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Background: Ankylosing spondylitis (AS) is a chronic inflammatory disease affecting the spine and sacroiliac joints. Recent genetic studies suggest certain plasma proteins may play a causal role in AS development. This study aims to identify and characterize these proteins using Mendelian randomization (MR) and colocalization analyses. Methods: Plasma protein data were obtained from recent publications in Nature Genetics, integrating data from five previous GWAS datasets, including 738 cis-pQTLs for 734 plasma proteins. GWAS summary data for AS were sourced from IGAS and other European cohorts. MR analyses were conducted using "TwoSampleMR" to assess causal links between plasma protein levels and AS. Colocalization analysis was performed with the coloc R package to identify shared genetic variants. Sensitivity analyses and protein-protein interaction (PPI) network analyses were conducted to validate findings and explore therapeutic targets. We performed Phenome-wide association study (PheWAS) to examine the potential side effects of drug protein on AS treatment. Results: After FDR correction, eight significant proteins were identified: IL7R, TYMP, IL12B, CCL8, TNFAIP6, IL18R1, IL23R, and ERAP1. Elevated levels of IL7R, IL12B, CCL8, IL18R1, IL23R, and ERAP1 increased AS risk, whereas elevated TYMP and TNFAIP6 levels decreased AS risk. Colocalization analysis indicated that IL23R, IL7R, and TYMP likely share causal variants with AS. PPI network analysis identified IL23R and IL7R as potential new therapeutic targets. Conclusions: This study identified eight plasma proteins with significant associations with AS risk, suggesting IL23R, IL7R, and TYMP as promising therapeutic targets. Further research is needed to explore underlying mechanisms and potential for drug repurposing.
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Biomarcadores , Proteínas Sanguíneas , Estudio de Asociación del Genoma Completo , Análisis de la Aleatorización Mendeliana , Espondilitis Anquilosante , Espondilitis Anquilosante/sangre , Espondilitis Anquilosante/tratamiento farmacológico , Espondilitis Anquilosante/genética , Espondilitis Anquilosante/diagnóstico , Humanos , Biomarcadores/sangre , Proteínas Sanguíneas/metabolismo , Proteínas Sanguíneas/genética , Mapas de Interacción de Proteínas , Polimorfismo de Nucleótido Simple , Predisposición Genética a la Enfermedad , Sitios de Carácter CuantitativoRESUMEN
Recent studies have suggested that ferroptosis participates in various renal diseases. However, its effect on focal segmental glomerulosclerosis remains unclear. This study analyzed the GSE125779 and GSE121211 datasets to identify the differentially expressed genes (DEGs) in renal tubular samples with and without FSGS. The Cytoscape was used to construct the protein-protein interaction network. Moreover, the ferroptosis-related genes (FRGs) were obtained from the ferroptosis database, while ferroptosis-related DEGs were obtained by intersection with DEGs. The target genes were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. The GSE108112 dataset was used to verify the expression of target FRGs. Besides, we built the mRNA-miRNA network regarding FRGs using the NetworkAnalyst database, and circRNAs corresponding to key miRNAs were predicted in the ENCORI database. In this study, 16 ferroptosis-related DEGs were identified between FSGS and healthy subjects, while five co-expressed genes were obtained by three topological algorithms in Cytoscape. These included the most concerned Hub genes JUN, HIF1A, ALB, DUSP1 and ATF3. The KEGG enrichment analysis indicated that FRGs were associated with mitophagy, renal cell carcinoma, and metabolic pathways. Simultaneously, the co-expressed hub genes were analyzed to construct the mRNA-miRNA interaction network and important miRNAs such as hsa-mir-155-5p, hsa-mir-1-3p, and hsa-mir-124-3p were obtained. Finally, 75 drugs targeting 54 important circRNAs and FRGs were predicted. This study identified the Hub FRGs and transcriptomic molecules from FSGS in renal tubules, thus providing novel diagnostic and therapeutic targets for FSGS.
