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1.
Inflamm Res ; 73(1): 145-155, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38085279

RESUMO

OBJECTIVE AND DESIGN: Changes in the immune status of patients with sepsis may have a major impact on their prognosis. Our research focused on changes in various immune cell subsets and T-cell activation during the progression of sepsis. METHODS AND SUBJECTS: We collected data from 188 sepsis patients at the First Affiliated Hospital of Zhejiang University School of Medicine. The main focus was on the patient's immunocyte subset typing, T-cell activation/Treg cell analysis, and cytokine assay, which can indicate the immune status of the patient. RESULTS: The study found that the number of CD4+ T cells, CD8+ T cells, NK cells, and B cells decreased early in the disease, and the decrease in CD4+ and CD8+ T cells was more pronounced in the death group. T lymphocyte activation was inhibited, and the number of Treg cells increased as the disease progressed. T lymphocyte inhibition was more significant in the death group, and the increase in IL-10 was more significant in the death group. Finally, we used patients' baseline conditions and immunological detection indicators for modeling and found that IL-10, CD4+ Treg cells, CD3+HLA-DR+ T cells, and CD3+CD69+ T cells could predict patients' prognosis well. CONCLUSION: Our study found that immunosuppression occurs in patients early in sepsis. Early monitoring of the patient's immune status may provide a timely warning of the disease.


Assuntos
Citocinas , Sepse , Humanos , Citocinas/metabolismo , Interleucina-10/metabolismo , Linfócitos T CD8-Positivos , Ativação Linfocitária , Linfócitos T Reguladores , Sepse/metabolismo , Subpopulações de Linfócitos T
2.
Am J Emerg Med ; 75: 198.e1-198.e5, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37925304

RESUMO

A 54-year-old woman in good health was admitted to our hospital with diquat poisoning. The patient drank an unknown dose of diquat, and acute kidney injury developed early. However, there were no obvious pulmonary abnormalities and no signs of central nervous system toxicity in the early stage. The woman underwent active treatment, which resulted in a significant decrease in blood diquat levels, but her lung condition progressively worsened and neurological symptoms developed. Fortunately, the patient survived after intensive hemoperfusion combined with continuous renal replacement therapy (CRRT), intracranial pressure reduction, and anti-infective treatment. This case report highlights the importance of being aware of the development of delayed pulmonary symptoms and neurologic complications when caring for patients poisoned with diquat, even in those with low diquat blood concentrations. Interestingly, we also detected the concentration of diquat in the cerebrospinal fluid (CSF) of patients with diquat poisoning, and found that the rate of decrease of diquat concentration in the CSF was considerably slower than that in the blood.Notably, a specific correlation was observed between the concentration of diquat in the CSF, rather than in the blood, and both the intracranial pressure (ICP) and the severity of cerebral edema in this patient.


Assuntos
Terapia de Substituição Renal Contínua , Hemoperfusão , Intoxicação , Humanos , Feminino , Pessoa de Meia-Idade , Diquat , Sistema Nervoso Central , Pulmão , Intoxicação/terapia
3.
Eur Radiol ; 33(12): 8936-8947, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37368104

RESUMO

OBJECTIVES: To evaluate the performance of a radiomics nomogram developed based on gadolinium-ethoxybenzyl-diethylenetriamine penta-acetic acid (Gd-EOB-DTPA) MRI for preoperative prediction of microvascular invasion (MVI) of hepatocellular carcinoma (HCC), and to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization (PA-TACE). METHODS: A total of 260 eligible patients were retrospectively enrolled from three hospitals (140, 65, and 55 in training, standardized external, and non-standardized external validation cohort). Radiomics features and image characteristics were extracted from Gd-EOB-DTPA MRI image before hepatectomy for each lesion. In the training cohort, a radiomics nomogram which incorporated the radiomics signature and radiological predictors was developed. The performance of the radiomics nomogram was assessed with respect to discrimination calibration, and clinical usefulness with external validation. A score (m-score) was constructed to stratify the patients and explored whether it could accurately predict patient who benefit from PA-TACE. RESULTS: A radiomics nomogram integrated with the radiomics signature, max-D(iameter) > 5.1 cm, peritumoral low intensity (PTLI), incomplete capsule, and irregular morphology had favorable discrimination in the training cohort (AUC = 0.982), the standardized external validation cohort (AUC = 0.969), and the non-standardized external validation cohort (AUC = 0.981). Decision curve analysis confirmed the clinical usefulness of the novel radiomics nomogram. The log-rank test revealed that PA-TACE significantly decreased the early recurrence in the high-risk group (p = 0.006) with no significant effect in the low-risk group (p = 0.270). CONCLUSIONS: The novel radiomics nomogram combining the radiomics signature and clinical radiological features achieved preoperative non-invasive MVI risk prediction and patient benefit assessment after PA-TACE, which may help clinicians implement more appropriate interventions. CLINICAL RELEVANCE STATEMENT: Our radiomics nomogram could represent a novel biomarker to identify patients who may benefit from the postoperative adjuvant transarterial chemoembolization, which may help clinicians to implement more appropriate interventions and perform individualized precision therapies. KEY POINTS: • The novel radiomics nomogram developed based on Gd-EOB-DTPA MRI achieved preoperative non-invasive MVI risk prediction. • An m-score based on the radiomics nomogram could stratify HCC patients and further identify individuals who may benefit from the PA-TACE. • The radiomics nomogram could help clinicians to implement more appropriate interventions and perform individualized precision therapies.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/irrigação sanguínea , Nomogramas , Estudos Retrospectivos
4.
Hepatobiliary Pancreat Dis Int ; 21(3): 257-266, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35168873

