Analysis of Complications in Multilevel Anterior Cervical Discectomy and Fusion Using Osteobiologics Other than Bone Morphogenetic Protein: A Systematic Review.

STUDY DESIGN: Systematic review. OBJECTIVES: The aim of this study is to analyze the complications related to multilevel anterior cervical discectomy and fusion (ACDF) using osteobiologics other than bone morphogenetic protein (BMP). METHODS: A systematic review of the literature was conducted using PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov databases. The search to identify studies reporting complications in multilevel ACDF surgery using osteobiologics other than bone morphogenetic protein was performed in August 2020. The study was reported in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). RESULTS: A total of 584 articles were found after searching the databases and removing duplicates. Next, screening was performed in a double reviewer process, and 153 eligible articles-with 4 retrospective studies-in full-text were selected; these met all inclusion criteria. A total of 197 patients received 3-level ACDF, while 72 patients received 4-level ACDF. Osteobiologics were used in all selected articles, allograft was used in 4 studies, autologous bone graft was utilized in 3 articles, and hydroxyapatite was used in 1 article. The main complications reported were dysphagia, adjacent segment disease, and pseudarthrosis. CONCLUSIONS: Given the limited evidence, no conclusions on complications in multilevel ACDF using osteobiologics other than BMP could be made. However, descriptively, the most common complications found were dysphagia, adjacent segment disease, and pseudoarthrosis. Further prospective studies separately analyzing complications in multilevel ACDF by osteobiologics and a number of treated levels are needed.

Development of an International AO Spine Guideline for the Use of Osteobiologics in Anterior Cervical Fusion and Decompression (AO-GO).

STUDY DESIGN: Methodological study for guideline development. OBJECTIVE: AO Spine Guideline for Using Osteobiologics (AO-GO) project for spine degenerative pathologies was an international, multidisciplinary collaborative initiative to identify and evaluate evidence on existing use of osteobiologics in Anterior Cervical Fusion and Decompression (ACDF). The aim was to formulate precisely defined, clinically relevant and internationally applicable guidelines ensuring evidence-based, safe and effective use of osteobiologics, considering regional preferences and cost-effectiveness. METHODS: Guideline was completed in two phases: Phase 1- evidence synthesis; Phase 2- recommendation development based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach. In Phase 1, key questions identified by a panel of experts were addressed in a series of systematic reviews of randomized and non-randomized studies. In Phase 2, the GRADE approach was used to formulate a series of recommendations, including expert panel discussions via web calls and face-to-face meetings. DISCUSSION: AO-GO aims to bridge an important gap between evidence and use of osteobiologics in spine fusion surgeries. Owing to differences in osteobiologics preparation and functional characteristics, regulatory requirements for approval may vary, therefore it is highly likely that these products enter market without quality clinical trials. With a holistic approach the guideline aims to facilitate evidence-based, patient-oriented decision-making processes in clinical practice, thus stimulating further evidence-based studies regarding osteobiologics usage in spine surgeries. In Phase 3, the guideline will be disseminated and validated using prospectively collected clinical data in a separate effort of the AO Spine Knowledge Forum Degenerative in a global multicenter clinical study.

AO Spine Guideline for the Use of Osteobiologics (AOGO) in Anterior Cervical Discectomy and Fusion for Spinal Degenerative Cases.

STUDY DESIGN: Guideline. OBJECTIVES: To develop an international guideline (AOGO) about the use of osteobiologics in anterior cervical discectomy and fusion (ACDF) for treating degenerative spine conditions. METHODS: The guideline development process was guided by AO Spine Knowledge Forum Degenerative (KF Degen) and followed the Guideline International Network McMaster Guideline Development Checklist. The process involved 73 participants with expertise in degenerative spine diseases and surgery from 22 countries. Fifteen systematic reviews were conducted addressing respective key topics and evidence was collected. The methodologist compiled the evidence into GRADE Evidence-to-Decision frameworks. Guideline panel members judged the outcomes and other criteria and made the final recommendations through consensus. RESULTS: Five conditional recommendations were created. A conditional recommendation is about the use of allograft, autograft or a cage with an osteobiologic in primary ACDF surgery. Other conditional recommendations are about the use of osteobiologic for single- or multi-level ACDF, and for hybrid construct surgery. It is suggested that surgeons use other osteobiologics rather than human bone morphogenetic protein-2 (BMP-2) in common clinical situations. Surgeons are recommended to choose 1 graft over another or 1 osteobiologic over another primarily based on clinical situation, and the costs and availability of the materials. CONCLUSION: This AOGO guideline is the first to provide recommendations for the use of osteobiologics in ACDF. Despite the comprehensive searches for evidence, there were few studies completed with small sample sizes and primarily as case series with inherent risks of bias. Therefore, high-quality clinical evidence is demanded to improve the guideline.

