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Antibiotics are playing an increasingly important role in clinical antibacterial applications. However, their abuse has also brought toxic and side effects, drug-resistant pathogens, decreased immunity and other problems. New antibacterial schemes in clinic are urgently needed. In recent years, nano-metals and their oxides have attracted wide attention due to their broad-spectrum antibacterial activity. Nano-silver, nano-copper, nano-zinc and their oxides are gradually applied in biomedical field. In this study, the classification and basic properties of nano-metallic materials such as conductivity, superplasticity, catalysis, and antibacterial activities were firstly introduced. Secondly, the common preparation techniques, including physical, chemical and biological methods, were summarized. Subsequently, four main antibacterial mechanisms, such as cell membrane, oxidative stress, DNA destruction and cell respiration reduction, were summarized. Finally, the effect of size, shape, concentration and surface chemical characteristics of nano-metals and their oxides on antibacterial effectiveness and the research status of biological safety such as cytotoxicity, genotoxicity and reproductive toxicity were reviewed. At present, although nano-metals and their oxides have been applied in medical antibacterial, cancer treatment and other clinical fields, some issues such as the development of green preparation technology, the understanding of antibacterial mechanism, the improvement of biosafety, and the expansion of application fields, require further exploration.
Subject(s)
Oxides/chemistry , Metal Nanoparticles/chemistry , Anti-Bacterial Agents/chemistry , Zinc , CopperABSTRACT
BACKGROUND: Recently, more and more people suffer from low back pain triggered by lumbar degenerative disc disease. The mechanical factor is one of the most significant causes of disc degeneration. This study aims to explore the biomechanical responses of the intervertebral disc, and investigate the process of disc injury by the theory of continuum damage mechanics. METHODS: A finite element model of the L4-L5 lumbar spine was developed and validated. The model not only considered changes in permeability coefficient with strain, but also included physiological factors such as osmotic pressure. Three loading conditions were simulated: (A) static loads, (B) vibration loads, (C) injury process. FINDINGS: The simulation results revealed that the facet joints shared massive stresses of the intervertebral discs, and prevented excessive lumbar spine movement. However, their asymmetrical position may have led to degeneration. The von Mises stress and pore pressure of annulus fibrosus showed significantly different trends under static loads and vibration loads. The von Mises stress of nucleus pulposus was not sensitive to vibration loads, but its pore pressure was conspicuously influenced by vibration loads. The injury first appeared at the posterior centre, and then, it gradually expanded along the edge of the intervertebral disc. With an increase in the loading steps, the damage rate of the intervertebral disc increased logarithmically. INTERPRETATION: The variation in the biomechanical performance of the intervertebral disc could be attributed to the periodic movement of internal fluids. This study might be helpful for understanding the mechanism of intervertebral disc degeneration.
Subject(s)
Intervertebral Disc Degeneration , Intervertebral Disc Displacement , Intervertebral Disc , Biomechanical Phenomena , Finite Element Analysis , Humans , Intervertebral Disc/physiology , Lumbar Vertebrae/physiology , Stress, MechanicalABSTRACT
Reports a case admitted in the Ward I of Department of Surgery of Zhengzhou Renji Hospital in June 2017. A young child who suffered destructive injury of left forearm, wrist and palm with severed 3rd-5th fingers. Tendon and neurovascular repairs of forearm, wrist and palm were performed with pedicled abdomina flap and the 3rd-5th fingers ectopic replantation in Phase I surgery. In the Phase II surgery, the abdomina flap division was carried out. The replantation of severed fingers after ectopic replantation and the reconstruction of foot defect with free anterolateral thigh flap(ALTF) were carried out in Phase III surgery. In Phase IV surgery, fingers functional reconstruction and foot flap thinning were performed. Four years after surgery, the thumb oppositions to middle, ring and little fingers could be completed, with slightly limitations. The appearance and texture of transferred foot flap were good, and the child could walk and run almost normally.
