ABSTRACT
Objective: To explore the clinical characteristics, prognostic risk factors and effective treatment of severe hemophagocytic syndrome (HPS) in children, so as to provide reference for the clinical diagnosis and treatment of the disease. Methods: The clinical data of 83 children with severe HPS admitted in Affiliated Hospital of Zunyi Medical University from January 2014 to April 2021 were collected, and their clinical characteristics, prognosis and prognostic risk factors were analyzed. The children were divided into central nervous system (CNS) dysfunction group and non-CNS dysfunction group according to whether they were accompanied with CNS dysfunction, and were divided into blood purification group and non-blood purification group according to whether they received blood purification, then the survival differences were compared. Results: Among the 83 children, there were 43 males and 40 females, aged[M(Q1,Q3)] 36(15,27)months. A total of 51 children were induced by infection, among which 41 children (80.4%) were infected with EB virus. All the children were accompanied by multiple organ dysfunction (MODS), and dysfunction of the blood system (72.3%), liver (71.1%), respiratory system (53.0%) and CNS (37.3%) were common. By the end of follow-up, 40 cases (48.2%) survived, 38 cases (45.8%) died, and 5 cases (6.0%) were lost to follow-up. CNS dysfunction was a risk factor (HR=3.358, 95%CI: 1.445-7.803, P=0.005) and blood purification was a protective factor (HR=0.362, 95%CI: 0.179-0.730, P=0.005) affecting the prognosis of children. The mortality of CNS dysfunction group was statistically higher than that of non-CNS dysfunction group (74.2% vs 28.8%) (P<0.001); The mortality of blood purification group was statistically lower than that of non-blood purification group (31.0% vs 61.0%) (P=0.010). Conclusions: Severe HPS in children was dangerous and had a poor overall prognosis. CNS dysfunction was a risk factor for death. Blood purification could significantly improve the prognosis and improve the survival rate of children.
Subject(s)
Lymphohistiocytosis, Hemophagocytic , Aged , Child , Female , Herpesvirus 4, Human , Humans , Male , Prognosis , Retrospective Studies , Risk FactorsABSTRACT
Objective: To explore the MRI features of the pure mucinous breast carcinoma(PMBC) and the correlation with cell density and the expression of immunohistochemistry. Methods: MRI features of 35 pure mucinous carcinomas were retrospectively analyzed from January 2011 to May 2016 in Guangdong General Hospital. MR images were reviewed for shape, margin, the signal intensity, enhancement patterns of tumors and diffusion weighted imaging (DWI) features and apparent diffusion coefficient (ADC) value. All the patients were detected by immunohistochemical staining with expression of ER, PR, CerbB-2, Ki-67 and Her-2. Correlations between MRI features of PMBC and cell density and the expression of immunohistochemistry were analyzed. Results: A total of 16 oval masses(16/35, 45.7%) and 10 round masses(10/35, 28.6%)were found in 35 PMBC with clear boundary(26/35, 74.3%) and lobulated shape(31/35, 88.6%). Very high signal intensity on T(2)-weighted images was found in 33 PMBC (33/35, 94.3%) and early enhancement rate was 115%±9% for PMBC. 28 PMBC demonstrated persistent enhancing pattern on time-signal intensity curve and 7 PMBC demonstrated plateau pattern.Mean ADC value was (1.91±0.06)×10(-3)mm(2)/s for PMBC. There was significant difference with early enhancement rate and ADC value between PMBC with more or less quantities of cellular mucin (P<0.05). There was no significant difference with ER, PR, CerbB-2, Her-2 and Ki-67 expression between PMBC with more or less quantities of cellular mucin (all P>0.05). Conclusions: PMBC has distinctive MRI features. The prognosis of PMBC is better from correlation between MRI features, cell density and the expression of immunohistochemistry.
