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1.
Zhongguo Zhong Yao Za Zhi ; 49(4): 1007-1016, 2024 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-38621908

RESUMO

Chondrocytes are unique resident cells in the articular cartilage, and the pathological changes of them can lead to the occurrence of osteoarthritis(OA). Ligusticum cycloprolactam(LIGc) are derivatives of Z-ligustilide(LIG), a pharmacodynamic marker of Angelica sinensis, which has various biological functions such as anti-inflammation and inhibition of cell apoptosis. However, its protective effect on chondrocytes in the case of OA and the underlying mechanism remain unclear. This study conducted in vitro experiments to explore the molecular mechanism of LIGc in protecting chondrocytes from OA. The inflammation model of rat OA chondrocyte model was established by using interleukin-1ß(IL-1ß) to induce. LIGc alone and combined with glycyrrhizic acid(GA), a blocker of the high mobility group box-1 protein(HMGB1)/Toll-like receptor 4(TLR4)/nuclear factor-kappa B(NF-κB) signaling pathway, were used to intervene in the model, and the therapeutic effects were systematically evaluated. The viability of chondrocytes treated with different concentrations of LIGc was measured by the cell counting kit-8(CCK-8), and the optimal LIGc concentration was screened out. Annexin V-FITC/PI apoptosis detection kit was employed to examine the apoptosis of chondrocytes in each group. The enzyme-linked immunosorbent assay(ELISA) was employed to measure the expression of cyclooxygenase-2(COX-2), prostaglandin-2(PGE2), and tumor necrosis factor-alpha(TNF-α) in the supernatant of chondrocytes in each group. Western blot was employed to determine the protein levels of B-cell lymphoma-2(Bcl-2), Bcl-2-associated X protein(Bax), caspase-3, HMGB1, TLR4, and NF-κB p65. The mRNA levels of HMGB1, TLR4, NF-κB p65, and myeloid differentiation factor 88(MyD88) in chondrocytes were determined by real-time fluorescent quantitative PCR(RT-qPCR). The safe concentration range of LIGc on chondrocytes was determined by CCK-8, and then the optimal concentration of LIGc for exerting the effect was clarified. Under the intervention of IL-1ß, the rat chondrocyte model of OA was successfully established. The modeled chondrocytes showed increased apoptosis rate, promoted expression of COX-2, PGE2, and TNF-α, up-regulated protein levels of Bax, caspase-3, HMGB1, TLR4, and NF-κB p65 and mRNA levels of HMGB1, TLR4, NF-κB p65, and MyD88, and down-regulated protein level of Bcl-2. However, LIGc reversed the IL-1ß-induced changes of the above factors. Moreover, LIGc combined with GA showed more significant reversal effect than LIGc alone. These fin-dings indicate that LIGc extracted and derived from the traditional Chinese medicine A. sinensis can inhibit the inflammatory response of chondrocytes and reduce the apoptosis of chondrocytes, and this effect may be related to the HMGB1/TLR4/NF-κB signaling pathway. The pharmacological effect of LIGc on protecting chondrocytes has potential value in delaying the progression of OA and improving the clinical symptoms of patients, and deserves further study.


Assuntos
Proteína HMGB1 , Ligusticum , Osteoartrite , Humanos , Ratos , Animais , NF-kappa B/genética , NF-kappa B/metabolismo , Condrócitos , Caspase 3/metabolismo , Proteína X Associada a bcl-2/metabolismo , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Proteína HMGB1/genética , Proteína HMGB1/metabolismo , Proteína HMGB1/farmacologia , Dinoprostona , Fator 88 de Diferenciação Mieloide/metabolismo , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Transdução de Sinais , Inflamação/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/genética , Apoptose , RNA Mensageiro/metabolismo
2.
Acta Pharmacol Sin ; 45(7): 1438-1450, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38565961