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Ferroptosis , Glomeruloesclerosis Focal y Segmentaria , Túbulos Renales , MicroARNs , Humanos , Ferroptosis/genética , Genes vif , Glomeruloesclerosis Focal y Segmentaria/genética , Glomeruloesclerosis Focal y Segmentaria/terapia , MicroARNs/genética , ARN Circular , ARN MensajeroRESUMEN
The optimal surgical approach and placement of plates for the treatment of distal third diaphyseal fracture of the humerus are the subjects of debate. The aim of this retrospective study was to evaluate the clinical and radiographic outcomes of modified medial minimally invasive plate osteosynthesis (MIPO) techniques using a double technique for the treatment of distal third diaphyseal fracture of the humerus. A total of 30 patients with a distal third diaphyseal fracture of the humerus were selected from our hospital. Patients were seen between January 2017 and October 2022. They were treated with a modified medial approach combined with MIPO using a double plate technique. Patient demographics, operation time, bleeding volume, union time, complications, the mean fracture length (FL) and distal cortical length (DCL), and the number of screws in the distal fragment were analyzed. The function of the shoulder and elbow was evaluated using Neer's assessment of the shoulder and Mayo's assessment of the elbow. The FL was 56.1 ± 7.2 mm and the DCL was 38.3 ± 5.3 mm. The mean operative time was 84.8 ± 13.4 min (range 60-110 min). The mean blood loss during surgical treatment was 46.5 ± 10.2 ml (range 30-60 ml). Bone healing was observed in all patients from 10 to 16 weeks (average 12.1 ± 1.7) postoperatively, and one case with poor surgical wound healing was recorded. All the patients had good function of both the shoulder and elbow. The maximum flexibility of the elbow ranged from 130° to 145° (average 138.1 ± 4.8°), with a maximum flexibility straightness ranging from 0° to 5° (average 2.2 ± 1.3°). The Mayo elbow joint function score was 80-100 (average 91.4 ± 5.0). The Neer shoulder joint function score ranged from 85 to 100 (average 92.5 ± 3.9). The modified medial approach was beneficial it did not cause any iatrogenic radial nerve or ulnar nerve injuries. The anterior and the medial side plates are fixed perpendicular to the distal humerus and provide excellent stability at the same time producing better shoulder and elbow joint function.
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Fracturas del Húmero , Humanos , Fracturas del Húmero/diagnóstico por imagen , Fracturas del Húmero/cirugía , Estudios Retrospectivos , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Húmero , Fijación Interna de Fracturas/métodos , Resultado del TratamientoRESUMEN
OBJECTIVE: Systemic lupus erythematosus (SLE) patients are at risk during the COVID-19 pandemic, yet the underlying molecular mechanisms remain incompletely understood. This study sought to analyze the potential molecular connections between COVID-19 and SLE, employing a bioinformatics approach to identify effective drugs for both conditions. METHODS: The data sets GSE100163 and GSE183071 were utilized to determine share differentially expressed genes (DEGs). These DEGs were later analyzed by various bioinformatic methods, including functional enrichment, protein-protein interaction (PPI) network analysis, regulatory network construction, and gene-drug interaction construction. RESULTS: A total of 50 common DEGs were found between COVID-19 and SLE. Gene ontology (GO) functional annotation revealed that "immune response," "innate immune response," "plasma membrane," and "protein binding" were most enriched in. Additionally, the pathways that were enriched include "Th1 and Th2 cell differentiation." The study identified 48 genes/nodes enriched with 292 edges in the PPI network, of which the top 10 hub genes were CD4, IL7R, CD3E, CD5, CD247, KLRB1, CD40LG, CD7, CR2, and GZMK. Furthermore, the study found 48 transcription factors and 8 microRNAs regulating these hub genes. Finally, four drugs namely ibalizumab (targeted to CD4), blinatumomab (targeted to CD3E), muromonab-CD3 (targeted to CD3E), and catumaxomab (targeted to CD3E) were found in gene-drug interaction. CONCLUSION: Four possible drugs that targeted two specific genes, which may be beneficial for COVID-19 patients with SLE.
