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1.
J Emerg Med ; 67(5): e425-e431, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39244486

RESUMO

BACKGROUND: Chest compression at a rate of 100-120 compressions per minute (cpm) during cardiopulmonary resuscitation (CPR) is associated with the highest survival rates. Performing compressions at a faster rate may exhaust the rescuers. OBJECTIVES: To compare a new cue of 'two compressions per second' to the traditional cue of '100-120 compressions per minute' on compression rate in CPR training. METHODS: In this cluster-randomized study, students from two senior high schools were assigned into two groups. For the experimental group, the cue for the compression rate was 'two compressions per second'. For the control group, the cue was '100-120 cpm'. Except the different cues, all participants underwent the same standardized CPR training program. Verbal compression rate-related feedback was not obtained during practice. Quality indicators of chest compressions were recorded by a sensorized manikin. The primary outcome measure was mean compression rate at course conclusion. The secondary outcome measures were individual compression quality indicators at course conclusion and 3 months after training. RESULTS: We included 164 participants (85 participants, experimental group; 79 participants, control group). Both groups had similar characteristics. The experimental group had a significantly lower mean compression rate at course conclusion (144.3 ± 16.17 vs. 152.7 ± 18.38 cpm, p = 0.003) and at 3 months after training (p = 0.09). The two groups had similar mean percentage of adequate compression rate (≥ 100 cpm), mean compression depth, and mean percentage of complete recoil at course conclusion and 3 months after training. CONCLUSION: The new cue of 'two compressions per second' resulted in participants having a lower compression rate, although it still exceeded 120 cpm.


Assuntos
Reanimação Cardiopulmonar , Manequins , Humanos , Reanimação Cardiopulmonar/educação , Reanimação Cardiopulmonar/métodos , Reanimação Cardiopulmonar/normas , Masculino , Feminino , Sinais (Psicologia) , Parada Cardíaca Extra-Hospitalar/terapia , Adolescente , Adulto Jovem , Fatores de Tempo , Massagem Cardíaca/métodos , Massagem Cardíaca/normas
3.
J Cell Mol Med ; 28(16): e70016, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39175122

RESUMO

Natural killer (NK) cell therapy, a developing approach in cancer immunotherapy, involves isolating NK cells from peripheral blood. However, due to their limited number and activity, it is essential to significantly expand these primary NK cells and enhance their cytotoxicity. In this study, we investigated how Raddeanin A potentiate NK activity using KHYG-1 cells. The results indicated that Raddeanin A increased the expression levels of cytolytic molecules such as perforin, granzymes A and granzymes B, granulysin and FasL in KHYG-1 cells. Raddeanin A treatment increased CREB phosphorylation, p65 phosphorylation, NFAT1 and acetyl-histone H3 expression. Raddeanin A elevated caspase 3 and PARP cleavage, increased t-Bid expression, promoting apoptosis in K562 cells. Furthermore, it reduced the expression of HMGB2, SET and Ape1, impairing the DNA repair process and causing K562 cells to die caspase-independently. Additionally, Raddeanin A increased ERK, p38 and JNK phosphorylation at the molecular level, which increased granzyme B production in KHYG-1 cells. Raddeanin A treatment increased Ras, Raf phosphorylation, MEK phosphorylation, NKG2D, NKp44 and NKp30 expression in KHYG-1 cells. Collectively, our data indicate that Raddeanin A enhances the cytotoxic activity of NK cells against different cancer cells.


Assuntos
Apoptose , Células Matadoras Naturais , Leucemia Mielogênica Crônica BCR-ABL Positiva , Humanos , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/metabolismo , Células K562 , Leucemia Mielogênica Crônica BCR-ABL Positiva/patologia , Leucemia Mielogênica Crônica BCR-ABL Positiva/metabolismo , Leucemia Mielogênica Crônica BCR-ABL Positiva/genética , Proteínas ras/metabolismo , Citotoxicidade Imunológica , Transdução de Sinais , Quinases raf/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Reparo do DNA , Granzimas/metabolismo
4.
Environ Toxicol ; 2024 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-39194337