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Objective:To detect the incidence and analyze the clinical significance of regions of homozygosity (ROH) through the single nucleotide polymorphism array (SNP array).Methods:The SNP array detection results of 5 116 pregnant women in the Third Affiliated Hospital of Guangzhou Medical University from January 2016 to December 2020 were retrospectively analyzed. The pregnant women with ROH (5 Mb as the threshold) were followed up to analyze the relationship between ROH and abnormal fetal phenotype. Whole exon sequencing was performed in 4 cases of consanguineous marriage to detect potential recessive causative genes in the ROH region.Results:(1) A total of 39 cases of ROH were detected, with a positive rate of 0.76% (39/5 116). Among them, 25 cases (64%, 25/39) were detected only on single chromosome, and chromosome 11 had the highest detection rate, suggesting the risk of uniparental disomy; fourteen cases (36%,14/39) were detected on multiple chromosomes, most commonly on chromosomes 11, 1, 3, 4 and 8. (2) The number of cases and detection rate of ROH detected by different prenatal diagnosis indicators were as follows: 12 cases (1.78%, 12/676) in pregnant women with abnormal non-invasive prenatal testing result, 12 cases (0.37%, 12/3 284) in pregnant women with ultrasound abnormality, 4 cases (4/4) in pregnant women with consanguineous marriage, 3 cases (0.92%, 3/326) in pregnant women with previous adverse pregnancy, 2 cases (1.15%, 2/174) in pregnant women with high risk of serology in screening, 2 cases (4.00%, 2/50) in pregnant women with abnormal fetal chromosomal karyotype, 2 cases (0.79%, 2/253) in pregnant women with advanced maternal age, 1 case (0.56%, 1/178) in pregnant women with related parental genetic factors and 1 case (0.58%, 1/171) in pregnant women with the other factors. (3) The follow-up results of 39 cases of prenatal ROH showed that there were 16 cases of term birth, 15 cases of termination of pregnancy, 2 cases of preterm births, 1 case of fetal death and 5 cases lost to follow-up.Conclusions:Chromosomal ROH phenomenon is not rare. By analyzing the detection rate of ROH in prenatal diagnosis, combined with the results of fetal phenotype and postpartum follow-up, the clinical characteristics of ROH are discussed, so as to better understand the relationship between ROH and its phenotype.
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Copy number variants (CNVs) are common causes of human genetic diseases. CNVs detection has become a routine component of genetic testing, especially for pediatric neurodevelopmental disorders, multiple congenital abnormalities, prenatal evaluation of fetuses with structural anomalies detected by ultrasound. Although the technologies for CNVs detection are continuously improving, the interpretation is still challenging, with significant discordance across different laboratories. In 2020, the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen) developed a guideline for the interpreting and reporting of constitutional copy number variants, which introduced a quantitative, evidence-based scoring framework. Here, we detailed the key points of interpreting the copy number gain based on the guideline, used six examples of different categories to illuminate the scoring process and principles. We encourage a professional understanding and application of this guideline for the detected copy number gains in China in order to further improve the clinical evaluation accuracy and consistency across different laboratories.
Subject(s)
Child , Female , Humans , Pregnancy , DNA Copy Number Variations , Genetic Testing , Genetics, Medical , Genome, Human/genetics , Genomics , United StatesABSTRACT
Genomic disorders caused by pathogenic copy number variation (pCNV) have proven to underlie a significant proportion of birth defects. With technological advance, improvement of bioinformatics analysis procedure, and accumulation of clinical data, non-invasive prenatal screening of pCNV (NIPS-pCNV) by high-throughput sequencing of maternal plasma cell-free DNA has been put to use in clinical settings. Specialized standards for clinical application of NIPS-pCNV are required. Based on the discussion, 10 pCNV-associated diseases with well-defined conditions and 5 common chromosomal aneuploidy syndromes are recommended as the target of screening in this consensus. Meanwhile, a standardized procedure for NIPS-pCNV is also provided, which may facilitate propagation of this technique in clinical settings.
