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BACKGROUND: For the treatment of coronoid process fractures, medial, lateral, anterior, anteromedial, and posterior approaches have been increasingly reported; however, there is no general consensus on the method of fixation of coronal fractures. Here, we present a highly-extensile minimally invasive approach to treat coronoid process fractures using a mini-plate that can achieve anatomic reduction, stable fixation, and anterior capsular repair. Further, the study aimed to determine the complication rate of the anterior minimally invasive approach and to evaluate functional and clinical patient-reported outcomes during follow-up. METHODS: Thirty-one patients diagnosed with coronoid fractures accompanied with a "terrible triad" or posteromedial rotational instability between April 2012 and October 2018 were included in the analysis. Anatomical reduction and mini-plate fixation of coronoid fractures were performed using an anterior minimally invasive approach. Patient-reported outcomes were evaluated using the Mayo Elbow Performance Index (MEPI) score, range of motion (ROM), and the visual analog score (VAS). The time of fracture healing and complications were recorded. RESULTS: The mean follow-up time was 26.7 months (range, 14-60 months). The average time to radiological union was 3.6 ± 1.3 months. During the follow-up period, the average elbow extension was 6.8 ± 2.9° while the average flexion was 129.6 ± 4.6°. According to Morrey's criteria, 26 (81%) elbows achieved a normal desired ROM. At the last follow-up, the mean MEPI score was 98 ± 3.3 points. There were no instances of elbow instability, elbow joint stiffness, subluxation or dislocation, infection, blood vessel complications, or nerve palsy. Overall, 10 elbows (31%) experienced heterotopic ossification. CONCLUSION: An anterior minimally invasive approach allows satisfactory fixation of coronoid fractures while reducing incision complications due to over-dissection of soft tissue injuries. In addition, this incision does not compromise the soft tissue stability of the elbow joint and allows the patient a more rapid return to rehabilitation exercises.
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Placas Óseas , Articulación del Codo , Fijación Interna de Fracturas , Fracturas Conminutas , Rango del Movimiento Articular , Fracturas del Cúbito , Humanos , Masculino , Femenino , Fracturas del Cúbito/cirugía , Fracturas del Cúbito/diagnóstico por imagen , Fijación Interna de Fracturas/métodos , Fijación Interna de Fracturas/instrumentación , Persona de Mediana Edad , Adulto , Fracturas Conminutas/cirugía , Fracturas Conminutas/diagnóstico por imagen , Articulación del Codo/cirugía , Articulación del Codo/diagnóstico por imagen , Articulación del Codo/fisiopatología , Resultado del Tratamiento , Estudios Retrospectivos , Estudios de Seguimiento , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/instrumentación , Curación de Fractura , Anciano , Medición de Resultados Informados por el Paciente , Adulto JovenRESUMEN
Purpose: The purpose of this study was to compare the clinical and radiographic outcomes with use of short-curved stems versus standard-length single wedged stems over a minimum follow-up period of five years. Materials and Methods: A retrospective study of primary total hip arthroplasties performed using the Fitmore® stem (127 hips, 122 patients) and the M/L taper® stem (195 hips, 187 patients) between October 2012 and June 2014 was conducted. The clinical and radiographic outcomes were obtained for evaluation over a minimum follow-up period of five years. Results: In both the Fitmore® and M/L taper® groups, the mean Harris hip score improved from 52.4 and 48.9 preoperatively to 93.3 and 94.5 at the final follow-up, respectively (P=0.980). The mean Western Ontario and McMaster Universities Osteoarthritis Index scores also improved from 73.3 and 76.8 preoperatively to 22.9 and 25.6 at the final follow-up, respectively (P=0.465). Fifteen hips (Fitmore®: 14 hips; M/L taper®: one hip, P<0.001) developed intraoperative cracks and were treated simultaneously with cerclage wiring. Radiography showed a radiolucent line in 24 hips in the Fitmore® group and 12 hips in the M/L taper® group (P=0.125). Cortical hypertrophy was detected in 29 hips (Fitmore® group: 28 hips; M/L taper® group: one hip, P<0.001). Conclusion: Similarly favorable clinical and radiographic outcomes were achieved with use of both short-curved stems and standard-length single wedged stems. However, higher cortical hypertrophy and a higher rate of femoral crack were observed with use of Fitmore® stems.
