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1.
FASEB J ; 34(6): 8416-8427, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32350948

RESUMO

During human erythroid maturation, Hsp70 translocates into the nucleus and protects GATA-1 from caspase-3 cleavage. Failure of Hsp70 to localize to the nucleus was found in Myelodysplastic syndrome (MDS) erythroblasts and can induce dyserythropoiesis, with arrest of maturation and death of erythroblasts. However, the mechanism of the nuclear trafficking of Hsp70 in erythroblasts remains unknown. Here, we found the hematopoietic transcriptional regulator, EDAG, to be a novel binding partner of Hsp70 that forms a protein complex with Hsp70 and GATA-1 during human normal erythroid differentiation. EDAG overexpression blocked the cytoplasmic translocation of Hsp70 induced by EPO deprivation, inhibited GATA-1 degradation, thereby promoting erythroid maturation in an Hsp70-dependent manner. Furthermore, in myelodysplastic syndrome (MDS) patients with dyserythropoiesis, EDAG is dramatically down-regulated, and forced expression of EDAG has been found to restore the localization of Hsp70 in the nucleus and elevate the protein level of GATA-1 to a significant extent. In addition, EDAG rescued the dyserythropoiesis of MDS patients by increasing erythroid differentiation and decreasing cell apoptosis. This study demonstrates the molecular mechanism of Hsp70 nuclear sustaining during erythroid maturation and establishes that EDAG might be a suitable therapeutic target for dyserythropoiesis in MDS patients.


Assuntos
Núcleo Celular/metabolismo , Eritroblastos/metabolismo , Eritropoese/fisiologia , Proteínas de Choque Térmico HSP70/metabolismo , Síndromes Mielodisplásicas/metabolismo , Proteínas Nucleares/metabolismo , Apoptose/fisiologia , Caspase 3/metabolismo , Diferenciação Celular/fisiologia , Células Cultivadas , Citoplasma/metabolismo , Regulação da Expressão Gênica/fisiologia , Doenças Hematológicas/metabolismo , Humanos
2.
Neurochem Res ; 41(6): 1238-49, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26758268

RESUMO

Parkinson's disease (PD) is a neurodegenerative disorder that is caused by a loss of dopaminergic (DAergic) neurons in mesencephalic substantia nigra (SN). Human umbilical cord mesenchymal stem cells (hUC-MSCs) are capable of self-renewal and differentiation into multiple cell lineages, including DAergic neurons. Thus, hUC-MSCs could be a promising alternative to compensate for the loss of DAergic neurons in PD. In the current study, hUC-MSCs and hUC-MSCs-derived DAergic-like neurons were transplanted into the striatum and SN of a rat model of PD that is induced by 6-hydroxydopamine (6-OHDA). We evaluated their therapeutic effects on improving rotation behavior in the rat and on modulating the level of heat shock protein 60 (Hsp60) expression in the brain. After transplantation, an amelioration of rotation behavior was observed in rats that underwent cell grafting, and hUC-MSCs-derived DAergic-like neurons were superior to hUC-MSCs at inducing behavioral improvement. Western blot and immunohistochemistry analysis indicated significantly elevated levels of Hsp60 in cell-grafted rats compared to 6-OHDA-lesioned (PD) rats. These results demonstrate that hUC-MSCs-based cell transplantation is potential therapeutic treatment for PD, and hUC-MSCs-derived DAergic-like neurons appear to be favorable candidates for cell replacement therapy in PD. Finally, Hsp60 could be involved in a mechanism of behavioral recovery.


Assuntos
Chaperonina 60/biossíntese , Neurônios Dopaminérgicos/transplante , Transplante de Células-Tronco Mesenquimais/métodos , Proteínas Mitocondriais/biossíntese , Transtornos Parkinsonianos/metabolismo , Transtornos Parkinsonianos/terapia , Cordão Umbilical/transplante , Animais , Comportamento Animal/fisiologia , Células Cultivadas , Corpo Estriado/metabolismo , Humanos , Masculino , Células-Tronco Mesenquimais/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Cordão Umbilical/citologia
3.
Stem Cells ; 32(8): 2278-89, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24740910

