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1.
Clin Res Hepatol Gastroenterol ; : 102413, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38960124

RESUMO

BACKGROUND: Prior typing methods fail to provide predictive insights into surgical complexities for extrahepatic choledochal cyst (ECC). This study aims to establish a new classification system for ECC through clustering of imaging results. Additionally, it seeks to compare the differences among the identified ECC types and assess the levels of surgical difficulty. METHODS: The imaging data of 124 patients were automatically grouped through a K-means clustering analysis. According to the characteristics of the new grouping, corrections and interventions were carried out to establish a new classification. Demographic data, clinical presentations, surgical parameters, complications, reoperation, and prognostic indicators were analyzed according to different types. Factors contributing to prolonged surgical time were also evaluated. RESULTS: A new classification system of ECC: Type A (upper segment), Type B (middle segment), Type C (lower segment), and Type D (entire bile duct). The incidences of comorbidities (calculus or infection) were significantly different (P=0.000, P=0.002). Additionally, variations in the incidence of postoperative cholangitis were statistically significant (P=0.046). The operative time was significantly different between groups (P=0.001). Age, BMI > 30, classification, and the presence of combined stones exhibit a significant association with prolonged operative time (P=0.002, P=0.000, P=0.011, P=0.011). CONCLUSION: In conclusion, our utilization of machine learning-driven cluster analysis has enabled the creation of a novel extrahepatic biliary dilatation typology. This classification, in conjunction with factors like age, combined stone occurrence, and obesity, significantly influences the complexity of laparoscopic choledochal cyst surgery, offering valuable insights for improved surgical treatment.

2.
J Am Chem Soc ; 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38968087

RESUMO

Molecule-inclusive closed cage compounds present a unique platform for molecular motion in an isolated environment. This study showcases the incorporation of a tadpole-like polar molecule (1-propyl-1H-imidazole, PIm) into a supramolecular cage formed by duad semicage p-tert-butylcalix[4]arene. The ferroelectric phase transition as well as the cage-confined motion of encapsulated PIm was studied in detail. The unusual quadrastable state of the PIm in the paraelectric phase allows for the modulation of dipolar polarization over a broad temperature/frequency range. This compound represents the first example of a clathrate molecular ferroelectric featuring a molecule-inclusive supramolecular cage, and it also contributes to the understanding of cage-confined molecular dynamics.

3.
J Med Microbiol ; 73(7)2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38967406

RESUMO

Introduction. Cold plasma is frequently utilized for the purpose of eliminating microbial contaminants. Under optimal conditions, it can function as plasma medicine for treating various diseases, including infections caused by Candida albicans, an opportunistic pathogen that can overgrow in individuals with weakened immune system.Gap Statement. To date, there has been less molecular study on cold plasma-treated C. albicans.Research Aim. The study aims to fill the gap in understanding the molecular response of C. albicans to cold plasma treatment.Methodology. This project involved testing a cold plasma generator to determine its antimicrobial effectiveness on C. albicans' planktonic cells. Additionally, the cells' transcriptomics responses were investigated using RNA sequencing at various treatment durations (1, 3 and 5 min).Results. The results show that our cold plasma effectively eliminates C. albicans. Cold plasma treatment resulted in substantial downregulation of important pathways, such as 'nucleotide metabolism', 'DNA replication and repair', 'cell growth', 'carbohydrate metabolism' and 'amino acid metabolism'. This was an indication of cell cycle arrest of C. albicans to preserve energy consumption under unfavourable conditions. Nevertheless, C. albicans adapted its GSH antioxidant system to cope with the oxidative stress induced by reactive oxygen species, reactive nitrogen species and other free radicals. The treatment likely led to a decrease in cell pathogenicity as many virulence factors were downregulated.Conclusion. The study demonstrated the major affected pathways in cold plasma-treated C. albicans, providing valuable insights into the molecular response of C. albicans to cold plasma treatment. The findings contribute to the understanding of the antimicrobial efficiency of cold plasma and its potential applications in the field of microbiology.


