION: All studies we screened were published online except for unpublished articles. Moreover, only a few data sources could be extracted from the published studies.There were only 5 randomized clinical trials and 7 prospective studies that met our inclusion criteria. CONCLUSION: Vertebral augmentation techniques, such as vertebroplasty and kyphoplasty, have been widely used to treat osteoporotic vertebral fractures in order to alleviate back pain and correct the deformity, and it has been frequently reported that many new vertebral fractures occurred after this operation. Our analysis did not reveal evidence of an increased risk of fracture of vertebral bodies, especially those adjacent to the treated vertebrae, following augmentation with either method compared with conservative treatment.Key words: Vertebroplasty, kyphoplasty, new osteoporotic compression vertebral fracture, meta-analysis.

Doença de Haff complicada por falência de múltiplos órgãos após ingestão de lagostim: estudo de caso / Haff disease complicated by multiple organ failure after crayfish consumption: a case study

A doença de Haff é uma síndrome que consiste de rabdomiólise não explicada. Pacientes que apresentam a doença de Haff relatam ter ingerido pescado nas últimas 24 horas antes do início da doença. A maioria dos pacientes sobrevive apresentando breve recuperação. O presente artigo é o primeiro relato de doença de Haff complicada por falência de múltiplos órgãos após ingestão de lagostim. Um homem chinês de 66 anos de idade ingeriu lagostim cozido na noite de 23 de junho de 2013. Chegou ao hospital 2 dias mais tarde, sendo admitido à unidade de terapia intensiva. Após a admissão, o paciente recebeu o diagnóstico de doença de Haff complicada por falência de múltiplos órgãos. Apesar dos tratamentos de suporte e sintomático, a condição do paciente deteriorou, vindo o mesmo a falecer em consequência da doença. A doença de Haff é uma rara síndrome clínica que é, às vezes, mal diagnosticada. O diagnóstico precoce e o tratamento adequado são essenciais para prevenir a progressão para falência de múltiplos órgãos.

Haff disease is a syndrome consisting of unexplained rhabdomyolysis. Patients suffering from Haff disease report having eaten fish within 24 hours before the onset of illness. Most patients survive and recover quickly. The present study is the first report of Haff disease complicated by multiple organ failure after crayfish consumption. A 66-year-old Chinese man ate cooked crayfish on the night of June 23, 2013. He arrived at our hospital 2 days later and was admitted to the intensive care unit. After admission, the patient was diagnosed with Haff disease complicated by multiple organ failure. Despite supportive and symptomatic treatments, the condition of the patient deteriorated, and he died due to his illness. Haff disease is a rare clinical syndrome that is sometimes misdiagnosed. Early diagnosis and proper treatment are essential to prevent progression to multiple organ failure.

Performance enhancement and fouling mitigation by organic flocculant addition in membrane bioreactor at high salt shock.

The main objective of this study was to investigate the effect of an organic flocculant (MPE50) addition on reducing membrane fouling and enhancing performance in membrane bioreactor (MBR) at the high salt shock. Results show that MPE50 addition is a reliable and effective approach in terms of both membrane fouling mitigation and pollutants removal improvement in the case of high salt shock. Compared to the control reactor, the MBR with MPE50 addition enhanced the average removal of COD, NH4(+)-N and TP by 4.1%, 13.2% and 21.2%, respectively. Due to the effect of flocculation and adsorption by MPE50, a significant reduction in the soluble microbial products (SMP) proteins amount was observed. As a result, the membrane fouling rate was mitigated successfully. Further, the increasing of mean particles size, Zeta potential and related hydrophobicity of the flocs would also have positive impacts on membrane fouling mitigation.

Haff disease complicated by multiple organ failure after crayfish consumption: a case study.

Haff disease is a syndrome consisting of unexplained rhabdomyolysis. Patients suffering from Haff disease report having eaten fish within 24 hours before the onset of illness. Most patients survive and recover quickly. The present study is the first report of Haff disease complicated by multiple organ failure after crayfish consumption. A 66-year-old Chinese man ate cooked crayfish on the night of June 23, 2013. He arrived at our hospital 2 days later and was admitted to the intensive care unit. After admission, the patient was diagnosed with Haff disease complicated by multiple organ failure. Despite supportive and symptomatic treatments, the condition of the patient deteriorated, and he died due to his illness. Haff disease is a rare clinical syndrome that is sometimes misdiagnosed. Early diagnosis and proper treatment are essential to prevent progression to multiple organ failure.