RESUMO

BACKGROUND: Amanita poisoning as a foodborne disease has raised concerning mortality issues. Reducing the interval between mushroom ingestion and medical intervention could greatly influence the outcomes of Amanita poisoning patients, while treatment is highly dependent on a confirmed diagnosis. To this end, we developed an early detection-guided intervention strategy by optimizing diagnostic process with performing α-amanitin detection, and further explored whether this strategy influenced the progression of Amanita poisoning. METHODS: This study was a retrospective analysis of 25 Amanita poisoning patients. Thirteen patients in the detection group were diagnosed mainly based on α-amanitin detection, and 12 patients were diagnosed essentially on the basis of mushroom consumption history, typical clinical patterns and mushroom identification (conventional group). Amanita poisoning patients received uniform therapy, in which plasmapheresis was executed once confirming the diagnosis of Amanita poisoning. We compared the demographic baseline, clinical and laboratory data, treatment and outcomes between the two groups, and further explored the predictive value of α-amanitin concentration in serum. RESULTS: Liver injury induced by Amanita appeared worst at the fourth day and alanine aminotransferase (ALT) rose higher than aspartate aminotransferase (AST). The mortality rate was 7.7% (1/13) in the detection group and 50.0% (6/12) in the conventional group (P = 0.030), since patients in the detection group arrived hospital much earlier and received plasmapheresis at the early stage of disease. The early detection-guided intervention helped alleviate liver impairment caused by Amanita and decreased the peak AST as well as ALT. However, the predictive value of α-amanitin concentration in serum was still considered limited. CONCLUSIONS: In the management of mushroom poisoning, consideration should be given to the rapid detection of α-amanitin in suspected Amanita poisoning patients and the immediate initiation of medical treatment upon a positive toxin screening result.


Assuntos
Amanita , Intoxicação Alimentar por Cogumelos , Alfa-Amanitina , Humanos , Fígado , Intoxicação Alimentar por Cogumelos/complicações , Intoxicação Alimentar por Cogumelos/diagnóstico , Intoxicação Alimentar por Cogumelos/terapia , Estudos Retrospectivos
5.
J Clin Psychol Med Settings ; 29(2): 432-445, 2022 06.
Artigo em Inglês | MEDLINE | ID: mdl-35249176

RESUMO

This meta-analysis was a systematic review of evidence on the effects of mindfulness-based stress reduction (MBSR) and mindfulness-based cognitive therapy (MBCT) on quality of life (QOL), pain, fatigue, anxiety, and depression in cancer patients. Until July 2020, PubMed, Cochrane Library, and Embase were searched for randomized controlled trials (RCTs). The study included 18 RCTs. The MBSR/MBCT intervention resulted in a significant effect on QOL (SMD 0.80, CI 0.28, 1.32, I2 = 94%). In subgroup analysis, MBSR/MBCT interventions had a significant effect in the early cancer stage on anxiety (SMD - 3.48, CI - 4.07, - 2.88), and QOL (SMD 4.30, CI 3.62, 4.99); in alleviating decreasing pain (SMD - 0.42, CI - 0.70, - 0.14) within 4 weeks after the end of intervention, and alleviating fatigue in younger participants (SMD - 0.64, CI - 1.09, - 0.19). MBSR/MBCT has short-term effects on cancer patients, especially in younger patients and early cancer stages.