Assuntos
Candida albicans , Perfilação da Expressão Gênica , Gases em Plasma , Candida albicans/genética , Candida albicans/efeitos dos fármacos , Gases em Plasma/farmacologia , Plâncton/genética , Transcriptoma , Estresse Oxidativo , Regulação Fúngica da Expressão Gênica , Espécies Reativas de Oxigênio/metabolismo , Humanos
4.
Bone Joint Res ; 13(7): 332-341, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38964744

RESUMO

Aims: Although low-intensity pulsed ultrasound (LIPUS) combined with disinfectants has been shown to effectively eliminate portions of biofilm in vitro, its efficacy in vivo remains uncertain. Our objective was to assess the antibiofilm potential and safety of LIPUS combined with 0.35% povidone-iodine (PI) in a rat debridement, antibiotics, and implant retention (DAIR) model of periprosthetic joint infection (PJI). Methods: A total of 56 male Sprague-Dawley rats were established in acute PJI models by intra-articular injection of bacteria. The rats were divided into four groups: a Control group, a 0.35% PI group, a LIPUS and saline group, and a LIPUS and 0.35% PI group. All rats underwent DAIR, except for Control, which underwent a sham procedure. General status, serum biochemical markers, weightbearing analysis, radiographs, micro-CT analysis, scanning electron microscopy of the prostheses, microbiological analysis, macroscope, and histopathology evaluation were performed 14 days after DAIR. Results: The group with LIPUS and 0.35% PI exhibited decreased levels of serum biochemical markers, improved weightbearing scores, reduced reactive bone changes, absence of viable bacteria, and decreased inflammation compared to the Control group. Despite the greater antibiofilm activity observed in the PI group compared to the LIPUS and saline group, none of the monotherapies were successful in preventing reactive bone changes or eliminating the infection. Conclusion: In the rat model of PJI treated with DAIR, LIPUS combined with 0.35% PI demonstrated stronger antibiofilm potential than monotherapy, without impairing any local soft-tissue.

5.
Sci Data ; 11(1): 735, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971852

RESUMO

The leaf beetle Ophraella communa LeSage (Coleoptera: Chrysomelidae) is an effective biological control agent of the common ragweed. Here, we assembled a chromosome-level genome of the O. communa by combining Illumina, Nanopore, and Hi-C sequencing technologies. The genome size of the final genome assembly is 733.1 Mb, encompassing 17 chromosomes, with an improved contig N50 of 7.05 Mb compared to the original version. Genome annotation reveals 25,873 protein-coding genes, with functional annotations available for 22,084 genes (85.35%). Non-coding sequence annotation identified 204 rRNAs, 626 tRNAs, and 1791 small RNAs. Repetitive elements occupy 414.41 Mb, constituting 57.76% of the genome. This high-quality genome is fundamental for advancing biological control strategies employing O. communa.


Assuntos
Besouros , Genoma de Inseto , Besouros/genética , Animais , Anotação de Sequência Molecular , Cromossomos de Insetos
6.
Artigo em Inglês | MEDLINE | ID: mdl-38973529

RESUMO

BACKGROUND: The objective of antiviral therapy for chronic viral hepatitis B infection (CHB) is to achieve a functional cure. An important viral marker in the serum of patients with CHB is the serum hepatitis B core-related antigen (HBcrAg). However, there is limited research on HBcrAg in juvenile patients with CHB. In this study, we aimed to investigate the correlation between serum HBcrAg and other hepatitis B virus (HBV) markers in children with CHB and its predictive significance for prognosis during antiviral therapy. METHODS: A single-center retrospective study was conducted involving 79 children with CHB, aged between 0 and 16 years. All the children were treated with interferon [or combined nucleos(t)ide analogs] for 48 weeks. HBcrAg, hepatitis B surface antigen (HBsAg), and HBV DNA were measured before treatment, and at 12 and 48 weeks after treatment. The enrolled children were classified into the seroclearance group and the nonseroclearance group based on the therapeutic outcome. RESULTS: HBsAg seroclearance was observed in 28 out of 79 patients and hepatitis B e antigen seroconversion without HBsAg seroclearance was observed in 14 out of 79 patients following the conclusion of the treatment, with baseline HBcrAg titer levels showing no statistical significance in both the seroclearance and nonseroclearance groups (P = 0.277). HBsAg and HBV DNA were positively correlated with HBcrAg in children with CHB (R2 = 0.3289, 0.4388). The area under the receiver operating characteristic curve of the decrease in HBcrAg at 12 weeks of treatment as a predictor of seroclearance at 48 weeks of treatment, exhibited a value of 0.77. CONCLUSION: A decrease in serum HBcrAg levels in children with hepatitis B serves as a prognostic indicator.