RESUMO

World Health Organization data indicate a continuous increase in melanoma incidence, with metastatic melanoma characterized by poor prognosis and drug resistance. The exploration of therapeutics derived from natural products remains an active area of in vitro research. The aim of this study was to determine the antitumor effects of picrasidine I, a natural compound extracted from Picrasma quassioides, against two melanoma cell lines. We selected two metastatic melanoma cell lines, HMY-1 and A2058, for molecular studies, including Western blotting, 4',6-diamidino-2-phenylindole staining, and flow cytometry. Picrasidine I demonstrated cytotoxic effects against the HMY-1 and A2058 melanoma cell lines. It induced cell cycle arrest in the sub-G1 phase and downregulated cell cycle-related proteins (e.g., cyclin A2, D1, cyclin-dependent kinases 4, and 6). In the intrinsic apoptosis pathway, picrasidine I activated proapoptotic proteins (e.g., Bax, Bak, t-Bid, BimL/S) and suppressed the expression of antiapoptotic proteins (e.g., Bcl-2, Bcl-xL), with an observed increase in the quantity of depolarized cells. In addition, the apoptotic effects of picrasidine I were linked to the activation of the c-Jun N-terminal kinase and extracellular signal-regulated kinase pathways and the inhibition of the protein kinase B signaling pathway. A human apoptosis array indicated claspin inhibition upon picrasidine I treatment, suggesting the potential involvement of picrasidine I in apoptosis and cell cycle regulation. Our findings suggest that picrasidine I has potential as a candidate for treating advanced melanoma, and thus these findings warrant further investigation. The modulation of claspin expression by picrasidine I could be investigated further as a potential biomarker to predict its efficacy in related to advanced stages of melanoma.

5.
J Cell Mol Med ; 28(16): e70015, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39159189

RESUMO

Pyrocurzerenone is a natural compound found in Curcuma zedoaria and Chloranthus serratus. However, the anticancer effect of pyrocurzerenone in oral cancer remains unclear. Using the MTT assay, wound healing assay, transwell assay and western blot analysis, we investigated the impact of pyrocurzerenone on antimetastatic activity, as well as the critical signalling pathways that underlie the processes of oral cancer cell lines SCC-9, SCC-1 and SAS in this work. Our findings suggested that pyrocurzerenone inhibits cell migration and invasion ability in oral cancer cell lines. Furthermore, phosphorylation of ERK1/2 had significant inhibitory effects in SCC-9 and SCC-1 cell lines. Combining ERK1/2 inhibitors with pyrocurzerenone decreased the migration and invasion activity of SCC-9 and SCC-1 cell lines. We also found that the expressed level of cathepsin S decreased under pyrocurzerenone treatment. This study showed that pyrocurzerenone reduced ERK1/2 expression of the proteins and cathepsin S, suggesting that it could be a valuable treatment to inhibit human oral cancer cell metastasis.


Assuntos
Catepsinas , Movimento Celular , Neoplasias Bucais , Humanos , Neoplasias Bucais/patologia , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Catepsinas/metabolismo , Catepsinas/antagonistas & inibidores , Fosforilação/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Metástase Neoplásica , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteína Quinase 3 Ativada por Mitógeno/metabolismo , Proteína Quinase 3 Ativada por Mitógeno/genética , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Proteína Quinase 1 Ativada por Mitógeno/genética , Invasividade Neoplásica , Proliferação de Células/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
6.
BMJ ; 386: e079878, 2024 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-39043416