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OBJECTIVE: To investigate the molecular mechanism of proteolytic cleavage of unusually large von Willebrand Factor(ULVWF) on endothelial cells by ADAMTS13 (a disintegrin and metalloprotease with thrombospondin type 1 repeats-13) in the absence of fluid shear stress, so as to provide a theoretical basis for the pathogenesis of thrombotic thrombocytopenic purpura (TTP) and other thrombotic disorders. METHODS: The ADAMTS13-mediated proteolysis of ULVWF on the surface of endothelial cells in the absence of fluid shear stress was observed through immunofluorescence microscopy. The variation in VWF antigen levels in the conditioned media were determined by ELISA assay. The levels of VWF and the proteolytic fragments released into the conditioned media were determined by ELISA assay and Western blot in the absence and presence of fluid shear stress or FVIII. The effect of ADAMTS13-mediated ULVWF cleavage on the normal distribution of plasma VWF multimers was evaluated by multimer analysis. Histamine stimulated human umbilical vein endothelial cells (HUVECs) were incubated with ADAMTS13 and various N- and C-terminally truncated mutants. Then the ULVWF that maintained binding to the cells were observed through immunofluorescence microscopy and the soluble ULVWF released from endothelial cells was determined by ELISA, so as to demonstrate the domains of ADAMTS13 required for proteolysis of ULVWF on endothelial cells. RESULTS: The ULVWF strings on the endothelial cell surface were rapidly proteolyzed by recombinant and plasma ADAMTS13 in the absence of fluid shear stress. This proteolytic processing of ULVWF depended on incubation time and ADAMTS13 concentration, but not shear stress and FVIII. The distribution of VWF releaseded by ADAMTS13-mediated proteolysis was quite similar to that secreted by endothelial cells under histamine stimulation, suggesting the ULVWF cleavage occured at the cell surface. The proteolysis of the ULVWF on endothelial cells required the Cys-rich(CysR) and spacer domains, but not the TSP1 2-8 and CUB domains of ADAMTS13. CONCLUSION: The ULVWF polymers on endothelial cells are sensitive to ADAMTS13-mediated cleavage even in the absence of fluid shear stress. The findings provide novel insight into the molecular mechanism of ADAMTS13-mediated ULVWF cleavage at the cellular level and may contribute to understanding of the pathogenesis of TTP and other thrombotic disorders.
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Proteína ADAMTS13 , Células Endoteliales , Estrés Mecánico , Factor de von Willebrand , Humanos , Proteínas ADAM/metabolismo , Proteína ADAMTS13/metabolismo , Células Endoteliales/metabolismo , Células Endoteliales de la Vena Umbilical Humana , Proteolisis , Púrpura Trombocitopénica Trombótica/metabolismo , Factor de von Willebrand/química , Factor de von Willebrand/metabolismoRESUMEN
BACKGROUND: The treatment of multiple myeloma has significantly progressed over the past half-century. The purpose of this study was to perform a systematic review and meta-analysis in order to explore the efficacy and safety of daratumumab in treating multiple myeloma. AIM: To explore the efficacy and safety of daratumumab in treating multiple myeloma. METHODS: A systematic literature search was performed using Chinese and English databases, including the China National Knowledge Infrastructure, Wanfang, China Biology Medicine, VIP, the Cochrane Library, Embase, and PubMed. The search encompassed studies in treating multiple myeloma with daratumumab, spanning from the inception of the database to June 2023. Revman 5.1 software was used for analysis. RESULTS: Our analysis included eight English articles and one Chinese article of high quality. The meta-analysis results indicated that compared to other therapies, daratumumab could improve the overall response rate (ORR) [odds ratio (OR) = 2.67, 95% confidence interval (CI) = 2.01, 3.53, Z = 6.85, P < 0.00001], complete remission (CR) (OR = 2.87, 95%CI = 2.16, 3.83, Z = 7.23, P < 0.00001) and progression-free survival (PFS) time (hazard ratio = 0.48, 95%CI = 0.38,0.60, Z = 6.54, P < 0.00001) in patients with multiple myeloma. These differences were statistically significant. Additionally, these results suggested that daratumumab increases the risk of neutropenia and thrombocytopenia with minimal effect on the incidences of anemia and upper respiratory tract infections. CONCLUSION: Daratumumab can improve ORR, CR rate, and PFS in patients with multiple myeloma. It also increases the risk of neutropenia and thrombocytopenia, necessitating careful monitoring during its clinical application.
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BACKGROUND: Our experience with the surgical flip-dislocation of the bicolumnar (SFDB) approach for type AO 13C3 humeral fractures indicates that this surgical approach can be performed safely and effectively in appropriately selected patients. We aimed to evaluate the clinical outcomes of the SFDB approach without olecranon osteotomy (OO) for type AO 13C3 distal humeral fractures. METHODS: We retrospectively reviewed 65 cases of type AO 13C3 distal humeral fractures treated between April 2008 and July 2018; 33 patients were treated with the SFDB approach, and the remaining were treated with OO. Propensity score matching was used to control for sex, age, and the American Society of Anesthesiology score. Elbow pain, range of motion, stability, and function were assessed using the Mayo Elbow Performance Index (MEPI) and the Disabilities of the Arm, Shoulder, and Hand questionnaire. Clinical complications, reoperation rates, and radiographic results were compared between the groups. RESULTS: Operative time and blood loss were significantly lower in the SFDB group than in the OO group (P = 0.001, P = 0.002, respectively). At the final follow-up, the mean postoperative MEPI did not significantly differ between the groups (P = 0.628). According to Morrey's criteria, a typical functional range of elbow motion was achieved in 12 and 15 patients in the SFDB and OO groups, respectively. CONCLUSIONS: The SFDB approach achieves superior exposure of the articular surface without injury to the extensor mechanism in type 13C3 articular surface fracture treatment. This approach also results in good early functional recovery and clinical outcomes, with a low risk of complications.