7.
Heliyon ; 10(12): e32173, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-38975162

RESUMO

A 19-year-old man presented with recurrent intermittent fever, progressive limbs weakness, numbness, and atrophy for 5 years. Biopsy of the sural nerve, spleen, lymph nodes, bone marrow and labial gland revealed that monomorphic small lymphoid cells infiltrated diffusely and that there was severe loss of large myelinated nerve fibers. Immunohistochemically, these cells were mainly CD8-positive T cells and were positive for CD3 and CD57. This patient was diagnosed as indolent CD8-positive T lymphoproliferative disorder (indolent CD8-positive T-LPD), emphasizing the need for a broad differential diagnosis under these conditions, and nerve biopsy should be performed.

8.
Chem ; 10(6): 1868-1884, 2024 Jun 13.
Artigo em Inglês | MEDLINE | ID: mdl-38975291

RESUMO

Phosphorus Fluoride Exchange (PFEx), recently debuted in small molecules, represents the forefront of click chemistry. To explore PFEx's potential in biological settings, we developed amino acids PFY and PFK featuring phosphoramidofluoridates and incorporated them into proteins through genetic code expansion. PFY/PFK selectively reacted with nearby His, Tyr, Lys, or Cys in proteins, both in vitro and in living cells, demonstrating that proximity enabled PFEx reactivity without external reagents. The reaction with His showed unique pH-dependent properties and created thermally sensitive linkages. Additionally, Na2SiO3 enhanced PFEx reactions with Tyr and Cys. PFEx, by generating defined covalent P-N/O linkages, extends the utility of phosphorus linkages in proteins, aligning with nature's use of phosphate connectors in other biomolecules. More versatile and durable than SuFEx, PFEx in proteins expands the latent bioreactive arsenal for covalent protein engineering and will facilitate the broad application of this potent click chemistry in biological and biomedical fields.

9.
Adv Healthc Mater ; : e2400784, 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38896790

RESUMO

Immunotherapy has emerged as a powerful weapon against lung cancer, yet only a fraction of patients respond to the treatment. Poly(I:C) (PIC) effectively triggers both innate and adaptive immunity. It can also induce immunogenic cell death (ICD) in tumor cells. However, its efficacy is hindered by its instability in vivo and limited cellular uptake. To address this, PIC is encapsulated in cRGD-functionalized polymersomes (t-PPIC), which significantly increases its stability and uptake, thus activating dendritic cells (DCs) and inducing apoptosis of lung tumor cells in vitro. In a murine LLC lung tumor model, systemic administration of t-PPIC effectively suppresses tumor growth and leads to survival benefits, with 40% of the mice becoming tumor-free. Notably, t-PPIC provokes stronger apoptosis and ICD in tumor tissue and elicits a more potent stimulation of DCs, recruitment of natural killer (NK) cells, and activation of CD8+ T cells, compared to free PIC and nontargeted PPIC controls. Furthermore, when combined with immune checkpoint inhibitors or radiotherapy, t-PPIC amplifies the antitumor immune response, resulting in complete regression in 60% of the mice. These compelling findings underscore the potential of integrin-targeted polymersomal PIC to enhance antitumor immunity by simultaneously inducing ICD and systemic immune activation.