RESUMO

Erythroid differentiation-associated gene (EDAG) has been considered to be a transcriptional regulator that controls hematopoietic cell differentiation, proliferation, and apoptosis. The role of EDAG in erythroid differentiation of primary erythroid progenitor cells and in vivo remains unknown. In this study, we found that EDAG is highly expressed in CMPs and MEPs and upregulated during the erythroid differentiation of CD34(+) cells following erythropoietin (EPO) treatment. Overexpression of EDAG induced erythroid differentiation of CD34(+) cells in vitro and in vivo using immunodeficient mice. Conversely, EDAG knockdown reduced erythroid differentiation in EPO-treated CD34(+) cells. Detailed mechanistic analysis suggested that EDAG forms complex with GATA1 and p300 and increases GATA1 acetylation and transcriptional activity by facilitating the interaction between GATA1 and p300. EDAG deletion mutants lacking the binding domain with GATA1 or p300 failed to enhance erythroid differentiation, suggesting that EDAG regulates erythroid differentiation partly through forming EDAG/GATA1/p300 complex. In the presence of the specific inhibitor of p300 acetyltransferase activity, C646, EDAG was unable to accelerate erythroid differentiation, indicating an involvement of p300 acetyltransferase activity in EDAG-induced erythroid differentiation. ChIP-PCR experiments confirmed that GATA1 and EDAG co-occupy GATA1-targeted genes in primary erythroid cells and in vivo. ChIP-seq was further performed to examine the global occupancy of EDAG during erythroid differentiation and a total of 7,133 enrichment peaks corresponding to 3,847 genes were identified. Merging EDAG ChIP-Seq and GATA1 ChIP-Seq datasets revealed that 782 genes overlapped. Microarray analysis suggested that EDAG knockdown selectively inhibits GATA1-activated target genes. These data provide novel insights into EDAG in regulation of erythroid differentiation.


Assuntos
Diferenciação Celular/fisiologia , Proteína p300 Associada a E1A/metabolismo , Fator de Transcrição GATA1/metabolismo , Hematopoese/fisiologia , Células-Tronco Hematopoéticas/citologia , Proteínas Nucleares/metabolismo , Acetilação , Animais , Western Blotting , Separação Celular , Células Eritroides/citologia , Células Eritroides/metabolismo , Feminino , Citometria de Fluxo , Células-Tronco Hematopoéticas/metabolismo , Xenoenxertos , Humanos , Camundongos , Camundongos Endogâmicos NOD , Camundongos SCID , Análise de Sequência com Séries de Oligonucleotídeos , Transcriptoma
4.
Ann Med ; 56(1): 2307504, 2024 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38465636

RESUMO

BACKGROUND: Despite the widespread administration of coronavirus disease 2019 (COVID-19) vaccines, the impact on patients with asymptomatic to mild illness remains unclear. Here, we aimed to assess the efficacy of various vaccine doses and types on the duration of isolation duration and discharge rates, the viral shedding duration, and negative rates in asymptomatic to mild COVID-19 patients. METHODS: We included adult patients at the Fangcang isolation centres in Pazhou or Yongning between November and December 2022. We analysed data on basic demographics, admission details, laboratory indicators and vaccination information. RESULTS: A total of 6560 infected patients were included (3584 from Pazhou and 2976 from Yongning). Of these, 90.6% received inactivated vaccines, 3.66% received recombinant SARS-CoV-2 spike protein subunit vaccines and 0.91% received adenovirus vaccines. Among the 6173 vaccinated individuals, 71.9% received a booster dose. By day 9, the isolation rate reached 50% among vaccinated patients. On day 7.5, the positive rate among vaccinated individuals reached 50%. CONCLUSIONS: Full vaccination was effective, with heterologous vaccines showing greater efficacy than inactivated vaccines alone. However, there was no significant difference in the vaccine protective effect 12 months after vaccination.


Assuntos
COVID-19 , Glicoproteína da Espícula de Coronavírus , Adulto , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Estudos Retrospectivos , SARS-CoV-2 , Vacinação , Vacinas de Produtos Inativados
5.
J Leukoc Biol ; 2024 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-38776408

RESUMO

BACKGROUND: Aim to investigate the predictive value of changes in presepsin (PSEP), procalcitonin (PCT), high-sensitivity C-reactive protein (hsCRP), and interleukin-6 (IL-6) levels to for mortality in septic patients in intensive care unit (ICU). METHOD: This study enrolled septic patients between November 2020 and December 2021. Levels of PSEP, PCT, hsCRP, and IL-6 were measured on 1st (PSEP_0, PCT_0, hsCRP_0, IL-6_0) and 3rd day (PSEP_3, PCT_3, hsCRP_3, IL-6_3). Follow-up was performed on days 3, 7, 14, 21, and 28 after enrollment. The outcome was all-cause death. RESULTS: The study included 119 participants, and the mortality was 18.5%. In univariable Cox proportional-hazards regression (Cox) analysis, △PSEP (= PSEP_3- PSEP_0) > 211.49 pg/ml (hazard ratio (HR) 2.70, 95% confidence interval (CI) 1.17-6.22), △PCT (= PCT_3- PCT_0) > -0.13 ng/ml (HR 7.31, 95% CI 2.68-19.80), △hsCRP (= hsCRP_3- hsCRP_0) > -19.29 mg/L (HR 6.89, 95% CI 1.61-29.40), and △IL-6 (= IL-6_3- IL-6_0) > 1.00 pg/ml (HR 3.13, 95% CI 1.35-7.24) indicated an increased risk of mortality. The composite concordance index for alterations in all four distinct biomarkers was highest (concordance index 0.83, 95% CI 0.76-0.91), suggesting the optimal performance of this panel in mortality prediction. In decision curve analysis, compared with the APACHE Ⅱ and SOFA scores, the combination of the four biomarkers had a larger net benefit. Interestingly, IL-6 was predominantly produced by monocytes upon LPS stimulation in PBMCs. CONCLUSIONS: △PSEP, △PCT, △hsCRP, and △IL-6 are reliable biomarkers for predicting mortality in septic patients in ICU, and their combination has the best performance.