Do Osteobiologics Augment Fusion in Anterior Cervical Discectomy and Fusion Surgery Performed With Mechanical Interbody Devices (Polyether ether ketone, Carbon Fiber, Metal Cages) and is the Fusion Rate Comparable to that With Autograft? A Systematic Review.

STUDY DESIGN: Systematic Review of the Literature. OBJECTIVE: The purpose of this study was to perform a systematic review describing fusion rates for anterior cervical discectomy and fusion (ACDF) using autograft vs various interbody devices augmented with different osteobiologic materials. METHODS: A systematic review limited to the English language was performed in Medline, Embase and Cochrane library using Medical Subject Heading (MeSH) terms. Studies that evaluated fusion after ACDF using autografts and osteobiologics combined with PEEK, carbon fibre, or metal cages were searched for. Articles in full text that met the criteria were included in the review. The main outcomes evaluated were the time taken to merge, the definition of the fusion assessment, and the modality of the fusion assessment. The risk of bias of each article was assessed by the MINORS score or ROB 2.0 depending on the randomisation process. RESULTS: The total number of references reviewed was six hundred and eighty-two. After applying the inclusion criteria, 54 were selected for the retrieval of the full text. Eight studies were selected and included for final analysis in this study. Fusion rates were reported between 83.3% and 100% for autograft groups compared to 46.5% and 100% for various interbody device/osteobiological combinations. The overall quality of the evidence in all radiographic fusion studies was considered insufficient due to a serious risk of bias. CONCLUSION: Mechanical interbody devices augmented with osteobiologics performed similarly to autografts in terms of reliability and efficacy. Their time to fusion and fusion rate were comparable to autografts at the end of the final follow-up.

Complications With Demineralized Bone Matrix, Hydroxyapatite and Beta-Tricalcium Phosphate in Single and Two-Level Anterior Cervical Discectomy and Fusion Surgery.

STUDY DESIGN: Systematic literature review. OBJECTIVES: To analyze the evidence available reporting complications in single or two-level anterior cervical discectomy and fusion (ACDF) using a demineralized bone matrix (DBM), hydroxyapatite (HA), or beta-tricalcium phosphate (ß-TCP). METHODS: A systematic review of the literature using PubMed, EMBASE, Cochrane Library, and ClinicalTrials.gov databases was performed in August 2020 to identify studies reporting complications in one or two-level ACDF surgery using DBM, HA, or ß-TCP. The study was reported following the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. RESULTS: A total of 1857 patients were included, 981 male and 876 female, across 17 articles; 5 prospective, and 12 retrospectives. We noted heterogeneity among the included studies concerning the study design and combination of graft materials utilized in them. However, we noted a higher incidence of adjacent segment disease (17.7%) and pseudoarthrosis (9.3%) in fusion constructs using DBM. Studies using ß-TCP reported a higher incidence of pseudoarthrosis (28.2%) and implant failures (17.9%). CONCLUSIONS: Degenerative cervical conditions treated with one or two-level ACDF surgery using DBM, HA, or ß-TCP with or without cervical plating are associated with complications such as adjacent segment disease, dysphagia, and pseudarthrosis. However, consequent to the study designs and clinical heterogeneity of the studies, it is not possible to correlate these complications accurately with any specific graft material employed. Further well-designed prospective studies are needed to correctly know the related morbidity of each graft used for achieving fusion in ACDF.

Do the Choice of Fusion Construct With and Without Autograft Influence the Fusion and Complication Rates in Patients Undergoing 1 or 2-Level Anterior Cervical Discectomy and Fusion Surgery? A PRISMA-Compliant Network Meta-Analysis.