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COVID-19 , Lupus Eritematoso Sistémico , MicroARNs , Humanos , Pandemias , COVID-19/genética , MicroARNs/genética , Biología Computacional/métodos , Lupus Eritematoso Sistémico/tratamiento farmacológico , Lupus Eritematoso Sistémico/genéticaRESUMEN
Objective: To investigate the risk factors associated with lower extremity deep vein thrombosis (LEDVT) and to establish a predictive model for patients who undergo gynecologic laparoscopic surgery. Methods: A review of clinical data was conducted on patients who underwent gynecologic laparoscopic surgery between November 1, 2020, and January 31, 2022. Patients who developed LEDVT after surgery were included as the observation group, while the control group comprised patients who did not experience complications. Multivariate forward stepwise logistic regression models were used to identify independent risk factors associated with LEDVT. A nomogram model was then developed based on these risk factors. Results: A total of 659 patients underwent gynecologic laparoscopic surgery during the study period, and 52 (7.89%) of these patients developed postoperative LEDVT. Multivariate logistic regression analysis showed that older age (adjusted OR, 1.085; 95% CI [1.034-1.138]; P < 0.05), longer operation duration (adjusted OR, 1.014; 95% CI [1.009-1.020]; P < 0.05), shorter activated partial thromboplastin time (APTT) (adjusted OR, 0.749; 95% CI [0.635-0.884]; P < 0.05), higher D-dimer (adjusted OR, 4.929; 95% CI [2.369-10.255]; P < 0.05), higher Human Epididymis Protein 4 (HE4) (adjusted OR, 1.007; 95% CI [1.001-1.012]; P < 0.05), and history of hypertension (adjusted OR, 3.732; 95% CI [1.405-9.915]; P < 0.05) were all independent risk factors for LEDVT in patients who underwent gynecologic laparoscopic surgery. A nomogram model was then created, which had an area under the curve of 0.927 (95% CI [0.893-0.961]; P < 0.05), a sensitivity of 96.1%, and a specificity of 79.5%. Conclusions: A nomogram model that incorporates information on age, operation duration, APTT, D-dimer, history of hypertension, and HE4 could effectively predict the risk of LEDVT in patients undergoing gynecologic laparoscopic surgery, potentially helping to prevent the development of this complication.
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Hipertensión , Laparoscopía , Femenino , Humanos , Laparoscopía/efectos adversos , Extremidad Inferior , Nomogramas , Estudios RetrospectivosRESUMEN
Immune dysregulation is not only a pathogenic mechanism in systemic lupus erythematosus (SLE) but also a potential cause of the link between SLE and cancer. The current understanding of SLE monocyte-associated biomarkers is limited, and the precise mechanism behind the link between SLE and cancer is uncertain. By using WGCNA and immune infiltration to analyze the GSE72326 dataset, we determined the most pertinent modules for monocytes and discovered eight candidate hub genes from them. The limma software was used to find genes that were differently expressed in SLE. The genes that overlapped between the two were chosen using a Venn diagram as the essential genes related to monocytes in SLE, and the essential genes were verified by several datasets. Correlation analysis and GSEA analysis were used to examine the probable immunological pathways connected to key genes. We examined the expression of hub genes in cancer and their interaction with monocytes using the GEPIA and TIMER databases to understand the significance of essential genes in tumorigenesis. In addition, we performed transcription factor identification. We discovered three biomarkers (IFI30, BLVRA, and RIN2) that are mostly involved in interferon-related signaling pathways and are associated with monocyte-mediated immune responses in SLE. The three important genes are also strongly expressed in a number of malignancies and have a relationship with monocytes. As a result, IFI30, BLVRA, and RIN2 may act as SLE-associated biomarkers of monocytes and as a bridge between SLE and tumors. We proposed that interferon-related signaling pathways might function as possible mediators of cancer risk in SLE.
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Lupus Eritematoso Sistémico , Neoplasias , Humanos , Monocitos , Lupus Eritematoso Sistémico/complicaciones , Biomarcadores/metabolismo , Neoplasias/genética , Neoplasias/complicaciones , Interferones , Proteínas Portadoras/metabolismo , Factores de Intercambio de Guanina Nucleótido/metabolismoRESUMEN
Desiccation is a stressful situation that decapods often experience during live transportation. This study investigated the effects of low-temperature aerial exposures (LTAEs) (dry exposure (DL) and moist exposure (ML) at 6 °C) and re-immersion on the antioxidative and immune responses and hepatopancreatic histopathology in P. clarkii. Compared to the control group (normally feeding at 24.0 °C water temperature), the crayfish under LTAEs showed overall severe hepatopancreatic oxidative damage, with significantly increased malondialdehyde (MDA) contents and significantly reduced total antioxidant capacity (T-AOC), and oxidant damage was not fully recovered even after 12 h of re-immersion; the expression of hsp70 was significantly increased within 24-48 h of stress and re-immersion. The activity of hemolymphatic acid phosphatase (ACP) was significantly increased during 24-48 h of the stress and at 12 h of re-immersion; the activity of aspartic aminotransferase (AST) and alanine aminotransferase (ALT) was significantly increased throughout the experiment; and the gene expression of proPO or TLR was significantly increased during 12-48 h of the stress. Severe histopathological changes (lumen dilatation, vacuolation of epithelial cells and reduced cell numbers) were observed in hepatopancreas at 48 h of stress and 12 h of re-immersion. These results indicated that 48 h of low-temperature aerial exposure stress stimulated the non-specific immunity but adversely affected the antioxidation and hepatopancreatic histomorphology of P. clarkii, whereas 12 h of re-immersion was not sufficient to restore crayfish from stress to a normal state.