10.
Hepatobiliary Surg Nutr ; 13(3): 494-499, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38911193

RESUMO

Laparoscopic anatomical hepatectomy (LAH) for patients with hepatocellular carcinoma (HCC) has been advocated by many surgeons in the hope of producing better oncological outcomes. Two recent techniques, 3D laparoscopic system and 2D real-time indocyanine green fluorescence imaging (r-ICG) guidance, are benefit for improving the operative precision of LAH in different aspects. However, these two techniques cannot be applied concomitantly because of the technical limitation. Although a new modern laparoscopic system with both 3D and indocyanine green (ICG) imaging mode has been designed, it has not been listed in many countries including China. Thus, we design a new procedure to perform the 3D LAH with 2D r-ICG guidance for HCCs with conventional laparoscopic systems. In this procedure, both 3D and 2D laparoscopic systems were used. A total of 11 patients with HCC received 3D laparoscopic right posterior sectionectomy (LRPS) with 2D r-ICG guidance. The right posterior Glissonian pedicle was clamped under the 3D vision. Then ICG solution was then intravenously administrated. The liver parenchyma was transected under the 3D vision and guided by 2D ICG vision simultaneously. There was no severe complications (Clavien-Dindo ≥III) and operation related death. The 90-day mortality was also nil. By using this procedure, the advantages of two techniques, 3D laparoscopic system and 2D r-ICG guidance, were combined so that LAH could be performed with more precision. However, it should be validated in more studies.

12.
Chem Rev ; 2024 Jun 24.
Artigo em Inglês | MEDLINE | ID: mdl-38913432

RESUMO

Interactions among biomacromolecules, predominantly noncovalent, underpin biological processes. However, recent advancements in biospecific chemistry have enabled the creation of specific covalent bonds between biomolecules, both in vitro and in vivo. This Review traces the evolution of biospecific chemistry in proteins, emphasizing the role of genetically encoded latent bioreactive amino acids. These amino acids react selectively with adjacent natural groups through proximity-enabled bioreactivity, enabling targeted covalent linkages. We explore various latent bioreactive amino acids designed to target different protein residues, ribonucleic acids, and carbohydrates. We then discuss how these novel covalent linkages can drive challenging protein properties and capture transient protein-protein and protein-RNA interactions in vivo. Additionally, we examine the application of covalent peptides as potential therapeutic agents and site-specific conjugates for native antibodies, highlighting their capacity to form stable linkages with target molecules. A significant focus is placed on proximity-enabled reactive therapeutics (PERx), a pioneering technology in covalent protein therapeutics. We detail its wide-ranging applications in immunotherapy, viral neutralization, and targeted radionuclide therapy. Finally, we present a perspective on the existing challenges within biospecific chemistry and discuss the potential avenues for future exploration and advancement in this rapidly evolving field.

13.
Front Immunol ; 15: 1402395, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38895112

RESUMO

Background: Circadian rhythm disruption (CRD) is thought to increase the risk of inflammatory bowel disease. The deletion of Bmal1, a core transcription factor, leads to a complete loss of the circadian rhythm and exacerbates the severity of dextran sodium sulfate (DSS)-induced colitis in mice. However, the underlying mechanisms by which CRD and Bmal1 mediate IBD are still unclear. Methods: We used a CRD mouse model, a mouse colitis model, and an in vitro model of colonic epithelial cell monolayers. We also knocked down and overexpressed Bmal1 in Caco-2 cells by transfecting lentivirus in vitro. The collected colon tissue and treated cells were assessed and analyzed using immunohistochemistry, immunofluorescence staining, quantitative reverse transcription-polymerase chain reaction, western blot, flow cytometry, transmission electron microscopy, and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labelling staining. Results: We found that CRD mice with downregulated Bmal1 expression were more sensitive to DSS-induced colitis and had more severely impaired intestinal barrier function than wild-type mice. Bmal1-/- mice exhibited more severe colitis, accompanied by decreased tight junction protein levels and increased apoptosis of intestinal epithelial cells compared with wild-type mice, which were alleviated by using the autophagy agonist rapamycin. Bmal1 overexpression attenuated Lipopolysaccharide-induced apoptosis of intestinal epithelial cells and impaired intestinal epithelial cells barrier function in vitro, while inhibition of autophagy reversed this protective effect. Conclusion: This study suggests that CRD leads to the downregulation of Bmal1 expression in the colon, which may exacerbate DSS-induced colitis in mice, and that Bmal1 may serve as a novel target for treating inflammatory bowel disease.