Subject(s)
Breast Neoplasms/diagnostic imaging , Carcinoma, Ductal, Breast/diagnostic imaging , Cell Count , Magnetic Resonance Imaging , Diffusion Magnetic Resonance Imaging , Female , Gene Expression Regulation, Neoplastic , Humans , Immunohistochemistry , PrognosisABSTRACT
BACKGROUND: Dysregulation of the striatum and altered corticostriatal connectivity have been associated with psychotic disorders. Social anhedonia has been identified as a predictor for the development of schizophrenia spectrum disorders. The aim of the present study was to examine corticostriatal functional connectivity in individuals with high social anhedonia. METHOD: Twenty-one participants with high social anhedonia score and 30 with low social anhedonia score measured by the Chinese version of the Revised Social Anhedonia Scale were recruited from university undergraduates (age 17-21 years) to undergo resting-state functional MRI scans. Six subdivisions of the striatum in each hemisphere were defined as seeds. Voxel-wise functional connectivity analyses were conducted between each seed and the whole brain voxels, followed by repeated-measures ANOVA for the group effect. RESULTS: Participants with high social anhedonia showed hyper-connectivity between the ventral striatum and the anterior cingulate cortex and the insula, and between the dorsal striatum and the motor cortex. Hypo-connectivity in participants with high social anhedonia was also observed between the ventral striatum and the posterior cingulate cortex. Partial correlation analyses further showed that the functional connectivity between the ventral striatum and the prefrontal cortex was associated with pleasure experience and emotional suppression. CONCLUSIONS: Our findings suggest that altered corticostriatal connectivity can be found in participants with high levels of social anhedonia. Since social anhedonia has been considered a predictor for schizophrenia spectrum disorders, our results may provide novel evidence on the early changes in brain functional connectivity in at-risk individuals.
Subject(s)
Anhedonia/physiology , Cerebral Cortex/physiopathology , Corpus Striatum/physiopathology , Frontal Lobe/physiopathology , Interpersonal Relations , Adolescent , Adult , Female , Humans , Magnetic Resonance Imaging , Male , Young AdultABSTRACT
The association of the programmed cell death-1 PD1.5 C>T polymorphism with cervical cancer risk has not been investigated. In this hospital-based case-control study, we analyzed 256 patients with cervical cancer and 250 healthy controls. Pearson chi-square test was used to examine differences in the distribution of genotypes between cases and controls. Association between the polymorphism and the susceptibility to cervical cancer was evaluated using unconditional logistic regression analysis. This revealed that the frequencies of the three genotypes (CC, CT, and TT) in cervical cancer cases and controls were 17.58, 65.23, and 17.19% and 24.80, 40.40, and 34.80%, respectively; the difference between the two groups was significant (P < 0.001). We found that the CT genotype was significantly associated with increased cervical cancer risk (adjusted OR = 2.18; 95%CI = 1.37-6.11; P = 0.009). Moreover, there was significant association between PD-1.5 C/T polymorphism and susceptibility to cervical cancer under dominant model (OR = 1.27, 95%CI = 1.01-2.15, P = 0.047). We conclude that the PD-1.5 C/T polymorphism may be associated with increased risk of cervical cancer. The study also highlights the importance of conducting genetic association studies in different ethnic populations.
Subject(s)
Programmed Cell Death 1 Receptor/genetics , Uterine Cervical Neoplasms/genetics , Asian People/genetics , Case-Control Studies , Female , Gene Frequency/genetics , Genetic Predisposition to Disease/genetics , Genotype , Humans , Polymorphism, Single Nucleotide/geneticsABSTRACT
Craniofacial hard tissue mainly includes craniofacial bone and tooth, which is one of the important parts of the mouth-jaw system. Congenital aplasia, tumors and trauma can cause large craniofacial hard tissue defects, which are detrimental to the facial appearance and function of patients, and affect the physical and mental health of patients. Histone acetylation modification is the earliest and most widely studied histone modification, which is an epigenetic modification mechanism jointly regulated by histone acetyltransferase and histone deacetylase. In this paper, we will review the research progress of histone acetylation mediated by histone acetyltransferase and histone deacetylase in the development and regeneration of craniofacial hard tissue.