Assuntos
Atenção Plena , Neoplasias , Ansiedade/etiologia , Ansiedade/psicologia , Ansiedade/terapia , Fadiga/etiologia , Fadiga/psicologia , Fadiga/terapia , Humanos , Atenção Plena/métodos , Neoplasias/complicações , Neoplasias/terapia , Dor , Qualidade de Vida
6.
Hu Li Za Zhi ; 69(3): 31-40, 2022 Jun.
Artigo em Zh | MEDLINE | ID: mdl-35644595

RESUMO

BACKGROUND: A valid and reliable nursing record audit tool can simplify nursing records and provide a basis for quality auditing. PURPOSE: To ensure the validity and reliability of the Nursing Process Scale to promote accurate monitoring of nursing record quality. METHODS: This study employed structural equation modeling to examine the content validity and reliability of the current Nursing Process Scale. A total of 660 results from a medical center were used to revise the content and then the validity and reliability of the revised scale were analyzed. Exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were used in three stages, namely item generation and content validity testing, item analysis and validity testing, and reliability testing. RESULTS: Validity, reliability, and organization based on clinical practice were used to identify and remove scale items with low factor loadings. The remaining items were organized under several factors in the revised Nursing Process Scale, which had good internal consistency with a Cronbach's α of .653 in the EFA, a Kaiser-Meyer-Olkin value of .614, and a significant Bartlett's test of sphericity value. Five factors and 22 questions were extracted from the original 32 questions. The CFA conducted after the model correction reduced the number of questions to 10 and the number of factors to 3, with each index reaching the ideal level. To improve ease-of-use in clinical settings, the important items were reduced from 32 to 22 questions, including the 10 questions suggested by the CFA. CONCLUSIONS: The validity, reliability, and organization based on clinical practice were considered in the removal of items with low factor loadings. Axial conversion was used to generate a component matrix, which allowed item rearrangement across factors and the revision of the Nursing Process Scale. The development of simple valid and reliable audit tools will save auditor time and allow the effective evaluation of nursing record quality and improvement in record integrity. This revised scale was reviewed and approved for implementation in 42 clinical wards.


Assuntos
Processo de Enfermagem , Registros de Enfermagem , Análise Fatorial , Humanos , Reprodutibilidade dos Testes
7.
J Clin Lab Anal ; 34(7): e23281, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32157743

RESUMO

BACKGROUND: Detection of hepatitis B virus (HBV) is vital for the diagnosis of hepatitis B infection. A novel test loop-mediated isothermal amplification (LAMP) has been successfully applied to detect various pathogens. However, the accuracy of LAMP in diagnosing HBV remains unclear. Therefore, in the present study, the accuracy of LAMP for HBV detection was evaluated systematically. METHODS: Embase, Cochrane Library, and PubMed databases were searched for studies using LAMP to detect HBV. Then, two researchers extracted data and assessed the quality of literature using the QUADAS-2 tool independently. I2 statistic and chi-square test were analyzed to investigate the heterogeneity, and Deek's funnel plot assessed the publication bias. The pooled sensitivity (SEN), specificity (SPE), positive LR (PLR), negative LR (NLR), diagnostic odds ratio (DOR), and 95% confidence intervals were displayed in forest plots. We calculated the area under the curve (AUC) to assess the overall efficiency of LAMP for HBV detection. RESULTS: A total of nine studies with 1298 samples were finally included in this evaluation. The pooled sensitivity and specificity of HBV detection were 0.91 (95% CI: 0.89 ~ 0.92) and 0.97 (95% CI: 0.94 ~ 0.99), respectively. The PLR, NLR, and DOR were 16.93 (95% CI: 6.15 ~ 46.55), 0.08 (95% CI: 0.05 ~ 0.14), and 397.57 (95% CI: 145.41 ~ 1087.07). Besides, the AUC was 0.9872, and Deek's plot suggested that there existed publication bias in the studies. CONCLUSION: Compared with PCR, LAMP is a simple, rapid, and effective assay to diagnose HBV. However, additional evidence is essential to confirm that LAMP can replace other methods in diagnosing HBV infection.


Assuntos
Hepatite B/diagnóstico , Técnicas de Diagnóstico Molecular/métodos , Técnicas de Amplificação de Ácido Nucleico/métodos , Hepatite B/sangue , Humanos , Controle de Qualidade , Sensibilidade e Especificidade
8.
Worldviews Evid Based Nurs ; 16(6): 433-443, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31621181

