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Osteoarthritis (OA) is one of the most prevalent chronic musculoskeletal diseases among the elderly population. In this study, macrophage-derived exosomes were isolated and identified. Exosomes were subjected to microRNA (miRNA) sequencing and bioinformatic analysis, and differentially expressed miRNAs were verified. miR-26b-5p target genes were confirmed through target-site mutation combined with a dual-luciferase reporter assay. The effects of miR-26b-5p on macrophage polarization and chondrocyte hypertrophy were assessed in vitro. miR-26b-5p agomir was applied to mice with OA induced by anterior cruciate ligament transection (ACLT). The therapeutic effects of miR-26b-5p were evaluated via pain behavior experiments and histological observations. In vitro, miR-26b-5p repolarized M1 macrophages to an anti-inflammatory M2 type by targeting the TLR3 signaling pathway. miR-26b-5p could target COL10A1, further inhibiting chondrocyte hypertrophy induced by M1 macrophage-conditioned medium (M1-CM). In vivo, miR-26b-5p agomir ameliorated gait abnormalities and mechanical allodynia in OA mice. miR-26b-5p treatment attenuated synovitis and cartilage degeneration, thereby delaying OA progression. In conclusion, M2 macrophage-derived exosomal miR-26b-5p could protect articular cartilage and ameliorate gait abnormalities in OA mice by targeting TLR3 and COL10A1. miR-26b-5p further affected macrophage polarization and chondrocyte hypertrophy. Thus, this exosomal miR-26b-5p-based strategy might be a potential method for OA treatment.
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MicroRNAs , Osteoartrite , Idoso , Animais , Humanos , Camundongos , Condrócitos/metabolismo , Hipertrofia/metabolismo , Hipertrofia/patologia , Macrófagos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Osteoartrite/metabolismo , Receptor 3 Toll-Like/metabolismo , Colágeno Tipo X/genética , Colágeno Tipo X/metabolismo , Exossomos/genéticaRESUMO
We investigated the potential involvement of pyroptosis, a proinflammatory form of regulated cell death, in rheumatoid arthritis (RA). Synovial fluid, synovial tissues and/or serum were compared among 32 patients with RA, 46 patients with osteoarthritis (OA) and 30 healthy controls. Samples were assayed for interleukin (IL)-1ß, IL-18 and lactate hydrogenase (LDH). Synovial expression of NLRP3, caspase-1 and cleaved gasdermin D (GSDMD) was assayed using immunohistochemistry and multiplex immunohistochemistry. Patients with RA showed significantly higher levels of IL-1ß and IL-18 in synovial fluid than patients with OA, and significantly higher levels of both cytokines in serum than healthy controls. RA was associated with higher levels of LDH in synovial fluid than OA. Among patients with RA, levels of IL-1ß, IL-18 and LDH were significantly higher in synovial fluid than in serum, and the levels in synovial fluid positively correlated with disease activity and inflammation. Synovial cells, particularly macrophages, showed upregulation of NLRP3, caspase-1 and cleaved GSDMD in RA compared to OA. Our results implicate pyroptosis in the pathogenesis of RA, perhaps as a driver of local inflammation in joints.
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Artrite Reumatoide , Osteoartrite , Humanos , Interleucina-18/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Gasderminas , Caspase 1/metabolismo , Piroptose , Artrite Reumatoide/metabolismo , Osteoartrite/metabolismo , InflamaçãoRESUMO
BACKGROUND: Sepsis-induced acute kidney injury (AKI) is a common in clinic. Circular RNAs (circRNAs) play significant roles in ameliorating AKI. The purpose of this study was aimed to identify the role of circ_0074371 and the potential action mechanism in sepsis-induced AKI. METHODS: AKI patients and healthy individual serum samples were collected and the relative expression of circ_0074371 was measured by real-time polymerase chain reaction (RT-PCR). HK2 cells were treated with different dose (0, 2.5, 5 and 10 µg/ml) lipopolysaccharide (LPS) to establish the AKI cell model. The cell viability and apoptosis of HK2 cells were detected using cell counting kit-8 (CCK-8) and flow cytometry, respectively. The contents of malondialdehyde (MDA), and superoxide dismutase (SOD) were evaluated using the relative commercial kits. The IL-1ß and TNF-α levels in cell culture supernatants were measured by ELISA. The interaction relationship between miR-330-5p and circ_0074371 or ELK1 was predicted by Targetscan database and further confirmed by the dual-luciferase reporter assay system. RESULTS: The circ_0074371 expression was up-regulated in sepsis patients and LPS-induced HK2 cells. Silencing circ_0074371 promoted HK2 cells viability and inhibited the HK2 cells apoptosis. miR-330-5p inhibitor weakened circ_0074371 inhibitor-induced cell viability, apoptosis and oxidative stress. Further mechanism analysis showed that circ_0074371 acted as a sponge for miR-330-5p to increase ELK1 expression level. Importantly, miR-330-5p downregulation or ELK1 upregulation reversed the action of circ_0074371 knockdown on LPS-induced HK2 cells. CONCLUSION: Knockdown of circ_0074371 ameliorated LPS-induced HK2 cells apoptosis, inflammation and oxidative stress via regulating miR-330-5p/ELK1, opening a new window into the pathogenesis AKI.