RESUMO

Angiogenesis plays a critical role in many pathological processes, including irreversible blindness in eye diseases such as retinopathy of prematurity. Endothelial mitochondria are dynamic organelles that undergo constant fusion and fission and are critical signalling hubs that modulate angiogenesis by coordinating reactive oxygen species (ROS) production and calcium signalling and metabolism. In this study, we investigated the role of mitochondrial dynamics in pathological retinal angiogenesis. We showed that treatment with vascular endothelial growth factor (VEGF; 20 ng/ml) induced mitochondrial fission in HUVECs by promoting the phosphorylation of dynamin-related protein 1 (DRP1). DRP1 knockdown or pretreatment with the DRP1 inhibitor Mdivi-1 (5 µM) blocked VEGF-induced cell migration, proliferation, and tube formation in HUVECs. We demonstrated that VEGF treatment increased mitochondrial ROS production in HUVECs, which was necessary for HIF-1α-dependent glycolysis, as well as proliferation, migration, and tube formation, and the inhibition of mitochondrial fission prevented VEGF-induced mitochondrial ROS production. In an oxygen-induced retinopathy (OIR) mouse model, we found that active DRP1 was highly expressed in endothelial cells in neovascular tufts. The administration of Mdivi-1 (10 mg·kg-1·d-1, i.p.) for three days from postnatal day (P) 13 until P15 significantly alleviated pathological angiogenesis in the retina. Our results suggest that targeting mitochondrial fission may be a therapeutic strategy for proliferative retinopathies and other diseases that are dependent on pathological angiogenesis.


Assuntos
Movimento Celular , Dinaminas , Células Endoteliais da Veia Umbilical Humana , Subunidade alfa do Fator 1 Induzível por Hipóxia , Camundongos Endogâmicos C57BL , Dinâmica Mitocondrial , Quinazolinonas , Espécies Reativas de Oxigênio , Neovascularização Retiniana , Fator A de Crescimento do Endotélio Vascular , Dinâmica Mitocondrial/efeitos dos fármacos , Animais , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Humanos , Espécies Reativas de Oxigênio/metabolismo , Dinaminas/metabolismo , Dinaminas/antagonistas & inibidores , Fator A de Crescimento do Endotélio Vascular/metabolismo , Quinazolinonas/farmacologia , Neovascularização Retiniana/metabolismo , Neovascularização Retiniana/patologia , Neovascularização Retiniana/tratamento farmacológico , Movimento Celular/efeitos dos fármacos , Camundongos , Proliferação de Células/efeitos dos fármacos , Mitocôndrias/metabolismo , Mitocôndrias/efeitos dos fármacos , Angiogênese
3.
ACS Sens ; 9(5): 2310-2316, 2024 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-38651676

RESUMO

The smart light-up probes have been extensively developed to image various enzymes and other bioactive molecules. Upon activation, these probes result in light-up fluorophores that exist in a protein-bound or a free form. The difference between these two forms has not yet been reported. Here, we present a pair of smart light-up probes that generate a protein-bound fluorophore and a free fluorophore upon activation by heme. Probe 8 generated a radical-attached fluorophore that predominantly existed in the free form, while probe 10 generated an α,ß-unsaturated ketone-attached fluorophore that showed extensive labeling of proteins. In live-cell imaging, probe 8 showed greater fluorescence intensity than probe 10 when low concentrations (0.1-5 µM) of the probes were used, but probe 8 was less fluorescent than probe 10 when the concentrations of the probes were high (10 µM). Finally, probe 8 was used to reflect the activation level of the endoperoxide bond in cancer cells and to effectively distinguish ART-sensitive cancer cells from ART-insensitive ones.


Assuntos
Artemisininas , Corantes Fluorescentes , Humanos , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Artemisininas/química , Artemisininas/farmacologia , Linhagem Celular Tumoral , Imagem Óptica , Neoplasias/diagnóstico por imagem , Radicais Livres/química
4.
Sci Rep ; 14(1): 5184, 2024 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-38431660

RESUMO

Host immune dysregulation involves in the initiation and development of osteosarcoma (OS). However, the exact role of immune cells in OS remains unknown. We aimed to distinguish the molecular subtypes and establish a prognostic model in OS patients based on immunocyte infiltration. The gene expression profile and corresponding clinical feature of OS patients were obtained from TARGET and GSE21257 datasets. MCP-counter and univariate Cox regression analyses were applied to identify immune cell infiltration-related molecular subgroups. Functional enrichment analysis and immunocyte infiltration analysis were performed between two subgroups. Furthermore, Cox regression and LASSO analyses were performed to establish the prognostic model for the prediction of prognosis and metastasis in OS patients. The subgroup with low infiltration of monocytic lineage (ML) was related to bad prognosis in OS patients. 435 DEGs were screened between the two subgroups. Functional enrichment analysis revealed these DEGs were involved in immune- and inflammation-related pathways. Three important genes (including TERT, CCDC26, and IL2RA) were identified to establish the prognostic model. The risk model had good prognostic performance for the prediction of metastasis and overall survival in OS patients. A novel stratification system was established based on ML-related signature. The risk model could predict the metastasis and prognosis in OS patients. Our findings offered a novel sight for the prognosis and development of OS.