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Articulación del Codo , Fracturas Humerales Distales , Fracturas del Húmero , Luxaciones Articulares , Olécranon , Humanos , Olécranon/cirugía , Estudios de Cohortes , Estudios Retrospectivos , Resultado del Tratamiento , Fijación Interna de Fracturas/métodos , Articulación del Codo/diagnóstico por imagen , Articulación del Codo/cirugía , Fracturas del Húmero/diagnóstico por imagen , Fracturas del Húmero/cirugía , Osteotomía/métodos , Rango del Movimiento Articular , Luxaciones Articulares/etiologíaRESUMEN
The closed suction surgical drainage system (CSSD) is routinely used after total hip arthroplasty (THA) by orthopedic surgeons in many institutions. However, it has not been shown to decrease the rate of wound infection significantly and may even increase blood loss. This study aimed to evaluate the usefulness of using skin adhesive without CSSD in uncomplicated THA. From July 2015 to September 2017, 200 patients undergoing unilateral THA were enrolled and divided into 2 groups, either receive CSSD (134 patients) or not receive CSSD (66 patients). Then, the propensity matched was performed. Calculated total blood loss, changes in hemoglobin (Hgb) level, transfusions were evaluated. In addition, data on the length of hospital stay, operation time, closure time, time to using crutches following THA were collected. Finally, Harris hip score (HHS), total estimated cost, and complications were assessed. The non-CSSD group had comparatively less blood loss (508.5 ± 280.3 mL compared with 742.1 ± 330.3 mL, P < .001), fewer transfusions (0.03 units compared with 0.3 units, P = .02), less transfusion rate (1.9% compared with 17.3 %, P = .02), lower change of Hgb from immediate postoperative period to 3 days later(1.6 ± 1.0 g/dL compared with 2.0 ± 0.8 g/dL, P = .03), than the CSSD group. There was a longer duration of hospital stay in the CSSD groups (7.2 days compared with 7.8 days, P = .03) The mean total cost in the non-CSSD group was $162.1, which was less than that of the CSSD group, which spent $288.5 on average (P < .001). there was 1 allergic reaction in the non-CSSD group (P = .32). The use of skin adhesive without CSSD could help decrease blood loss, the need for transfusion, and the length of hospital stay, and seems to more cost-effectiveness than using CSSD. It may also provide superior results and allow the patient to recover faster. Using this type of skin adhesive without CSSD is an efficient wound closure method for patients undergoing uncomplicated THA. However, care must be taken for allergic reactions, especially for patients with known or suspected allergies to cyanoacrylate or formaldehyde.
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Artroplastia de Reemplazo de Cadera , Hipersensibilidad , Humanos , Artroplastia de Reemplazo de Cadera/efectos adversos , Puntaje de Propensión , Estudios Retrospectivos , Succión , PielRESUMEN
Objective: Extranodal natural killer/T-cell lymphoma comprises less than 1% of all non-Hodgkin lymphomas. It is rare in Western countries but is common in East Asia and Central and South America. The pathological features are angiocentricity /angioinvasion and significant tissue necrosis. Case Presentation: A 72-year-old woman was diagnosed with primary breast extranodal natural killer/T-cell lymphoma. The patient presented with a painless right breast tumor and had uneven internal echo and strip blood flow signal on breast ultrasonography. After right breast tumor resection, the pathological diagnosis was extranodal natural killer/T-cell lymphoma. Despite receiving CHOP chemotherapy, the patient died of lymphoma and multiple organ dysfunction syndrome 27 months after diagnosis. Conclusion: Extranodal natural killer/T-cell lymphoma with breast tissue as the primary site is very rare. The disease is prone to misdiagnosis and missed diagnosis, and diagnosis by ultrasound is difficult, so pathological examination after biopsy is particularly important.
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Neoplasias de la Mama , Linfoma de Células T , Femenino , Humanos , Anciano , Células Asesinas Naturales/patología , Linfoma de Células T/patología , Neoplasias de la Mama/diagnóstico por imagenRESUMEN
To survive poor nutritional conditions, tumor cells activate the unfolded protein response, which is composed of the IRE1, PERK, and ATF6 arms, to maintain the homeostasis of the endoplasmic reticulum, where secretory and transmembrane proteins destined for the secretory pathway gain their correct three-dimensional structure. The requirement of the IRE1 and PERK arms for tumor growth in nude mice is established. Here we investigated the requirement for the ATF6 arm, which consists of ubiquitously expressed ATF6α and ATF6ß, by constructing ATF6α-knockout (KO), ATF6ß-KO, and ATF6α/ß-double KO (DKO) in HCT116 cells derived from human colorectal carcinoma. Results showed that these KO cells grew similarly to wild-type (WT) cells in nude mice, contrary to expectations from our analysis of ATF6α-KO, ATF6ß-KO, and ATF6α/ß-DKO mice. We then found that the loss of ATF6α in HCT116 cells resulted in sustained activation of the IRE1 and PERK arms in marked contrast to mouse embryonic fibroblasts, in which the loss of ATF6α is compensated for by ATF6ß. Although IRE1-KO in HCT116 cells unexpectedly did not affect tumor growth in nude mice, IRE1-KO HCT116 cells with ATF6α knockdown grew significantly more slowly than WT or IRE1-KO HCT116 cells. These results have unraveled the situation-dependent differential compensation strategies of ATF6α.