Subject(s)
Female , Humans , Pregnancy , Aneuploidy , Cell-Free Nucleic Acids/genetics , Consensus , DNA Copy Number Variations , High-Throughput Nucleotide Sequencing , Prenatal DiagnosisABSTRACT
The overall prevalence of uniparental disomy (UPD) across all chromosomes was estimated to be around one birth in 2000. To date, more than 4170 UPD cases have been registered. UPD for chromosomes 6, 7, 11, 14, 15, and 20 can result in clinically recognizable imprinting disorders due to abnormal levels of imprinted gene expression. For other chromosomes, the clinical consequences associated with UPD are not apparent, unless when a recessive genetic disorder is unmasked by UPD or regions of homozygosity (ROH). A clinical practice guideline will assist in strengthening the precise analysis and interpretation of the clinical significance of ROH/UPD. This guideline summarizes the conception, mechanism and clinical consequences of ROH/UPD, as well as the principles for data analysis, with an aim to standardize the clinical application and data interpretation.
Subject(s)
Humans , Gene Expression , Genomic Imprinting , Homozygote , Practice Guidelines as Topic , Uniparental Disomy/geneticsABSTRACT
The overall prevalence of uniparental disomy (UPD) across all chromosomes was estimated to be around one birth in 2000. To date, more than 4170 UPD cases have been registered. UPD for chromosomes 6, 7, 11, 14, 15, and 20 can result in clinically recognizable imprinting disorders due to abnormal levels of imprinted gene expression. For other chromosomes, the clinical consequences associated with UPD are not apparent, unless when a recessive genetic disorder is unmasked by UPD or regions of homozygosity (ROH). A clinical practice guideline will assist in strengthening the precise analysis and interpretation of the clinical significance of ROH/UPD. This guideline summarizes the conception, mechanism and clinical consequences of ROH/UPD, as well as the principles for data analysis, with an aim to standardize the clinical application and data interpretation.
Subject(s)
Humans , Gene Expression , Genomic Imprinting , Homozygote , Uniparental Disomy/geneticsABSTRACT
Bats are responsible for the zoonotic transmission of several major viral diseases including the 2003 SARS outbreak and the ongoing COVID-19 pandemic. While bat genomic sequencing studies have revealed characteristic adaptations of the innate immune system, functional genomic studies are urgently needed to provide a foundation for the molecular dissection of the tolerance of viral infections in bats. Here we report the establishment and screening of genome-wide RNAi library and CRISPR library for the model megabat, Pteropus Alecto. We used the complementary RNAi and CRISPR libraries to interrogate Pteropus Alecto cells for infection with two different viruses, mumps virus and Influenza A virus, respectively. Screening results converged on the endocytosis pathway and the protein secretory pathway as required for both viral infections. Additionally, we revealed a general dependence of the C-1-tetrahydrofolate synthase gene, MTHFD1, for viral replication in bat cells as well as in human cells. MTHFD1 inhibitor carolacton potently blocked replication of several RNA viruses including SARS-CoV-2. Our studies provide a resource for systematic inquiry into the genetic underpinnings of bat biology and a potential target for developing broad spectrum antiviral therapy.
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Chromosomal microdeletions and microduplications have been proven to be a significant proportion of genetic factors underlying birth defects. Chromosomal microarray analysis (CMA) and next generation sequencing-based copy number variation (CNV-seq) assay have been recommended as first-tier tests for prenatal evaluation of disease-causing CNV across the genome. With the broad application of such technologies in prenatal genetic diagnosis, there is a needed to enhance the consistency in interpretation and reporting of CNV results in clinical laboratories across China. In addition, a standard guideline for prenatal analysis and reporting of regions of homozygosity (ROH) is also required. To assist the classification, interpretation and reporting of CNV/ROH, the following recommendations have been developed, which may enhance a standard application of CMA/CNV-seq techniques in prenatal genetic diagnosis.