RESUMO

OBJECTIVE: To compare the effectiveness of intraosseous versus intravenous vascular access in the treatment of adult patients with out-of-hospital cardiac arrest. DESIGN: Cluster randomised controlled trial. SETTING: The VICTOR (Venous Injection Compared To intraOsseous injection during resuscitation of patients with out-of-hospital cardiac arrest) trial involved emergency medical service agencies with all four advanced life support ambulance teams in Taipei City, Taiwan. The enrolment period spanned 6 July 2020 to 30 June 2023 and was temporarily suspended between 20 May 2021 and 31 July 2021 owing to the covid-19 pandemic. PARTICIPANTS: Adult (age 20-80 years) patients with non-traumatic out-of-hospital cardiac arrest. INTERVENTIONS: Biweekly randomised clusters of four participating advanced life support ambulance teams were assigned to insert either intravenous or intraosseous access. MAIN OUTCOME MEASURES: The primary outcome was survival to hospital discharge. Secondary outcomes included return of spontaneous circulation, sustained return of spontaneous circulation (≥2 hours), and survival with favourable neurological outcomes (cerebral performance category score ≤2) at hospital discharge. RESULTS: Among 1771 enrolled patients, 1732 (741 in the intraosseous group and 991 in the intravenous group) were included in the primary analysis (median age 65.0 years; 1234 (71.2%) men). In the intraosseous group, 79 (10.7%) patients were discharged alive, compared with 102 (10.3%) patients in the intravenous group (odds ratio 1.04, 95% confidence interval 0.76 to 1.42; P=0.81). The odds ratio of intraosseous versus intravenous access was 1.23 (0.89 to 1.69; P=0.21) for pre-hospital return of spontaneous circulation, 0.92 (0.75 to 1.13; P=0.44) for sustained return of spontaneous circulation, and 1.17 (0.82 to 1.66; P=0.39) for survival with favourable neurological outcomes. CONCLUSIONS: Among adults with non-traumatic out-of-hospital cardiac arrest, initial attempts to establish vascular access through the intraosseous route did not result in different outcomes compared with intravenous access in terms of the proportion of patients surviving to hospital discharge, pre-hospital return of spontaneous circulation, sustained return of spontaneous circulation, and favourable neurological outcomes. TRIAL REGISTRATION: NCT04135547ClinicalTrials.gov NCT04135547.


Assuntos
Infusões Intraósseas , Parada Cardíaca Extra-Hospitalar , Humanos , Parada Cardíaca Extra-Hospitalar/terapia , Parada Cardíaca Extra-Hospitalar/mortalidade , Feminino , Masculino , Infusões Intraósseas/métodos , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Taiwan/epidemiologia , Serviços Médicos de Emergência/métodos , Extremidade Superior , COVID-19 , Resultado do Tratamento , Reanimação Cardiopulmonar/métodos , Adulto Jovem , Injeções Intravenosas , SARS-CoV-2
7.
Acta Cardiol Sin ; 40(4): 412-420, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-39045376

RESUMO

Background: Prehospital electrocardiogram (PHECG) shortens door-to-balloon time in patients with ST-elevation myocardial infarction. However, it may increase the prehospital service time, thus offsetting the benefits gained. The performance of PHECG could be influenced by the proficiency of the emergency medical technicians (EMTs). Objectives: To investigate whether there are differences in the performance of PHECG between EMT-II and EMT-paramedics (EMT-P). Methods: This prospectively designed, retrospectively analyzed study of PHECG was conducted in Taipei from February 2019 to April 2021. Comparisons were made between EMT-II and EMT-P teams. The primary outcomes were the acceptance of PHECG suggestions and prehospital service time. The secondary outcomes were gender disparities in the primary outcomes. Results: A total of 2,991 patients were included, of whom 2,617 received PHECG. For the primary outcomes, the acceptance of PHECG was higher in those approached by EMT-P (99.6% vs. 71.5%, p < 0.001). The scene time and scene-to-hospital time showed no significant differences. For gender disparities, the acceptance of PHECG in female patients was significantly lower in those approached by EMT-II (59.3% vs. 99.2%, p < 0.001). The scene time and scene-to-hospital time were generally longer in the female patients, especially in the younger and middle age groups. Compared to EMT-P, both were significantly longer in the female patients approached by EMT-II. Conclusions: The acceptance of PHECG was lower in those approached by EMT-II, especially in females. Although there were generally no significant differences between EMT-II and EMT-P, the scene time and scene-to-hospital time were significantly longer in female patients, especially in those aged < 75 years approached by EMT-II.