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Injúria Renal Aguda , MicroRNAs , Sepse , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Proliferação de Células/fisiologia , Lipopolissacarídeos/toxicidade , Apoptose/genética , Injúria Renal Aguda/genética , Sepse/complicações , Sepse/genética , Proteínas Elk-1 do Domínio ets/genéticaRESUMO
BACKGROUND: Operative treatment has become the current trend for displaced intra-articular calcaneus fracture (DIACF), while using cannulated screw fixation or plate fixation is still controversial for treating DIACF. The purpose of this meta-analysis is to compare the outcome of the two fixation methods. METHODS: We searched literature comparing cannulated screw fixation and plate fixation from PubMed, Embase, Web of Science, and Cochrane Library. Only randomized controlled trials were included. The outcomes of post-operative function, radiological measurement, time efficiency, and wound complications were pooled in the meta-analysis. RESULT: Seven RCTs with 902 cases of DIACF were included. Pooled results showed the two fixation methods that had similar function satisfactory of AOFAS score (RR = 0.95, 95% CI = [0.83, 1.09], P = 0.47, I2 = 0%) and Maryland Foot score (RR = 0.93, 95% CI = [0.68, 1.28], P = 0.66, I2 = 84%). Compared to plate fixation, cannulated screw fixation had better improvement of Bohler's angle (WMD = 0.56, 95% CI = [0.20, 0.91], P = 0.002, I2 = 34%) and Gissane's angle (WMD = 1.36, 95% CI = [0.56, 2.16], P = 0.0008, I2 = 7%), better recovery of calcaneal height (WMD = 0.49, 95% CI = [0.02, 0.95], P = 0.04, I2 = 6%), shorter time to operation (WMD = - 2.91, 95% CI = [- 4.99, - 0.84], P = 0.006, I2 = 97%), less operation time (WMD = - 21.58, 95% CI = [- 37.31, - 5.85], P = 0.007, I2 = 98%), reduced length of hospital stay (WMD = - 2.00, 95% CI = [- 3.69, - 0.31], P = 0.02, I2 = 97%), and less wound complications (RR = 0.16, 95% CI = [0.08, 0.32], P < 0.00001, I2 = 0%). CONCLUSION: Cannulated screw fixation and plate fixation have similar postoperative functional satisfactory. Cannulated screw fixation is superior to plate fixation in reduction quality, time efficiency, and wound complications.
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Calcâneo , Fraturas Ósseas , Fraturas Intra-Articulares , Placas Ósseas , Parafusos Ósseos , Calcâneo/cirurgia , Fixação Interna de Fraturas , Fraturas Ósseas/cirurgia , Humanos , Fraturas Intra-Articulares/cirurgia , Resultado do TratamentoRESUMO
BACKGROUND: Patient-specific instrument (PSI) may theoretically make total ankle arthroplasty (TAA) more accurate. Several studies have reported the outcomes of PSI TAA. The aim of this study is to systematically review the literature of PSI TAA. METHODS: PubMed, Embase, Web of Science, and Cochrane Library databases were systematically reviewed according to the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) guidelines for PSI TAA. The quality of the included studies was evaluated according to Methodological Index for Non-Randomized Studies (MINORS). RESULT: Nine articles were ultimately included in the systematic review. The implant position and function outcome of TAA was similar between PSI and SI. Prediction accuracy of implant size remained great difference. PSI can shorten the operative time and fluoroscopy time. The quality of current studies on PSI TAA is insufficient to produce high-level evidence. CONCLUSION: PSI can get similar implant position and clinical outcome in TAA compared to SI, but current evidence is not strong enough to evaluate PSI TAA.