RESUMO

BACKGROUND: Findings from previous studies examining the effectiveness of symptom management on patients with diabetes that were implemented in home settings were inconclusive. Exploring the effects of a diabetes symptom management program on patients with type 2 diabetes mellitus (T2DM) in clinical settings is useful for healthcare providers to improve their diabetes care. AIMS: To examine the effects of a diabetes symptom management program (DSMP) on HbA1c levels, self-care behaviors, quality of life (QoL), and symptom severity in clinics in patients with T2DM. METHODS: This study was a single-blind randomized controlled trial. The control group (n = 30) received usual care. The experimental group (n = 30) received DSMP and usual care. The primary outcome variable was HbA1c levels; the secondary outcome variables were self-care behaviors, QoL, and diabetes symptom severity. Outcome variables were measured at baseline (T0), 3 months (T1) and 6 months after the intervention (T2), and HbA1c levels were further collected at 9 months after the intervention (T3). RESULTS: The decreasing levels of HbA1c from T0 to T2 and from T0 to T3 and for severity of diabetes symptoms from T0 to T2 in the experimental group were significantly better than those in the control group. The increasing levels of self-care behavior and QoL from T0 to T1 and from T0 to T2 in the experimental group were significantly higher than those in the control group. LINKING EVIDENCE TO ACTION: DSMP implemented in the clinic setting has effects on improving HbA1c, self-care behaviors, QoL, and preventing worsening severity of diabetes symptoms for outpatients with T2DM. Healthcare providers could assess diabetes symptoms of patients with high HbA1c levels and provide symptom management care rather than merely providing education on improvement of self-care behaviors.


Assuntos
Diabetes Mellitus Tipo 2/terapia , Idoso , Distribuição de Qui-Quadrado , Diabetes Mellitus Tipo 2/enfermagem , Gerenciamento Clínico , Prática Clínica Baseada em Evidências/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Autogestão/métodos , Método Simples-Cego , Inquéritos e Questionários , Síndrome
9.
Proc Natl Acad Sci U S A ; 112(36): 11229-34, 2015 Sep 08.
Artigo em Inglês | MEDLINE | ID: mdl-26305948

RESUMO

Polyamines are organic polycations essential for cell growth and differentiation; their aberrant accumulation is often associated with diseases, including many types of cancer. To maintain polyamine homeostasis, the catalytic activity and protein abundance of ornithine decarboxylase (ODC), the committed enzyme for polyamine biosynthesis, are reciprocally controlled by the regulatory proteins antizyme isoform 1 (Az1) and antizyme inhibitor (AzIN). Az1 suppresses polyamine production by inhibiting the assembly of the functional ODC homodimer and, most uniquely, by targeting ODC for ubiquitin-independent proteolytic destruction by the 26S proteasome. In contrast, AzIN positively regulates polyamine levels by competing with ODC for Az1 binding. The structural basis of the Az1-mediated regulation of polyamine homeostasis has remained elusive. Here we report crystal structures of human Az1 complexed with either ODC or AzIN. Structural analysis revealed that Az1 sterically blocks ODC homodimerization. Moreover, Az1 binding triggers ODC degradation by inducing the exposure of a cryptic proteasome-interacting surface of ODC, which illustrates how a substrate protein may be primed upon association with Az1 for ubiquitin-independent proteasome recognition. Dynamic and functional analyses further indicated that the Az1-induced binding and degradation of ODC by proteasome can be decoupled, with the intrinsically disordered C-terminal tail fragment of ODC being required only for degradation but not binding. Finally, the AzIN-Az1 structure suggests how AzIN may effectively compete with ODC for Az1 to restore polyamine production. Taken together, our findings offer structural insights into the Az-mediated regulation of polyamine homeostasis and proteasomal degradation.


Assuntos
Proteínas de Transporte/química , Homeostase , Ornitina Descarboxilase/química , Poliaminas/química , Proteínas/química , Sequência de Aminoácidos , Biocatálise , Proteínas de Transporte/metabolismo , Cristalografia por Raios X , Inibidores Enzimáticos/química , Inibidores Enzimáticos/metabolismo , Humanos , Cinética , Modelos Moleculares , Dados de Sequência Molecular , Ornitina Descarboxilase/metabolismo , Poliaminas/metabolismo , Complexo de Endopeptidases do Proteassoma/metabolismo , Ligação Proteica , Conformação Proteica , Multimerização Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Proteínas/metabolismo , Proteólise , Homologia de Sequência de Aminoácidos
10.
Nucleic Acids Res ; 43(15): 7612-23, 2015 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-26150423