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Antioxidantes , Astacoidea , Animales , Antioxidantes/metabolismo , Astacoidea/fisiología , Temperatura , Estrés Oxidativo , Frío , Inmunidad InnataRESUMEN
Recent studies have demonstrated the close relationship between parathyroid adenoma (PA) and thyroid follicular adenoma (FTA). However, the underlying pathogenesis remains unknown. This study focused on exploring common pathogenic genes, as well as the pathogenesis of these two diseases, through bioinformatics methods. This work obtained PA and FTA datasets from the Integrated Gene Expression Database to identify the common differentially expressed genes (DEGs) of two diseases. The functions of the genes were investigated by GO and KEGG enrichment. The program CytoHubba was used to select the hub genes, while receiver operating characteristic curves were plotted to evaluate the predictive significance of the hub genes. The DGIbd database was used to identify gene-targeted drugs. This work detected a total of 77 DEGs. Enrichment analysis demonstrated that DEGs had activities of 3',5'-cyclic AMP, and nucleotide phosphodiesterases and were associated with cell proliferation. NOS1, VWF, TGFBR2, CAV1, and MAPK1 were identified as hub genes after verification. The area under the curve of PA and FTA was>0.7, and the hub genes participated in the Relaxin Signaling Pathway, focal adhesion, and other pathways. The construction of the mRNA-miRNA interaction network yielded 11 important miRNAs, while gene-targeting drug prediction identified four targeted drugs with possible effects. This bioinformatics study demonstrated that cell proliferation and tumor suppression and the hub genes co-occurring in PA and FTA, have important effects on the occurrence and progression of two diseases, which make them potential diagnostic biomarkers and therapeutic targets.
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MicroARNs , Neoplasias de las Paratiroides , Neoplasias de la Tiroides , Humanos , Neoplasias de las Paratiroides/diagnóstico , Neoplasias de las Paratiroides/genética , Proliferación Celular , AMP Cíclico , Bases de Datos Factuales , Perfilación de la Expresión GénicaRESUMEN
This study investigated the effects of air temperature and ventilation on the sleep quality of elderly subjects and elucidated the mechanisms involved. Sixteen subjects aged over 65 years old were exposed to four conditions in a 2 × 2 design: air temperatures of 27°C and 30°C (with a ceiling fan in operation at 30°C) and two ventilation conditions (with and without mechanical ventilation) in experimental bedrooms. Their electroencephalogram, electrooculogram, chin electromyogram, electrocardiogram, respiration, oxygen saturation, and wrist skin temperature were measured continuously during sleep. Saliva samples were collected, and blood pressure was measured both before and after sleep. The results showed that at the temperature of 30°C, the total sleep time, sleep efficiency, and duration of REM sleep of the elderly decreased by 26.3 min, 5.5%, and 5.3 min, respectively, and time awake increased by 27.0 min, in comparison with 27°C, indicating that the sleep quality of the elderly is very vulnerable to heat exposure. Even a small heat load led to an overactive sympathetic nervous system and increased wrist skin temperature, which reduced sleep quality. Improving the ventilation increased the duration of deep sleep and REM sleep by 10.3 min and 3.7 min, respectively. Higher pollutant concentrations affected the respiration and autonomous nervous systems to reduce sleep quality. The benefits of improved thermal environment and ventilation on sleep quality were found to be additive. Good ventilation and the avoidance of raised temperatures in the bedroom are thus both important for the sleep quality of the elderly.