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Tornozelo , Artroplastia de Substituição do Tornozelo , Tornozelo/cirurgia , Artroplastia de Substituição do Tornozelo/instrumentação , Humanos , Duração da CirurgiaRESUMO
BACKGROUND/AIMS: We previously showed that urine and serum Angiopoietin-2 (Ang-2) levels increased significantly with the degree of albuminuria in diabetes patients, but the reasons remain unclear. Consequently we aimed to determine whether there was an association between Ang-2, inflammatory cytokines (TNF-α and IL-18) and reactive oxygen species (8-OHdG and SOD) in type 2 diabetes patients with albuminuria. METHODS: This retrospective study evaluated 113 patients with type 2 diabetes and normoalbuminuria, microalbuminuria, or macroalbuminuria and 30 healthy controls. Serum and urine TNF-α, IL-18 and 8-OHdG levels were measured by ELISA. Superoxide dismutase (SOD) activity was determined by spectrophotometry. RESULTS: Serum and urine TNF-α, IL-18 and 8-OHdG levels increased significantly with the degree of albuminuria, and were positively correlated with increased Ang-2. In contrast, SOD activity decreased with the degree of albuminuria and was negatively correlated with Ang-2. Multivariable linear regression analysis revealed that serum Ang-2 level was independently associated with serum levels of TNF-α (P<0.001), 8-OHdG (P=0.001), and IL-18 (P=0.003). Urinary Ang-2 level was independently associated with urinary TNF-α (P<0.001) and 8-OHdG (P=0.004) levels. CONCLUSION: TNF-α and 8-OHdG are associated with elevated urinary Angiopoietin-2 levels in type 2 diabetic patients with albuminuria.
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Albuminúria/sangue , Angiopoietina-2/urina , Desoxiguanosina/análogos & derivados , Diabetes Mellitus Tipo 2/sangue , Fator de Necrose Tumoral alfa/metabolismo , 8-Hidroxi-2'-Desoxiguanosina , Adulto , Estudos Transversais , Desoxiguanosina/metabolismo , Feminino , Humanos , Interleucina-18/metabolismo , Glomérulos Renais/metabolismo , Masculino , Pessoa de Meia-Idade , NADPH Oxidase 4 , NADPH Oxidases/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Estudos Retrospectivos , Superóxido Dismutase/sangue , Superóxido Dismutase/metabolismo , Superóxido Dismutase-1RESUMO
Purpose: Although magnesium sulfate (MgSO4) is widely used as an analgesic adjuvant to peripheral analgesic cocktails, its efficacy in total knee arthroplasty (TKA) is still controversial. Therefore, we systematically reviewed and meta-analyzed the literature to assess the analgesic efficacy of MgSO4 as an adjuvant to the analgesic cocktail in TKA. Methods: The PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched. The meta-analysis was performed according to the PRISMA guidelines. Data were qualitatively synthesized or meta-analyzed using a random-effects model. Results: Five randomized controlled trials involving 432 patients were included. Meta-analyses detected significant differences between the MgSO4 and control groups in the visual analog scale (VAS) pain scores (rest) at 6, 12, and 24 h postoperatively; VAS pain scores (motion) at 12, 24, and 48 h postoperatively; morphine consumption within 24 h, 24-48 h, and during the total hospitalization period; time to first rescue analgesia after TKA; and length of hospital stay. Regarding the functional recovery, the meta-analysis demonstrated significant differences between groups in terms of knee range of motion on postoperative day 1; daily mobilization distance on postoperative day 1; and daily mobilization distance. There was no significant intergroup difference in surgical complications. Conclusion: The findings suggest that MgSO4 is a promising adjunct to the analgesic cocktail, achieving significant improvements in pain scores and total opioid consumption during the early postoperative period after TKA.