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Carcinoma , Fibroblastos , Animales , Humanos , Ratones , Factor de Transcripción Activador 6/metabolismo , Línea Celular , Estrés del Retículo Endoplásmico , Fibroblastos/metabolismo , Ratones Desnudos , Proteínas Serina-Treonina Quinasas/metabolismo , Respuesta de Proteína DesplegadaRESUMEN
Dysregulation of circular RNAs (circRNAs) has been observed in multiple diseases including rheumatoid arthritis (RA), and we investigated the role of the circ_0088194/microRNA (miR)-30a-3p/a disintegrin and metalloproteinase 10 (ADAM10) axis in RA. Circ_0088194, miR-30a-3p, and ADAM10 contents in RA tissues and RA-fibroblast-like synoviocytes (RA-FLSs) were analyzed by real-time quantitative polymerase chain reaction (RT-qPCR) and western blot. Cell proliferation, migration, apoptosis, and inflammatory factor secretion of RA-FLSs were detected using 5-ethynyl-2'-deoxyuridine (EdU), wound healing assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). Targeting relationship between miR-30a-3p and circ_0088194 or ADAM10 was validated by luciferase reporter system, RNA immunoprecipitation (RIP), and RNA pull-down assays. Circ_0088194 and ADAM10 levels were increased, while miR-30a-3p was decreased in RA tissues and RA-FLSs. Circ_0088194 knockdown suppressed the growth, migration, and inflammation of RA-FLSs, while the upregulation of circ_0088194 showed opposite effects. Circ_0088194 directly targeted miR-30a-3p, ADAM10 was a target of miR-30a-3p, and circ_0088194 regulated the expression of ADAM10 by sponging miR-30a-3p. MiR-30a-3p inhibition restored the inhibition effects of circ_0088194 knockdown or RA-FLSs. Moreover, miR-30a-3p re-expression repressed growth, migration, and inflammatory response in RA-FLSs, which were reversed by ADAM10 overexpression. Circ_0088194 acted on miR-30a-3p/ADAM10 axis to promote the proliferation, migration, and inflammatory response, and inhibit apoptosis in RA-FLSs.
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Artritis Reumatoide , MicroARNs , Sinoviocitos , Humanos , Artritis Reumatoide/genética , Inflamación , Apoptosis , Proliferación Celular , Fibroblastos , MicroARNs/genética , Proteína ADAM10/genética , Proteínas de la Membrana/genética , Secretasas de la Proteína Precursora del Amiloide/genéticaRESUMEN
Mutations in MYH9, the gene encoding the heavy chain of nonmuscle myosin IIa (NMII-A), cause MYH9-related disease (MYH9-RD), which is an autosomal-dominant thrombocytopenia with bleeding tendency. Previously, we showed that NMII-A in endothelial cells (ECs) is critical for hemostasis via regulating von Willebrand factor (VWF) release from Weibel-Palade bodies (WPBs). The aim of this study was to determine the role of the expression of MYH9 mutants in ECs in the pathogenesis of the MYH9-RD bleeding symptom. First, we expressed the 5 most common NMII-A mutants in ECs and found that E1841K mutant-expressing ECs secreted less VWF than the controls in response to a cyclic adenosine monophosphate (cAMP) signaling agonist. Then, we generated 2 knockin mouse lines, 1 with Myh9 E1841K in ECs and the other in megakaryocytes. Endothelium-specific E1841K mice exhibited impaired cAMP-induced VWF release and a prolonged bleeding time with normal platelets, whereas megakaryocyte-specific E1841K mice exhibited macrothrombocytopenia and a prolonged bleeding time with normal VWF release. Finally, we presented mechanistic findings that E1841K mutation not only interferes with S1943 phosphorylation and impairs the peripheral distribution of Rab27a-positive WPBs in Ecs under quiescent condition but also interferes with S1916 phosphorylation by disrupting the interaction with zyxin and CKIIα and reduces actin framework formation around WPBs and subsequent VWF secretion under the stimulation by a cAMP agonist. Altogether, our results suggest that impaired cAMP-induced endothelial VWF secretion by E1841K mutant expression may contribute to the MYH9-RD bleeding phenotype.
