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1.
Metabolomics ; 19(4): 32, 2023 03 30.
Artigo em Inglês | MEDLINE | ID: mdl-36997715

RESUMO

INTRODUCTION: Acute ischemic stroke (AIS) accounts for the majority of all stroke, globally the second leading cause of death. Due to its rapid development after onset, its early diagnosis is crucial. OBJECTIVES: We aim to identify potential highly reliable blood-based biomarkers for early diagnosis of AIS using quantitative plasma lipid profiling via a machine learning approach. METHODS: Lipidomics was used for quantitative plasma lipid profiling, based on ultra-performance liquid chromatography tandem mass spectrometry. Our samples were divided into a discovery and a validation set, each containing 30 AIS patients and 30 health controls (HC). Differentially expressed lipid metabolites were screened based on the criteria VIP > 1, p < 0.05, and fold change > 1.5 or < 0.67. The least absolute shrinkage and selection operator (LASSO) and random forest algorithms in machine learning were used to select differential lipid metabolites as potential biomarkers. RESULTS: Three key differential lipid metabolites, CarnitineC10:1, CarnitineC10:1-OH and Cer(d18:0/16:0), were identified as potential biomarkers for early diagnosis of AIS. The former two, associated with thermogenesis, were down-regulated, whereas the latter, associated with necroptosis and sphingolipd metabolism, was upregulated. Univariate and multivariate logistic regressions showed that these three lipid metabolites and the resulting diagnostic model exhibited a strong ability in discriminating between AIS patients and HCs in both the discovery and validation sets, with an area under the curve above 0.9. CONCLUSIONS: Our work provides valuable information on the pathophysiology of AIS and constitutes an important step toward clinical application of blood-based biomarkers for diagnosing AIS.


Assuntos
AVC Isquêmico , Lipidômica , Humanos , Metabolômica , Biomarcadores , Diagnóstico Precoce , Lipídeos
2.
J Biochem Mol Toxicol ; 37(10): e23435, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37352117

RESUMO

Vestigial like family member 4 (VGLL4), a member of the Hippo pathway, is a transcriptional cofactor involved in many biological processes, such as tumor progression, postnatal heart growth, and muscle regeneration. However, the VGLL4 expression pattern in vivo remains unclear. To detect and trace Vgll4-expressing cells and their progeny, we generated and characterized a new tamoxifen-inducible Dre knock-in mouse line, Vgll4-DreER. This mouse line expressed DreER (Dre recombinase fused to the estrogen receptor) under the control of the endogenous Vgll4 promoter. After crossing the Vgll4-DreER mouse line with the Dre-responsive reporter H11-rRFP, Dre-mediated recombination in the tissue was monitored on the basis of red fluorescent protein (RFP) signals, which indicated the distribution of VGLL4-positive cells in vivo. Our data revealed that VGLL4 is widely expressed in various cell types at embryonic and neonatal stages. After comparison with our previously reported Vgll4-GFP mouse, we found that the RFP signal profile was wider than the green fluorescent protein (GFP) pattern, indicating that Vgll4-DreER is more sensitive for labeling VGLL4-expressing cells. We next used a dual-recombination system to simultaneously label VGLL4- and keratin 5 (KRT5)-positive cell populations, and no crosstalk was observed in the Krt5-CreER;Vgll4-DreER;R26-rGlR mice. Taken together, the Vgll4-DreER mouse line is a valuable new tool for examining the precise VGLL4 expression profile and conditional manipulating of VGLL4-expressing cells and their progeny.