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Objective To establish a refined model of trunk composed of different lumbar segments, lumped thoracic spine and pelvis, analyze the kinematic differences between patients with lumbar disc herniation (LDH) and healthy people during three daily activities, and to compare the refined trunk model with the simplified trunk model adopting the whole lumbar segment, and discuss the necessity of using the refined trunk model for kinematic analysis of LDH patients. Methods Motion capture system NDI was used to collect kinematic parameters of each segment from 15 healthy people and 7 male LDH patients during level walking, trunk flexion and contralateral pickup, then the kinematic differences between patients and healthy people by the two models were compared respectively. Results During level walking, the rotation of the thoracic segment and pelvis for LDH patients increased, while no significant change was found in motion angle of the whole lumbar segment, and the rotation angle of L4-5 segment significantly reduced. During trunk flexion, the flexion angles of all lumbar segments for LDH patients were reduced by varying degrees, and the flexion angle of L3-4 segment was significantly different from that of healthy people. During contralateral pickup, the performance on the sagittal plane was similar to that during flexion. However, the lateral bending angles of L3-4 segment and L4-5 segment for LDH patients were significantly lower than those for healthy people. ConclusionsLDH patients mainly restrict the motion of injured lumbar segments in daily activities. During some motions, only refined model can discover the abnormal motion of injured lumbar segments. Therefore, it is necessary to subdivide the lumbar spine into 5 independent segments for analyzing the kinematic characteristics of LDH patients.
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In recent years, with the growth of social development, the incidence of lumbar vertebrae diseases has increased year by year, and many surgical methods have been developed. These treatment methods mark the accumulation of surgical experience and the development of medical technology. However, a new issue appears, i.e. how to evaluate the degree of lumbar disease and postoperative rehabilitation. There is an urgent need to establish a quantitative index of preoperative examination and postoperative rehabilitation criteria for lumbar disease from both doctors’ and patients’ perspectives. The current studies show that the measurement of the center of rotation (COR) for lumbar vertebrae and surface electromyography (sEMG) can reduce the error in the evaluation of clinical curative effect for treating lumbar disease and can be applied widely. This review summarizes the relationship between COR and lumbar disease, as well as the role of COR and sEMG joint evaluation in clinical operation and postoperative rehabilitation.
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Total lumbar disc replacement is an alternative to interbody fusion for the effective treatment of symptomatic degenerative disc disease. This paper reviewed the history of ball-on-socket type artificial lumbar disc (ALD) prosthesis, which is a typical ALD prosthesis and summarized the ALD prosthesis research progress, according to different materials such as metal-on-metal, metal-on-polymer, and polymer-on-polymer prosthesis. The structural design factors of ball-on-socket type ALD prosthesis were analyzed and its prospect of development was also presented. The purpose of this paper is to provide a theoretical reference for the design of the ball-on-socket ALD prosthesis by reviewing the current state of ball-on-socket type ALD prosthesis.
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Objective To study the biomechanical properties of porous titanium cages used for different lumbar interbody fusion surgeries. Methods The three-dimensional (3D) finite element model of the lumbar spine was constructed, and mechanical parameters of porous materials were obtained by mechanical test. The biomechanical properties of porous titanium cages in anterior lumbar interbody fusion (ALIF), posterior lumbar interbody fusion (PLIF), transforaminal lumbar interbody fusion (TLIF), direct lateral interbody fusion (DLIF) were compared. Results After lumbar interbody surgery, the predicted range of motion (ROM) and the maximum stress in cage of DLIF model and ALIF model were substantially lower than those of PLIF model and TLIF model. The maximum stress in endplate of DLIF model, ALIF model and TLIF model were obviously lower than that of PLIF model. Conclusions DLIF with the porous cage showed advantages in biomechanical properties, which was simple to operate and suitable for minimally invasive surgery in clinical practice. DLIF performed the superior comprehensive properties.