6.
Neurochem Res ; 38(10): 2180-9, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23943523

RESUMO

In Parkinson's disease, dopaminergic neuron damage/death causes the release of soluble substances that are selectively toxic to neighboring/additional dopaminergic neurons through the activation of microglia. Hsp60 can be released from injured cells of central nervous system to activate microglia. However, its expression and role in Parkinson's disease has not been well understood. Here, we performed a 6-OHDA treated Parkinson's disease model in adult rats. Western blot analysis showed a time-course expression of Hsp60, which decreased gradually and then rose back. Immunofluorescence staining showed that Hsp60 was decreased in dopaminergic neuron, and most Hsp60 located on the surface of activated microglia. Furthermore, in cellular Parkinson's disease model, Hsp60 was obviously detected in the culture supernatants after 6-OHDA treatment, and a concomitant decrease in cell extracts. Taken together, our results suggested that Hsp60 could be released extracellularly to activate microglia in Parkinson's disease model.


Assuntos
Chaperonina 60/biossíntese , Proteínas Mitocondriais/biossíntese , Oxidopamina , Doença de Parkinson/fisiopatologia , Animais , Chaperonina 60/metabolismo , Modelos Animais de Doenças , Neurônios Dopaminérgicos/metabolismo , Masculino , Microglia/efeitos dos fármacos , Proteínas Mitocondriais/metabolismo , Células PC12 , Ratos
7.
IEEE Trans Neural Netw Learn Syst ; 34(12): 9727-9741, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35333726

RESUMO

Percutaneous coronary intervention (PCI) has increasingly become the main treatment for coronary artery disease. The procedure requires high experienced skills and dexterous manipulations. However, there are few techniques to model PCI skill so far. In this study, a learning framework with local and ensemble learning is proposed to learn skill characteristics of different skill-level subjects from their PCI manipulations. Ten interventional cardiologists (four experts and six novices) were recruited to deliver a medical guidewire to two target arteries on a porcine model for in vivo studies. Simultaneously, translation and twist manipulations of thumb, forefinger, and wrist are acquired with electromagnetic (EM) and fiber-optic bend (FOB) sensors, respectively. These behavior data are then processed with wavelet packet decomposition (WPD) under 1-10 levels for feature extraction. The feature vectors are further fed into three candidate individual classifiers in the local learning layer. Furthermore, the local learning results from different manipulation behaviors are fused in the ensemble learning layer with three rule-based ensemble learning algorithms. In subject-dependent skill characteristics learning, the ensemble learning can achieve 100% accuracy, significantly outperforming the best local result (90%). Furthermore, ensemble learning can also maintain 73% accuracy in subject-independent schemes. These promising results demonstrate the great potential of the proposed method to facilitate skill learning in surgical robotics and skill assessment in clinical practice.


Assuntos
Intervenção Coronária Percutânea , Robótica , Humanos , Animais , Suínos , Redes Neurais de Computação , Algoritmos , Aprendizagem
8.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 4674-4678, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34892256

RESUMO

Percutaneous coronary intervention (PCI) has gradually become the most common treatment of coronary artery disease (CAD) in clinical practice due to its advantages of small trauma and quick recovery. However, the availability of hospitals with cardiac catheterization facilities and trained interventionalists is extremely limited in remote and underdeveloped areas. Remote vascular robotic system can assist interventionalists to complete operations precisely, and reduce occupational health hazards occurrence. In this paper, a bionic remote vascular robot is introduced in detail from three parts: mechanism, communication architecture, and controller model. Firstly, human finger-like mechanisms in vascular robot enable the interventionalists to advance, retract and rotate the guidewires or balloons. Secondly, a 5G-based communication system is built to satisfy the end-to-end requirements of strong data transmission and packet priority setting in remote robot control. Thirdly, a generalized predictive controller (GPC) is developed to suppress the effect of time-varying network delay and parameter identification error, while adding a designed polynomial compensation module to reduce tracking error and improve system responsiveness. Then, the simulation experiment verifies the system performance in comparison with different algorithms, network delay, and packet loss rate. Finally, the improved control system conducted PCI on an experimental pig, which reduced the delivery integral absolute error (IAE) by at least 20% compared with traditional methods.