Assuntos
Tamoxifeno , Fatores de Transcrição , Camundongos , Animais , Camundongos Transgênicos , Tamoxifeno/farmacologia , Fatores de Transcrição/genética
3.
J Clin Lab Anal ; 37(5): e24855, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36916827

RESUMO

BACKGROUND: Pharmacogenomics (PGx) examines the influence of genetic variation on drug responses. With more and more Clinical Pharmacogenetics Implementation Consortium (CPIC) guidelines published, PGx is gradually shifting from the reactive testing of single gene toward the preemptive testing of multiple genes. But the profile of PGx genes, especially for the intra-country diversity, is not well understood in China. METHODS: We retrospectively collected preemptive PGx testing data of 22,918 participants from 20 provinces of China, analyzed frequencies of alleles, genotypes and phenotypes of pharmacogenes, predicted drug responses for each participant, and performed comparisons between different provinces. RESULTS AND CONCLUSION: After analyzing 15 pharmacogenes from CPIC guidelines of 31 drugs, we found that 99.97% of individuals may have an atypical response to at least one drug; the participants carry actionable genotypes leading to atypical dosage recommendation for a median of eight drugs. Over 99% of the participants were recommended a decreased warfarin dose based on genetic factors. There were 20 drugs with high-risk ratios from 0.18% to 58.25%, in which clopidogrel showed the highest high-risk ratio. In addition, the high-risk ratio of rasburicase in GUANGDONG (risk ratio (RR) = 13.17, 95%CI:4.06-33.22, p < 0.001) and GUANGXI (RR = 23.44, 95%CI:8.83-52.85, p < 0.001) were significantly higher than that in all provinces. Furthermore, the diversity we observed among 20 provinces suggests that preemptive PGx testing in different geographical regions in China may need to pay more attention to specific genes. These results emphasize the importance of preemptive PGx testing and provide essential evidence for promoting clinical implementation in China.


Assuntos
Farmacogenética , Testes Farmacogenômicos , Humanos , Estudos Retrospectivos , China , Farmacogenética/métodos , Genótipo
4.
BMC Musculoskelet Disord ; 23(1): 820, 2022 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-36042443

RESUMO

BACKGROUND: The influence of thread profile on the fixation stability of bone screws remains unclear. This study aimed to compare the fixation stability of screws with different thread profiles under several loading conditions. METHODS: Bone screws that differed in thread profile (buttress, triangle, and square thread) only were made of stainless steel. Their fixation stabilities were evaluated individually by the axial pullout test and lateral migration test, besides, they were also evaluated in pairs together with a dynamic compression plate and a locking plate in polyurethane foam blocks under cyclic craniocaudal and torsional loadings. RESULTS: The triangle-threaded and square-threaded screws had the highest pullout forces and lateral migration resistance. When being applied to a dynamic compression plate, higher forces and more cycles were required for both triangle- and square-threaded screws to reach the same displacement under cyclic craniocaudal loading. On the other hand, the triangle-threaded screws required a higher torque and more cycles to reach the same angular displacement under cyclic torsional loading. When being applied to a locking plate, the square-threaded screws needed higher load, torque, and more cycles to reach the same displacement under both cyclic craniocaudal and torsion loadings. CONCLUSIONS: The triangle-threaded screws had superior pullout strength, while square-threaded screws demonstrated the highest lateral migration resistance. Moreover, dynamic compression plate fixation with triangle- and square-threaded screws achieved more favorable fixation stability under craniocaudal loading, while triangle-threaded screws demonstrated superior fixation stability under torsional loading. Locking plate fixation with a square-threaded screw achieved better fixation stability under both loading types.


Assuntos
Placas Ósseas , Parafusos Ósseos , Fenômenos Biomecânicos , Fixação Interna de Fraturas , Humanos , Aço Inoxidável , Torque
5.
Anal Chem ; 92(14): 10114-10120, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32580543

RESUMO

A gold nanoparticle (AuNPs)/gallium nitride (GaN) Schottky junction was fabricated by growing AuNPs in situ on the surface of GaN and then etched by H2O2 to appropriate diameter. The photogenerated electrons of GaN can be captured and transferred by the AuNPs to increase the migration efficiency, and the electron-hole pairs were separated, which results in the enhancement of the photoelectric performance of the system. The Fermi energy level of AuNPs and the charge transfer efficiency of the AuNPs/GaN can be adjusted by controlling the size of the AuNPs. Then the AuNPs/GaN Schottky photoelectrode had been applied to develop a novel photoelectrochemical (PEC) aptasensor for the epithelial ovarian cancer marker-CA125 detection. The DNA aptamer of CA125 was modified on the surface of the AuNPs via Au-S bonds. The aptamer can bind with the target with high selectivity, and the photoelectron transfer process of the system can be blocked by the protein, which results in the decrease of the photocurrent of the system. The ratio of photocurrent before and after incubation with CA125 (I1/I0) has a linear with the concentration of CA125 in the range of 1-100 U/mL with a detection limit of 0.3 U/mL. The standard addition recovery rates were between 86.01% and 90.09%. This method showed good sensitivity, selectivity, and reliability in detecting CA125 in serum.