RESUMO

The mer operon confers bacterial resistance to inorganic mercury (Hg(2+)) and organomercurials by encoding proteins involved in sensing, transport and detoxification of these cytotoxic agents. Expression of the mer operon is under tight control by the dual-function transcriptional regulator MerR. The metal-free, apo MerR binds to the mer operator/promoter region as a repressor to block transcription initiation, but is converted into an activator upon Hg(2+)-binding. To understand how MerR interacts with Hg(2+) and how Hg(2+)-binding modulates MerR function, we report here the crystal structures of apo and Hg(2+)-bound MerR from Bacillus megaterium, corresponding respectively to the repressor and activator conformation of MerR. To our knowledge, the apo-MerR structure represents the first visualization of a MerR family member in its intact and inducer-free form. And the Hg(2+)-MerR structure offers the first view of a triligated Hg(2+)-thiolate center in a metalloprotein, confirming that MerR binds Hg(2+) via trigonal planar coordination geometry. Structural comparison revealed the conformational transition of MerR is coupled to the assembly/disassembly of a buried Hg(2+) binding site, thereby providing a structural basis for the Hg(2+)-mediated functional switching of MerR. The pronounced Hg(2+)-induced repositioning of the MerR DNA-binding domains suggests a plausible mechanism for the transcriptional regulation of the mer operon.


Assuntos
Proteínas de Bactérias/química , Proteínas de Ligação a DNA/química , Mercúrio/química , Proteínas Repressoras/química , Transativadores/química , Bacillus megaterium/genética , Sítios de Ligação , Modelos Moleculares , Óperon , Ligação Proteica , Conformação Proteica
11.
Hu Li Za Zhi ; 64(2): 55-65, 2017 Apr.
Artigo em Zh | MEDLINE | ID: mdl-28393339

RESUMO

BACKGROUND: Hospitalized patients generally have elevated levels of emotional distress. Gaining a better under-standing of the problem of emotional distress among hospitalized patients is conducive to providing appropriate emotional care and promoting their recovery. PURPOSE: To analyze the scores for the "sixth vital sign" (i.e., emotional distress), diversification, and the health-related problems of hospitalized patients at a medical center in Taiwan. The results may offer an important reference for providing effective emotional care to hospitalized patients. METHODS: A retrospective descriptive research design was used. Data were collected from all of the 27,885 inpatients that were registered at the target hospital in 2013. Further, a total of 245,814 attendance records were assessed to extract the data that were relevant to emotional distress. RESULTS: The findings revealed that 58.3% of hospitalized patients had earned a sixth vital sign score ≥ 1 and that 0.8% of these patients had earned a score ≥ 4. On the whole, the sixth vital sign scores of hospitalized patients were found to decrease progressively with the number of hospitalization days except for hematology and oncology, neurosurgery, and plastic surgery patients. The highest emotional distress scores were found among family medicine, dermatology, and plastic surgery patients. Moreover, emotional distress scores were significantly higher in patients who had health problems that involved pain, anxiety, or sleep disorder. CONCLUSIONS / IMPLICATIONS FOR PRACTICE: The present study suggests that improving the emotional care of hematology, oncology, neurosurgery, family medicine, dermatology, and plastic surgery patients and of patients with health problems involving pain, anxiety, or sleep disorder may significantly improve the quality of inpatient holistic healthcare. Only 0.8% of the subjects in the present study had an emotional distress score ≥ 4, which is significantly lower than the level reported in other similar studies. Our findings suggest that related education and training for nursing staffs may improve their assessment and care practices in caring for patients with emotional distress. Furthermore, using more appropriate words, methods, and environments to evaluate the emotional distress of patients holds the potential to improve assessment and care for these patients.


Assuntos
Pacientes Internados/psicologia , Estresse Psicológico/epidemiologia , Sinais Vitais , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Hospitalização , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
12.
Biochem J ; 462(1): 53-65, 2014 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-24844634

RESUMO

The E3 ubiquitin ligase RNF4 (RING finger protein 4) contains four tandem SIM [SUMO (small ubiquitin-like modifier)-interaction motif] repeats for selective interaction with poly-SUMO-modified proteins, which it targets for degradation. We employed a multi-faceted approach to characterize the structure of the RNF4-SIMs domain and the tetra-SUMO2 chain to elucidate the interaction between them. In solution, the SIM domain was intrinsically disordered and the linkers of the tetra-SUMO2 were highly flexible. Individual SIMs of the RNF4-SIMs domains bind to SUMO2 in the groove between the ß2-strand and the α1-helix parallel to the ß2-strand. SIM2 and SIM3 bound to SUMO with a high affinity and together constituted the recognition module necessary for SUMO binding. SIM4 alone bound to SUMO with low affinity; however, its contribution to tetra-SUMO2 binding avidity is comparable with that of SIM3 when in the RNF4-SIMs domain. The SAXS data of the tetra-SUMO2-RNF4-SIMs domain complex indicate that it exists as an ordered structure. The HADDOCK model showed that the tandem RNF4-SIMs domain bound antiparallel to the tetra-SUMO2 chain orientation and wrapped around the SUMO protamers in a superhelical turn without imposing steric hindrance on either molecule.