Assuntos
Doença da Artéria Coronariana , Intervenção Coronária Percutânea , Robótica , Algoritmos , Animais , Simulação por Computador , Suínos
9.
Annu Int Conf IEEE Eng Med Biol Soc ; 2021: 4679-4682, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34892257

RESUMO

The robotic-assisted percutaneous coronary intervention is an emerging technology with great potential to solve the shortcomings of existing treatments. However, the current robotic systems can not manipulate two guidewires or ballons/stents simultaneously for coronary bifurcation lesions. This paper presents VasCure, a novel bio-inspired vascular robotic system, to deliver two guidewires and stents into the main branch and side branch of bifurcation lesions in sequence. The system is designed in master-slave architecture to reduce occupational hazards of radiation exposure and orthopedic injury to interventional surgeons. The slave delivery device has one active roller and two passive rollers to manipulate two interventional devices. The performance of the VasCure was verified by in vitro and in vivo animal experiments. In vitro results showed the robotic system has good accuracy to deliver guidewires and the maximum error is 0.38mm. In an animal experiment, the interventional surgeon delivered two guidewires and balloons to the left circumflex branch and the left anterior descending branch of the pig, which confirmed the feasibility of the vascular robotic system.


Assuntos
Intervenção Coronária Percutânea , Procedimentos Cirúrgicos Robóticos , Robótica , Animais , Desenho de Equipamento , Stents , Suínos
10.
Clin Med Insights Oncol ; 15: 11795549211049750, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34646064

RESUMO

BACKGROUND: It is valuable to predict the time to the development of castration-resistant prostate cancer (CRPC) in patients with advanced prostate cancer (PCa). This study aimed to build and validate a nomogram incorporating the clinicopathologic characteristics and the parameters of contrast-enhanced ultrasonography (CEUS) to predict the time to CRPC after androgen deprivation therapy (ADT). METHODS: Patients with PCa were divided into the training (n = 183) and validation cohorts (n = 37) for nomogram construction and validation. The clinicopathologic characteristics and CEUS parameters were analyzed to determine the independent prognosis factors and serve as the basis of the nomogram to estimate the risk of 1-, 2-, and 3-year progress to CRPC. RESULTS: T stage, distant metastasis, Gleason score, area under the curve (AUC), prostate-specific antigen (PSA) nadir, and time to PSA nadir were the independent predictors of CRPC (all P < 0.05). Three nomograms were built to predict the time to CRPC. Owing to the inclusion of CEUS parameter, the discrimination of the established nomogram (C-index: 0.825 and 0.797 for training and validation datasets) was improved compared with the traditional prediction model (C-index: 0.825 and 0.797), and when it excluded posttreatment PSA, it still obtained an acceptable discrimination (C-index: 0.825 and 0.797). CONCLUSIONS: The established nomogram including regular prognostic indicators and CEUS obtained an improved accuracy for the prediction of the time to CRPC. It was also applicable for early prediction of CRPC when it excluded posttreatment PSA, which might be helpful for individualized diagnosis and treatment.

11.
World J Stem Cells ; 12(5): 323-338, 2020 May 26.
Artigo em Inglês | MEDLINE | ID: mdl-32547681

RESUMO

Neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis, are a group of incurable neurological disorders, characterized by the chronic progressive loss of different neuronal subtypes. However, despite its increasing prevalence among the ever-increasing aging population, little progress has been made in the coincident immense efforts towards development of therapeutic agents. Research interest has recently turned towards stem cells including stem cells-derived exosomes, neurotrophic factors, and their combination as potential therapeutic agents in neurodegenerative diseases. In this review, we summarize the progress in therapeutic strategies based on stem cells combined with neurotrophic factors and mesenchymal stem cells-derived exosomes for neurodegenerative diseases, with an emphasis on the combination therapy.