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Background: Although adhesive capsulitis (AC) is a common condition, the pathological mechanisms remain understudied. The purpose of our research was to evaluate variations in gene expression across the entire genome in the subacromial bursa tissue of individuals with rotator cuff tears (RCT), with or without AC, and to explore the factors that may influence the occurrence and progression of AC. Methods: Transcription profiles of subacromial bursa samples from 12 RCT patients, of whom 6 had also AC, were evaluated. Data were generated using RNA-seq. DESeq2 was utilized to identify the differentially expressed genes (DEGs) in both groups. In order to conduct a more in-depth examination of the DEGs, we performed Gene Ontology (GO) functional enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. A network of interactions between proteins was built, and the central genes were determined using Cytoscape. The hub genes were confirmed through qRT-PCR and immunohistochemistry. Results: 324 of the 16,251 detected genes were identified as DEGs. Analysis of GO functional enrichment showed that the DEGs were enriched in domains of biological process, molecule function and cellular component. Analysis of KEGG pathways revealed enrichment of DEGs in pathways like IL-17 signaling and ECM-receptor interaction. We verified that the association between AC and the increase in expression of the PPI network hub genes. Conclusion: This study investigated the transcriptome differences of subacromial bursa in RCT patients with or without AC. Using bioinformatics technology, we identified the DEGs and screened out the hub genes. The research enhanced the data on gene expression profiles of DEGs in the subacromial bursa tissue of patients with RCT, offering fresh perspectives on the regulation of gene transcription.
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Background: Cannabis use may be increasing as countries legalize it and it becomes socially acceptable. A history of cannabis use may increase risk of complications after various kinds of surgery and compromise functional recovery. Here we systematically reviewed and meta-analyzed available evidence on how history of cannabis use affects recovery after hip or knee arthroplasty (THA/TKA). Methods: The PubMed, EMBASE, and Web of Science databases were comprehensively searched and studies were selected and analyzed in accordance with the PRISMA guidelines. The methodological quality of included studies was assessed based on the Newcastle-Ottawa Scale, while quality of evidence was evaluated according to the "Grading of recommendations assessment, development, and evaluation" system. Data on various outcomes were pooled when appropriate and meta-analyzed. Results: The systematic review included 16 cohort studies involving 5.91 million patients. Meta-analysis linked history of cannabis use to higher risk of the following outcomes: revision (RR 1.68, 95% CI 1.31-2.16), mechanical loosening (RR 1.77, 95% CI 1.52-2.07), periprosthetic fracture (RR 1.85, 95% CI 1.38-2.48), dislocation (RR 2.10, 95% CI 1.18-3.73), cardiovascular events (RR 2.49, 95% CI 1.22-5.08), cerebrovascular events (RR 3.15, 95% CI 2.54-3.91), pneumonia (RR 3.97, 95% CI 3.49-4.51), respiratory failure (RR 4.10, 95% CI 3.38-4.97), urinary tract infection (RR 2.46, 95% CI 1.84-3.28), acute kidney injury (RR 3.25, 95% CI 2.94-3.60), venous thromboembolism (RR 1.48, 95% CI 1.34-1.63), and deep vein thrombosis (RR 1.42, 95% CI 1.19-1.70). In addition, cannabis use was associated with significantly greater risk of postoperative transfusion (RR 2.23, 95% CI 1.83-2.71) as well as higher hospitalization costs. Conclusion: History of cannabis use significantly increases the risk of numerous complications and transfusion after THA or TKA, leading to greater healthcare costs. Clinicians should consider these factors when treating cannabis users, and pre-surgical protocols should give special consideration to patients with history of cannbis use.
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Artroplastia de Quadril , Artroplastia do Joelho , Complicações Pós-Operatórias , Humanos , Artroplastia do Joelho/estatística & dados numéricos , Artroplastia do Joelho/efeitos adversos , Artroplastia de Quadril/estatística & dados numéricos , Artroplastia de Quadril/efeitos adversos , Complicações Pós-Operatórias/epidemiologiaRESUMO
Stress-induced immunosuppression (SIIS) is one of common problems in the intensive poultry industry, affecting the effect of vaccine immunization and leading to high incidences of diseases. In this study, the expression characteristics and regulatory mechanisms of miR-214 in the processes of SIIS and its influence on the immune response to avian influenza virus (AIV) vaccine in chicken were explored. The qRT-PCR results showed that serum circulating miR-214 was significantly differentially expressed (especially on 2, 5, and 28 days post immunization (dpi)) in the processes, so had the potential as a molecular marker. MiR-214 expressions from multiple tissues were closely associated with the changes in circulating miR-214 expression levels. MiR-214-PTEN regulatory network was a potential key regulatory mechanism for the heart, bursa of Fabricius, and glandular stomach to participate in the process of SIIS affecting AIV immune response. This study can provide references for further understanding of stress affecting immune response.