STUDY DESIGN: Network meta-analysis. OBJECTIVES: To compare the fusion outcome and complications of different 1 or 2-level anterior cervical decompression and fusion (ACDF) constructs performed with and without the application of autografts. METHODS: We performed an independent and duplicate search in electronic databases including PubMed, Embase, Web of Science, Cochrane, and Scopus for relevant articles published between 2000 and 2020. We included comparative studies reporting fusion rate and complications with and without the use of autografts in ACDF across 5 different fusion constructs. A network meta-analysis was performed in Stata, categorized based on the type of fusion constructs utilized. Fusion constructs were ranked based on p-score approach and surface under cumulative ranking curve (SUCRA) scores. The confidence of results from the analysis was appraised with Cochrane's CINeMA approach. RESULTS: A total of 2216 patients from 22-studies including 6 Randomized Controlled Trials (RCTs) and 16 non-RCTs were included in network analysis. The mean age of included patients was 49.3 (±3.62) years. Based on our meta-analysis, we could conclude that use of autograft in 1- or 2-level ACDF did not affect the fusion and mechanical implant-related complications. The final fusion and mechanical complication rates were also not significantly different across the different fusion constructs. The use of plated constructs was associated with a significant increase in post-ACDF dysphagia rates [OR 3.42; 95%CI (.01,2.45)], as compared to stand-alone constructs analysed. CONCLUSION: The choice of fusion constructs and use of autografts does not significantly affect the fusion and overall complication rates following 1 or 2-level ACDF surgery.

Does the choice of chemoprophylaxis affect the prevention of deep vein thrombosis in lumbar fusion surgery? A systematic review of the literature.

Introduction: To date, the available guidance on venous thromboembolism (VTE) prevention in elective lumbar fusion surgery is largely open to surgeon interpretation and preference without any specific suggested chemoprophylactic regimen. Research question: This study aimed to comparatively analyze the incidence of deep vein thrombosis (DVT) and pulmonary embolism (PE) with the use of commonly employed chemoprophylactic agents such as unfractionated heparin (UH) and low molecular weight heparin (LMWH) in lumbar fusion surgery. Material and methods: An independent systematic review of four scientific databases (PubMed, Scopus, clinicaltrials.gov, Web of Science) was performed to identify relevant articles as per the preferred reporting in systematic reviews and meta-analysis (PRISMA) guidelines. Studies reporting on DVT/PE outcomes of lumbar fusion surgery in adult patients with UH or LMWH chemoprophylaxis were included for analysis. Analysis was performed using the Stata software. Results: Twelve studies with 8495 patients were included in the analysis. A single-arm meta-analysis of the included studies found a DVT incidence of 14% (95%CI [8%-20%]) and 1% (95%CI [-6% - 8%]) with LMWH and UH respectively. Both the chemoprophylaxis agents prevented PE with a noted incidence of 0% (95%CI [0%-0.1%]) and 0% (95%CI [0%-1%]) with LMWH and UH respectively. The risk of bleeding-related complications with the usage of LMWH and UH was 0% (95% CI [0.0%-0.30%]) and 3% (95% CI [0.3%-5%]) respectively. Discussion and conclusion: Both LMWH and UH reduces the overall incidence of DVT/PE, but there is a paucity of evidence analyzing the comparative effectiveness of the chemoprophylaxis regimens in lumbar fusion procedures. The heterogeneity in data prevents any conclusions, as there remains an evidence gap. We recommend future high-quality randomized controlled trials to investigate in this regard to help develop recommendations on thromboprophylaxis usage.

AO Spine Adult Spinal Deformity Patient Profile: A Paradigm Shift in Comprehensive Patient Evaluation in Order to Optimize Treatment and Improve Patient Care.