12.
Cancer Manag Res ; 12: 4959-4968, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32636672

RESUMO

BACKGROUND: Some patients with prostate cancer (PCa) will experience biochemical recurrence (BCR) after treatment. Current researches have identified the influencing factors of BCR, but these factors are difficult to quantify and hence unable to accurately predict the BCR in PCa patients. OBJECTIVE: To explore the value of contrast-enhanced ultrasound (CEUS) indicators in predicting the BCR after treatment by evaluating the association between them. PATIENTS AND METHODS: In a retrospective cohort study, 157 PCa patients were recruited and received prostate specific antigen (PSA) measurement, CEUS, pathological classification, and immunohistochemistry after puncture biopsy. PCa patients with BCR were included in the recurrence group, while the remaining patients were included in the non-recurrence group after a 5-year follow-up. The clinical characteristics and CEUS indicators were compared between the two groups, and the multivariable COX regression was used for screening the influencing factors of BCR. Receiver operating characteristic (ROC) curves were used to analyze the value of potential factors in predicting BCR. The effect of the combined prediction model was explored to improve the accuracy of the prediction. RESULTS: Twelve patients are lost during the follow-up period and the final analysis included 145 patients. The 5-year BCR rate of PCa patients was 27%, with 43 patients in the recurrence group and 102 patients in the non-recurrence group. Multivariate analysis showed that lymph node metastasis (P<0.001), distant metastasis (P<0.001), Gleason score (P<0.001), pretreatment PSA (P<0.001), treatment method (P<0.001), peak intensity (PI) (P=0.001), and time to peak (TTP) (P=0.003) were independent influencing factors for BCR after treatment. ROC analysis showed that the AUCs of all indicators in predicting BCR were not high (all <0.9). The combination of lymph node metastasis, Gleason score, pretreatment PSA, and treatment method can improve the predictive accuracy (AUC = 0.85), but the AUC was still under 0.9. The combined prediction model including CEUS time-intensity curve (TIC) indicators (PI and TTP) could accurately predict the BCR after treatment (AUC=0.953). The sensitivity and specificity were 93.02% and 88.24%, respectively. CONCLUSION: The prediction model including TIC indicators and common influencing factors can more accurately predict the BCR in PCa patients.

13.
J Food Sci ; 84(7): 1966-1978, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31206695

RESUMO

The evolution of volatile aldehydes and the conversion of oxygenated ityß-unsaturated aldehydes (OαßUAs) into furans were compared in four vegetable oils (soybean oil, olive oil [OVO], peanut oil [PO], and perilla oil [PAO]) thermally oxidized at temperatures of 150, 180, and 210 °C for 10 hr/day over a 3-day period. Results showed that 2 alkyl furans and 23 volatile aldehydes including 4 toxic OdßUAs were detected by GC-MS. The original fatty acid compositions of the oils played a key role in the type and concentration of those volatile compounds. 4-Hydroxy-2-hexenal (HHE) and ethyl furan were only detected in PAO with a high content of linolenic acid, while the greatest level of pentyl furan was detected in PO with abundant linoleic acid. Greater amounts of 4-hydroxy-(E)-2-nonenal (HNE) and 4-oxo-(E)-2-nonenal (ONE) were formed in the OVO with abundant oleic acid. The close relativity of HHE and ethyl furan was also demonstrated. With principal component analysis, these vegetable oils could be discriminated based on their fatty acids and volatile compounds. The loading plot confirmed that HHE and ethyl furan were derived from the linolenic acid oxidation and degradation. PRACTICAL APPLICATION: The chemometric results showed that the formation of the volatile components during heating in different vegetable oils has close correlation with the original fatty acids composition of vegetable oils. Our research has also confirmed the presence of toxic OɑßUAs in oils after heating. Considering that they are proven to generate lots of degenerative diseases, further studies are needed to establish the risk level of using certain oils in frying and seek effective methods to inhibit their formation.


Assuntos
Aldeídos/química , Furanos/química , Azeite de Oliva/química , Óleo de Amendoim/química , Óleo de Soja/química , Ácido alfa-Linolênico/química , Ácidos Graxos/química , Cromatografia Gasosa-Espectrometria de Massas , Temperatura Alta , Oxirredução , Óleos de Plantas/química
14.
Journal of Leukemia & Lymphoma ; (12): 230-234, 2023.
Artigo em Chinês | WPRIM | ID: wpr-988977

RESUMO

Objective:To investigate the effectiveness and safety of bortezomib combined with conventional chemotherapy regimens for treatment of relapsed/refractory acute B lymphoblastic leukemia (B-ALL).Methods:Twenty patients with relapsed/refractory B-ALL treated with bortezomib combined with chemotherapy in Jiaozuo People's Hospital Affiliated to Xinxiang Medical College, Jiaozuo Coal Industry Group Central Hospital and the Second People's Hospital of Jiaozuo from September 2021 to June 2022 were collected, and their treatment response and prognosis were retrospectively analyzed.Results:The median age of the 20 patients was 49.5 years old (25.0-58.5 years old); 12 were male and 8 were female; 12 were relapsed and 8 were refractory. All patients completed 1 course of bortezomib (1.6 mg/m 2, subcutaneous injection on days 2 and 16) combined with chemotherapy. Before bortezomib treatment, there were 0 case of complete remission (CR), 7 cases of partial remission (PR) and 13 cases of non-remission (NR) in 20 patients, the objective remission rate (ORR) was 35% (7/20), and all were positive for minimal residual disease (MRD). After bortezomib treatment, there were 13 cases of CR, 3 cases of PR and 4 cases of NR, and the ORR was 80% (16/20); the MRD of all patients decreased, among which 13 cases (65%) turned to negative; the differences were statistically significant when comparing CR rate, ORR and MRD negative conversion rate before and after bortezomib treatment ( χ2 values were 65.41, 8.83 and 19.30, all P < 0.05). Four of the 20 patients developed central nervous system infiltration despite bone marrow remission, and one died from post-chemotherapy infection. Myelosuppression occurred in all patients, the incidence of infection was 90% (18/20), and the incidence of digestive system adverse effects was 75% (15/20). Conclusions:Bortezomib combined with conventional chemotherapy regimens is effective and well tolerated in the treatment of relapsed/refractory ALL, and has the potential to enable patients with multi-drug resistant relapse to overcome resistance and to achieve deep remission.