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Contaminación del Aire Interior , Calidad del Sueño , Anciano , Humanos , Temperatura , Respiración , Sueño/fisiologíaRESUMEN
Traditional Chinese medicine for invigorating the kidney and promoting blood circulation is commonly prescribed for the treatment of osteoarthritis associated with kidney deficiency and blood stasis. However, the specific mechanisms of these medicines are still unclear. The present study aimed to evaluate the protective effects of Bugu granules against sodium nitroprusside-induced chondrocyte apoptosis and elucidate the underlying molecular mechanisms. Drug-containing serum was prepared by administering rats with Bugu granules and harvesting the serum. Chondrocytes were exposed to different dilutions of serum, and apoptosis assessed by flow cytometry after staining with annexin VFITC/PI. Flow cytometry showed that chondrocyte apoptosis increased significantly after incubation with 2â¯mol/L sodium nitroprusside for 24â¯h (tâ¯= -48.221, Pâ¯= 0.000), and the apoptotic rate of chondrocytes decreased with increasing concentrations of drug-containing serum (Fâ¯= 33.965, Pâ¯= 0.000). Cellular levels of Trx2, ASK1, caspase3, and reactive oxygen species (ROS) were detected by enzyme-linked immunosorbent assay. The cellular content of Trx2 increased gradually with increasing concentrations of drug-containing serum (Fâ¯= 2610.593, Pâ¯= 0.000), while that of ASK1 (Fâ¯= 2473.545, Pâ¯= 0.000), caspase3 (Fâ¯= 209.921, Pâ¯= 0.000), and ROS (Fâ¯= 1666.435, Pâ¯= 0.000) all decreased significantly. The mRNA expression levels were analyzed by RT-qPCR, which revealed that expression levels of Trx2 and caspase3 mRNA increased and decreased significantly, respectively, following exposure to Bugu granules in the drug-containing serum (Fâ¯= 6.974, Pâ¯= 0.003 and Fâ¯= 3.691, Pâ¯= 0.191; respectively), but the expression of ASK1 mRNA was not significantly different between treatment groups (Fâ¯= 1.784, Pâ¯= 0.191). Taken together, these results support the hypothesis that the Trx2 signaling pathway is activated by Bugu granules, which in turn inhibits chondrocyte apoptosis. This may play a role in preventing the development of osteoarthritis.
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Condrocitos , Medicamentos Herbarios Chinos/farmacología , Osteoartritis , Animales , Apoptosis/efectos de los fármacos , Células Cultivadas , Condrocitos/efectos de los fármacos , Ratas , Transducción de SeñalRESUMEN
The effect of elevated airflow on sleep quality was investigated with 18 elderly. Three airflow conditions were set: ceiling fan/30°C/max.0.8 m/s and mean 0.7 m/s, task fan/30°C/max.0.8 m/s and mean 0.6 m/s, and thermally neutral /27°C/0.2 m/s. Sleep quality was evaluated objectively by analysis of electroencephalogram signals that were continuously monitored during the sleeping period. Urinary cortisol concentrations were analyzed to measure the activity of sympathetic nervous system. No significant difference in sleep quality, thermal comfort, or cortisol concentration was found between the ceiling fan and the neutral condition. The duration of total sleep time decreased by 35 minutes, the duration of REM sleep decreased by 15 minutes, and the cortisol concentration in the morning increased by 50 ng/mL in the task fan than the other two conditions. Compared with ceiling fan, less heat load was removed in the task fan condition, possibly due to the lower air speed. This study shows that even small heat load led to reduced sleep quality and overactive sympathetic nervous system of the elderly. By supplying an airflow of 0.8 m/s evenly over the human body, the elderly could maintain sleep quality and thermal comfort at an air temperature that was 3 K higher than the neutral temperature.
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Aire Acondicionado/métodos , Calor/efectos adversos , Trastornos del Inicio y del Mantenimiento del Sueño/prevención & control , Sueño/fisiología , Anciano , Temperatura Corporal , Femenino , Humanos , Hidrocortisona/orina , Masculino , Polisomnografía , Fenómenos Fisiológicos Respiratorios , Trastornos del Inicio y del Mantenimiento del Sueño/etiología , Trastornos del Inicio y del Mantenimiento del Sueño/orina , Factores de TiempoRESUMEN
BACKGROUND: Tibiofibular syndesmosis injury leads to ankle pain and dysfunction when ankle injuries are not treated properly. Despite several studies having been performed, many questions about diagnosis and treatment remain unanswered, especially in ankle syndesmosis injury with interosseous membrane injury. Therefore, the purpose of this study was to help guide best practice recommendations. METHODS: This review explores the mechanism of injury, clinical features, diagnosis methods, and the treatment strategy for ankle syndesmosis injury with interosseous membrane injury to highlight the current evidence in terms of the controversies surrounding the management of these injuries. RESULTS: Radiological and CT examination are an important basis for diagnosing ankle syndesmosis injury. Physical examination combined with MRI to determine the damage to the interosseous membrane is significant in guiding the treatment of ankle syndesmosis injury with interosseous membrane injury. In the past, inserting syndesmosis screws was the gold standard for treating ankle syndesmosis injury. However, there were increasingly more controversies regarding loss of reduction and broken nails, so elastic fixation has become more popular in recent years. CONCLUSIONS: Anatomical reduction and effective fixation are the main aspects to be considered in the treatment of ankle syndesmosis injury with interosseous membrane injury and are the key to reducing postsurgery complications.