STUDY DESIGN: Modified Delphi study. OBJECTIVE: Adult spinal deformity (ASD) is an increasingly recognized condition, comprising a spectrum of pathologies considerably impacting patients' health and functional status. Patients present with a combination of pain, disability, comorbidities and radiological deformity. The study aims to propose a systematic approach of gathering information on the factors that drive decision-making by developing a patient profile. METHODS: The present study comprises of 3 parts. Part 1: Development of prototype of patient profile: The data from the Core Outcome Study on SCOlisis (COSSCO) by Scoliosis Research Society (SRS) was categorized into a conceptual framework. Part 2: Modified Delphi study: Items reaching >70% agreement were included in a 4 round iterative process with 51 panellists across the globe. Part 3: Pilot testing-feasibility: Content validity and usability were evaluated quantitatively. RESULTS: The profile consisted of 4 domains. 1. General health with demographics and comorbidities, 2.Spine-specific health with spine related health and neurological status, 3. Imaging with radiographic and MRI parameters and 4. Deformity type. Each domain consisted of 1 or 2 components with various factors and their measuring instruments. Profile was found to have an excellent content validity (I-CVIr 0.78-1.00; Ave-CVI 0.92) appropriateness, relevance and usefulness. CONCLUSIONS: The present study, is first to provide a universally applicable multimodal ASD patient profile to methodically describe patients. Physicians are encouraged to assess ASD patients holistically using this profile and not just based on radiographic findings.

Mechanical Properties and Failure Behavior of Dry and Water-Saturated Foliated Phyllite under Uniaxial Compression.

Phyllite is widely distributed in nature, and it deserves to be studied considering rock engineering applications. In this study, uniaxial compression tests were conducted on foliated phyllite with different foliation angles under dry and water-saturated conditions. The impacts of water content and foliation angle on the stress-strain curves and basic mechanical properties of the Phyllite were analyzed. The experimental results indicate that the peak stress and peak strain decrease first and then increase with increasing foliation angle as a U-shape or V-shape, and the phyllite specimens are weakened significantly by the presence of water. Moreover, an approach with acoustic emission, digital image correlation, and scanning electron microscopic is employed to observe and analyze the macroscopic and mesoscopic failure process. The results show that tensile microcracks dominate during the progressive failure of phyllite, and their initiation, propagation, and coalescence are the main reasons for the failure of the phyllite specimens. The water acts on biotite and clay minerals that are main components of phyllite, and it contributes to the initiation, propagation, and coalescence of numerous microcracks. Finally, four failure modes are classified as followed: (a) for the specimens with small foliation angles α = 0° or 30° (Saturated), both shear sliding and tensile-split across the foliation planes; (b) for the specimens with low to medium foliation angles α = 30° (Dry) or 45°(Saturated), shear sliding dominates the foliation planes; (c) for the specimens with medium to high foliation angles α = 45° (Dry) or 60°, shear sliding dominates the foliation planes; (d) for the specimens with high foliation angles α = 90°, tensile-split dominates the foliation planes.

Diagnostic value of bronchoalveolar lavage fluid metagenomic next-generation sequencing in pediatric pneumonia.

Objectives: The aim of this study was to evaluate the diagnostic value of bronchoalveolar lavage fluid (BALF) metagenomic next-generation sequencing (mNGS) versus conventional microbiological tests (CMTs) for pediatric pneumonia. Methods: This retrospective observational study enrolled 103 children who were diagnosed with pneumonia and hospitalized at Hubei Maternity and Child Health Care Hospital between 15 October 2020 and 15 February 2022. The pneumonia diagnosis was based on clinical manifestations, lung imaging, and microbiological tests. Pathogens in the lower respiratory tract were detected using CMTs and BALF mNGS (of DNA and RNA). The diagnostic performance of BALF mNGS was compared with that of CMTs. Results: In 96 patients, pathogens were identified by microbiological tests. The overall pathogen detection rate of mNGS was significantly higher than that of CMTs (91.3% vs. 59.2%, p = 0.000). The diagnostic performance of mNGS varied for different pathogens; however, its sensitivity and accuracy for diagnosing bacterial and viral infections were both higher than those of CMTs (p = 0.000). For the diagnosis of fungi, the sensitivity of mNGS (87.5%) was higher than that of CMTs (25%); however, its specificity and accuracy were lower than those of CMTs (p < 0.01). For the diagnosis of Mycoplasma pneumoniae, the specificity (98.8%) and accuracy (88.3%) of mNGS were high; however, its sensitivity (42.1%) was significantly lower than that of CMTs (100%) (p = 0.001). In 96 patients with definite pathogens, 52 cases (50.5%) were infected with a single pathogen, while 44 cases (42.7%) had polymicrobial infections. Virus-bacteria and virus-virus co-infections were the most common. Staphylococcus aureus, Haemophilus influenzae, rhinovirus, cytomegalovirus, parainfluenza virus, and fungi were more likely to be associated with polymicrobial infections. Conclusions: BALF mNGS improved the detection rate of pediatric pneumonia, especially in mixed infections. The diagnostic performance of BALF mNGS varies according to pathogen type. mNGS can be used to supplement CMTs. A combination of mNGS and CMTs may be the best diagnostic strategy.