Assuntos
Fatores de Transcrição ARNTL , Ritmo Circadiano , Colite , Sulfato de Dextrana , Modelos Animais de Doenças , Regulação para Baixo , Mucosa Intestinal , Camundongos Knockout , Animais , Fatores de Transcrição ARNTL/genética , Fatores de Transcrição ARNTL/metabolismo , Colite/induzido quimicamente , Colite/metabolismo , Camundongos , Mucosa Intestinal/metabolismo , Mucosa Intestinal/patologia , Humanos , Ritmo Circadiano/genética , Células CACO-2 , Camundongos Endogâmicos C57BL , Apoptose , Masculino , Transtornos Cronobiológicos/metabolismo , Transtornos Cronobiológicos/genética
14.
Hip Pelvis ; 36(2): 101-107, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38825819

RESUMO

Treatment of femoral bone defects continues to be a challenge in revision total hip arthroplasty (THA); therefore, meticulous preoperative evaluation of patients and surgical planning are required. This review provides a concise synopsis of the etiology, classification, treatment strategy, and prosthesis selection in relation to femoral bone loss in revision THA. A search of literature was conducted for identification of research articles related to classification of bone loss, management of femoral revision, and comparison of different types of stems. Findings of a thorough review of the included articles were as follows: (1) the Paprosky classification system is used most often when defining femoral bone loss, (2) a primary-length fully coated monoblock femoral component is recommended for treatment of types I or II bone defects, (3) use of an extensively porouscoated stem and a modular fluted tapered stem is recommended for management of types III or IV bone defects, and (4) use of an impaction grafting technique is another option for improvement of bone stock, and allograft prosthesis composite and proximal femoral replacement can be applied by experienced surgeons, in selected cases, as a final salvage solution. Stems with a tapered design are gradually replacing components with a cylindrical design as the first choice for femoral revision; however, further confirmation regarding the advantages and disadvantages of modular and nonmodular stems will be required through conduct of higher-level comparative studies.

15.
Arthroplasty ; 6(1): 31, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38840191

RESUMO

The management of periprosthetic joint infection (PJI) and surgical site infection (SSI) after joint arthroplasty poses a major challenge in orthopedic surgery. This Editorial provides an overview of the studies published in the special issue "Management of PJI/SSI after Joint Arthroplasty", summarizing the key findings from these studies, which cover a wide range of topics, including stringent preventive strategies, comprehensive diagnostic methods, and personalized treatment modalities. The authors concluded the editorial with their perspectives regarding the status quo of research in this field and future directions for research, such as the development of novel antibiotics, biofilm research, patient-specific risk factors, and the integration of technological advancements (such as machine learning and artificial intelligence) into clinical practice. The authors emphasized the need for continued research, interdisciplinary collaboration, and the application of innovative technologies to enhance patient outcomes and mitigate the burden of these infections on healthcare systems.

16.
Front Oncol ; 14: 1366449, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38846978

RESUMO

Background: Kidney cancer is a prevalent malignancy with an increasing incidence worldwide. Blood cell indices and inflammation-related markers have shown huge potential as biomarkers for predicting cancer incidences, but that is not clear in kidney cancer. Our study aims to investigate the correlations of blood cell indices and inflammation-related markers with kidney cancer risk. Methods: We performed a population-based cohort prospective analysis using data from the UK Biobank. A total of 466,994 participants, free of kidney cancer at baseline, were included in the analysis. The hazard ratios (HRs) and 95% confidence intervals (CIs) for kidney cancer risk were calculated using Cox proportional hazards regression models. Restricted cubic spline models were used to investigate nonlinear longitudinal associations. Stratified analyses were used to identify high-risk populations. The results were validated through sensitivity analyses. Results: During a mean follow-up of 12.4 years, 1,710 of 466,994 participants developed kidney cancer. The Cox regression models showed that 13 blood cell indices and four inflammation-related markers were associated with kidney cancer incidence. The restricted cubic spline models showed non-linear relationships with kidney cancer. Finally, combined with stratified and sensitivity analyses, we found that the mean corpuscular hemoglobin concentration (MCHC), red blood cell distribution width (RDW), platelet distribution width (PDW), systemic immune-inflammation index (SII), and product of platelet count and neutrophil count (PPN) were related to enhanced kidney cancer risk with stable results. Conclusion: Our findings identified that three blood cell indices (MCHC, RDW, and PDW) and two inflammation-related markers (SII and PPN) were independent risk factors for the incidence of kidney cancer. These indexes may serve as potential predictors for kidney cancer and aid in the development of targeted screening strategies for at-risk individuals.