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Células Endoteliales , Hemostasis , Cadenas Pesadas de Miosina , Trombocitopenia , Factor de von Willebrand , Animales , Células Endoteliales/metabolismo , Hemostasis/genética , Hemostasis/fisiología , Ratones , Cadenas Pesadas de Miosina/genética , Cadenas Pesadas de Miosina/metabolismo , Trombocitopenia/congénito , Trombocitopenia/genética , Factor de von Willebrand/genética , Factor de von Willebrand/metabolismoRESUMEN
Spatial manipulation of nanoparticles (NPs) in a controlled manner is critical for the fabrication of 3D hybrid materials with unique functions. However, traditional fabrication methods such as electron-beam lithography and stereolithography are usually costly and time-consuming, precluding their production on a large scale. Herein, for the first time the ultrafast laser direct writing is combined with external magnetic field (MF) to massively produce graphene-coated ultrafine cobalt nanoparticles supported on 3D porous carbon using metal-organic framework crystals as precursors (5 × 5 cm2 with 10 s). The MF-confined picosecond laser scribing not only reduces the metal ions rapidly but also aligns the NPs in ultrafine and evenly distributed order (from 7.82 ± 2.37 to 3.80 ± 0.84 nm). ≈400% increment of N-Q species within N compositionis also found as the result of the special MF-induced laser plasma plume. (). The importance of MF is further exmined by electrochemical water-splitting tests. Significant overpotential improvements of 90 and 150 mV for oxygen evolution reaction and hydrogen evolution reaction are observed, respectively, owing to the MF-induced alignment of the NPs and controlled elemental compositions. This work provides a general bottom-up approach for the synthesis of metamaterials with high outputs yet a simple setup.
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Mesenchymal stem cells (MSCs) play important roles in tissue repair and regeneration, such as the induction of angiogenesis, particularly under hypoxic conditions. However, the molecular mechanisms underlying hypoxic MSC activation remain largely unknown. MSC-derived extracellular vesicles (EVs) are vital mediators of cell-to-cell communication and can be directly utilized as therapeutic agents for tissue repair and regeneration. Here, we explored the effects of EVs from human hypoxic olfactory mucosa MSCs (OM-MSCs) on angiogenesis and its underlying mechanism. EVs were isolated from normoxic (N) OM-MSCs (N-EVs) and hypoxic (H) OM-MSCs (H-EVs) using differential centrifugation and identified by transmission electron microscopy and flow cytometry. In vitro and in vivo, both types of OM-MSC-EVs promoted the proliferation, migration, and angiogenic activities of human brain microvascular endothelial cells (HBMECs). In addition, angiogenesis-stimulatory activity in the H-EV group was significantly enhanced compared to the N-EV group. MicroRNA profiling revealed a higher abundance of miR-612 in H-EVs than in N-EVs, while miR-612 inactivation abolished the N-EV treatment benefit. To explore the roles of miR-612, overexpression and knock-down experiments were performed using a mimic and inhibitor or agomir and antagomir of miR-612. The miR-612 target genes were confirmed using the luciferase reporter assay. Gain- and loss-of-function studies allowed the validation of miR-612 (enriched in hypoxic OM-MSC-EVs) as a functional messenger that stimulates angiogenesis and represses the expression of TP53 by targeting its 3'-untranslated region. Further functional assays showed that hypoxic OM-MSC-EVs promote paracrine Hypoxia-inducible factor 1-alpha (HIF-1α)-Vascular endothelial growth factor (VEGF) signaling in HBMECs via the exosomal miR-612-TP53-HIF-1α-VEGF axis. These findings suggest that hypoxic OM-MSC-EVs may represent a promising strategy for ischemic disease by promoting angiogenesis via miR-612 transfer.
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Hipoxia de la Célula/genética , Micropartículas Derivadas de Células , MicroARNs , Neovascularización Patológica/genética , Mucosa Olfatoria/citología , Adulto , Animales , Micropartículas Derivadas de Células/genética , Micropartículas Derivadas de Células/metabolismo , Femenino , Humanos , Masculino , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/fisiología , Ratones , Ratones Desnudos , MicroARNs/genética , MicroARNs/metabolismo , Persona de Mediana Edad , Adulto JovenRESUMEN
OBJECTIVE: To investigate the biological function of Cysteine rich (CysR) domain of a disintegrin and metalloprotease with thrombospondin type 1 repeats-13 (ADAMTS13) on cleavage of von Willebrand factor (vWF) and provide experimental evidence for exploring the pathogenesis of thrombotic thrombocytopenic purpura (TTP). METHODS: The six amino acids (EDGTLS) in ADAMTS13 CysR domain were point mutated one by one, and the mutant ADAMTS13 proteins were expressed and purified. The cleavage products of vWF polymer by wild-type or mutant ADAMTS13 under denaturing condition or shear stress were separated by 1% SeaKem HGT agarose gel and detected by Western blot. RESULTS: The mutant ADAMTS13 plasmids (M1: Glu515Ala; M2: Asp516Ala; M3: Gly517Ala; M4: Thr518Ala; M5: Leu519Ala; M6: Ser520Ala) were successfully constructed and the proteins of wild-type and mutant ADAMTS13 were purified. Wild-type ADAMTS13 almost completely cleaved the vWF polymer under denaturing condition, while the cleavage activity of M1 mutant was significantly reduced in the same condition (P<0.01). The cleavage activity of M1 mutant of ADAMTS13 was also significantly reduced compared with that of the wild-type under shear stress (P<0.01). The activity of M1 mutant to cleave the FRETS-vWF73 was dramatically reduced compared with that of wild-type ADAMTS13. However, the binding ability of M1 mutant to vWF was similar with that of wild-type ADAMTS13. CONCLUSION: The CysR domain of ADAMTS13 plays an important role in the digestion of vWF under denaturing condition and shear stress. The Glu515 amino acid residue might be an important site for substrate recognition.