Assuntos
Neoplasias Ósseas , Osteossarcoma , Humanos , Genes Reguladores , Osteossarcoma/genética , Prognóstico , Fatores de Transcrição , Neoplasias Ósseas/genética
5.
BMJ Open ; 14(2): e077941, 2024 Feb 20.
Artigo em Inglês | MEDLINE | ID: mdl-38382963

RESUMO

INTRODUCTION: The lumbar puncture (LP) technique is widely used for diagnostic and therapeutic purposes. In recent years, the paramedian approach technique (PAT) has gained increasing interest due to its advantages over the conventional midline approach technique (MAT) that has been traditionally employed in clinical practice for LP. However, there have been inconsistent discussions regarding the efficacy of different LP techniques. Based on digital virtual human and computer simulation techniques, a new approach called computerised modified PAT (CMPAT) was proposed. Therefore, the aim of this study is to discuss a randomised controlled trial (RCT) protocol to investigate and compare the effects of CMPAT and MAT in patients undergoing LP. METHODS AND ANALYSIS: We will conduct a prospective, multicentre RCT. The study will recruit 84 patients aged 18-99 years who require LP. Participants will be randomly assigned to either the CMPAT treatment group (group A) or the MAT treatment group (group B). The primary outcome measure will be the number of needle insertion attempts required for a successful LP. Secondary outcomes will include the puncture success rate, pain assessment in the back, head, and legs, and the occurrence of complications. The measurement of these secondary outcomes will be taken during the procedure, as well as at specific time points: 30 min, 6 hours, 1 day, 3 days, 7 days, 2 weeks and 4 weeks after the procedure. Pain levels will be assessed using a Numerical Rating Scale. ETHICS AND DISSEMINATION: Ethical approval (2022YF052-01) has been obtained from the Ethics Committee of Fujian Medical University Union Hospital, Fuzhou, China. The research findings will be published in an international peer-reviewed scientific journal and presented at scientific conferences. TRIAL REGISTRATION NUMBER: ChiCTR2300067937.


Assuntos
Punção Espinal , Humanos , China , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Estudos Multicêntricos como Assunto , Estudos Prospectivos
6.
Quant Imaging Med Surg ; 13(8): 5130-5140, 2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37581085

RESUMO

Background: The choice of treatment for scapular fractures is a topic worth discussing. The type of scapular fracture is often complex, and more and more scholars prefer surgical treatment to obtain better shoulder joint function. In addition, because of the rich blood supply and muscles of the scapula, some scholars believe that simple suspension can also achieve satisfactory clinical effects. The aim of this study was to investigate the curative effect and prognostic factors of patients with scapular fracture with indications for surgery after receiving conservative treatment. Methods: Patients with scapular fracture who did not receive surgical treatment from July 2016 to May 2021 were recruited from the orthopedic trauma database of Nanjing Gulou Hospital, and the data from patients with indications for surgery were screened out for a retrospective analysis. The data were obtained from the database of orthopaedic trauma patients in Nanjing Drum Tower Hospital. The relevant data were recorded during telephone and video follow-up visits. Linear regression was used to analyze the factors associated with disabilities of the arm, shoulder and hand (DASH) score after receiving conservative treatment. Results: A total of 21 patients were included in the final statistical analysis. All patients were followed up for 31.0±20.3 (range, 6-63) months, aged 52.9±12.7 (range, 27-71) years. All fractures had clinical healing with a 100% recovery satisfaction rate. Outcome measures of efficacy [both DASH scores and visual analogue scale (VAS) scores], were correlated with whether the fracture involved the superior border of the scapular, were not associated with the following variables: age (P=0.18), Injury Severity Score (ISS) score (P=0.10), the glenopolar angle (GPA) value (P=0.76), superior shoulder suspensory complex (SSSC) injury (P=0.82), and glenoid fracture (P=0.84). The range of motion of the affected shoulder was significantly reduced compared to the healthy shoulder (P<0.01), but the range of forward flexion and elevation was not significantly different from that of the healthy shoulder (P>0.05). Patients with fractures not involving the superior border of the scapula had a much lower range of motion in the affected shoulder than in the healthy shoulder during abduction (P<0.05). Conclusions: The range of surgical indications for scapular fractures with scapular fractures involving the lower margin of the scapular can be appropriately narrowed. Some patients with scapular fracture who have surgical indications can regain satisfactory shoulder function after receiving conservative treatment.