17.
Sci Data ; 11(1): 582, 2024 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-38834623

RESUMO

The western flower thrips Frankliniella occidentalis (Thysanoptera: Thripidae) is a global invasive species that causes increasing damage by direct feeding on crops and transmission of plant viruses. Here, we assemble a previously published scaffold-level genome into a chromosomal level using Hi-C sequencing technology. The assembled genome has a size of 302.58 Mb, with a contig N50 of 1533 bp, scaffold N50 of 19.071 Mb, and BUSCO completeness of 97.8%. All contigs are anchored on 15 chromosomes. A total of 16,312 protein-coding genes are annotated in the genome with a BUSCO completeness of 95.2%. The genome contains 492 non-coding RNA, and 0.41% of interspersed repeats. In conclusion, this high-quality genome provides a convenient and high-quality resource for understanding the ecology, genetics, and evolution of thrips.


Assuntos
Genoma de Inseto , Tisanópteros , Tisanópteros/genética , Animais
18.
Int J Biol Sci ; 20(8): 3008-3027, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38904013

RESUMO

SET domain containing 7(SETD7), a member of histone methyltransferases, is abnormally expressed in multiple tumor types. However, the biological function and underlying molecular mechanism of SETD7 in clear cell renal cell carcinoma (ccRCC) remain unclear. Here, we explored the biological effects of SETD7-TAF7-CCNA2 axis on proliferation and metastasis in ccRCC. We identified both SETD7 and TAF7 were up-regulated and significantly promoted the proliferation and migration of ccRCC cells. Concurrently, there was a significant positive correlation between the expression of SETD7 and TAF7, and the two were colocalized in the nucleus. Mechanistically, SETD7 methylates TAF7 at K5 and K300 sites, resulting in the deubiquitination and stabilization of TAF7. Furthermore, re-expression of TAF7 could partially restore SETD7 knockdown inhibited ccRCC cells proliferation and migration. In addition, TAF7 transcriptionally activated to drive the expression of cyclin A2 (CCNA2). And more importantly, the methylation of TAF7 at K5 and K300 sites exhibited higher transcriptional activity of CCNA2, which promotes formation and progression of ccRCC. Our findings reveal a unique mechanism that SETD7 mediated TAF7 methylation in regulating transcriptional activation of CCNA2 in ccRCC progression and provide a basis for developing effective therapeutic strategies by targeting members of SETD7-TAF7-CCNA2 axis.


Assuntos
Carcinoma de Células Renais , Movimento Celular , Proliferação de Células , Histona-Lisina N-Metiltransferase , Neoplasias Renais , Humanos , Carcinoma de Células Renais/metabolismo , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Proliferação de Células/genética , Histona-Lisina N-Metiltransferase/metabolismo , Histona-Lisina N-Metiltransferase/genética , Movimento Celular/genética , Neoplasias Renais/metabolismo , Neoplasias Renais/genética , Neoplasias Renais/patologia , Linhagem Celular Tumoral , Fatores Associados à Proteína de Ligação a TATA/metabolismo , Fatores Associados à Proteína de Ligação a TATA/genética , Metilação , Fator de Transcrição TFIID/metabolismo , Fator de Transcrição TFIID/genética , Regulação Neoplásica da Expressão Gênica
19.
Arthroplasty ; 6(1): 38, 2024 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-38907318