Assuntos
Aptâmeros de Nucleotídeos/química , Biomarcadores Tumorais/análise , Antígeno Ca-125/análise , Carcinoma Epitelial do Ovário/diagnóstico , Técnicas Eletroquímicas , Proteínas de Membrana/análise , Neoplasias Ovarianas/diagnóstico , Feminino , Gálio/química , Ouro/química , Humanos , Nanopartículas Metálicas/química , Tamanho da Partícula , Processos Fotoquímicos , Propriedades de Superfície
6.
Biochem Biophys Res Commun ; 502(2): 269-275, 2018 07 12.
Artigo em Inglês | MEDLINE | ID: mdl-29803672

RESUMO

Neuroinflammation plays a critical role in the process of neurodegenerative disorders, during which microglia, the principal resident immune cells in the central nervous system, are activated and produce proinflammatory mediators. Yin-Yang 1 (YY1), a multi-functional transcription factor, is widely expressed in cells of the immune system and participate in various cellular processes. However, whether YY1 is involved in the process of neuroinflammation is still unknown. In the present study, we found that YY1 was progressively up-regulated in BV2 microglial cells stimulated with lipopolysaccharide (LPS), which was dependent on the transactivation function of nuclear factor kappa B (NF-κB). Furthermore, YY1 knockdown notably inhibited LPS-induced the activation of NF-κB signaling and interleukin-6 (IL-6) expression in BV-2 cells, but not mitogen-activated protein kinase (MAPK) signaling. Moreover, YY1 strengthened p65 binding to IL-6 promoter by interacting with p65 but decreased H3K27ac modification on IL-6 promoter, eventually increasing IL-6 transcription. Taken together, these results for the first time uncover the regulatory mechanism of YY1 on IL-6 expression during neuroinflammation responses and provide new lights into neuroinflammation.


Assuntos
Interleucina-6/genética , Interleucina-6/metabolismo , Microglia/metabolismo , Fator de Transcrição RelA/metabolismo , Fator de Transcrição YY1/metabolismo , Animais , Linhagem Celular , Técnicas de Silenciamento de Genes , Histona Desacetilase 1/metabolismo , Inflamação/etiologia , Inflamação/genética , Inflamação/metabolismo , Lipopolissacarídeos/toxicidade , Camundongos , Microglia/efeitos dos fármacos , Regiões Promotoras Genéticas , Transdução de Sinais , Ativação Transcricional , Regulação para Cima/efeitos dos fármacos , Fator de Transcrição YY1/antagonistas & inibidores , Fator de Transcrição YY1/genética
7.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 36(12): 1515-1517, 2016 Dec.
Artigo em Zh | MEDLINE | ID: mdl-30650300

RESUMO

Modern pathological studies of Parkinson's disease. (PD) reveal that 70% -80% sub- stantia nigra striatum nerve endings degenerate before -motor symptoms occur. But till now, Chinese medicine (CM) infers its pathogeneses still at the theoretical level. Braak H, et al. raised six pathological stages of PD. They also beleived that symptoms of PD occurred one by one acocrding to staging sequence. All these indicated important evidence for the developing process of PD's pathogenesis. Authors expounded modern CM pathogenesis of PD.