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The mechanical properties of artificial intervertebral disc (AID) are related to long-term reliability of prosthesis. There are three testing methods involved in the mechanical performance evaluation of AID based on different tools: the testing method using mechanical simulator, specimen testing method and finite element analysis method. In this study, the testing standard, testing equipment and materials of AID were firstly introduced. Then, the present status of AID static mechanical properties test (static axial compression, static axial compression-shear), dynamic mechanical properties test (dynamic axial compression, dynamic axial compression-shear), creep and stress relaxation test, device pushout test, core pushout test, subsidence test, etc. were focused on. The experimental techniques using specimen testing method and testing results of available artificial discs were summarized. The experimental methods and research status of finite element analysis were also summarized. Finally, the research trends of AID mechanical performance evaluation were forecasted. The simulator, load, dynamic cycle, motion mode, specimen and test standard would be important research fields in the future.
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Aiming at the background and significance of biomechanical researches on lumbar interbody fusion, the research progress of interbody cage and interbody fusion was reviewed and its prospect was forecasted. The related work was summarized, including research method of lumbar biomechanics, biomechanics of interbody cage, and biomechanics of lumbar interbody fusion. The main research directions on biomechanical study of lumbar interbody fusion were: modeling refinement of finite element method, geometrical optimization of traditional fusion device, clinical application of new porous fusion device, and diversification of the supplemented fixation method. Finally, the prospect of biomechanics of lumbar interbody fusion was discussed. The review and prospect on biomechanics of lumbar interbody fusion will provide references for clinical treatment of lumbar spine diseases.
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The research progress of finite element method (FEM) applied in biomechanics of lumbar fusion and artificial lumbar disc replacement was reviewed and its prospect was forecasted. The main research directions of FEM are optimal selection of operation plans before the surgery, performance evaluation of implanted devices and prediction of postoperative outcomes. Based on the recent research progress, the application prospects of FEM in simulation of personalized surgery, evaluation of elastic implants and postoperative prediction of novel operation method were discussed. By reviewing and prospecting the application of FEM in biomechanical research of lumbar fusion and artificial lumbar disc replacement, the purpose of this paper is to provide theoretical references and practical guidance for the treatment of lumbar diseases in clinic.
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This article reviews the progress of biomechanical studies on anterior cervical fusion and non-fusion surgery in recent years. The similarities and differences between animal and human cervical spines as well as the major three biomechanical test methods are introduced. Major progresses of biomechanical evaluation in anterior cervical fusion and non-fusion devices, hybrid surgery, coupled motion and biomechanical parameters, such as the instant center of rotation, are classified and summarized. Future development of loading method, multilevel hybrid surgery and coupling character are also discussed.
Subject(s)
Animals , Humans , Biomechanical Phenomena , Cervical Vertebrae , General Surgery , Rotation , Spinal Fusion , MethodsABSTRACT
BACKGROUND:Some studies have shown that more copy number variations are present in early passage human induced pluripotent stem cells than later passage human human induced pluripotent stem cells, their parental somatic fibroblasts or human embryonic stem cells. OBJECTIVE:To investigate whether the reprogramming process itself compromises genomic stability and further explore the efficiency of induced pluripotent stem cellestablishment. METHODS:Using high-resolution Affymetrix CytoScan HD array, we compared copy number variations and loss of heterozygosity in early passage induced pluripotent stem cells with their fibroblast cellorigins from genetic epilepsy patients. RESULTS AND CONCLUSION:Compared with somatic fibroblasts from genetic epilepsy patient, there was no difference in the loss of heterozygosity between the two types of cells, but more copy number variations were present in early passage human induced pluripotent stem cells which were characterized as microduplication and involved oncogenic genes. Results demonstrate the dynamic nature of genomic abnormalities during reprogramming process and the necessity of frequent monitoring human induced pluripotent stem cells to assure their genomic stability and clinical safety.
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10.3969/j.issn.2095-4344.2013.26.019