7.
World J Clin Cases ; 10(28): 10120-10129, 2022 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-36246801

RESUMO

BACKGROUND: Nocardia paucivorans is an infrequently found bacterium with the potential to cause severe infection, with a predilection for the central nervous system, both in immunocompromised and immunocompetent individuals. Rapid etiological diagnosis of nocardiosis can facilitate timely and rational antimicrobial treatment. Metagenomic next-generation sequencing (mNGS) can improve the rate and reduce the turnaround time for the detection of Nocardia. CASE SUMMARY: A 49-year-old man was admitted to hospital with cough and hemoptysis. Imaging revealed pulmonary consolidation as well as multiple brain lesions. Nocardia asiatica and Nocardia beijingensis were rapidly detected by mNGS of bronchoalveolar lavage fluid (BALF) while bacterial culture of BALF and pathological biopsy of lung tissue were negative. In early stages, he was treated with trimethoprim-sulfamethoxazole (TMP-SMZ) and linezolid by individual dose adjustment based on serum concentrations and the adverse effects of thrombocytopenia and leukopenia. The treatment was then replaced by TMP-SMZ and ceftriaxone or minocycline. He was treated with 8 mo of parenteral and/or oral antibiotics, and obvious clinical improvement was achieved with resolution of pulmonary and brain lesions on repeat imaging. CONCLUSION: mNGS provided fast and precise pathogen detection of Nocardia. In disseminated nocardiosis, linezolid is an important alternative that can give a better outcome with the monitoring of linezolid serum concentrations and platelet count.

9.
Zhongguo Gu Shang ; 35(7): 692-7, 2022 Jul 25.
Artigo em Chinês | MEDLINE | ID: mdl-35859384

RESUMO

OBJECTIVE: To explore the risk factors of limb fracture complicated with pleural effusion, and to provide reference for the prevention of pleural effusion. METHODS: From January 2010 to December 2019, 137 patients with multiple limb fractures were treated surgically, including 102 males and 35 females, aged 16 to 92(48.34±15.85) years. Multiple limb fractures were defined as more than two limb fractures in the whole body, so the selected patients had complete clinical, impact and laboratory examination data before operation, including preoperative chest CT, gender, age, body mass index(BMI), hematocrit(HCT), American Society of Anesthesiologists(ASA), injury severity score (ISS), smoking history of operation, history of diabetes, history of hypertension, admission to operation time, fracture site, platelet count, albumin, C-reactive protein and D-dimer. Whether the patient was complicated with pleural effusion, calculate the amount of pleural effusion were recorded, and the relevant risk factors were statistically analyzed. RESULTS: All limb fractures received surgical treatment. The incision healed well after operation, and there were no complications such as wound infection, acute lung injury or acute respiratory distress syndrome. Multivariate regression analysis showed that ISS higher than 16(P=0.000), smoking history(P=0.001) and rib fracture(P=0.000) were the risk factors of multiple limb fractures complicated with pleural effusion. Multivariate linear regression analysis showed that smoking history, ISS and rib fracture were the risk factors for the increase of pleural effusion in multiple limb fractures. CONCLUSION: Multiple fractures of limbs combined with pleural effusion are related to ISS, smoking history and rib fracture;the amount of pleural effusion was related to smoking history, ISS and rib fracture. Patients with multiple fractures with ISS greater than 16, smoking history or rib fracture should be vigilant and intervene as soon as possible to reduce the risk of pleural effusion.