Assuntos
Medicina Tradicional do Leste Asiático , Doença de Parkinson , Corpo Estriado/patologia , Humanos
9.
Aging (Albany NY) ; 15(11): 4699-4713, 2023 05 23.
Artigo em Inglês | MEDLINE | ID: mdl-37294538

RESUMO

Lipid remodeling regulators are now being investigated as potential therapeutic targets for cancer therapy as a result of their involvement, which includes promoting cancer cells' adaptation to the restricted environment. Lysophosphatidylcholine acyltransferases (LPCATs, LPCAT1-4) are enzymes that regulate the remodeling of bio-membranes. The functions of these enzymes in cancer are largely unknown. In the current study, we found that genes belonging to the LPCAT family participated in tumor advancement and were strongly linked to dismal prognosis in many different malignancies. We constructed the LPCATs scores model and explored this model in pan-cancer. Malignant pathways in pan-cancer were positively related to LPCATs scores, and all pathways had strong links to the tumor microenvironment (TME). Multiple immune-associated features of the TME in pan-cancer were likewise associated with higher LPCATs scores. In addition, the LPCATs score functioned as a prognostic marker for immune checkpoint inhibitor (ICI) therapies in patients with cancer. LPCAT4 enhanced cell growth and cholesterol biosynthesis by up-regulating ACSL3 in hepatocellular carcinoma (HCC). WNT/ß-catenin/c-JUN signaling pathway mediated LPCAT4's regulation on ACSL3. These findings demonstrated that genes in the LPCAT family might be used as cancer immunotherapy and prognosis-related biomarkers. Specifically, LPCAT4 could be a treatment target of HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , beta Catenina/genética , beta Catenina/metabolismo , Prognóstico , Cateninas , Biomarcadores , Microambiente Tumoral/genética , 1-Acilglicerofosfocolina O-Aciltransferase/genética
10.
Artigo em Inglês | MEDLINE | ID: mdl-36636603

RESUMO

Atherosclerosis (AS) is an inflammatory disease, whose occurrence and development mechanism is related to a great number of inflammatory cytokines. ß-sitosterol (BS), a natural compound extracted from numerous vegetables and plant medicines, has been suggested to improve AS, but the underlying mechanism remains vague. This work focused on investigating how BS affected the lipopolysaccharide (LPS)-treated human umbilical vein endothelial cells (HUVECs) and further exploring the potential targets and mechanisms through network pharmacology (NP) and molecular docking (MD). According to in vitro experiments, LPS resulted in an increase in the expression of inflammatory cytokines like tumor necrosis factor-α (TNF-α), cyclooxygenase-2 (Cox-2), and interleukin-6 (IL-6). Besides, secretion of IL-6, interleukin-1ß (IL-1ß), and TNF-α also increased in HUVECs, whereas BS decreased the expression and secretion of these cytokines. NP analysis revealed that the improvement effect of BS on AS was the result of its comprehensive actions targeting 99 targets and 42 pathways. In this network, MAPKs signaling pathway was the core pathway, whereas MAPK1, MAPK8, MAPK14, and NFKB1 were the hub targets. MD analysis also successfully validated the interactions between BS and these targets. Moreover, verification test results indicated that BS downregulated the abnormal expression and activation of MAPKs and NF-κB signaling pathways in LPS-treated cells, including p38, JNK, ERK, NF-κB, and IκB-α phosphorylation expressions. Furthermore, p65 nuclear translocation was also regulated by BS treatment. In conclusion, the BS-related mechanisms in treating AS are possibly associated with inflammatory response inhibition by regulating MAPKs and NF-κB signaling pathways.