Assuntos
Proteínas Nucleares/metabolismo , Proteínas Modificadoras Pequenas Relacionadas à Ubiquitina/metabolismo , Fatores de Transcrição/metabolismo , Motivos de Aminoácidos/fisiologia , Ressonância Magnética Nuclear Biomolecular , Ligação Proteica , Estrutura Terciária de Proteína , Espalhamento a Baixo Ângulo , Ubiquitina-Proteína Ligases/metabolismo , Difração de Raios X
13.
Proc Natl Acad Sci U S A ; 109(17): 6496-501, 2012 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-22493270

RESUMO

Bacterial transpeptidase and transglycosylase on the surface are essential for cell wall synthesis, and many antibiotics have been developed to target the transpeptidase; however, the problem of antibiotic resistance has arisen and caused a major threat in bacterial infection. The transglycosylase has been considered to be another excellent target, but no antibiotics have been developed to target this enzyme. Here, we determined the crystal structure of the Staphylococcus aureus membrane-bound transglycosylase, monofunctional glycosyltransferase, in complex with a lipid II analog to 2.3 Å resolution. Our results showed that the lipid II-contacting residues are not only conserved in WT and drug-resistant bacteria but also significant in enzymatic activity. Mechanistically, we proposed that K140 and R148 in the donor site, instead of the previously proposed E156, are used to stabilize the pyrophosphate-leaving group of lipid II, and E100 in the acceptor site acts as general base for the 4-OH of GlcNAc to facilitate the transglycosylation reaction. This mechanism, further supported by mutagenesis study and the structure of monofunctional glycosyltransferase in complex with moenomycin in the donor site, provides a direction for antibacterial drugs design.


Assuntos
Glicosiltransferases/química , Lipídeos/química , Peptidoglicano/biossíntese , Staphylococcus aureus/enzimologia , Sequência de Aminoácidos , Cristalografia por Raios X , Modelos Moleculares , Dados de Sequência Molecular , Conformação Proteica , Homologia de Sequência de Aminoácidos
14.
BMC Gastroenterol ; 14: 147, 2014 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-25135360

RESUMO

BACKGROUND: To evaluate the safety, efficacy and outcomes of fast-track rehabilitation applied to gastric cancer proximal, distal and total gastrectomy. METHODS: Eighty consecutive patients undergoing gastric cancer resection performed by a single surgeon, received perioperative multimodal rehabilitation. Demographic and operative data, gastrointestinal function, postoperative hospital stays, surgical and general complications and mortality were assessed prospectively. RESULTS: Of the 80 patients (mean age 56.3 years), 10 (12.5%) received proximal subtotal gastrectomy (Billroth I), 38 (47.5%) received distal (Billroth II), and 32 (40%) received total gastrectomy (Roux-en-Y). Mean operative time was 104.9 minutes and intraoperative blood loss was 281.9 ml. Time to first flatus was 2.8 ± 0.5 postoperative days. Patients were discharged at a mean of 5.3 ± 2.2 postoperative days; 30-day readmission rate was 3.8%. In-hospital mortality was 0%; general and surgical complications were both 5%. CONCLUSIONS: Fast-track multimodal rehabilitation is feasible and safe in patients undergoing gastric cancer resection and may reduce time to first flatus and postoperative hospital stays.


Assuntos
Gastrectomia/reabilitação , Assistência Perioperatória/métodos , Complicações Pós-Operatórias , Neoplasias Gástricas/cirurgia , Idoso , Protocolos Clínicos , Estudos de Coortes , Deambulação Precoce/métodos , Estudos de Viabilidade , Feminino , Humanos , Tempo de Internação/estatística & dados numéricos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Estudos Prospectivos , Neoplasias Gástricas/patologia , Resultado do Tratamento
15.
Radiat Oncol ; 18(1): 155, 2023 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-37735389