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Traumatismos del Tobillo/diagnóstico por imagen , Traumatismos del Tobillo/cirugía , Fijación Interna de Fracturas/efectos adversos , Membrana Interósea/lesiones , Membrana Interósea/cirugía , Adulto , Fracturas de Tobillo/complicaciones , Fracturas de Tobillo/diagnóstico por imagen , Fracturas de Tobillo/cirugía , Traumatismos del Tobillo/complicaciones , Peroné/diagnóstico por imagen , Peroné/lesiones , Peroné/cirugía , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Fracturas Óseas/diagnóstico por imagen , Fracturas Óseas/cirugía , Humanos , Masculino , Guías de Práctica Clínica como Asunto , Traumatismos de los Tejidos Blandos/complicaciones , Traumatismos de los Tejidos Blandos/diagnóstico por imagen , Traumatismos de los Tejidos Blandos/cirugía , Tibia/diagnóstico por imagen , Tibia/lesiones , Tibia/cirugíaRESUMEN
PURPOSE: Postoperative knee flexion protocol has been widely recognized as a highly attractive, simple, and cost-effective tactic to improve patient's outcomes after primary total knee arthroplasty (TKA). However, optimal knee position and duration of knee flexion are still controversial. The purpose of this meta-analysis was to compare the effectiveness of different postoperative knee flexion protocols, as an aid to find out optimal limb management strategy following TKA. METHODS: We conducted a meta-analysis to identify the available and relevant randomized controlled trials (RCTs) with regard to the influence of different postoperative knee positions on clinical outcomes after primary TKA in electronic databases, including PubMed, EMBASE, the Cochrane Library, Web of Science, CNKI, Wanfang Med Online, and VIP, up to May 2018. In this meta-analysis, three major subgroups based on diverse postoperative knee flexion protocols were considered: long-term (≥ 24 h) high flexion (> 30°), short term (< 24 h) high flexion (> 30°), and long-term (≥ 24 h) mild flexion (≤ 30°). The statistical analysis was performed using the Review Manager (RevMan) version 5.3 software. RESULTS: A total of 16 trials were finally included in this meta-analysis. The result of subgroup analysis indicated that keeping the knee in high flexion (> 30°) postoperatively for a long time (≥ 24 h) significantly reduced total blood loss (P < 0.00001), hidden blood loss (P < 0.00001), and transfusion requirements (P = 0.003) and led to a significant improvement in range of motion (ROM) at 1 week after operation (P < 0.00001); keeping the knee in high flexion (> 30°) postoperatively for a short time (< 24 h) significantly reduced total blood loss (P = 0.006) and hidden blood loss (P < 0.00001) but not significantly improved ROM at 1 week after operation (P = 0.34) and reduced transfusion requirements (P = 0.62); and keeping the knee in mild flexion (≤ 30°) postoperatively for a long time (≥ 24 h) significantly reduced total blood loss (P = 0.02) and transfusion requirements (P = 0.02) and improved ROM at 1 week after operation (P < 0.00001) but not significantly reduced hidden blood loss (P = 0.11). Furthermore, there was no significant difference with respect to the rates of wound-related infection and DVT between the three knee flexion subgroups. CONCLUSIONS: This meta-analysis showed that the long-term (≥ 24 h) high flexion (> 30°) protocol could be an optimal limb management to reduce blood loss and blood transfusion requirements and facilitate early postoperative rehabilitation exercises in patients after primary TKA without increasing in complication rate.