15.
Artigo em Chinês | WPRIM | ID: wpr-1008102

RESUMO

Objective To compare the surgical safety of elderly hospitalized patients in different age groups undergoing general surgery,and provide references for preoperative evaluation and treatment decision-making.Methods The inpatients ≥ 60 years old in the department of general surgery were selected from a national multi-center survey conducted from January to June in 2015 and from January to June in 2016.The patient characteristics and postoperative outcomes were described,and the risk factors for adverse postoperative outcomes of patients in different age groups were explored.Results The elderly patients (≥75 years old) accounted for 17.33%.The non-elderly patient (< 75 years old) group and the elderly patient (≥75 years old) group had significant differences in the proportions of patients with three or more chronical diseases (13.18% vs.5.36%,P<0.001),emergency surgery (16.64% vs.7.62%,P<0.001),American Society of Anesthesiologists score≥3 (48.68% vs.27.28%,P<0.001),and postoperative return to the intensive care unit(33.64% vs.12.00%,P<0.001).The occurrence of postoperative infectious complications showed no significant difference between the two age groups (7.29% vs.6.40%,P=0.410),while severe complications differed between the two groups (6.51% vs.2.60%,P<0.001).Besides,emergency surgery was a common independent risk factor for the two age groups.Conclusions Advanced age is not a contraindication to surgery of elderly patients.With consideration to patient's physical conditions and available surgical resources,elderly patients can still benefit from surgery.


Assuntos
Humanos , Pessoa de Meia-Idade , Idoso , Complicações Pós-Operatórias/epidemiologia , Período Pós-Operatório , Fatores de Risco
16.
J Neurosci ; 26(44): 11387-96, 2006 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-17079667

RESUMO

Modification of arginine residues by citrullination is catalyzed by peptidylarginine deiminases (PADs), of which five are known, generating irreversible protein structural modifications. We have shown previously that enhanced citrullination of myelin basic protein contributed to destabilization of the myelin membrane in the CNS of multiple sclerosis (MS) patients. We now report increased citrullination of nucleosomal histones by PAD4 in normal-appearing white matter (NAWM) of MS patients and in animal models of demyelination. Histone citrullination was attributable to increased levels and activity of nuclear PAD4. PAD4 translocation into the nucleus was attributable to elevated tumor necrosis factor-alpha (TNF-alpha) protein. The elevated TNF-alpha in MS NAWM was not associated with CD3+ or CD8+ lymphocytes, nor was it associated with CD68+ microglia/macrophages. GFAP, a measure of astrocytosis, was the only cytological marker that was consistently elevated in the MS NAWM, suggesting that TNF-alpha may have been derived from astrocytes. In cell cultures of mouse and human oligodendroglial cell lines, PAD4 was predominantly cytosolic but TNF-alpha treatment induced its nuclear translocation. To address the involvement of TNF-alpha in targeting PAD4 to the nucleus, we found that transgenic mice overexpressing TNF-alpha also had increased levels of citrullinated histones and elevated nuclear PAD4 before demyelination. In conclusion, high citrullination of histones consequent to PAD4 nuclear translocation is part of the process that leads to irreversible changes in oligodendrocytes and may contribute to apoptosis of oligodendrocytes in MS.