Inhibition of Smad3 expression decreases collagen synthesis in keloid disease fibroblasts.

BACKGROUND: Keloids represent a dysregulated response to cutaneous wounding that result in an excessive deposition of extracellular matrix (ECM), especially types I and III collagen. In keloid scars, the ratio of 'type I to type III collagen' varies compared to normal skin. Transforming growth factor beta (TGF-beta) plays a central role in the pathogenesis of fibrosis by inducing and sustaining activation of keloid fibroblasts. However, the underlying mechanisms are poorly understood. RNA interference (RNAi) is an evolutionally conserved mechanism for repressing targeted gene expression. In mammalian cells, RNAi is mediated by small interfering RNA (siRNA). In this paper, we examined the function of Sma and Drosophila mothers against decapentaplegic homolog 3 (Smad3), recently characterized as intracellular effector of TGF-beta signalling, in keloid fibroblasts using siRNA. METHODS: Dermal fibroblasts obtained from one female patient aged 21 years were maintained in Dulbecco's modified Eagle's medium. Cells (<6 passages) were treated with or without Smad3 siRNA and the expression levels of related genes were examined by Reverse Transcription Polymerase Chain Reaction (RT-PCR) and Western Blot. Statistical analysis was performed using one-way ANOVA (Dunnett correction) and the Excel 7.0 software, with significance set at p<0.05. RESULTS: The knockdown of Smad3 expression in mRNA and protein levels was confirmed using RT-PCR and Western Blot. Compared to blank, the mRNA levels of types I and III procollagen were also significantly and uniquely decreased following the reduction of Smad3 by siRNA (p<0.05). The results indicate that Smad3 plays an important role in the TGF-beta induced fibrosis in keloid. Downregulation of Smad3 expression in keloid fibroblasts can significantly decrease procollagen gene expression. SiRNA targeting Smad3 was an efficient reagent to reduce ECM deposition and attenuate process of fibrosis. It could be a new promising therapeutic approach to improve skin wound healing and inhibit progression of fibrotic conditions by interrupting the TGF-beta signal pathway.

Modulation of collagen synthesis in keloid fibroblasts by silencing Smad2 with siRNA.

BACKGROUND: Keloids represent a dysregulated response to cutaneous wounding that results in an excessive deposition of extracellular matrix, especially types I and III collagen. Transforming growth factor (TGF)-beta plays a central role in the pathogenesis of fibrosis by inducing and sustaining activation of keloid fibroblast. However, the underlying mechanisms are poorly understood. In this study, the authors examined the function of Smad2, a recently characterized intracellular effector of TGF-beta signaling, in keloid fibroblasts using small interfering RNA (siRNA). METHODS: Three pairs of siRNA duplexes targeting human Smad2 were designed; the most efficient one was selected and used for further research. Keloid fibroblasts were treated with or without Smad2 siRNA, and the expression levels of related genes were examined by reverse-transcriptase polymerase chain reaction and immunofluorescence. RESULTS: The down-regulation of Smad2 by siRNA led to a significant decrease in mRNA levels of Smad2 in both a dose-dependent and time-dependent manner. The knockdown of Smad2 expression in protein level was confirmed using immunofluorescence. The mRNA levels of types I and III procollagen were also significantly and uniquely decreased following the reduction of Smad2 by siRNA. CONCLUSIONS: The results indicate that Smad2 plays an important role in TGF-beta-induced fibrosis in keloids. Down-regulation of Smad2 expression in keloid fibroblasts can significantly decrease procollagen gene expression. Also, siRNA targeting Smad2 was an efficient reagent with which to reduce extracellular matrix deposition and attenuate process of fibrosis. It could be a new, promising therapeutic approach for improving skin wound healing and inhibiting progression of fibrotic conditions by interrupting the TGF-beta signaling pathway.