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Artroplastia de Reemplazo de Rodilla/rehabilitación , Posicionamiento del Paciente/métodos , Cuidados Posoperatorios/métodos , Transfusión Sanguínea/estadística & datos numéricos , Humanos , Articulación de la Rodilla/fisiopatología , Hemorragia Posoperatoria/prevención & control , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Rango del Movimiento ArticularRESUMEN
Rett syndrome is a severe neurodevelopmental disorder. It is caused by a mutation in methyl-CpG binding protein 2 (MecP2), a transcriptional regulator that recruits protein complexes involved in histone modification and chromatin remodeling. However, the role of Mecp2 in Rett syndrome remains unclear. In this study, we investigated the function of Mecp2 in neuronal development using zebrafish embryos. Mecp2 expression was detected ubiquitously in the central nervous system and muscles at 28 h postfertilization (hpf). We injected an antisense morpholino oligonucleotide (AMO) to induce Mecp2 knockdown phenotype. In mecp2 morphants (embryos with Mecp2 knockdown by AMO) at 28 and 72 hpf, we found an increase in abnormal axonal branches of caudal primary motor neurons and a decrease in motor activity. In mecp2 morphants at 24 hpf, we observed an increase in the expression of an mecp2 downstream candidate gene, brain derived neurotrophic factor (bdnf). In mecp2 morphants at 72 hpf, the presynaptic area stained by an anti-SV2 antibody was increased at the neuromuscular junction (NMJ). Interestingly, the size of SV2-positive presynaptic area at the NMJ was also increased following bdnf mRNA injection, while it was normalized in a double knockdown of mecp2 and bdnf. These results imply that Mecp2 is an important functional regulator of bdnf gene expression during neural circuit formation in zebrafish embryo. © 2017 Wiley Periodicals, Inc. Develop Neurobiol 77: 1101-1113, 2017.
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Regulación del Desarrollo de la Expresión Génica/fisiología , Proteína 2 de Unión a Metil-CpG/metabolismo , Neuronas Motoras/citología , Unión Neuromuscular/metabolismo , Proyección Neuronal/fisiología , Factores de Edad , Animales , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Diferenciación Celular , Embrión no Mamífero , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Larva , Proteína 2 de Unión a Metil-CpG/genética , Actividad Motora/efectos de los fármacos , Actividad Motora/fisiología , Neuronas Motoras/efectos de los fármacos , Unión Neuromuscular/efectos de los fármacos , Proyección Neuronal/efectos de los fármacos , Oligonucleótidos Antisentido/farmacología , Estimulación Física , Terminales Presinápticos/efectos de los fármacos , Terminales Presinápticos/fisiología , ARN Mensajero/metabolismo , ARN Mensajero/farmacología , Tubulina (Proteína)/metabolismo , Pez CebraRESUMEN
The pH-sensitive hydrogels composed of sodium caseinate (SC) and N,O-carboxymethyl chitosan (NOCC) were prepared and a new method to characterize the gelation process was presented in this work. Reological tests suggested that RSC/NOCC=3/7 (the weight ratio of SC and NOCC) was the best ratio of hydrogel. The well-developed three-dimensional network structures in the hydrogel were confirmed by AFM. Two structural parameters, tIS and tCS, denoted as the initial and critical structure formation time, respectively, were used to provide an exact determination of the start of structure formation and description of gelation process. The gelation process strongly depended on temperature changes, a high temperature resulted in an early start of gelation. The non-kinetic model suggested the higher activation energy in the higher temperatures was disadvantageous to structure formation, and vice versa. Due to the smart gel reported here was very stable at room temperature, we believed that the gel is required for applications in drug delivery or could be exploited in the development of potential application as molecular switches in the future.