Assuntos
Encéfalo/metabolismo , Citrulina/metabolismo , Modelos Animais de Doenças , Histonas/metabolismo , Hidrolases/metabolismo , Esclerose Múltipla/metabolismo , Fator de Necrose Tumoral alfa/fisiologia , Transporte Ativo do Núcleo Celular/fisiologia , Animais , Encéfalo/patologia , Doenças Desmielinizantes/genética , Doenças Desmielinizantes/metabolismo , Doenças Desmielinizantes/patologia , Feminino , Histonas/genética , Humanos , Hidrolases/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Esclerose Múltipla/genética , Esclerose Múltipla/patologia , Proteína-Arginina Desiminase do Tipo 4 , Desiminases de Arginina em Proteínas
17.
Artigo em Chinês | WPRIM | ID: wpr-930748

RESUMO

Objective:To construct a set of sensitive quality indexes for specialized nursing in dental clinics. These indicators are used to monitor and evaluate the quality of dental outpatient nursing care.Methods:Based on "structure-process-outcome" three-dimensional theory, through literature research, semi-structured interviews with 14 medical and nursing staff in Hefei Stomatological Hospital and two rounds of Delphi expert consultation with 19 stomatological management experts in stomatology departments of 19 first-class hospitals or third-class stomatological specialized hospitals in 11 provinces and cities in China, the three-level index system was determined, the calculation formula and data collection method of each index were clarified, and the weight of each index was determined by analytic hierarchy process.Results:The effective recovery rate of the two rounds of expert consultation was 100% and 89.47%. The expert authority coefficient were 0.905 and 0.906. Kendall′s W coefficients of the first, second and third level indicators in the second round of consultation were 0.206, 0.122 and 0.114. The differences were statistically significant ( χ2=7.00, 18.61, 149.23, all P<0.05). These indicators were assigned importance values ranged from 4.12 to 4.88 (>3.50), and coefficient of variations ranged from 0.07 to 0.23(<0.25). The final indicators included 3 first-level indicators, 10 second-level indicators and 26 third-level indicators. Conclusions:The research method of the constructed index is scientific, the content is reliable and the pertinence is strong. These indicators are conducive to the objective evaluation of the quality of dental outpatient care.

18.
Nutr. hosp ; 39(2): 256-265, mar.- abr. 2022. tab
Artigo em Inglês | IBECS (Espanha) | ID: ibc-209692

RESUMO

Objectives: this study aimed to evaluate the relationship of Nutritional Risk Screening 2002 (NRS2002) and in-hospital major adverse cardiac events (MACE) in patients with severe heart failure. Methods: an observational study was conducted at the emergency intensive care units (EICU) of Shandong University Qilu Hospital from January 2017 to December 2019. Nutritional screening and assessment were performed at the time of admission to hospital with the NRS2002. Results: of the 209 patients included, 16 cases (7.66 %) were not at nutritional risk, and 193 cases (92.34 %) were at risk. Among them, 12 cases (5.74 %) were malnourished, 38 cases (18.18 %) were at high nutritional risk, and 115 cases (55.02 %) were overweight and obese. The differences in prealbumin (PA) and N-terminal B-type natriuretic peptide precursor (NT-proBNP) between the 2 groups were statistically signific ant (p < 0.05). A total of 134 cases (64.12 %) received nutrition treatment support, of which 39 cases (29.10 %) received enteral nutrition (EN), 77 cases (57.46 %) parenteral nutrition, and 18 cases (13.43 %) enteral nutrition combined with parenteral nutrition (EN + SPN) support treatment. In all, 31 cases (54.39 %) reached 100 % of the target dose. Patients in the EN and EN + SPN groups had 37 MACE (64.91 %) and 31 enteral nutrition complications (54.39 %), with differences between the 3 groups being statistically significant (p < 0.05). Conclusion: the nutritional risk of patients with severe heart failure is high, and age and heart function are positively correlated with nutritional risk. The complications rate of patients with high nutritional risk is significantly higher than in those with low risk; the higher the nutritional risk, the higher the hospital mortality rate — that is, nutritional risk affects disease outcome (AU)


Objetivos: este estudio tuvo como objetivo evaluar la relación del Nutritional Risk Screening 2002 (NRS2002) con los eventos cardiacos adversos mayores intrahospitalarios (MACE) en pacientes con insuficiencia cardiaca grave. Métodos: se realizó un estudio observacional en las unidades de cuidados intensivos de emergencia (UCIE) del Hospital Qilu de la Universidad de Shandong desde enero de 2017 a diciembre de 2019. Se realizaron un cribado y una evaluación nutricional en el momento del ingreso hospitalario con el NRS2002. Resultados: de los 209 pacientes incluidos, 16 casos (7,66 %) no tenían riesgo nutricional y 193 casos (92,34 %) sí lo tenían. Entre ellos, 12 casos (5,74 %) estaban desnutridos, 38 casos (18,18 %) tenían un alto riesgo nutricional y 115 casos (55,02 %) tenían sobrepeso u obesidad. Las diferencias de prealbúmina (PA) y precursor del péptido natriurético de tipo B N-terminal (NT-proBNP) entre los 2 grupos fueron estadísticamente significativas (p < 0,05). En total, 134 casos (64,12 %) recibieron soporte de tratamiento nutricional, de los que 39 casos (29,10 %) recibieron nutrición enteral (NE), 77 casos (57,46 %) nutrición parenteral y 18 casos (13,43 %) nutrición enteral combinada con nutrición parenteral (NE + SPN) como tratamiento de apoyo. Treinta y un casos (54,39 %) alcanzaron la dosis objetivo al 100 %. Los pacientes de los grupos EN y EN + SPN tuvieron 37 MACE (64,91 %) y 31 complicaciones de la nutrición enteral (54,39 %), siendo la diferencia entre los 3 grupos estadísticamente significativa (p < 0,05). Conclusiones: el riesgo nutricional de los pacientes con insuficiencia cardíaca grave es alto; la edad y la función cardiaca se correlacionan positivamente con el riesgo nutricional. La complicación de los pacientes con alto riesgo nutricional es significativamente mayor que la de los de bajo riesgo; cuanto mayor es el riesgo nutricional (AU)