8.
J Formos Med Assoc ; 2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38902123

RESUMO

BACKGROUND: Ambulance-based telestroke may be a promising solution to improving stroke care. We assessed the technical feasibility and reliability of prehospital evaluations using commercial mobile phones with fifth-generation wireless communication technology. METHODS: Six standardized patients portrayed scripted stroke scenarios during ambulance transport in an urban city and were remotely evaluated by independent raters using tablets (three neurologists and three emergency physicians) in a hospital, assisted by paramedics (trained in National Institute of Health Stroke Scale [NIHSS] assessment) in the ambulance; commercial cellular networks were utilized for videoconferencing transmission. The primary outcomes were mean difference (MD) and correlation of NIHSS scores between the face-to-face and remote assessments. We also examined the Bland-Altman plot for itemized NIHSS components, and Kaplan-Meier curves were used to compare the differences in the duration of the two evaluations between neurologists and emergency physicians. RESULTS: We conducted 32 ambulance runs and successfully completed all NIHSS examinations. No significant difference was found between the face-to-face and remote evaluations (MD, 0.782; 95% confidence interval [CI], -0.520-0.395). The correlation of NIHSS scores between the two methods was 0.994 (95% CI, 0.945-1.026), and three items exhibited the highest frequency of runs, with score differences between the two methods. There were no significant differences between neurologists and emergency physicians in the mean evaluation duration and NIHSS scores for the two methods. CONCLUSION: Prehospital evaluation using commercial mobile phones with fifth-generation wireless communication technology is feasible and reliable during ambulance transport in urban areas. Emergency physicians and neurologists performed similarly in stroke evaluations.

9.
Int J Mol Sci ; 25(7)2024 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-38612772

RESUMO

Oral cancer ranks fourth among malignancies among Taiwanese men and is the eighth most common cancer among men worldwide in terms of general diagnosis. The purpose of the current study was to investigate how low-density lipoprotein receptor-related protein 1B (LDL receptor related protein 1B; LRP1B) gene polymorphisms affect oral squamous cell carcinoma (OSCC) risk and progression in individuals with diabetes mellitus (DM). Three LRP1B single-nucleotide polymorphisms (SNPs), including rs10496915, rs431809, and rs6742944, were evaluated in 311 OSCC cases and 300 controls. Between the case and control groups, we found no evidence of a significant correlation between the risk of OSCC and any of the three specific SNPs. Nevertheless, in evaluating the clinicopathological criteria, individuals with DM who possess a minimum of one minor allele of rs10496915 (AC + CC; p = 0.046) were significantly associated with tumor size compared with those with homozygous major alleles (AA). Similarly, compared to genotypes homologous for the main allele (GG), rs6742944 genotypes (GA + AA; p = 0.010) were more likely to develop lymph node metastases. The tongue and the rs6742944 genotypes (GA + AA) exhibited higher rates of advanced clinical stages (p = 0.024) and lymph node metastases (p = 0.007) when compared to homozygous alleles (GG). LRP1B genetic polymorphisms appear to be prognostic and diagnostic markers for OSCC and DM, as well as contributing to genetic profiling research for personalized medicine.


Assuntos
Carcinoma de Células Escamosas , Diabetes Mellitus , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Masculino , Humanos , Neoplasias Bucais/genética , Metástase Linfática , Carcinoma de Células Escamosas/genética , Polimorfismo de Nucleotídeo Único , Carcinoma de Células Escamosas de Cabeça e Pescoço , Receptores de LDL/genética
10.
Expert Opin Ther Targets ; 28(5): 461-471, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38659296

RESUMO

BACKGROUND: The high recurrence rate and incidence of distant metastasis of nasopharyngeal carcinoma (NPC) result in poor prognosis. It is necessary to identify natural compounds that can complement combination radiation therapy. Arenobufagin is commonly used for heart diseases and liver cancer, but its effectiveness in NPC is unclear. STUDY DESIGN AND METHODS: The effect of arenobufagin-induced apoptosis was measured by a cell viability assay, tumorigenic assay, fluorescence assay, and Western blot assay through NPC-039 and NPC-BM cell lines. The protease array, Western blot assay, and transient transfection were used to investigate the underlying mechanism of arenobufagin-induced apoptosis. An NPC xenograft model was established to explore the antitumor activity of arenobufagin in vivo. RESULTS: Our findings indicated that arenobufagin exerted cytotoxic effects on NPC cells, inhibiting proliferation through apoptosis activation. Downregulation of claspin was confirmed in arenobufagin-induced apoptosis. Combined treatment with arenobufagin and mitogen-activated protein kinase inhibitors demonstrated that arenobufagin induced NPC apoptosis through the c-Jun N-terminal kinases (JNK) pathway inhibition. Furthermore, arenobufagin suppressed NPC tumor proliferation in vivo. CONCLUSION: Our results revealed the antitumor effect of arenobufagin in vitro and in vivo. Arenobufagin may have clinical utility in treating NPC due to its suppression of claspin and inhibition of the JNK pathway.