11.
CNS Neurosci Ther ; 29(1): 140-157, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36284437

RESUMO

INTRODUCTION: Recent advances have highlighted the relationships between gut dysbiosis and Parkinson's disease (PD). Microbiota transplantation from PD patients to mice can induce increased alpha-synuclein-mediated motor deficits. Human studies have identified differences in the gut microbiota of PD patients compared to healthy controls. We undertook a systematic review to evaluate the available evidence for the involvement of gut bacteria in the etiology of PD. METHODS: The PubMed databank, the China National Knowledge Infrastructure databank, and Wanfang Data were searched from inception until June 2021 to identify human case-control studies that investigated relationships between PD and microbiota quantified from feces. We evaluated the resulting studies focusing on bacterial taxa that were different between PD patients and healthy controls. RESULTS: Twenty-six studies were found in which 53 microbial families and 98 genera exhibited differences between patients with PD and healthy controls. The genera identified by more than two studies as increased in PD were Bifidobacterium, Alistipes, Christensenella, Enterococcus, Oscillospira, Bilophila, Desulfovibrio, Escherichia/Shigella, and Akkermansia, while Prevotella, Blautia, Faecalibacterium, Fusicatenibacter, and Haemophilus had three or more reports of being lower in PD patients. More than one report demonstrated that Bacteroides, Odoribacter, Parabacteroides, Butyricicoccus, Butyrivibrio, Clostridium, Coprococcus, Lachnospira, Lactobacillus, Megasphaera, Phascolarctobacterium, Roseburia, Ruminococcus, Streptococcus, and Klebsiella were altered in both directions. CONCLUSION: Our review shows that the involvement of the gut microbiome in the etiology of PD may involve alterations of short-chain fatty acids (SCFAs)-producing bacteria and an increase in putative gut pathobionts. SCFAs-producing bacteria may vary above or below an "optimal range," causing imbalances. Considering that Bifidobacterium, Lactobacillus, and Akkermansia are beneficial for human health, increased Bifidobacterium and Lactobacillus in the PD gut microbiome may be associated with PD medications, especially COMT inhibitors, while a high level of Akkermansia may be associated with aging.


Assuntos
Microbioma Gastrointestinal , Doença de Parkinson , Humanos , Animais , Camundongos , Bactérias , Fezes/microbiologia , Ácidos Graxos Voláteis
12.
Front Genet ; 14: 1126099, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36861132

RESUMO

Background: Thalassemia presents a higher incidence in southern China. The objective of this study is to analyze the genotype distribution of thalassemia in Yangjiang, a western city of Guangdong Province in China. Methods: The genotypes of suspected cases with thalassemia were tested by PCR and reverse dot blot (RDB). Unidentified rare thalassemia genotypes of the samples were further ascertained by PCR and direct DNA sequencing. Results: Among 22467 suspected cases with thalassemia, 7658 cases were found with thalassemia genotypes using our PCR-RDB kit. Among these 7658 cases, 5313 cases were found with α-thalassemia (α-thal) alone, --SEA/αα was the most common genotype, accounting for 61.75% of α-thal genotypes, and the following mutations were found: α3.7/αα, -α4.2/αα, αCSα/αα, αWSα/αα, and αQSα/αα. A total of 2032 cases were found with ß-thalassemia (ß-thal) alone. ßCD41-42/ßN, ßIVS-II-654/ßN, and ß-28/ßN accounted for 80.9% of all ß-thal genotypes, and the following genotypes were found: ßCD17/ßN, ßCD71-72/ßN, and ßE/ßN. Compound heterozygotes of ß-thal and ß-thalassemia homozygotes were identified in 11 and five cases, respectively, in this study. α-thal combined with ß-thal was identified in 313 cases, showing 57 genotype combinations of the coincidence of both Hb disorders; one extreme patient had a genotype of --SEA/αWSα and ßCD41-42/ß-28. In addition, four rare α-mutations (--THAI, HKαα, Hb Q-Thailand, and CD31 AGG>AAG) and six rare ß-mutations (CD39 CAG>TAG, IVS-Ⅱ-2 (-T), -90(C>T), Chinese Gγ+(Aγδß)0, CD104 (-G), and CD19 A>G) were also found in this study population. Conclusion: This study provided detailed genotypes of thalassemia in Yangjiang of western Guangdong Province in China and reflected the complexity of genotypes in this high-prevalence region, and this would be valuable for diagnosis and counseling for thalassemia in this area.