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Galinhas , Vacinas contra Influenza , Influenza Aviária , MicroRNAs , PTEN Fosfo-Hidrolase , Estresse Fisiológico , Animais , MicroRNAs/genética , MicroRNAs/metabolismo , Galinhas/virologia , Vacinas contra Influenza/imunologia , Influenza Aviária/virologia , Influenza Aviária/imunologia , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/imunologia , Tolerância Imunológica , Transdução de Sinais , Vírus da Influenza A/imunologiaRESUMO
Postoperative breast cancer recurrence is tricky due to the limited therapeutic options. Transforming growth factors-ß (TGF-ß) is vital in promoting postoperative tumor recurrence. However, conventional blocking strategies fail to satisfy both bio-safety and sufficient relapse correction. Neutrophil extracellular traps (NETs) are essential for the spatiotemporal dynamics of TGF-ß at tumor-resection sites, whose unique mechanism for local TGF-ß amplification could remarkably increase the risk of relapse after surgery. Herein, the principle of NETs formation is ingeniously utilized to construct a surgical residual cavity hydrogel that mimics NETs formation. The hydrogel is prepared based on the electrostatic interaction between histidine (His) and sodium alginate (Alg). Then, arginine deiminase 4 (PAD4) protein is released during NETs formation. Simultaneously, the electrical property of His in hydrogel changes automatically, which further lead to promising localized release of anti-TGF-ß. The hydrogel system can realize specific and selective drug release at targeted NETs site over a prolonged period while exhibiting excellent biocompatibility. Superior breast cancer recurrence inhibition is achieved by suppressing TGF-ß and related indicators, impeding epithelial-mesenchymal transition (EMT) progression, and rectifying the locally exacerbated immunosuppressive environment within NETs. The novel NETs local microenvironment drug release functional hydrogel will provide inspiration for postoperative recurrence correction strategies.
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Computed Tomography (CT) imaging is an effective non-invasive examination. It is widely used in the diagnosis of fractures, arthritis, tumor, and some anatomical characteristics of patients. The density value (Hounsfield unit, HU) of a material in computed tomography can be the same for materials with varying elemental compositions. This value depends on the mass density of the material and the degree of X-ray attenuation. Computed Tomography Osteoabsorptiometry (CTOAM) imaging technology is developed on the basis of CT imaging technology. By applying pseudo-color image processing to the articular surface, it is used to analyze the distribution of bone mineralization under the articular cartilage, evaluate the position of prosthesis implantation, track the progression of osteoarthritis, and determine the joint injury prognosis. Furthermore, this technique was combined with indentation testing to discuss the relationship between the high bone density area of the articular surface, the mechanical strength of the bone, and the anchorage stability of the implant, in addition to the study of the relationship between mechanical strength and bone density. This narrative study discusses the pre- and postoperative evaluation of medical device implantation position, orthopedic surgery, and the clinical treatment of bone injury and degeneration. It also discusses the research status of CTOAM technology in image post-processing engineering and the relationship between bone material and mechanical strength.
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According to the prediction of the International Diabetes Federation, global diabetes mellitus (DM) patients will reach 783.2 million in 2045. The increasing incidence of DM has led to a global epidemic of diabetic retinopathy (DR). DR is a common microvascular complication of DM, which has a significant impact on the vision of working-age people and is one of the main causes of blindness worldwide. Substantial research has highlighted that microangiopathy and chronic low-grade inflammation are widespread in the retina of DR. Meanwhile, with the introduction of the gut-retina axis, it has also been found that DR is associated with gut microecological disorders. The disordered structure of the GM and the destruction of the gut barrier result in the release of abnormal GM flora metabolites into the blood circulation. In addition, this process induced alterations in the expression of various cytokines and proteins, which further modulate the inflammatory microenvironment, vascular damage, oxidative stress, and immune levels within the retina. Such alterations led to the development of DR. In this review, we discuss the corresponding alterations in the structure of the GM flora and its metabolites in DR, with a more detailed focus on the mechanism of gut microecology in DR. Finally, we summarize the potential therapeutic approaches of DM/DR, mainly regulating the disturbed gut microecology to restore the homeostatic level, to provide a new perspective on the prevention, monitoring, and treatment of DR.