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Caseínas/química , Quitosano/química , Hidrogeles/química , Portadores de Fármacos , Concentración de Iones de Hidrógeno , Microscopía de Fuerza Atómica , Transición de Fase , Reología , Propiedades de Superficie , Temperatura , TermodinámicaRESUMEN
PURPOSE: To investigate the treatment of acetabular anterior column fractures using a two-incision minimally invasive (TIMI) approach and minimally invasive plate osteosynthesis (MIPO) technique using a preshaped 3D plate. METHODS: A group of 12 consecutive cases of acetabular fractures from March 2013 to July 2014 were treated with the TIMI approach. 3D mirror models of the uninjured side of the hemipelvis were printed preoperatively; the plates used in surgery were preshaped according to these models. MIPO surgical techniques were applied. All patients had a minimum one year radiographic and clinical follow-up. RESULTS: Seven fractures involved the anterior column, four were anterior column with posterior hemitransverse, and one was anterior column with the pubic symphysis. The average surgery time was 200 minutes, and mean blood loss was 1004 ml. The fracture reduction results as assessed by Matta radiographic outcome scores were good in eight, satisfactory in three, and poor in one patient. Functional outcomes according to the Harris hip scores were excellent for seven, good for three, and fair for two. Post-operative complications included incomplete femoral nerve damage and abdominal cavity injury. CONCLUSIONS: The TIMI approach is an alternative to the ilioinguinal approach for anterior column acetabular fracture treatment, especially for fractures involving the dome and quadrilateral plate that are feasible for application of MIPO techniques. The technique of preshaping the 3D plate makes the plate better accommodated to the fracture surface and easier to apply in MIPO procedures. All dissection was between the anatomical interval, which allowed less soft tissue injury and related complications, and caused less bleeding. The fracture types in our case series were relatively simple, and follow-up time was short; more clinical trials are necessary for evaluation of middle- and late-term results.
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Acetábulo/cirugía , Fijación Interna de Fracturas/métodos , Fracturas Óseas/cirugía , Acetábulo/lesiones , Adulto , Anciano , Placas Óseas , Disección , Femenino , Fijación Interna de Fracturas/instrumentación , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Mínimamente Invasivos , Impresión Tridimensional , Sínfisis Pubiana/cirugíaRESUMEN
To investigate the association of serum semaphorin 4D (Sema4D) levels with lumbar spine bone mineral density (BMD) and bone turnover markers in patients with postmenopausal osteoporosis (PO). Lumbar spine BMD was measured by dual-energy X-ray absorptiometry in 257 PO patients (aged from 50 to 75) and 90 healthy controls (aged from 51 to 83). Serum Sema4D, BAP, BGP and TRACP-5b levels were measured by enzyme linked immunosorbent assay. Serum cross linked N-telopeptides of type I (NTX), 25-hydroxyvitamin D (25(OH)D) and N-mid fragment of osteocalcin (N-MID-OT) levels were measured using automated electrochemiluminescence system. Sema4D level was significantly higher in PO women compared to healthy controls (1.40±0.33 vs. 0.58±0.18 µg/L, P=0.006). Sema4D level was positively correlated with serumTRACP-5b and NTX levels and negatively correlated with lumbar spine BMD and serum BAP and BGP levels. There were no correlations between Sema4D level and age, body mass index, and serum 25(OH)D and N-MID-OT levels. Lumbar spine BMD (ß=-0.354, P<0.001) and serum BAP level (ß=0.127, P=0.019) were independent predictors of serum Sema4D level in PO patients. Sema4D may be involved in the pathogenesis of PO and play a critical role in bone formation and resorption. Sema4D may represent a novel therapeutic target for treatment of PO and function as a predictive indicator of PO.
RESUMEN
OBJECTIVE: To investigate the outcomes of treating middle-up part long-segment fractures of the femur by long proximal femoral nail antirotation (PFNA-long). METHODS: From June 2006 to December 2013, 139 cases (35 women, 104 men; mean age 48.8, range, 18-86 years) of long-segment femoral fracture in middle-up part were treated with long proximal femoral nail antirotation (PFNA, 320-380 mm) by minimally invasive percutaneous fixation and autogenous iliac bone graft. Fifty-eight cases were graded as type IA long-segment femoral fractures (41.73%), 25 type IB (17.99%), four type IC (2.88%), 28 type II (20.14%), 12 type IIIA (8.63%), five type IIIB (3.60%), and seven type IV (5.04%). Clinical efficacy was evaluated with Harris hip function scores and postoperative pain with visual analogue scale. RESULTS: The operative time was 35-90 min (mean, 45 min) and mean intraoperative blood loss 78.6 mL (range 30-200 mL). Most patients were walking with assistance 4-10 days postoperatively. All patients were followed up for 3-37 months (mean, 19 months). There were no serious complications. All fractures healed after 2.8-6.8 months (mean, 3.9 months). According to Harris criteria, the clinical results were excellent in 108 patients, good in 22, fair in eight and poor in one. Ninety-three cases had no pain, 33 mild pain, 13 moderate pain and 25 occasionally needed non-steroidal analgesics. CONCLUSION: Closed reduction or limited open reduction with PFNA-long is an effective treatment for long-segment femoral fracture in middle-up part, with good strength in fixation, high rate of fracture union, early functional recovery and low rate of complications.