Subject(s)
Histone Acetyltransferases , Histones , Regeneration , Acetylation , Humans , Histones/metabolism , Histone Acetyltransferases/metabolism , Histone Deacetylases/metabolism , Epigenesis, Genetic , Tooth/metabolism , Facial Bones , Skull/metabolismABSTRACT
Objective: To analyze the trends in literature related to oral microbiology and regenerative medicine from 2014 to 2023. By identifying key research countries, institutions, and their collaboration networks, as well as exploring research hotspots and development directions, the study seeks to provide references for researchers and decision-makers in the field of oral microbiology and regenerative medicine, thereby guiding the direction of future research. Methods: Relevant literature was retrieved using the Web of Science Core Collection database, with data processing and analysis conducted using CiteSpace 6.2.R6 software. Time slicing, node type selection, and the application of the g-index (g-index) were used for filtering, analyzing countries, institutions, authors, journals, and keywords. Results: The volume of literature in the field of oral microbiology and regenerative medicine has steadily increased from 2014 to 2023, with the number of publications first exceeding one hundred in 2020 and reaching 134 in 2022, accompanied by a citation frequency of 3 363 times. China and the United States have been at the forefront in terms of the volume of publications, while the United States and Germany lead in terms of intermediary centrality. The research primarily spans disciplines such as oral medicine, interdisciplinary studies, materials science, and immunology. High-frequency keywords include stem cells, scaffold materials, and gut microbiota, while cluster analysis indicates that inflammation, drug delivery, and antimicrobial activity remain consistent research themes. In recent years, the research heat in "tissue regeneration""gut microbiota " and "maxillofacial surgery" has risen, suggesting these may become focal points of future research. Conclusions: Over the past decade, the volume of literature published in the fields of oral microbiology and regenerative medicine, along with their citation frequencies, has increased annually. The research focus has shifted over time. Understanding the interactions between oral and gut microbiomes is crucial for developing innovative regenerative treatment strategies.
Subject(s)
Regenerative Medicine , Humans , Mouth/microbiology , United States , ChinaABSTRACT
With the extensive use of telbivudine, more and more studies reported its association with creatine kinase (CK) elevations and myopathy. However, clinical features of these adverse effects were poorly understood. The aim of the present study was to investigate the clinical features and risk factors of CK elevations and myopathy associated with telbivudine. The serum CK levels of 200 patients who were treated with telbivudine for chronic hepatitis B (CHB) between January 2007 and July 2010 were monitored and analysed along with clinical manifestations. The 3-year cumulative incidence of CK elevations and myopathy was 84.3% and 5%, respectively. CK elevations occurred more frequently in men than in women, and patients aged ≤45 years and with negative HBeAg had higher incidence of CK elevations. There was no difference in CK elevations among patients with different HBV DNA levels. Male, younger age and HBeAg negativity were independent predictors of CK elevations by multivariate Cox regression analysis. There was no association between the occurrence of myopathy and variables including age, sex, HBeAg and HBV DNA. No risk factors of myopathy were identified. CK elevations usually occurred 21 months after starting treatment, and most patients resolved spontaneously without interruption of telbivudine therapy except three patients who had to switch to other agents. In conclusion, CK elevations are common adverse reactions associated with telbivudine therapy, while myopathy is rare. Male, younger age and HBeAg negativity might be risk factors of CK elevations.
Subject(s)
Antiviral Agents/adverse effects , Creatine Kinase/blood , Muscular Diseases/chemically induced , Muscular Diseases/pathology , Nucleosides/adverse effects , Pyrimidinones/adverse effects , Adolescent , Adult , Age Distribution , Aged , Antiviral Agents/administration & dosage , Female , Hepatitis B, Chronic/drug therapy , Humans , Incidence , Male , Middle Aged , Muscular Diseases/epidemiology , Nucleosides/administration & dosage , Pyrimidinones/administration & dosage , Risk Factors , Sex Distribution , Telbivudine , Thymidine/analogs & derivatives , Young AdultABSTRACT
The application of bone tissue engineering regeneration technology is expected to repair maxillofacial bone tissue defects caused by tumors, trauma, etc. Surface patterning occupies an important position in bone tissue engineering. Microcontact printing is an emerging technology through which the elastic stamp contacts with the substance and materials used as ink can be transferred from stamp to substance to form patterns. The biggest characteristic of the technology is to fabricate high-throughput and high-accuracy patterned surface, making it widely applied. This review summarized the application and optimization of microcontact printing, and prospected its application in bone tissue engineering.