13.
Front Genet ; 14: 1345537, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38264207

RESUMO

Objectives: The prevalence of G6PD deficiency has not been reported in Yangjiang, a western city in Guangdong province. This study aims to investigate the molecular characteristics of G6PD deficiency in this region. Methods: Blood samples were collected from adults at a local hospital to screen for G6PD deficiency. The deficient samples were subjected to further analysis using PCR and reverse dot blot to determine the specific G6PD variants. Results: Among the 3314 male subjects, 250 cases of G6PD deficiency were found using the G6PD enzyme quantitative assay, resulting in a prevalence of 7.54% (250/3314) in the Yangjiang region. The prevalence of G6PD deficiency in females was 3.42% (176/5145). Out of the 268 cases of G6PD deficiency tested for G6PD mutations, reverse dot blot identified 20 different G6PD variants. The most common G6PD variant was c.1388G>A (81/268), followed by c.1376G>T (48/268), c.95A>G (32/268), c.1024C>T (9/268), c.392G>T (7/268), and c.871G>A/c.1311C>T (6/268). It was observed that c.871G>A was always linked to the polymorphism of c.1311C>T in this population. Conclusion: This investigation into G6PD deficiency in this area is expected to significantly improve our understanding of the prevalence and molecular characterization of this condition.

14.
Injury ; 53(7): 2533-2540, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35249737

RESUMO

BACKGROUND: Locking screws with a typical buttress thread have high levels of failure in patients with osteoporotic bones. This study aims to develop a novel thread design for the locking screw and compare its fixation stability with the typical buttress thread. METHODS: Locking screws with a novel thread design that possess an undercut feature and locking screws with a typical buttress thread were manufactured from stainless steel. Their fixation stabilities were then evaluated individually under a lateral migration test and evaluated in pairs together with a locking plate (LP) in an osteoporotic bone substitute under cyclic craniocaudal and torsional loadings. A finite element analysis (FEA) model was constructed to analyze the stress distributions present in the bone tissue adjacent to the novel thread versus the buttress thread. RESULTS: The biomechanical test revealed that the novel thread had a significantly higher lateral migration strength than the buttress thread. When applied to a LP, the locking screw with the novel thread requires more cycles and higher forces or torque to resist migration up to 5 mm or 10° than the buttress thread. The FEA simulation showed that the novel thread can make the stress distribute more evenly at the adjacent bone tissue when compared with the buttress thread. CONCLUSIONS: The locking screw with the novel undercut thread had superior lateral migration resistance during both initial and continued migration and superior fixation stability when applied to a LP under both cyclic craniocaudal loading and torsional loading than the locking screw with a typical buttress thread.


Assuntos
Placas Ósseas , Parafusos Ósseos , Fenômenos Biomecânicos , Análise de Elementos Finitos , Fixação Interna de Fraturas , Humanos , Torque
15.
Hematology ; 27(1): 494-498, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35465846

RESUMO

OBJECTIVES: The characteristic of glucose-6-phosphate dehydrogenase (G6PD) deficiency is red blood cell (RBC) destruction in response to oxidative stress. Patients requiring RBC transfusions may simultaneously receive oxidative medications or have concurrent infections, both of which can induce hemolysis in G6PD-deficient RBCs. We intend to investigate the incidence of G6PD deficiency in voluntary blood donors and to evaluate the transfusion risk associated with G6PD deficiency in Guangdong province. METHODS: G6PD enzyme was analyzed in 3042 donors and gene mutations were genotyped in G6PD-deficient samples. RESULTS: The G6PD-deficient prevalence of voluntary blood donors was 6.97% (212/3042), 55.19% blood donors with G6PD deficiency donated blood more than twice. Eighty-five cases of G6PD deficiency were genotyped, and the common types of G6PD mutations were c.1376 G > T, c.1388 G > A, c.95 A > G, c.1024 C > T, and c.871 G > A. CONCLUSIONS: Due to the high prevalence of G6PD deficiency in Foshan area, we recommended that the screening of G6PD deficiency should be carried out for the regular blood donors to ensure the safety of blood users.