Assuntos
Fraturas Múltiplas , Derrame Pleural , Fraturas das Costelas , Feminino , Humanos , Masculino , Derrame Pleural/complicações , Derrame Pleural/etiologia , Estudos Retrospectivos , Fraturas das Costelas/complicações , Fraturas das Costelas/cirurgia , Fatores de Risco
10.
J Orthop Surg Res ; 17(1): 200, 2022 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-35379285

RESUMO

BACKGROUND: The diagnostic value of platelet indices has been evaluated in various infectious diseases but not in infected nonunion. The purpose of this study was to assess the usefulness of platelet indices for diagnosis of infected nonunion after open reduction and internal fixation. METHODS: This retrospective study was performed in patients who underwent primary fracture nonunion revision surgeries from January 2016 to December 2021. A total of 297 patients were included in the study: 96 with infected nonunion (group A) and 201 with aseptic nonunion (group B). Receiver operator characteristic (ROC) curve analysis was performed to evaluate diagnostic value of each index. Area under the curve (AUC), sensitivity, specificity, and positive and negative predictive values were calculated and compared. RESULTS: Demographic characteristics were comparable between the two groups. White blood cell (WBC) count, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), plasma fibrinogen, plasma D-dimer, platelet count (PC), plateletcrit, and ratio of platelet count to mean platelet volume (PC/MPV) were significantly higher, and MPV and platelet distribution width (PDW) significantly lower, in group A than in group B (P < 0.05). ROC analysis showed PC/MPV and plasma fibrinogen to have better diagnostic value than the other coagulation indicators (AUC of 0.801 and 0.807, respectively). The combination of ESR, plasma fibrinogen, and PC/MPV had good sensitivity and specificity for diagnosis of infected nonunion. PC/MPV had better diagnostic value than ESR and plasma fibrinogen in the subgroup of patients with coagulation-related comorbidities. CONCLUSIONS: Plasma fibrinogen and PC/MPV ratio might be useful parameters for early diagnosis of infected nonunion.


Assuntos
Volume Plaquetário Médio , Área Sob a Curva , Sedimentação Sanguínea , Humanos , Contagem de Plaquetas , Estudos Retrospectivos
13.
Pharmacol Res ; 174: 105934, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34648968

RESUMO

Drug resistance in small cell lung cancer (SCLC) significantly affects the efficacy of chemotherapy treatment. However, due to the lack of tumor tissue samples, especially serial tumor samples during chemotherapy, the mechanism of chemotherapy resistance has not been fully studied. Circulating tumor DNA, which can be obtained in a noninvasive manner, can complement tumor sampling approaches for research in this field. We identified an SCLC patient with acquired drug resistance from 52 SCLC patients for whom follow-up data were available. By comparing somatic mutations in circulating tumor DNA before and after chemotherapy, for the first time, we found that the somatic mutation eIF3A R803K may be related to acquired chemotherapy resistance. Then, the association between the eIF3A R803K mutation and chemotherapy resistance was confirmed by samples from 254 lung cancer patients receiving chemotherapy. We found that the eIF3a R803K mutation weakened the proliferation ability of tumor cells but increased their resistance to chemotherapy. Further studies revealed that the eIF3A R803K mutation promotes cellular senescence. In addition, fisetin showed a synergistic effect with chemotherapy in eIF3A R803K mutant cells. These results suggest that the eIF3A R803K somatic mutation has the potential to predict chemotherapy resistance in SCLC. Moreover, the eIF3A R803K mutation promotes chemotherapy resistance by inducing senescence. Furthermore, a senolytic drug, fisetin, can reverse chemotherapy resistance mediated by the eIF3A R803K mutation.


Assuntos
Senescência Celular/genética , Resistencia a Medicamentos Antineoplásicos/genética , Fator de Iniciação 3 em Eucariotos/genética , Neoplasias Pulmonares/genética , Carcinoma de Pequenas Células do Pulmão/genética , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular , Movimento Celular , Sobrevivência Celular , Feminino , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Mutação , Inibidores da Síntese de Proteínas/farmacologia , Inibidores da Síntese de Proteínas/uso terapêutico , Carcinoma de Pequenas Células do Pulmão/tratamento farmacológico , Carcinoma de Pequenas Células do Pulmão/mortalidade
14.
Front Pharmacol ; 12: 709528, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34603024