ABSTRACT
INTRODUCTION: Necrotising fasciitis with sepsis is a life threatening disease. The aim of this study was to analyse the association between international normalised ratio (INR) and mortality in sepsis patients with necrotising fasciitis. METHODS: A retrospective review was undertaken of 106 patients suffering from necrotising fasciitis with sepsis between November 2007 and December 2016. Data on comorbidities, clinical manifestations, laboratory findings, causative microbiological organisms, APACHE II (Acute Physiology and Chronic Health Evaluation II) score and outcomes were extracted. Logistic regression was carried out to examine the factors affecting mortality. RESULTS: Forty patients (37.7%) died. There was no significant difference in the white blood count (WBC) for the survivor and non-survivor groups. Non-survivors had a lower mean oxygenation index (OI) (288.7mmHg vs 329.4mmHg, p=0.032) and platelet count (PC) (139.5 vs 214.8 x 109/l, p=0.028), and a higher mean INR (1.9 vs 1.3, p=0.000), activated partial thromboplastin time (APTT) (54.6 vs 44.2 seconds, p=0.005) and serum creatinine (2.3mg/dl vs 1.4mg/dl, p=0.007). Mortality in patients with INR >1.5 was significantly higher than in those with INR <1.5 when all risk factors (WBC, PC, OI, INR, APTT, creatinine) were considered (odds ratio: 4.414, 95% confidence interval: 1.263-15.428, p=0.020). Even after adjusting for age, sex, bacteraemia, diabetes and hepatic disorders, the data still exhibited elevated mortality for patients with INR >1.5 (odds ratio: 5.600, 95% confidence interval: 1.415-22.166, p=0.014). CONCLUSIONS: INR is a significant independent predictor of mortality in sepsis patients diagnosed with necrotising fasciitis.
Subject(s)
Fasciitis, Necrotizing/mortality , Gram-Negative Bacteria/isolation & purification , International Normalized Ratio , Sepsis/mortality , Adult , Aged , Aged, 80 and over , Fasciitis, Necrotizing/blood , Fasciitis, Necrotizing/complications , Fasciitis, Necrotizing/surgery , Female , Humans , Male , Middle Aged , Prognosis , ROC Curve , Retrospective Studies , Risk Factors , Sepsis/blood , Sepsis/microbiology , Sepsis/surgery , Survival Analysis , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE: Titanium oxide nanotube layers by anodization have excellent potential for dental implants because of good bone cell promotion. It is necessary to evaluate osteoblast behavior on different annealing temperature titania nanotubes for actual implant designs. MATERIALS AND METHODS: Scanning Electron Microscopy, X-Ray polycrystalline Diffractometer (XRD), X-ray photoelectron Spectroscope, and Atomic Force Microscopy (AFM) were used to characterize the different annealing temperature titania nanotubes. Confocal laser scanning microscopy, MTT, and Alizarin Red-S staining were used to evaluate the MC3T3-E1 preosteoblast behavior on different annealing temperature nanotubes. RESULTS: The tubular morphology was constant when annealed at 450°C and 550°C, but collapsed when annealed at 650°C. XRD exhibited the crystal form of nanotubes after formation (amorphous), after annealing at 450°C (anatase), and after annealing at 550°C (anatase/rutile). Annealing led to the complete loss of fluorine on nanotubes at 550°C. Average surface roughness of different annealing temperature nanotubes showed no difference by AFM analysis. The proliferation and mineralization of preostoblasts cultured on anatase or anatase/rutile nanotube layers were shown to be significantly higher than smooth, amorphous nanotube layers. CONCLUSION: Annealing can change the crystal form and composition of nanotubes. The nanotubes after annealing can promote osteoblast proliferation and mineralization in vitro.