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A promising approach to the next generation of low-power, functional, and energy-efficient electronics relies on novel materials with coupled magnetic and electric degrees of freedom. In particular, stripy antiferromagnets often exhibit broken crystal and magnetic symmetries, which may bring about the magnetoelectric (ME) effect and enable the manipulation of intriguing properties and functionalities by electrical means. The demand for expanding the boundaries of data storage and processing technologies has led to the development of spintronics toward two-dimensional (2D) platforms. This work reports the ME effect in the 2D stripy antiferromagnetic insulator CrOCl down to a single layer. By measuring the tunneling resistance of CrOCl on the parameter space of temperature, magnetic field, and applied voltage, we verified the ME coupling down to the 2D limit and probed its mechanism. Utilizing the multi-stable states and ME coupling at magnetic phase transitions, we realize multi-state data storage in the tunneling devices. Our work not only advances the fundamental understanding of spin-charge coupling, but also demonstrates the great potential of 2D antiferromagnetic materials to deliver devices and circuits beyond the traditional binary operations.
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Pancreatic cancer is a highly malignant tumor with poor prognosis. Currently available Western medical management strategies are unable to prolong the survival time and reduce the mortality of patients with pancreatic cancer. Traditional Chinese medicine has achieved promising results in many clinical studies. This systematic review and meta-analysis (SR/MA) aimed to explore the benefits and evaluate the quality of evidence of traditional Chinese medicine-based interventions for preventing and treating pancreatic cancer. A systematic search of eight databases for SRs/MAs of randomized controlled trials on traditional Chinese medicine treatment for pancreatic cancer was conducted (from inception to April 2022). The methodological quality of the SRs/MAs was assessed using AMSTAR 2.0, and the quality of evidence was evaluated using the GRADE guide. Nine SRs/MAs, including 145 randomized controlled trials, were considered eligible for this study. The literature were published between 2014 and 2022. The sample size of randomized controlled trials in the MAs ranged from 336 to 1,989. The methodological quality of the nine studies was critically low. Among the 59 outcome indicators of the nine SRs/MAs, seven, 33, and 19 had moderate-, low-, and critically low-quality evidence, respectively, while high-quality evidence was not identified. The results for the long-term indicators, short-term indicators, and adverse reactions in the SRs/MAs displayed consistencies and differences. In conclusion, the methodological and evidence quality of the current evidence is generally low, highlighting the need for additional focus on implementation processes. Some evidence with moderate quality validated that several specific traditional Chinese medicine were optimum for improving the short-term clinical efficacy. However, more objective and high-quality investigations are warranted to verify the efficacy of traditional Chinese medicine for pancreatic cancer.
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Objective: We aimed to analyze the possible molecular mechanism of Xihuang pill (XHP) in the treatment of pancreatic cancer based on methods of network pharmacology, molecular docking, and bioinformatics. Methods: The main active components and targets were obtained through the TCMSP database, the BATMAN-TCM database, and the Chemistry database. The active ingredients were screened according to the "Absorption, Distribution, Metabolism, Excretion" (ADME) principle and supplemented with literature. We searched GeneCards, OMIM, TTD, and DrugBank databases for pancreatic cancer targets. The targets of disease and ingredients were intersected to obtain candidate key targets. Then, we constructed a protein-protein interaction (PPI) network for protein interaction analysis and a composition-key target map to obtain essential effective ingredients. Metascape was used to perform functional enrichment analysis to screen critical targets and pathways. The expression and prognosis of key targets were examined and analyzed, and molecular docking was carried out. Results: A total of 52 active ingredients of XHP, 121 candidate targets, and 52 intersecting targets were obtained. The core active ingredients of XHP for the treatment of pancreatic cancer were quercetin, 17-ß-estradiol, ursolic acid, and daidzein. The core targets were EGFR, ESR1, MAPK1, MAPK8, MAPK14, TP53, and JUN, which were highly expressed genes of pancreatic cancer. Among them, EGFR and MAPK1 were significantly correlated with the survival of pancreatic cancer patients. The key pathway was the EGFR/MAPK pathway. The molecular docking results indicated that four active compositions had good binding ability to key targets. Conclusion: The molecular mechanism of XHP for the treatment of pancreatic cancer involved multiple components, multiple targets, and multiple pathways. This research theoretically elucidated the ameliorative effect of XHP against pancreatic cancer and might provide new ideas for further research on the treatment of pancreatic cancer.