Assuntos
Deficiência de Glucosefosfato Desidrogenase , Doadores de Sangue , China/epidemiologia , Transfusão de Eritrócitos , Eritrócitos/metabolismo , Glucosefosfato Desidrogenase/genética , Glucosefosfato Desidrogenase/metabolismo , Deficiência de Glucosefosfato Desidrogenase/epidemiologia , Deficiência de Glucosefosfato Desidrogenase/genética , Humanos
16.
J Orthop Res ; 40(12): 2813-2821, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-35267202

RESUMO

High failure rates have been associated with nonlocking cancellous screws with a typical buttress thread in patients with osteoporotic bone. This study aimed to develop a novel thread design and compare its fixation stability with that of a typical buttress thread. Nonlocking cancellous screws with a novel thread design (proximal flank angle of 120 degrees, a flat crest feature, a tip-facing undercut feature) and nonlocking cancellous screws with a typical buttress thread were manufactured using stainless steel. Fixation stabilities were evaluated individually by the axial pullout and lateral migration tests, and they were evaluated in pairs together with a dynamic compression plate in an osteoporotic bone substitute (10 PCF polyurethane foam per ASTM F1839) under cyclic craniocaudal and torsional loadings. Pullout strength and lateral migration resistance for the individual screw test and the force, torque, and number of cycles required to achieve specific displacement and torsion for the multi-screw test were comparatively analyzed between both screw types. A finite element analysis model was constructed to analyze the stress distributions in the bone tissue adjacent to the threads. The biomechanical test revealed the novel undercut thread had superior axial pullout strength, lateral migration resistance, and superior fixation stability when applied to a dynamic compression plate under cyclic craniocaudal loading and torsional loading than those in the typical buttress thread. The finite element analysis simulation revealed that the novel thread can distribute stress more evenly without high-stress concentration at the adjacent bone tissue when compared to that of a typical buttress thread.


Assuntos
Parafusos Ósseos , Osteoporose , Humanos , Placas Ósseas , Torque , Fenômenos Mecânicos , Fenômenos Biomecânicos
17.
Oncol Res ; 30(2): 77-87, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-37305324

RESUMO

In this study, we investigated the functional role of eukaryotic initiation factor 5B (EIF5B) in hepatocellular carcinoma (HCC) and the underlying mechanisms. Bioinformatics analysis demonstrated that the EIF5B transcript and protein levels as well as the EIF5Bcopy number were significantly higher in the HCC tissues compared with the non-cancerous liver tissues. Down-regulation of EIF5B significantly decreased proliferation and invasiveness of the HCC cells. Furthermore, EIF5B knockdown suppressed epithelial-mesenchymal transition (EMT) and the cancer stem cell (CSC) phenotype. Down-regulation of EIF5B also increased the sensitivity of HCC cells to 5-fluorouracil (5-FU). In the HCC cells, activation of the NF-kappa B signaling pathway and IkB phosphorylation was significantly reduced by EIF5B silencing. IGF2BP3 increased the stability of the EIF5B mRNA in an m6A-dependent manner. Our data suggested that EIF5B is a promising prognostic biomarker and therapeutic target in HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/genética , Neoplasias Hepáticas/genética , Linhagem Celular , Biologia Computacional , Fluoruracila
18.
J Int Med Res ; 50(2): 3000605221078785, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35225055

RESUMO

OBJECTIVE: To evaluate a novel reverse dot blot assay for the simultaneous detection six types of common α-thalassaemia alleles (three deletional and three common non-deletional mutations) and 19 types of common ß-thalassaemia alleles in a Chinese population. METHODS: Genomic DNA samples were collected from three hospitals in southern China. The novel thalassaemia gene assay involved one multiplex polymerase chain reaction amplification system and one round of hybridization. Each of the clinically validated DNA samples was re-tested using the new multiplex polymerase chain reaction/reverse dot blot assay II (M-PCR/RDB II) assay in a double-blind manner. RESULTS: A total of 1060 unrelated study participants, including 829 patients with thalassaemia and 231 healthy control subjects, were analysed. The whole PCR and RDB procedures were completed in 260 min. All the samples, including heterozygous thalassaemia, homozygous thalassaemia and compound heterozygous thalassaemia, were correctly genotyped, yielding 100% concordance with the reference assays. HKαα/--SEA and HKαα/-α4.2, which were not included in the detection panel, yielded a contradictory result with this new assay. CONCLUSION: The novel M-PCR/RDB II assay was simple, rapid and accurate, suggesting that it could be used for the genetic screening and clinical diagnosis of common α-thalassaemia and ß-thalassaemia variants in Chinese populations.