Subject(s)
Biocompatible Materials/chemistry , Nanotubes/chemistry , Osteoblasts/physiology , Titanium/chemistry , 3T3 Cells , Animals , Anthraquinones , Calcification, Physiologic/physiology , Cell Adhesion/physiology , Cell Culture Techniques , Cell Proliferation , Cell Shape/physiology , Cell Survival/physiology , Coloring Agents , Crystallization , Crystallography , Fluorine/chemistry , Hot Temperature , Materials Testing , Mice , Microscopy, Atomic Force , Microscopy, Confocal , Microscopy, Electron, Scanning , Osteoblasts/cytology , Photoelectron Spectroscopy , Surface Properties , Tetrazolium Salts , Thiazoles , X-Ray DiffractionABSTRACT
Different educational and professional developments within the dental field create different sets of missions, norms, and practices regarding dental diseases and their appropriate treatment. This review has addressed differences in dental education and professional development between mainland China and North America. Many factors influence the choice of model and it is very difficult to predict which model will become predominant. However, there is growing sentiment that the independent faculty model in North America is logical and superior to the model, which 'integrates' dental and medical education in mainland China. Many North America dental schools place a high priority on preclinical and clinical training in the curriculum in order to expose students to patient oral health needs and systemic dental problems much earlier than in mainland China. North America dental schools promote and embrace students self-learning skills by the use of PBL, CRL, and TRAD education methodologies and new e-based technologies and approaches whereby students learn rather than are taught. In mainland China, the traditional lecture-based format is still employed in the majority of dental schools; however, strategies to enhance students self-learning skills is increasingly utilised in most well-known Chinese dental schools. The Chinese dental education model, which treats dentistry as a sub-specialty of medicine, has brought about fundamental differences, with the dentist functioning essentially as a stomatologist. For example, China has built up a large oral and maxillofacial surgery society, and craniofacial surgery is performed to a much broader extent by Chinese dentists than by most North American counterparts. In North America, dentists engage in full-time work, attend continuing training/education programmes, belong to an association, gain legal status, and construct a code of ethics emphasising the quality of care delivered to the public. Currently, continuing dental education in North America is available through a variety of venues involving licensing authorities, universities and private programmes. The concept of professional development in mainland China is relatively new and is still considered primarily in the context of promotion or achieving a higher professional title. Mandatory continuing dental professional education requirements do not guarantee the competence of members of the profession. Today, the Chinese government and society place increasing emphasis upon the accountability of self-regulating professions. Rather than attempting to summarise the current scope of dental education and professional development between mainland China and North America, this paper hopes to enhance mutual understanding, and promote greater academic exchanges in dental education.
Subject(s)
Education, Dental/methods , Models, Educational , Professional Practice/organization & administration , Schools, Dental/organization & administration , Canada , Certification , China , Curriculum , Education, Dental/economics , Educational Measurement , Humans , Licensure , School Admission Criteria , Schools, Dental/economics , Specialties, Dental/education , United StatesABSTRACT
OBJECTIVE: Renal injury caused by sepsis is a difficult point in the field of critical care medicine today, which seriously endangers the health of patients. The aim of our paper was to study the role of irisin in the inflammation and apoptosis of renal injury caused by sepsis and its potential mechanism of action. MATERIALS AND METHODS: Lipopolysaccharide (LPS) was utilized to establish an acute kidney injury model. HK-2 cells were divided into 3 groups: control group, LPS group, LPS+irisin group. The expression of TNF-α, IL-1ß, Bcl-2, and Bax were detected using Western blot. Commercial enzyme-linked immunosorbent assay (ELISA) kits were used to detect the levels of TNF-α, IL-6, and IL-1ß in the cell supernatant. The LDH content was detected to observe cell damage. TUNEL staining and flow cytometry were to investigate the apoptosis in three groups. The viability of HK-2 cells was detected using Cell Counting Kit-8 (CCK-8) assay. RESULTS: After HK-2 cells were treated with LPS, the LDH content in the cell supernatant was greatly increased, and the expression of TNF-α, IL-6, and IL-1ß was also significantly increased. However, after treatment with irisin, LDH content and expression of inflammatory factors were significantly suppressed. Similarly, LPS treatment greatly elevated the levels of TNF-α, IL-1ß, Bax, p65 and IκKα, as well as inhibited the expression of Bcl-2 and IκB-α. However, irisin treatment reversed these situations. In addition, the number of TUNEL-positive cells and the apoptotic rate were also greatly decreased in LPS+irisin group compared with those in LPS group. CONCLUSIONS: Irisin could inhibit inflammation and apoptosis of HK-2 cells treated with LPS via the NF-κB pathway.