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Proteínas ADAM , Púrpura Trombocitopénica Trombótica , Proteína ADAMTS13/genética , Humanos , Púrpura Trombocitopénica Trombótica/genética , Factor de von Willebrand/genéticaRESUMEN
BACKGROUND: The procedure of femoral stem revision is challenging, and bone conservation with less stress shielding is a mandatory effort in these cases. Although there are several reports of stem revision with stems designed for primary total hip arthroplasty (THA), there is no report on stem revision with the Wagner cone prosthesis. METHODS: Between 1996 and 2008, 41 hips of 41 consecutive patients were subjected to femoral revision THA using the Wagner cone prosthesis. The mean age during revision surgery was 56.1 years, and the mean follow-up period was 14.8 years. The clinical results were evaluated, and the femoral component was assessed radiologically. RESULTS: The results showed that the average period from the first operation to revision THA was 8.0 years. Additionally, the mean Harris hip score improved from 52 points preoperatively to 83 points at the final follow-up. All stems showed bone integration in the radiological evaluation. A subsidence of more than 5 mm was observed in 3 out of 28 (10.7%) femoral stems. Two patients needed an acetabular revision for acetabular cup loosening during the follow-up period. Furthermore, one patient had recurrent dislocation and had to undergo revision surgery for soft tissue augmentation. CONCLUSIONS: We achieved favorable clinical and radiological long-term outcomes in femoral stem revision using the Wagner cone prosthesis. This cementless femoral stem could be an option for femoral stem revision in cases with relatively good bone stock.
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Artroplastia de Reemplazo de Cadera/métodos , Fémur/cirugía , Prótesis de Cadera , Diseño de Prótesis , Reoperación/métodos , Femenino , Fémur/diagnóstico por imagen , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Falla de Prótesis , Radiografía , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: The metastasis and recurrence of Non-Hodgkin's lymphoma (NHL) is a major cause of morbidity and mortality. Recent work suggests that drugs capable of targeting epigenetic regulatory mechanisms may be well suited to the treatment of such disease progression. METHODS: This study was thus designed to evaluate the ability of the novel histone deacetylase (HDAC) inhibitor CUDC-101 to synergize with gemcitabine in order to kill human HUT78 and Pfeiffer NHL cells. To that end, we analyzed the viability of these NHL cells via CCK-8 assay, while the incidence of apoptosis among treated cells was evaluated via Annexin V-FITC/PI staining and by the Western blotting-mediated evaluation of proteins associate with apoptosis and related signaling pathways. RESULTS: We found that CUDC-101 and gemcitabine interacted synergistically to reduce NHL cell viability and to induce the apoptotic death of these cells via the EGFR/ PI3K/Akt and Erk pathways, which were regulated by HDAC signaling pathways. CONCLUSION: Together, our results highlight the anti-cancer properties of CUDC-101 alone or in combination with gemcitabine as an approach to inducing the apoptotic death of lymphoma cells in vitro, while also offering insight into the underlying molecular mechanisms governing this activity.