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Pellegrini-Stieda lesion is described as ossification on the origin of medial collateral ligament. We present a case of end-stage knee osteoarthritis with the Pellegrini-Stieda lesion treated by unicompartmental knee arthroplasty (UKA). During the postoperative follow-up, an interesting change occurred such that the ossification lesion disappeared gradually and did not relapse. It is supposed that the disappearance was caused by UKA changing the abnormal biomechanics of the varus osteoarthritic knee.
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The most important procedure of mobile-bearing unicompartmental knee arthroplasty (UKA) is to balance the knee flexion and extension gap. Conventionally, the balance was determined by the subjective assessment of plugging out the feeling gauge. Since it mainly depended on the surgeons' experience, the accuracy was always in doubt. In the past 10 years, pressure sensors have been introduced to guide the gap balance in total knee arthroplasty (TKA). However, the sensor technique was introduced to UKA very recently. Herein is our sensor assessment of the gap balance in 20 cases UKA by one experienced surgeon. The sensor was a custom-designed force sensor matrix according to the shape of the tibial trial of mobile-bearing UKA. The postoperative clinical outcomes and radiographic results were recorded for future comparison. We aim to use this method to assess more than 200 cases of UKA by various surgeons to ultimately standardize the gap-balance result.
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Artroplastia do Joelho , Osteoartrite do Joelho , Artroplastia do Joelho/métodos , Humanos , Articulação do Joelho , Osteoartrite do Joelho/diagnóstico por imagem , Osteoartrite do Joelho/cirurgia , Tíbia/cirurgia , Resultado do TratamentoRESUMO
Stress-induced immunosuppression is one of the most common hazards in poultry intensive production, which often leads to vaccination failure and severe economic losses. At present, there is no report about the function and mechanism of circulating miRNA on stress-induced immunosuppression affecting immune response. In this study, the changes of circulating miR-20a-5p under stress-induced immunosuppressive condition were analyzed by qRT-PCR, and the key time points, tissues and mechanisms for functional regulation of miR-20a-5p in the process of stress-induced immunosuppression affecting avian influenza virus (AIV) vaccine immune response were identified. The results showed that stress-induced immunosuppression down-regulated miR-20a-5p and further affected AIV vaccine immune response, in which 5 day post immunization (dpi) was a key time point, and the heart, lung, and proventriculus were the important tissues. The game relationship analysis between miR-20a-5p and its target nuclear receptor subfamily 4 group A member 3 (NR4A3) gene showed that "miR-20a-5p/NR4A3" pathway was the potential key mechanism of this process, especially for heart and lung. This study provides insights into the molecular mechanisms of stress-induced immunosuppression affecting immune response.
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Vacinas contra Influenza , Influenza Aviária , MicroRNAs , Animais , Galinhas/genética , Imunidade , Terapia de Imunossupressão/veterinária , Influenza Aviária/prevenção & controle , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
Introduction: Secondary hyperparathyroidism (SHPT) is a common complication in hemodialysis patients with chronic renal failure uremia. For severe SHPT, parathyroidectomy is effective. Owing to the variability in parathyroid anatomy, surgical parathyroidectomy can be complex and many patients experience recurrent SHPT, which may require repeated surgery. These cases pose significant challenges to surgeons. Case description: An elderly woman with recurrent severe SHPT was admitted to our hospital. Preoperative methoxyisobutylisonitrile (MIBI) examination found a large ectopic parathyroid gland in the superior mediastinum, and she underwent reoperative parathyroidectomy. A large parathyroid gland in the right anterior mediastinum and another parathyroid gland in the left lingual lobe of the thymus were removed. The patient had postoperative hypocalcemia that was successfully corrected with calcium supplementation via femoral vein catheterization. During the 1-year postoperative follow-up, the patient's iPTH was well controlled and her blood calcium was within the normal range. Conclusion: We report a case of parathyroidectomy to remove multifocal ectopic hyperplastic parathyroid tissue in the mediastinum. Preoperative MIBI accurately detected the lesions. Calcium supplementation via femoral vein catheterization successfully corrected postoperative hypocalcemia. Postoperative follow-up for 1 year indicated that the surgery was successful.