Assuntos
Humanos , Masculino , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Insuficiência Cardíaca/complicações , Distúrbios Nutricionais/etiologia , Índice de Gravidade de Doença , Estudos Prospectivos , Avaliação Nutricional , Estado Nutricional , Prognóstico
19.
Arch Oral Biol ; 74: 108-113, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-27930932

RESUMO

OBJECTIVE: Endogenous hydrogen sulfide (H2S) has recently been shown to play an important role in inflammation, but the role of endogenous H2S in the human gingival tissue is unknown. The aim of this study was to investigate whether gingiva had enzymes for H2S synthesis, and whether the effect of these enzymes for H2S production changed with periodontal inflammation. DESIGN: Gingival tissues were collected from patients undergoing periodontal operation including gingivitis, moderate chronic periodontitis, severe chronic periodontitis and normal controls. RT-PCR and western blotting were performed to measure mRNA and protein levels of cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE) for H2S production. Immunohistochemistry was carried out to detect the location of the enzymes. H2S levels and synthesis in gingival tissue were evaluated with modified methylene blue method. RESULTS: The mRNA and protein of CBS and CSE were both expressed in human gingiva and raised significantly in moderate and severe periodontitis compared of that in healthy control. CBS, but not CSE, increased in gingivitis (p<0.05). However, there was no significant difference of H2S level and synthesis among these groups (p>0.05). CONCLUSIONS: Both CBS and CSE were expressed in human gingival tissue. The mRNA and protein levels of CBS and CSE were up-regulated in periodontitis.


Assuntos
Cistationina beta-Sintase/metabolismo , Cistationina gama-Liase/metabolismo , Gengiva/enzimologia , Sulfeto de Hidrogênio/metabolismo , Adolescente , Adulto , Idoso , Periodontite Crônica/enzimologia , Periodontite Crônica/metabolismo , Cistationina beta-Sintase/genética , Cistationina gama-Liase/genética , Feminino , Gengiva/patologia , Gengivite/enzimologia , Gengivite/metabolismo , Humanos , Sulfeto de Hidrogênio/análise , Imuno-Histoquímica , Inflamação , Pessoa de Meia-Idade , Gravidez , RNA Mensageiro/análise , Regulação para Cima , Adulto Jovem
20.
Artigo em Inglês | WPRIM | ID: wpr-925220

RESUMO

Background@#and Purpose This study aimed to construct an optimal dynamic nomogram for predicting malignant brain edema (MBE) in acute ischemic stroke (AIS) patients after endovascular thrombectomy (ET). @*Methods@#We enrolled AIS patients after ET from May 2017 to April 2021. MBE was defined as a midline shift of >5 mm at the septum pellucidum or pineal gland based on follow-up computed tomography within 5 days after ET. Multivariate logistic regression and LASSO (least absolute shrinkage and selection operator) regression were used to construct the nomogram. The area under the receiver operating characteristic curve (AUC) and decisioncurve analysis were used to compare our nomogram with two previous risk models for predicting brain edema after ET. @*Results@#MBE developed in 72 (21.9%) of the 329 eligible patients. Our dynamic web-based nomogram (https://successful.shinyapps.io/DynNomapp/) consisted of five parameters: basal cistern effacement, postoperative National Institutes of Health Stroke Scale (NIHSS) score, brain atrophy, hypoattenuation area, and stroke etiology. The nomogram showed good discrimination ability, with a C-index (Harrell’s concordance index) of 0.925 (95% confidence interval=0.890–0.961), and good calibration (Hosmer-Lemeshow test, p=0.386). All variables had variance inflation factors of 0.7, suggesting no significant collinearity among them. The AUC of our nomogram (0.925) was superior to those of Xiang-liang Chen and colleagues (0.843) and Ming-yang Du and colleagues (0.728). @*Conclusions@#Our web-based dynamic nomogram reliably predicted the risk of MBE in AIS patients after ET, and hence is worthy of further evaluation.

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