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Antineoplásicos/farmacología , Resistencia a Antineoplásicos/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Ácidos Hidroxámicos/farmacología , Quinazolinas/farmacología , Apoptosis/efectos de los fármacos , Proteínas Reguladoras de la Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Supervivencia Celular/efectos de los fármacos , Desoxicitidina/análogos & derivados , Desoxicitidina/farmacología , Sinergismo Farmacológico , Humanos , Transducción de Señal/efectos de los fármacos , GemcitabinaRESUMEN
BACKGROUND: Failed treatment of subtrochanteric fractures commonly leads to pain, limping, and poor limb function. Cementless total hip arthroplasty (THA) could serve as an efficient salvage procedure in such cases. This study aimed to evaluate the outcomes and complications of salvage THA in failed subtrochanteric fracture fixation cases. METHODS: From January 2001 to December 2017, cementless THA for failed treatment of subtrochanteric fractures was performed in 18 hips of 11 men and 7 women (average age, 74 years; age range, 57.0-89.0 years). Patients were followed up for clinical and radiological assessments in terms of implant survival and complications after a minimum follow-up of 2 years. The Wagner femoral stems (Zimmer, Warsaw, USA) were used in all 18 patients (100%), with the long-length stem (Wagner SL stem) and standard-length stem (Wagner cone stem) used in 11 and 7 patients, respectively. RESULTS: The mean follow-up period was 5.2 years (range: 2.2-10.8 years). The mean Harris hip score (HHS) was 38.2 (range: 24-56) preoperatively and 85.4 (range: 79-92) at the last follow-up. The mean postoperative limb length discrepancy was 6.4 mm (range: 4-9 mm). Only one patient underwent revision due to bone in-growth failure of the femoral stem. One patient had an episode of postoperative dislocation and was treated with closed reduction without reoccurrence. Delayed union of the fracture site occurred in one patient. Patients who were previously treated with an intramedullary nail had a significantly shorter surgical duration, lesser intraoperative blood loss, and fewer blood transfusions than those who were previously treated with plate and screws. Kaplan-Meier survival rate with an endpoint of revision was 94.4% (95% confidence interval 72.7-99.9) at 5 years. CONCLUSION: Our results indicate that cementless THA is a beneficial and effective procedure for salvaging the failed treatment of subtrochanteric fractures. The Wagner conical prosthesis has shown satisfactory function outcomes, stable fixation, and survival rate for these complex situations. However, attention should be paid to increased operation time, blood loss, and complications when performing THA for subtrochanteric fractures with failed fixation devices especially, plates and screws.
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Artroplastia de Reemplazo de Cadera , Fracturas de Cadera , Prótesis de Cadera , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/efectos adversos , Femenino , Fémur/cirugía , Estudios de Seguimiento , Fracturas de Cadera/diagnóstico por imagen , Fracturas de Cadera/cirugía , Humanos , Masculino , Persona de Mediana Edad , Reoperación , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Some propitious mid- and long-term studies had been reported for MoM bearings; however, most studies have addressed specific patient groups rather than younger, active patients, who probably represent the most suitable population for investigations on wear and osteolysis. The purpose of this study to evaluate the long-term results of second-generation metal-on-metal cementless total hip arthroplasty (THA) in patients aged <50 years. METHODS: From December 1997 to January 2004, primary THA using a metal-on-metal bearing cementless implant was performed in 63 patients (72 hips) aged <50 years. The mean follow-up duration was 18.6 (range, 15.9-22.1) years, and the mean age at initial operation was 39 (range, 22-49) years. Clinical results, complications, survivorship, osteolysis, and aseptic loosening were evaluated. RESULTS: The mean Harris hip score and Western Ontario and McMaster Universities Arthritis Index scores were improved from 57.8 (range, 28-69) points and 73.4 (range, 63-94) points preoperatively to 91.7 (range, 80-100) points and 25.5 points (range, 17-38) points, respectively, at the last follow-up. Osteolysis lesions were found in 12 hips (acetabulum, 6 and femur, 6). The notching occurred on the femoral stem neck occurred in 12 hips. The mean serum cobalt and chromium concentrations were 2.3 (range, 0.2-10.6) µg/L and 1.7 (range, 0.4-8.1) µg/L, respectively, at a mean follow-up of 12.7 years in 32 patients (50.1%). The Kaplan-Meier survivorship curve analysis with revision for any reason as the endpoint revealed that 93.1% survived at 18.6 years' follow-up. CONCLUSIONS: Second-generation metal-on-metal cementless THA was found to produce satisfactory clinical and radiographic results with a low revision rate for osteolysis and aseptic loosening in patients aged less than 50 years.
Asunto(s)
Artroplastia de Reemplazo de Cadera/métodos , Prótesis Articulares de Metal sobre Metal , Adulto , Factores de Edad , Artroplastia de Reemplazo de Cadera/efectos adversos , Artroplastia de Reemplazo de Cadera/mortalidad , Biosimilares Farmacéuticos , Femenino , Humanos , Masculino , Prótesis Articulares de Metal sobre Metal/efectos adversos , Persona de Mediana Edad , Osteólisis/epidemiología , Osteólisis/etiología , Osteólisis/cirugía , Falla de Prótesis/etiología , Reoperación/estadística & datos numéricos , Tasa de Supervivencia , Factores de Tiempo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: This study aimed to explore mid-term clinical results of cementless total hip arthroplasty (THA) with modified trochanteric osteotomy in Crowe type IV developmental dysplasia of the hip (DDH). METHODS: Thirteen patients (13 hips) with Crowe type IV DDH who underwent THA with modified trochanteric osteotomy between May 2013 and October 2015 were retrospectively analyzed. The mean follow-up duration was 5.2 years (range, 4.9-6.1 years). RESULTS: The mean Harris Hip Score (HHS) significantly (p < 0.05) improved from 30.7 (range, 22-38) to 87.5 (range, 83-93). The mean leg length discrepancy (LLD) was 53.4 mm (range, 42.1-68.5 mm) preoperatively. The final LLD was 5.6 mm (range, 2.4-9.1 mm; p < 0.05). The mean leg length after surgery was 47.4 mm (range, 33.6-67.2 mm) and the femur shortening distance was 43.8 mm (range, 31.2-53.4 mm). The average duration of bone union for the greater trochanter (GT) was 2.5 months (range, 1.5-3.6 months). There was no infection, GT non-union, or loosening (septic or aseptic) of the stem or cup in any case. CONCLUSIONS: THA with modified trochanteric osteotomy with a cementless cup is an effective treatment for Crowe type IV DDH. It can rebuild complex biomechanics and biology of hip dysplasia without increasing complications.