RESUMO

BACKGROUND: The use of long stems for severe femoral bone defects is suggested by many scholars, but it is associated with further bone loss, intraoperative fracture, increased surgical trauma, and complications. With better bone retention, simple and quick surgical procedures, and minimal complications, the short cementless stems with a tapered rectangular shape may be an alternative for femoral revision. This study aimed to evaluate the results of this type of stem in treating selected Paprosky II-IV bone defects. METHODS: This retrospective study included 73 patients (76 hips involved) who underwent conservative femoral revision using the short cementless stems with a tapered rectangular shape between January 2012 and December 2020. The preoperative femoral bone defects were identified as follows: 54 cases of type II, 11 cases of type IIIA, 7 cases of type IIIB, and 4 cases of type IV. Indications for revision included aseptic loosening (76.3%) and prosthetic joint infection (23.7%). Six cementless stems with a tapered rectangular shape from three companies were used in all patients. Among them, SLR-Plus, SL-Plus MIA, and Corail stems were employed in most patients (40.8%, 23.7%, and 17.1%, respectively). The average length of these stems measured 171.7 mm (SD 27 mm; 122-215 mm). Radiographic results, Harris hip scores (HHS), complications, and survivorship were analyzed. The follow-up lasted for 7 years on average (range 3-11 years). RESULTS: The subsidence was observed in three hips (3.9%), and all stems achieved stable bone ingrowth. Proximal femoral bone restoration in the residual osteolytic area was found in 67 hips (88.2%), constant defects in nine hips (11.8%), and increasing defects in 0 cases. There was no evidence of stem fractures and stem loosening in this series. The mean HHS significantly improved from 32 (range 15-50) preoperatively to 82 (range 68-94) at the last follow-up (t = - 36.297, P < 0.001). Five hips developed prosthesis-related complications, including three infection and two dislocation cases. The mean 5- and 10-year revision-free survivorships for any revision or removal of an implant and reoperation for any reason were 94.6% and 93.3%, respectively. Both mean 5- and 10-year revision-free survivorships for aseptic femoral loosening were 100%. CONCLUSION: Conservative femoral revision using short cementless stems with a tapered rectangular shape can provide favorable radiographic outcomes, joint function, and mid-term survivorship with minimal complications. Of note, a sclerotic proximal femoral bone shell with continued and intact structure and enough support strength is the indication for using these stems.

20.
Cell Death Dis ; 15(6): 427, 2024 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-38890303

RESUMO

As the second most common malignant tumor in the urinary system, renal cell carcinoma (RCC) is imperative to explore its early diagnostic markers and therapeutic targets. Numerous studies have shown that AURKB promotes tumor development by phosphorylating downstream substrates. However, the functional effects and regulatory mechanisms of AURKB on clear cell renal cell carcinoma (ccRCC) progression remain largely unknown. In the current study, we identified AURKB as a novel key gene in ccRCC progression based on bioinformatics analysis. Meanwhile, we observed that AURKB was highly expressed in ccRCC tissue and cell lines and knockdown AURKB in ccRCC cells inhibit cell proliferation and migration in vitro and in vivo. Identified CDC37 as a kinase molecular chaperone for AURKB, which phenocopy AURKB in ccRCC. AURKB/CDC37 complex mediate the stabilization of MYC protein by directly phosphorylating MYC at S67 and S373 to promote ccRCC development. At the same time, we demonstrated that the AURKB/CDC37 complex activates MYC to transcribe CCND1, enhances Rb phosphorylation, and promotes E2F1 release, which in turn activates AURKB transcription and forms a positive feedforward loop in ccRCC. Collectively, our study identified AURKB as a novel marker of ccRCC, revealed a new mechanism by which the AURKB/CDC37 complex promotes ccRCC by directly phosphorylating MYC to enhance its stability, and first proposed AURKB/E2F1-positive feedforward loop, highlighting AURKB may be a promising therapeutic target for ccRCC.


Assuntos
Aurora Quinase B , Carcinoma de Células Renais , Proteínas de Ciclo Celular , Progressão da Doença , Fator de Transcrição E2F1 , Neoplasias Renais , Proteínas Proto-Oncogênicas c-myc , Humanos , Carcinoma de Células Renais/genética , Carcinoma de Células Renais/patologia , Carcinoma de Células Renais/metabolismo , Fator de Transcrição E2F1/metabolismo , Fator de Transcrição E2F1/genética , Neoplasias Renais/patologia , Neoplasias Renais/genética , Neoplasias Renais/metabolismo , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Fosforilação , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Proto-Oncogênicas c-myc/genética , Aurora Quinase B/metabolismo , Aurora Quinase B/genética , Proliferação de Células , Animais , Regulação Neoplásica da Expressão Gênica , Camundongos Nus , Camundongos , Movimento Celular/genética , Chaperoninas
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