RESUMO

Purpose: Lung cancer is the largest cause of cancer deaths in the world. Platinum-based chemotherapy is a foundation of first-line chemotherapy. However, the prognosis of lung cancer treated with platinum-based chemotherapy is still a challenge. Single nucleotide polymorphism of non-coding RNA has the potential to be a biomarker, but its effectiveness has yet to be comprehensively assessed. In this study, we explored the association between polymorphisms of non-coding RNA and prognosis of lung cancer patients receiving platinum-based chemotherapy. Materials and Methods: For 446 lung cancer patients receiving platinum-based chemotherapy, 22 single nucleotide polymorphisms of microRNA and long noncoding RNA were genotyped by MALDI-TOF mass spectrometry. Cox regression analysis, Kaplan-Meier method, and long-rank test have been performed to assess the association of overall and progression-free survival with polymorphisms. Results: In the additive and dominant models, genetic polymorphism of ANRIL rs1333049 (G > C) was significantly associated with progression-free survival. Additive model: CC vs GC vs GG [HR = 0.84, p = 0.021, 95% CI (0.73-0.97)]; Recessive model: CC vs GG + GC [HR = 0.77, p = 0.026, 95% CI (0.61-0.97)]. In the dominant model, compared with the CC genotype patients, lower risk of death [HR = 0.81, p = 0.036, 95% CI (0.66-0.99)] and lower risk of progression [HR = 0.81, p = 0.040, 95% CI (0.67-0.99)] have been observed on the patients with CG or GG genotype in miR-146A rs2910164. Conclusion: Our research demonstrated the potential of using ANRIL rs1333049 (G > C) and miR-146A rs2910164 (C > G) as biomarkers to support the prediction of a better prognosis for lung cancer patients receiving platinum-based chemotherapy.

15.
J Orthop Surg Res ; 16(1): 530, 2021 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-34433474

RESUMO

BACKGROUND: Volar locking plating remains a popular method for the surgical management of distal radius fractures. Dorsal metaphyseal comminution (DMC) is a common fracture pattern which weakens the stability during fracture fixation. In this study, we aimed to compare the radiographic and functional outcome of the intra- and extra-articular distal radius fractures with DMC following single volar locking plate fixation. MATERIALS AND METHODS: Patients suffered from a distal radius fracture with DMC were reviewed in the clinical database of the authors' institution between Jan 2016 and Jan 2020. The included patients were classified into the extra-articular (A3) group or the intra-articular (C2 and C3) group according to the AO/OTA system. The radiological parameters, wrist range of motion, and functional outcomes were evaluated following open reduction and volar locking plate fixation. RESULTS: A total of 130 patients were included in this study with a mean follow-up length of 17.2 months. Compared with the A3 fracture group, no significant fracture re-displacement or reduced wrist ROMs was observed in the C2 fractures after 12-month's follow-up. However, significantly decreased volar tilt (P = 0.003) as well as the extension/flexion ROMs were observed in the C3 fractures comparing to the A3 fractures. Most of the patients achieved an excellent (n = 75) or good (n = 51) Gartland and Werley wrist score. Four patients with C3 fractures resulted in a fair functional outcome due to a significant loss of volar tilt during follow-up. CONCLUSIONS: The single volar locking plate fixation provided sufficient stability for distal radius fractures with DMC, and resulted in similar radiological and functional outcomes in the intra-articular distal radius fractures with a simple articular component (C2 fractures) as those in the extra-articular fractures. Considering the intra-articular fractures with multifragmentary articular component (C3 fracture), despite of the subsequent loss of volar tilt, the majority of the patients achieved good to excellent wrist function following single volar locking plating. TRIAL REGISTRATION: This study has been registered on the ClinicalTrials.gov.


Assuntos
Fraturas Cominutivas , Fraturas do Rádio , Placas Ósseas , Fixação Interna de Fraturas , Humanos , Fraturas do Rádio/diagnóstico por imagem , Fraturas do Rádio/cirurgia , Amplitude de Movimento Articular/fisiologia , Resultado do Tratamento
16.
Phytomedicine ; 84: 153520, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33662920