Asunto(s)
Artroplastia de Reemplazo de Cadera , Displasia del Desarrollo de la Cadera/cirugía , Luxación Congénita de la Cadera , Adulto , Anciano , Displasia del Desarrollo de la Cadera/diagnóstico por imagen , Femenino , Fémur/diagnóstico por imagen , Fémur/cirugía , Luxación Congénita de la Cadera/diagnóstico por imagen , Luxación Congénita de la Cadera/cirugía , Humanos , Masculino , Persona de Mediana Edad , Osteotomía , Estudios RetrospectivosRESUMEN
BACKGROUND: This retrospective study was conducted to know clinical and radiographic outcomes, complication rate, and survival of THA in patients with high hip dislocation secondary to developmental dysplasia(DDH) or septic arthritis of the hip(SSH). METHODS: Between March 2005 and September 2014, there were consecutive series of 53 THAs in patients with a highly dislocated hip secondary to DDH or SSH. Of these, 48 hips (DDH 24 and SSH 24) were reviewed at a mean follow-up of 7.9 years(range, 5.0-14.3 years). The mean age at the time of THA was 39.1 years(range, 18.0-59.0 years). RESULTS: Intraoperative blood loss, total drainage and blood transfusion amounts, and mean time to greater trochanter union were significantly lower in the DDH group than in the SSH group (P = .001, P = .039 and P = .014, and P = .015, respectively). No significant difference in Kaplan-Meier survivorship was observed between groups (log-rank, P = .343). The survival rates with an endpoint of cup aseptic loosening in cases with a cemented cup at 7.9 and 10 years (68.1% and 60.5%, respectively) were significantly lower than those in cementless cup cases (100%) at the same checkpoints (P = .019).. CONCLUSION: We found similar clinical outcomes between the DDH and SSH groups. However, due to poor bone quality and a lack of containment, cementless acetabular cups could not be performed in more than 50% of patients. Our experience shows that revision cementless fixation cup was possible due to reconstitution of the acetabulum in cases with failed cemented fixation.
Asunto(s)
Artritis Infecciosa , Artroplastia de Reemplazo de Cadera , Luxación de la Cadera , Prótesis de Cadera , Acetábulo/cirugía , Artritis Infecciosa/etiología , Artritis Infecciosa/cirugía , Artroplastia de Reemplazo de Cadera/efectos adversos , Estudios de Seguimiento , Luxación de la Cadera/epidemiología , Luxación de la Cadera/etiología , Luxación de la Cadera/cirugía , Prótesis de Cadera/efectos adversos , Humanos , Falla de Prótesis , Reoperación , Estudios Retrospectivos , Análisis de SupervivenciaRESUMEN
INTRODUCTION: Prosthesis of antibiotic-loaded acrylic cement (PROSTALAC) is widely used in two-stage revision arthroplasty in periprosthetic joint infection (PJI) after total hip arthroplasty (THA). In our institution, we encountered several cases of acetabular cement spacer dislodgement. The aim of this study was to compare the results of two-stage revision arthroplasties with antibiotic-loaded cement spacers with or without screws on the acetabulum for PJI. PATIENTS AND METHODS: This retrospective study included 44 patients who underwent a two-stage revision THA for PJI from June 2007 to May 2017. We divided the patients into two groups: group 1 consisted of 21 patients (21 hips) who underwent two-stage revision arthroplasty with screw augmentation, while group 2 consisted of 23 patients (23 hips) who underwent the same surgery without screw augmentation at the acetabular cement spacer. We compared the migration and dislodgement of the acetabular cement spacer between the two groups. RESULTS: Before the second-stage surgery, there was less vertical migration of the cement spacer in group 1 compared to group 2 (1.2 mm vs 3.1 mm, p < 0.001). There was also less medial migration of the cement spacer in group 1 (0.6 mm vs 1.6 mm, p = 0.001). After the first stage, the mean Harris Hip score was significantly higher in group 1 than in group 2 (75 vs 65, p = 0.033). Cement spacer rotation or total movement out of the acetabular area occurred in six patients, all in group 2. After first stage reinfection occurred in two patients, one in each group. CONCLUSIONS: Screw augmentation to the acetabulum in the first-stage surgery provides better stability of acetabular antibiotic cement spacers without increasing reinfection rate.