RESUMO

BACKGROUND: To investigate the frequency of temporal lobe necrosis (TLN) soon after radiotherapy (RT) and identify differences among patients with various types of head and neck cancer (HNC) and between different RT methods. METHODS: We retrospectively reviewed 483 patients with HNC who had completed RT in our hospital after January, 2015. These patients were followed-up at the radio-oncology department and received contrast-enhanced magnetic resonance imaging (MRI) or computed tomography (CT) to identify metastases or recurrence of cancer at regular intervals. Meanwhile, the occurrence of TLN, graded according to the Common Terminology Criteria for Adverse Events V5.0, was recorded. We categorized the patients into nasopharyngeal carcinoma (NPC) and non-NPC groups and compared the cumulative occurrence of TLN between the groups using Kaplan-Meier and Cox regression analyses. We further compared the cumulative occurrence of TLN between proton beam therapy (PBT) and volumetric modulated arc therapy (VMAT) in patients with any HNC, NPC, and non-NPC HNC. RESULTS: Compared with the non-NPC group, the NPC group had a higher frequency of TLN (5.6% vs. 0.4%, p < 0.01) and were more commonly associated with TLN in the Kaplan-Meier analysis (p < 0.01) and the Cox regression model after covariates were adjusted for (adjusted hazard ratio: 13.35, 95% confidence interval: 1.37-130.61) during the follow-up period. Furthermore, the frequency of TLN was similar between patients receiving PBT and those receiving VMAT (PBT vs. VMAT: 4.7% vs. 6.3%, p = 0.76). Kaplan-Meier analysis revealed that the accumulated risks of TLN were similar between PBT and VMAT in patients with any HNC (p = 0.44), NPC (p = 0.84), and non-NPC HNC (p = 0.70). CONCLUSION: Our study demonstrated that patients with NPC are susceptible to TLN during the early period after RT. In addition, PBT may be associated with an equivalent risk of TLN when compared with VMAT in patients with NPC or other HNCs.


Assuntos
Neoplasias de Cabeça e Pescoço , Neoplasias Nasofaríngeas , Radioterapia de Intensidade Modulada , Humanos , Radioterapia de Intensidade Modulada/efeitos adversos , Prótons , Estudos Retrospectivos , Carcinoma Nasofaríngeo/radioterapia , Neoplasias de Cabeça e Pescoço/radioterapia , Necrose , Neoplasias Nasofaríngeas/radioterapia
16.
Ann Plast Surg ; 69(6): 627-32, 2012 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-23154333

RESUMO

Kasabach-Merritt phenomenon (KMP) is a rare and life-threatening disease of vascular tumor combined with severe consumptive coagulopathy. Currently, there is no established effective treatment of KMP. In this case series, from 2006 to 2008, we treated 6 pediatric patients with newly diagnosed KMP using intralesional corticosteroid injections. The severity and progression of the disease were closely monitored with clinical photographs, blood sampling, and tissue biopsies. The 6 pediatric patients (5 females and 1 male) showed tumor regression after treatments. All coagulopathies were corrected. The average duration of treatment was 3.8 months. Complete tumor regression was observed at approximately 3 years. Treatment was complicated in 1 patient with transient growth retardation. Treatment based on intralesional corticosteroid injections is effective for pediatric patients with KMP. Treatment-associated complications seemed to be reversible and acceptable by severity level.


Assuntos
Corticosteroides/administração & dosagem , Síndrome de Kasabach-Merritt/tratamento farmacológico , Feminino , Humanos , Lactente , Recém-Nascido , Injeções Intralesionais , Masculino , Indução de Remissão
17.
World J Emerg Med ; 13(5): 361-366, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36119775

RESUMO

BACKGROUND: Traumatic aortic dissection (TAD) has a low incidence but extremely high mortality. It always presents atypical clinical manifestations that are easily missed or misdiagnosed. This study mainly aims to describe the imaging characteristics and management of TAD patients. METHODS: A retrospective analysis of 27 blunt TAD patients was performed between 2013 and 2020. Demographic features, imaging characteristics, and management were analyzed. RESULTS: Twenty-seven patients with type B aortic dissection (age 56.04±16.07 years, 20 men) were included. Aortic intimal tears were mostly initiated from the aortic isthmus. The sizes of the proximal intimal tears in the greater curvature were larger than those in the lesser curvature (1.78±0.56 cm vs. 1.24±0.52 cm, P=0.031). Compared with those in the control group, the maximum diameters of the aortic arch, thoracic aorta, and abdominal aorta in the TAD patients were all significantly widened (all P<0.050). Multivariate logistic regression analysis showed that the maximum diameter of the thoracic aorta was an independent risk factor for TAD, with a predictive value with an area under the receiver operating characteristic curve (AUC) of 0.673. Finally, 26 patients successfully underwent delayed thoracic endovascular aortic repair (TEVAR), and the remaining one patient was treated conservatively. No progression of aortic dissection or death occurred during the six-month follow-up period. CONCLUSIONS: In blunt trauma, the aortic isthmus is the most common site of proximal intimal tears. An accurate diagnosis of TAD requires an overall consideration of medical history and imaging characteristics. Delayed TEVAR might be an effective therapeutic option for TAD.