RESUMO

BACKGROUND: Schisandrol B (SolB) is one of the bioactive components from a traditional Chinese medicine Schisandra chinensis or Schisandra sphenanthera. It has been demonstrated that SolB exerts hepatoprotective effects against drug-induced liver injury and promotes liver regeneration. It was found that SolB can induce hepatomegaly but the involved mechanisms remain unknown. PURPOSE: This study aimed to explore the mechanisms involved in SolB-induced hepatomegaly. METHODS: Male C57BL/6 mice were injected intraperitoneally with SolB (100 mg/kg) for 5 days. Serum and liver samples were collected for biochemical and histological analyses. The mechanisms of SolB were investigated by qRT-PCR and western blot analyses, luciferase reporter gene assays and immunofluorescence. RESULTS: SolB significantly increased hepatocyte size and proliferation, and then promoted liver enlargement without liver injury and inflammation. SolB transactivated human PXR, activated PXR in mice and upregulated hepatic expression of its downstream proteins, such as CYP3A11, CYP2B10 and UGT1A1. SolB also significantly enhanced nuclear translocation of PXR and YAP in human cell lines. YAP signal pathway was activated by SolB in mice. CONCLUSION: These findings demonstrated that SolB can significantly induce liver enlargement, which is associated with the activation of PXR and YAP pathways.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Ciclo-Octanos/toxicidade , Dioxóis/toxicidade , Hepatomegalia/induzido quimicamente , Lignanas/toxicidade , Receptor de Pregnano X/metabolismo , Fatores de Transcrição/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/genética , Animais , Proliferação de Células/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/química , Regulação da Expressão Gênica/efeitos dos fármacos , Células Hep G2 , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Hepatócitos/patologia , Hepatomegalia/metabolismo , Hepatomegalia/patologia , Humanos , Fígado/efeitos dos fármacos , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Tamanho do Órgão/efeitos dos fármacos , Receptor de Pregnano X/genética , Schisandra/química , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/genética , Proteínas de Sinalização YAP
17.
Acta Pharmacol Sin ; 42(12): 1970-1980, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33589795

RESUMO

PARP inhibitors are a group of inhibitors targeting poly(ADP-ribose) polymerases (PARP1 or PARP2) involved in DNA repair and transcriptional regulation, which may induce synthetic lethality in BRCAness tumors. Systematic analyzes of genomic sequencing in prostate cancer show that ~10%-19% of patients with primary prostate cancer have inactivated DNA repair genes, with a notably higher proportion of 23%-27% in patients with metastatic castration-resistant prostate cancer (mCRPC). These characteristic genomic alterations confer possible vulnerability to PARP inhibitors in patients with mCRPC who benefit only modestly from other therapies. However, only a small proportion of patients with mCRPC shows sensitivity to PARP inhibitors, and these sensitive patients cannot be fully identified by existing response prediction biomarkers. In this review, we provide an overview of the potential response prediction biomarkers and synergistic combinations studied in the preclinical and clinical stages, which may expand the population of patients with prostate cancer who may benefit from PARP inhibitors.


Assuntos
Antineoplásicos/uso terapêutico , Biomarcadores/metabolismo , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Neoplasias da Próstata/tratamento farmacológico , Ensaios Clínicos como Assunto , Humanos , Masculino , Poli(ADP-Ribose) Polimerase-1/metabolismo , Neoplasias da Próstata/metabolismo
18.
Infect Drug Resist ; 13: 4003-4008, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33177850

RESUMO

BACKGROUND: The timely and accurate diagnosis of infected nonunion is challenging, and there is a need for more efficient biomarkers. Previous studies have shown that fibrinogen plays an important role in mediating inflammation in bacterial infections and, therefore, could be a valuable biomarker for infected nonunion. The purpose of this study was to evaluate and compare the performance of plasma fibrinogen and other traditional blood markers for the diagnosis of infected nonunion. MATERIALS AND METHODS: We retrospectively studied 146 patients who underwent surgery for primary nonunion between January 2018 and January 2020. The patients were divided into those with infected nonunion (n = 55) and those with aseptic nonunion (n = 91). The preoperatively analyzed parameters were plasma fibrinogen, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP) level, and white blood cell (WBC) count. Receiver operating characteristic (ROC) curve analysis was used to assess the sensitivity and specificity of the biomarkers, and Youden's index was calculated to determine their optimal cut-off values. RESULTS: The plasma fibrinogen values were significantly higher (p < 0.001) in the patients with infected nonunion than in those with aseptic nonunion. ROC curve analysis showed that plasma fibrinogen had a high value of area under the curve (0.816), which indicated that it had good diagnostic ability. Further, at the optimal threshold value of 2.75 g/L, plasma fibrinogen had the highest sensitivity (78.2%; 95% CI = 64.6-87.8) and good specificity (82.4%; 95% CI, 72.7-89.3). CONCLUSION: In comparison to the traditional markers of infection, plasma fibrinogen showed good diagnostic ability for the detection of infected nonunion. It may have potential as a practical and cost-efficient biomarker for the diagnosis of infected nonunion.