Efficacy and safety of integrated traditional Chinese and Western medicine for the treatment of infant bronchiolitis: A systematic review, meta-analysis and GRADE evaluation.

BACKGROUND: Infant bronchiolitis has a high death rate in severe cases. In China, traditional Chinese medicine (TCM) is commonly used to treat infant bronchiolitis. However, it has not received enough international attention. OBJECTIVE: We aimed to assess the efficacy and safety of integrated TCM and Western medicine for treating infant bronchiolitis. METHODS: We conducted a systematic review through 7 databases that included randomized controlled trials on integrated TCM and Western medicine for treating bronchiolitis, published in English or Chinese before February 4, 2021. To assess the risk of bias, the Cochrane Collaboration tool was employed to determine the quality of the included studies. We investigated clinical efficacy endpoints, hospitalization time, rates of recurrence, and adverse reactions and meta-analyzed the odds ratio (OR), mean difference (MD), and relative risk (RR), respectively. We assessed the overall certainty of the effect estimates using the GRADE approach. This study is registered with PROSPERO (CRD42021245294). Ethical approval is not required. RESULTS: Forty-six studies (6427 children) were available for inclusion. We used 41 (5490 participants), 11 (1350 participants), 5 (1083 participants), and 11 (1295 participants) studies to analyze clinical efficacy endpoints (OR: 3.31; 95% confidence interval [CI]: 2.93, 3.74; P < .5), hospitalization time (MD: -2.10; 95% CI: -2.87, -1.34; P < .5), recurrence rate (RR: 0·41; 95% CI: 0.30, 0.56; P < .01), and adverse reaction rate (RR: 0.87; 95% CI: 0.55, 1.39; P = .57), respectively. CONCLUSIONS: Integrated TCM and Western medicine is superior to Western medicine alone for treating bronchiolitis in terms of clinical efficacy, hospitalization time, and recurrence rate, with no increase in the adverse reaction rate. TCM is useful as an alternative therapy for viral bronchiolitis. Although further studies are needed to establish specific protocols for the use of TCM in clinical practice, these results may strengthen guideline recommendations regarding the use of TCM.

Urinary peptidomics reveals proteases involved in idiopathic membranous nephropathy.

BACKGROUND: Idiopathic membranous nephropathy (IMN) is a cause of nephrotic syndrome that is increasing in incidence but has unclear pathogenesis. Urinary peptidomics is a promising technology for elucidating molecular mechanisms underlying diseases. Dysregulation of the proteolytic system is implicated in various diseases. Here, we aimed to conduct urinary peptidomics to identify IMN-related proteases. RESULTS: Peptide fingerprints indicated differences in naturally produced urinary peptide components among 20 healthy individuals, 22 patients with IMN, and 15 patients with other kidney diseases. In total, 1,080 peptide-matched proteins were identified, 279 proteins differentially expressed in the urine of IMN patients were screened, and 32 proteases were predicted; 55 of the matched proteins were also differentially expressed in the kidney tissues of IMN patients, and these were mainly involved in the regulation of proteasome-, lysosome-, and actin cytoskeleton-related signaling pathways. The 32 predicted proteases showed abnormal expression in the glomeruli of IMN patients based on Gene Expression Omnibus databases. Western blot revealed abnormal expression of calpain, matrix metalloproteinase 14, and cathepsin S in kidney tissues of patients with IMN. CONCLUSIONS: This work shown the calpain/matrix metalloproteinase/cathepsin axis might be dysregulated in IMN. Our study is the first to systematically explore the role of proteases in IMN by urinary peptidomics, which are expected to facilitate discovery of better biomarkers for IMN.

Toward the Development of a Comprehensive Clinically Oriented Patient Profile: A Systematic Review of the Purpose, Characteristic, and Methodological Quality of Classification Systems of Adult Spinal Deformity.