18.
J Patient Saf ; 18(6): e1004-e1009, 2022 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-35532975

RESUMO

OBJECTIVES: In the medical environment, teamwork among medical care personnel is closely related to patient safety and care quality. This research has developed an Intranet-based call-for-help system to establish an emergency support system. Few studies have explored the effects of the timely call-for-help system on teamwork. This study explored the effects of the timely call-for-help system intervention. METHODS: This study was designed by 2 groups of pretest and posttest. This research was conducted at a medical center in Taiwan. The subjects of the study were nurses in inpatient wards. The newly established call-for-help system was used in the 4 experimental wards, enabling nurses to immediately seek help from each other when faced with challenges and difficulties. This study was blind with the outcome evaluator and data analyst blinded to the group of participants. RESULTS: A total of 165 nurses were included in the study, 84 in the intervention group and 81 in the control group. After the intervention of the call-for-help system, the experimental group had significantly better teamwork, work efficiency, job satisfaction, and lower job stress than the control group ( P < 0.01). The generalized estimating equation showed that the progress scores of the experimental group on the 4 scales were significantly higher than those of the control group ( P < 0.01). CONCLUSIONS: The implementation of timely call-for-help system can enable nursing staff to get immediate support, strengthen teamwork, create a positive nursing practice environment, and improve patient safety and quality of care. These improvements in teamwork and support are very important and worthy of promotion.


Assuntos
Recursos Humanos de Enfermagem Hospitalar , Estresse Ocupacional , Redes de Comunicação de Computadores , Humanos , Satisfação no Emprego , Qualidade da Assistência à Saúde , Inquéritos e Questionários , Taiwan
19.
Abdom Radiol (NY) ; 47(10): 3468-3477, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35842888

RESUMO

PURPOSE: This study aimed to establish a reliable diagnostic score model for the preoperative determination of pathological grade in HCC based on gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced MRI and biochemical indicators. METHODS: In this retrospective study, we analyzed 139 patients with HCC who underwent Gd-EOB-DTPA MRI between 2014 and 2020, including an establishment cohort of 76 patients and a validation cohort of 63 patients. Based on the imaging features demonstrated on Gd-EOB-DTPA MRI images and biochemical indicators of the establishment cohort, a scoring model based on logistic regression was developed, and compared with postoperative pathological findings in terms of effective determination of pathological grade. The validity of the scoring model was assessed by ROC curves and an independent external validation cohort. RESULTS: Three parameters related to pathological grades were identified, including maximum diameter of the tumor, peritumoral hypointensity in the hepatobiliary phase, and [alkaline phosphatase (U/L) + gamma glutamyl transpeptidase (U/L)]/ lymphocyte count (× 109/L) (AGLR) ratios. Based on these three parameters, a scoring model was developed. ROC curve showed that a score of > 5 was set as the threshold for determining pathological grades with accuracy, sensitivity, specificity, PPV, and NPV of 89.5%, 75.0%, 95.1%, 85.7%, and 90.7%, respectively. CONCLUSION: The study provided the groundwork for a promising and easily implementable scoring model for preoperative determination of HCC pathological grades, for which further validation should be pursued.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Carcinoma Hepatocelular/diagnóstico por imagem , Carcinoma Hepatocelular/cirurgia , Meios de Contraste , Gadolínio DTPA , Humanos , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/cirurgia , Imageamento por Ressonância Magnética/métodos , Estudos Retrospectivos
20.
J Med Chem ; 65(7): 5642-5659, 2022 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-35293758

RESUMO

Class I histone deacetylase (HDAC) enzymes 1, 2, and 3 organize chromatin as the catalytic subunits within seven distinct multiprotein corepressor complexes and are established drug targets. We report optimization studies of benzamide-based Von Hippel-Lindau (VHL) E3-ligase proteolysis targeting chimeras (PROTACs) and for the first time describe transcriptome perturbations resulting from these degraders. By modifying the linker and VHL ligand, we identified PROTACs 7, 9, and 22 with submicromolar DC50 values for HDAC1 and/or HDAC3 in HCT116 cells. A hook effect was observed for HDAC3 that could be negated by modifying the position of attachment of the VHL ligand to the linker. The more potent HDAC1/2 degraders correlated with greater total differentially expressed genes and enhanced apoptosis in HCT116 cells. We demonstrate that HDAC1/2 degradation by PROTACs correlates with enhanced global gene expression and apoptosis, important for the development of more efficacious HDAC therapeutics with reduced side effects.


Assuntos
Histona Desacetilases , Neoplasias , Apoptose , Quimera/metabolismo , Histona Desacetilase 1/metabolismo , Histona Desacetilases/metabolismo , Humanos , Ligantes , Neoplasias/tratamento farmacológico , Proteólise , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo
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