Subject(s)
Acute Kidney Injury/metabolism , Fibronectins/metabolism , NF-kappa B/metabolism , Sepsis/metabolism , Acute Kidney Injury/chemically induced , Acute Kidney Injury/pathology , Animals , Apoptosis/drug effects , Cells, Cultured , Disease Models, Animal , Dose-Response Relationship, Drug , Humans , Lipopolysaccharides , Sepsis/chemically induced , Sepsis/pathology , Signal TransductionABSTRACT
OBJECTIVES: To study the effects of maxillary sinus floor elevation by a tissue-engineered bone complex with beta tricalcium phosphate (beta-TCP) and bone morphogenetic protein-2 (BMP-2) gene-modified bone marrow stromal cells (bMSCs) in rabbits. MATERIAL AND METHODS: bMSCs derived from New Zealand rabbit bone marrow were cultured and transduced with the adenovirus with BMP-2 (AdBMP-2), adenovirus with enhanced green fluorescent protein gene (AdEGFP) in vitro. Gene transfer efficiency was detected by EGFP expression. These gene-modified autologous bMSCs were then combined with a beta-TCP granule scaffold at a concentration of 2 x 10(7) cells/ml and used to elevate the maxillary sinus floor in rabbits. Twenty rabbits were randomly allocated into groups and sacrificed at weeks 2 and 8. For each time point, 20 maxillary sinus floor elevation surgeries were made bilaterally in 10 rabbits for the following groups (n=5 per group): group A (beta-TCP alone), group B (untransduced bMSCs/beta-TCP), group C (AdEGFP-bMSCs/beta-TCP), and group D (AdBMP-2-bMSCs/beta-TCP). All samples were evaluated by histology and histomorphometric analysis. The fate of implanted bMSCs was traced initially by a confocol fluorescent microscope in the AdEGFP group. RESULTS: Gene transfer efficiency reached up to 60-80% with 50 PFU/cell transduction as demonstrated by fluorescent microscopic analysis in the AdEGFP group. The augmented maxillary sinus height was maintained for the four groups till 8 weeks post-surgery, while new bone area increased over the time. At week 2, bone areas in groups B-D were significantly larger than those in group A, while at week 8, in group D, the BMP-2 gene-enhanced tissue-engineered bone had the largest bone area among the groups (P<0.05, ANOVA). In that group, a mature bone structure was detected in the center of the elevated space. Under a confocal microscope, green fluorescence in newly formed bone was observed for the EGFP group, which suggested that those implanted bMSCs might have contributed to the new bone formation. CONCLUSION: bMSCs modified with the AdBMP-2 gene can promote new bone formation and maturation in the rabbit maxillary sinus. BMP-2 regional gene therapy and a tissue engineering technique could be effectively used in maxillary sinus elevation and bone regeneration.
Subject(s)
Alveolar Bone Loss/surgery , Bone Morphogenetic Protein 2/pharmacology , Calcium Phosphates/pharmacology , Genetic Therapy/methods , Maxillary Sinus/surgery , Oral Surgical Procedures, Preprosthetic/methods , Stromal Cells/transplantation , Tissue Engineering , Adenoviridae , Alveolar Bone Loss/pathology , Alveolar Ridge Augmentation/methods , Analysis of Variance , Animals , Cell Differentiation , Cell Transplantation/methods , Cells, Cultured , Gene Transfer Techniques , Male , Microscopy, Fluorescence , RabbitsABSTRACT
Cemented total hip replacement has become a standard surgical technique to treat patients with osteoarthritis and osteonecrosis. The stem-cement interface experiences fretting wear in vivo due to low-amplitude oscillatory micromotion under physiological loading, and this wear is currently becoming important as a potential mechanism for the overall wear of cemented total hip replacements. However, the relative micromotion at the stem-cement interface has not been widely reported. In the present study, a new micromotion sensor is developed that is based on the deformation of a strain gauge, and this sensor is used to probe the migration of a polished Exeter stem within a Simplex P cement mantle through an in vitro wear simulation. It is demonstrated that the stem migration value generally increases with an increase in the number of loading cycles, with a gradual decrease of migration rate. Additionally, fretting wear is successfully replicated on the stem surface, and the micropores in the cement surface are considered to contribute to initiation and propagation of the fretting damage on the stem. This is confirmed by the observation that no evidence of fretting wear is detected on the stem where the surface is in contact with the pore-free areas on the cement. This study allows a deep insight into the micromotion at the stem-cement interface, and provides evidence highlighting the significance of the micropores in the cement surface in the generation of fretting wear on a polished femoral stem.