BACKGROUND: Existing adult spinal deformity (ASD) classification systems are based on radiological parameters but management of ASD patients requires a holistic approach. A comprehensive clinically oriented patient profile and classification of ASD that can guide decision-making and correlate with patient outcomes is lacking. OBJECTIVE: To perform a systematic review to determine the purpose, characteristic, and methodological quality of classification systems currently used in ASD. METHODS: A systematic literature search was conducted in MEDLINE, EMBASE, CINAHL, and Web of Science for literature published between January 2000 and October 2018. From the included studies, list of classification systems, their methodological measurement properties, and correlation with treatment outcomes were analyzed. RESULTS: Out of 4470 screened references, 163 were included, and 54 different classification systems for ASD were identified. The most commonly used was the Scoliosis Research Society-Schwab classification system. A total of 35 classifications were based on radiological parameters, and no correlation was found between any classification system levels with patient-related outcomes. Limited evidence of limited quality was available on methodological quality of the classification systems. For studies that reported the data, intraobserver and interobserver reliability were good (kappa = 0.8). CONCLUSION: This systematic literature search revealed that current classification systems in clinical use neither include a comprehensive set of dimensions relevant to decision-making nor did they correlate with outcomes. A classification system comprising a core set of patient-related, radiological, and etiological characteristics relevant to the management of ASD is needed.

COVID-19 Epidemic: Clinical Characteristics of Patients in Pediatric Isolation Ward.

In order to accurately admit children with COVID-19 to an isolation ward, our study retrospectively analyzed the clinical characteristics of children in isolation wards during the COVID-19 epidemic. It was found that 55 cases (83.3%) had fever and 48 cases (72.7%) coughed in the isolated area, 31 cases (47%) had a history of exposure, 26 cases (39.4%) had a decrease in lymphocytes (LYM), more than half had an increase in lactate dehydrogenase and creatine kinase isoenzyme, 14 cases (21.2%) had positive SARS-CoV-2 nucleic acid, 58 cases (87.9%) had abnormal chest computed tomography (CT), and 11 cases (16.7%) had sinus arrhythmia. Therefore, for some suspected children with COVID-19, we can make a comprehensive judgment through clinical symptoms, epidemiological history, LYM number, myocardial enzyme spectrum, chest CT, and electrocardiogram; put these children in an isolation ward for treatment; and then transfer them to a general ward for treatment after excluding COVID-19.

Study on the Mechanism of Olfactomedin 4-shRNA Plasmid Chitosan Magnetic Nanoparticles in Intestinal Metaplasia of Chronic Atrophic Gastritis.

Intestinal metaplasia (IM) refers to the replacement of gastric epithelial cells by intestinal epithelial cells. This is often accompanied by chronic atrophic gastritis (CAG), which is a precancerous lesion of gastric cancer. The incidence rates of CAG and IM are increasing gradually, which generates an enormous economic burden to individuals and society. To explore the pathogenesis of CAG with IM, we screened out the differentially expressed gene olfactomedin 4 (OLFM4) by bioinformatics and constructed OLFM4-shRNA plasmid chitosan magnetic nanoparticles to knockdown this gene. This caused a downregulation of caudal type homeobox 2 (CDX2), a marker of IM, suggesting that knocking down OLFM4 may slow the pathological process of IM, thus providing putative relevant targets for the treatment of CAG with IM.

Linkage mapping and genome-wide association study reveals conservative QTL and candidate genes for Fusarium rot resistance in maize.