19.
Orthop Surg ; 12(3): 809-818, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32462816

RESUMO

OBJECTIVES: To evaluate the long-term efficacy of cannulated internal fixation in patients who sustain femoral neck fracture (FNF) and risk factors influencing the outcomes. METHODS: This retrospective study analyzed data from 73 elderly patients aged ≥60 years old, hospitalized for FNF and treated with cannulated internal fixation between August 2008 and July 2016. The inclusion criteria were: (i) patients aged ≥60 years; (ii) patients with recent femoral neck fracture, with times of injury ranging from 12-72 h; and (iii) patients who underwent Garden II-IV closed reduction and internal fixation. Patients were classified based on the Garden fracture type and Pauwels angle. Clinical data and radiographs before and after the surgery were collected. Subsequently, surgery was performed with the patient in supine position, under general or lumbar epidural anesthesia. Closed reduction was performed until satisfactory fracture reduction quality was achieved. The weight of all included patients were <75 kg, and thus, minimal internal fixation was performed. The ischemic necrosis of the femoral head was diagnosed by considering the symptoms, signs, and radiological findings. Harris hip scores were used to evaluate postoperative recovery of hip function. Furthermore, relationships between Garden fracture type and necrosis rate of the femoral head, Pauwels angle and necrosis rate of the femoral head, Garden fracture type and Harris hip score, and age and Harris hip score were analyzed. RESULTS: The mean duration of surgery was 1 ± 0.17 h and blood loss for all the patients was approximately 15 mL. The included patients were followed up for 13-128 months, with an average follow-up of 61 months. Among the included 73 patients, 65 (89.0%) exhibited satisfactory union, seven (9.6%) had femoral head necrosis, and one (1.4%) had nonunion. For seven patients with femoral head necrosis, there were two, two, and three patients classified as Garden IV, Garden III, and Garden II, respectively, and two and five patients classified as Pauwels II and Pauwels III, respectively. Among the seven cases, four underwent hip replacement. Garden fracture type was not significantly associated with femoral head necrosis (χ2 = 0.44, P > 0.05) or Harris score (χ2 = 1.43, P > 0.05). Patients with Pauwels I (0%) and II (4.3%) fractures exhibited a significantly lower necrosis rate than those with Pauwels III fractures (41.7%) (P < 0.05). CONCLUSIONS: Cannulated internal fixation was more suitable for older Chinese patients with Pauwels I/II fractures than those with Pauwels III fractures.


Assuntos
Fraturas do Colo Femoral/classificação , Fraturas do Colo Femoral/cirurgia , Necrose da Cabeça do Fêmur/epidemiologia , Fixação Interna de Fraturas/métodos , Idoso , Idoso de 80 Anos ou mais , Redução Fechada/métodos , Avaliação da Deficiência , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco
20.
Med Hypotheses ; 136: 109506, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31841766

RESUMO

Infected nonunion is still a challenge for orthopaedic surgeons. The goal of treatment is to eliminate infection and achieve bone union. Surgery is the only effective method currently. However, it is invasive and the results are still unsatisfactory. Therefore, seeking a noninvasive and effective method to resolve infected nonunion is necessary. Pulsed electromagnetic field (PEMF) has been used for the treatment of nonunion for more than 40 years. PEMF could promote bone formation at tissue, cell and subcellular levels. Furthermore, our study showed that PEMF had bactericidal effect. The hypothesis we proposed herein is that PEMF may be an adjuvant treatment for infected nonunion by controlling infection and inducing bone formation.


Assuntos
Campos Eletromagnéticos , Consolidação da Fratura , Magnetoterapia , Infecções Estafilocócicas/prevenção & controle , Infecção dos Ferimentos/prevenção & controle , Osso e Ossos/microbiologia , Fraturas Ósseas , Fraturas não Consolidadas/fisiopatologia , Fraturas não Consolidadas/terapia , Humanos , Risco , Staphylococcus aureus , Fraturas da Tíbia/fisiopatologia , Fraturas da Tíbia/terapia
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