Subject(s)
Bone Cements , Cementation/methods , Femur/physiology , Femur/surgery , Hip Prosthesis , Adhesiveness , Equipment Failure Analysis , Motion , Prosthesis DesignABSTRACT
OBJECTIVE: The aim of this study was to investigate the effect of dexmedetomidine (DEX) on kidney injury in sepsis rats through the Toll-like receptor 4 (TLR4)/myeloid differential protein-88 (MyD88)/nuclear factor-κB (NF-κB)/inducible nitric oxide synthase (iNOS) signaling pathway. MATERIALS AND METHODS: A total of 30 Sprague-Dawley (SD) rats were randomly divided into three groups, including the control group (n=10), lipopolysaccharide (LPS)-induced acute kidney injury (AKI) group (model group, n=10) and DEX treatment group (DEX group, n=10). The model of sepsis was successfully established in rats. The levels of serum creatinine (Cr), blood urea nitrogen (BUN), serum interleukin-6 (IL-6), IL-1ß, IL-10 and tumor necrosis factor-α (TNF-α) were detected via enzyme-linked immunosorbent assay (ELISA). The pathological changes in kidney tissues were detected via hematoxylin-eosin (HE) staining. Furthermore, the mRNA and protein expressions of TLR4, MyD88, NF-κB, and iNOS in the kidney were detected via fluorescence quantitative Polymerase Chain Reaction (PCR) and Western blotting, respectively. RESULTS: Compared with the control group, rats in the model group showed significant kidney injury, markedly increased levels of serum Cr, BUN and pro-inflammatory cytokines, remarkably decreased the level of IL-10 (p<0.05), and significantly increased mRNA and protein expressions of TLR4, MyD88, NF-κB, and iNOS. In the DEX group, AKI was markedly improved, while the expressions of inflammatory cytokines were remarkably declined. Furthermore, the mRNA and protein expressions of TLR4, MyD88, NF-κB, and iNOS decreased significantly. CONCLUSIONS: DEX has a protective effect on LPS-induced AKI, whose mechanism may be related to the inhibition of the TLR4/MyD88/NF-κB/iNOS pathway.
Subject(s)
Acute Kidney Injury/drug therapy , Adrenergic alpha-2 Receptor Agonists/pharmacology , Dexmedetomidine/pharmacology , Sepsis/complications , Signal Transduction/drug effects , Acute Kidney Injury/immunology , Acute Kidney Injury/pathology , Administration, Oral , Adrenergic alpha-2 Receptor Agonists/therapeutic use , Animals , Dexmedetomidine/therapeutic use , Disease Models, Animal , Humans , Kidney/drug effects , Kidney/immunology , Kidney/pathology , Lipopolysaccharides/administration & dosage , Lipopolysaccharides/immunology , Male , Myeloid Differentiation Factor 88/metabolism , NF-kappa B/metabolism , Nitric Oxide Synthase Type II/metabolism , Rats , Sepsis/drug therapy , Sepsis/immunology , Signal Transduction/immunology , Specific Pathogen-Free Organisms , Toll-Like Receptor 4/metabolismABSTRACT
Bone homeostasis is continually maintained by the process of bone remodeling throughout life. Recent studies have demonstrated that Wnt signaling pathways play a fundamental role in the process of bone homeostasis and remodeling. Intracellular Wnt signaling cascades are initially triggered by a Wnt ligand-receptor complex formation. In previous studies, the blocking of Wnt ligands from different osteoblastic differentiation stages could cause defective bone development at an early stage. Osteocytes, the most abundant and long-lived type of bone cell, are a crucial orchestrator of bone remodeling. However, the role of Wnt ligands on osteocyte and bone remodeling remains unclear. In our present study, we found that, besides osteoblasts, osteocytes also express multiple Wnt ligands in the bone environment. Then, we used a Dmp1-Cre mouse line, in which there is expression in a subset of osteoblasts but mainly osteocytes, to study the function of Wnt ligands on osteocyte and bone remodeling in vivo. Furthermore, we explored the role of Wnt ligands on osteocytic mineralization ability, as well as the regulatory function of osteocytes on the process of osteoblastic differentiation and osteoclastic migration and maturity in vitro. We concluded that Wnt proteins play an important regulatory role in 1) the process of perilacunar/canalicular remodeling, as mediated by osteocytes, and 2) the balance of osteogenesis and bone resorption at the bone surface, as mediated by osteoblasts and osteoclasts, at least partly through the canonical Wnt/ß-catenin signaling pathway and the OPG/RANKL signaling pathway.