BACKGROUND: Fusarium ear rot (FER) caused by Fusarium verticillioides is a major disease of maize that reduces grain yield and quality globally. However, there have been few reports of major loci for FER were verified and cloned. RESULT: To gain a comprehensive understanding of the genetic basis of natural variation in FER resistance, a recombinant inbred lines (RIL) population and one panel of inbred lines were used to map quantitative trait loci (QTL) for resistance. As a result, a total of 10 QTL were identified by linkage mapping under four environments, which were located on six chromosomes and explained 1.0-7.1% of the phenotypic variation. Epistatic mapping detected four pairs of QTL that showed significant epistasis effects, explaining 2.1-3.0% of the phenotypic variation. Additionally, 18 single nucleotide polymorphisms (SNPs) were identified across the whole genome by genome-wide association study (GWAS) under five environments. Compared linkage and association mapping revealed five common intervals located on chromosomes 3, 4, and 5 associated with FER resistance, four of which were verified in different near-isogenic lines (NILs) populations. GWAS identified three candidate genes in these consistent intervals, which belonged to the Glutaredoxin protein family, actin-depolymerizing factors (ADFs), and AMP-binding proteins. In addition, two verified FER QTL regions were found consistent with Fusarium cob rot (FCR) and Fusarium seed rot (FSR). CONCLUSIONS: These results revealed that multi pathways were involved in FER resistance, which was a complex trait that was controlled by multiple genes with minor effects, and provided important QTL and genes, which could be used in molecular breeding for resistance.

Roles of CaMKIIß in the neurotoxicity induced by ropivacaine hydrochloride in dorsal root ganglion.

Neurotoxicity of local anesthetics is often reported in the clinic, more and more people pay attention to them. CaMKIIß, a subtype of CaMKII, is detected in the central nervous system. Previous study found that CaMKIIß mRNA are up-regulated in DRG neurons treated with ropivacaine hydrochloride, as well as inhibition of Cav3.2 and Cav3.3 expression can improve the local anesthetics neurotoxicity. In this study, we observed the effect of CaMKIIß on neurotoxicity injury induced by ropivacaine hydrochloride with DRG cell in vitro. We first constructed the pAd-shRNA-CaMKIIß-DRG to inhibit CaMKIIß mRNA expression and detected the cell viability, cell apoptosis rate, CaMKIIß, Cav3.2 and Cav3.3 expression. The results showed that ropivacaine hydrochloride caused the DRG cell injury with cell viability decreased and cell apoptosis rate increased, CaMKIIß, Cav3.2 and Cav3.3 expression up-regulated. Interestingly, inhibition of CaMKIIß expression protected the DRG cell from the neurotoxicity injury induced by ropivacaine hydrochloride, increased the cell viability and decreased the apoptosis rate, as well as inhibition of CaMKIIß expression down-regulated Cav3.2 and Cav3.3 expression. In other words, CaMKIIß is involved with the DRG injury induced by ropivacaine hydrochloride. Inhibition CaMKIIß expression improved DRG injury, increased the cell viability and decreased cell apoptosis rate.

MicroRNA-196a/-196b regulate the progression of hepatocellular carcinoma through modulating the JAK/STAT pathway via targeting SOCS2.

microRNAs (miRNAs) play essential roles in progression of hepatocellular carcinoma (HCC). However, the roles of miR-196a and miR-196b as well as mechanism in HCC progression remain poorly understood. The expressions of miR-196a, miR-196b and suppressor of cytokine signaling 2 (SOCS2) were measured in HCC tissues and cells by quantitative real-time polymerase chain reaction or immunohistochemistry. HCC progression was investigated by cell proliferation, glycolysis, cycle, clones, apoptosis, and necrosis. The interaction between SOCS2 and miR-196a or miR-196b was explored by luciferase activity and RNA immunoprecipitation analyses. The expressions of proteins in Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway were measured by western blot. A xenograft model was established to investigate the roles of miR-196a or miR-196b in vivo. We found that miR-196a and miR-196b were highly expressed in HCC tissues and cells. High expression of miR-196a or miR-196b was correlated with tumor size, tumor-node-metastasis stage, lymph node metastasis, albumin-bilirubin grade and poor 5-year survival. Knockdown of miR-196a or miR-196b suppressed cell proliferation, glycolysis, cell cycle process, colony formation but induced apoptosis or necrosis in HCC cells. SOCS2 was targeted by miR-196a and miR-196b and its interference ablated abrogation of miR-196a or miR-196b-mediated inhibitory effect on HCC progression. SOCS2 was negatively associated with activation of the JAK/STAT pathway. Besides, knockdown of miR-196a or miR-196b limited xenograft tumor growth by blocking the JAK/STAT pathway. We concluded that downregulation of miR-196a or miR-196b inhibited HCC progression through regulating the JAK/STAT pathway via targeting SOCS2, providing novel targets for prognosis and therapeutics of HCC.