Assuntos
Talassemia alfa , Talassemia beta , Povo Asiático/genética , China/epidemiologia , Método Duplo-Cego , Humanos , Reação em Cadeia da Polimerase/métodos , Talassemia alfa/diagnóstico , Talassemia alfa/genética , Talassemia beta/diagnóstico , Talassemia beta/genética
19.
Clin Chim Acta ; 535: 82-91, 2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-35964702

RESUMO

BACKGROUND: Pulmonary tuberculosis (TB) is a serious infectious disease that lacks robust blood-based biomarkers to identify cured TB. Some discharged patients are not fully cured and may relapse or even develop multidrug-resistant TB. This study is committed to finding proteomic-based plasma biomarkers to support establishing laboratory standards for clinical TB cure. METHODS: Data-independent acquisition (DIA) was used to obtain the plasma protein expression profiles of TB patients at different treatment stages compared with healthy controls. Multivariate statistical methods and bioinformatics were used to analyze the data. RESULTS: Bioinformatic analysis suggests coagulation dysfunction and vitamin and lipid metabolism disturbances in TB. Albumin (ALB), haptoglobin (HP), out at first protein homolog (OAF), and retinol-binding protein 4 (RBP4) can be used to establish a diagnostic model for the efficacy evaluation of TB with an area under the curve of 0.963, which could effectively distinguish untreated TB patients from cured patients. CONCLUSIONS: Our research demonstrated that ALB, HP, OAF and RBP4 can be potential biomarkers for evaluating the efficacy of TB. These findings may provide experimental data for establishing the laboratory indicators of clinical TB cure and providing clinicians with new targets for exploring the underlying mechanisms of TB pathogenesis.


Assuntos
Tuberculose Pulmonar , Humanos , Albuminas/análise , Biomarcadores/sangue , Haptoglobinas/análise , Proteômica , Proteínas Plasmáticas de Ligação ao Retinol/análise , Tuberculose Pulmonar/sangue , Tuberculose Pulmonar/diagnóstico , Tuberculose Pulmonar/tratamento farmacológico
20.
Sci Rep ; 11(1): 12510, 2021 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-34131183

RESUMO

Conventional evaluation of the stability of bone screws focuses on pullout strength, while neglecting lateral migration resistance. We measured pullout strength and lateral migration resistance of bone screws and determined how these characteristics relate to screw stability of locking plate (LP) and dynamic compression plate (DCP) fixation. Pullout strength and lateral migration resistance of individual bone screws with buttress, square, and triangular thread designs were evaluated in polyurethane foam blocks. The screw types with superior performance in each of these characteristics were selected. LP and DCP fixations were constructed using the selected screws and tested under cyclic craniocaudal and torsional loadings. Subsequently, the association between individual screws' biomechanical characteristics and fixation stability when applied to plates was established. Screws with triangular threads had superior pullout strength, while screws with square threads demonstrated the highest lateral migration resistance; they were selected for LP and DCP fixations. LPs with square-threaded screws required a larger force and more cycles to trigger the same amount of displacement under both craniocaudal and torsional loadings. Screws with triangular and square threads showed no difference in DCP fixation stability under craniocaudal loading. However, under torsional loading, DCP fixation with triangular-threaded screws demonstrated superior fixation stability. Lateral migration resistance is the primary contributor to locking screw fixation stability when applied to an LP in resisting both craniocaudal and torsional loading. For compression screws applied to a DCP, lateral migration resistance and pullout strength work together to resist craniocaudal loading, while pullout strength is the primary contributor to the ability to resist torsional loading.


Assuntos
Placas Ósseas/normas , Parafusos Ósseos/normas , Fraturas Ósseas/terapia , Fenômenos Mecânicos , Fenômenos Biomecânicos , Densidade Óssea , Fraturas Ósseas/patologia , Humanos , Vértebras Lombares/patologia , Vértebras Lombares/cirurgia , Teste de Materiais , Fusão Vertebral/normas
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