Subject(s)
Bone Remodeling , Bone Resorption , Osteocytes/cytology , Wnt Signaling Pathway , Animals , Ligands , MiceABSTRACT
Total joint replacement is one of the most common elective surgical procedures performed worldwide, with an estimate of 1.5x 10(6) operations performed annually. Currently joint replacements are expected to function for 10-15 years; however, with an increase in life expectancy, and a greater call for knee replacement due to increased activity levels, there is a requirement to improve their function to offer longer-term improved quality of life for patients. Wear analysis of total joint replacements has long been an important means in determining failure mechanisms and improving longevity of these devices. The effectiveness of the coordinate-measuring machine (CMM) technique for assessing volumetric material loss during simulated life testing of a replacement knee joint has been proved previously by the present authors. The purpose of the current work is to present an improvement to this method for situations where no pre-wear data are available. To validate the method, simulator tests were run and gravimetric measurements taken throughout the test, such that the components measured had a known wear value. The implications of the results are then discussed in terms of assessment of joint functionality and development of standardized CMM-based product standards. The method was then expanded to allow assessment of clinically retrieved bearings so as to ascertain a measure of true clinical wear.
Subject(s)
Equipment Failure Analysis/methods , Knee Joint/physiology , Knee Prosthesis , Models, Structural , Arthroplasty, Replacement, Knee , Evaluation Studies as Topic , Friction , Gravitation , Humans , Materials Testing/methods , Polyethylenes/chemistry , Polyethylenes/therapeutic use , Prosthesis Design/standards , Weight-Bearing , Weights and Measures/standardsABSTRACT
The great success of cemented total hip replacement to treat patients with endstage osteoarthritis and osteonecrosis has been well documented. However, its long-term survivorship has been compromised by progressive development of aseptic loosening, and few hip prostheses could survive beyond 25 years. Aseptic loosening is mainly attributed to bone resorption which is activated by an in-vivo macrophage response to particulate debris generated by wear of the hip prosthesis. Theoretically, wear can occur not only at the articulating head-cup interface but also at other load-bearing surfaces, such as the stem-cement interface. Recently, great progress has been made in reducing wear at the head-cup interface through the introduction of new materials and improved manufacture; consequently femoral stem wear is considered to be playing an increasingly significant role in the overall wear of cemented total hip replacement. In this review article, the clinical incidences of femoral stem wear are comprehensively introduced, and its significance is highlighted as a source of generation of wear debris and corrosion products. Additionally, the relationship between femoral stem surface finish and femoral stem wear is discussed and the primary attempts to reproduce femoral stem wear through in-vitro wear testing are summarized. Furthermore, the initiation and propagation processes of femoral stem wear are also proposed and a better understanding of the issue is considered to be essential to reduce femoral stem wear and to improve the functionality of cemented total hip replacement.
Subject(s)
Arthroplasty, Replacement, Hip/instrumentation , Arthroplasty, Replacement, Hip/methods , Cementation/methods , Equipment Failure Analysis/methods , Hip Prosthesis , Prosthesis Failure , Femur Head , Humans , Materials Testing , Prosthesis Design , Surface Properties , Tensile StrengthABSTRACT
The treatment of large jaw bone defects remains an urgent clinical problem to be solved. With the development of biomaterials, stem cells and bone tissue engineering, new ideas and hopes for the regeneration of jaw have been offered. In addition to meeting the basic requirements of bone repair materials, scaffolds for the regeneration of large jaw bones require the ability of stem cells to participate in bone regeneration. Methods like optimization of scaffolds composition, design of porous structure and combination of gel and microsphere technology can enhance stem cell delivery in vivo, and the osteogenic differentiation of stem cells can be stimulated through controlled release of drugs, preparation of surface micron/nano topography and modifications of ionic components. Moreover, application of three-dimensional printing and channel structure in large-scale scaffolds fabrication present promising strategies for customized, accurate bone reconstruction and vascularization. It is only through synergistic optimization in all aspects that it is possible to obtain scaffold materials suitable for regeneration of large jaw bones. This article focuses on biological materials regulation, stem cell delivery, survival and differentiation, and their role in bone regeneration.