Assuntos
Apoptose , Bufanolídeos , Proliferação de Células , Sistema de Sinalização das MAP Quinases , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Animais , Feminino , Humanos , Masculino , Camundongos , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Bufanolídeos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Regulação para Baixo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Camundongos Endogâmicos BALB C , Camundongos Nus , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/patologia , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/patologia , Ensaios Antitumorais Modelo de Xenoenxerto
11.
J Formos Med Assoc ; 123(9): 1004-1009, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38614907

RESUMO

BACKGROUND/PURPOSE: This study addresses the delicate balance between healthcare personnel burnout and medical accessibility in the context of endovascular thrombectomy (EVT) services in urban areas. We aimed to determine the minimum number of hospitals providing EVT on rotation each day without compromising patient access. METHODS: Employing an optimization model, we developed shift schedules based on patient coverage rates and volumes during the pre-pandemic (2016-2018) and pandemic (2019-2021) periods. Starting with a minimum of two hospitals on duty per day, we gradually increased to a maximum of eight. Patient coverage rates, defined as the proportion of patients meeting bypass criteria and transported to rotating hospitals capable of EVT, were the primary outcomes. Sensitivity analyses explored the impact of varying patient transport intervals and accumulating patients over multiple years. RESULTS: Results from 7024 patient records revealed patient coverage rates of 92.5% (standard deviation [SD] 2.8%) during the pre-pandemic and 91.4% (SD 2.8%) during the pandemic, with at least two rotating hospitals daily. No significant differences were observed between schedules based on the highest patient volume and coverage rate months. A patient coverage rate of 98.99% was achieved with four rotating hospitals per day during the pre-pandemic period, with limited improvement beyond this threshold. Changing patient transport intervals and accumulating patients over six years (p = 0.83) had no significant impact on coverage rates. CONCLUSION: Our optimization model supports reducing the number of daily rotating hospitals by half while preserving a balance between patient accessibility and alleviating strain on medical teams.


Assuntos
Acessibilidade aos Serviços de Saúde , Trombectomia , Humanos , Taiwan , COVID-19/epidemiologia , Procedimentos Endovasculares , Masculino , Feminino , Idoso , Pessoa de Meia-Idade
12.
World J Emerg Surg ; 19(1): 10, 2024 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-38504263

RESUMO

BACKGROUND: Tourniquets (TQ) have been increasingly adopted in pre-hospital settings recently. This study examined the effectiveness and safety of applying TQ in the pre-hospital settings for civilian patients with traumatic vascular injuries to the extremities. MATERIALS AND METHODS: We systematically searched the Ovid Embase, PubMed, and Cochrane Central Register of Controlled Trials databases from their inception to June 2023. We compared pre-hospital TQ (PH-TQ) use to no PH-TQ, defined as a TQ applied after hospital arrival or no TQ use at all, for civilian vascular extremity trauma patients. The primary outcome was overall mortality rate, and the secondary outcomes were blood product use and hospital stay. We analyzed TQ-related complications as safety outcomes. We tried to include randomized controlled trials (RCTs) and non-randomized studies (including non-RCTs, interrupted time series, controlled before-and-after studies, cohort studies, and case-control studies), if available. Pooled odds ratios (ORs) were calculated and the certainty of evidence was assessed using Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. RESULTS: Seven studies involving 4,095 patients were included. In the primary outcome, pre-hospital TQ (PH-TQ) use significantly decrease mortality rate in patients with extremity trauma (odds ratio [OR], 0.48, 95% confidence interval [CI] 0.27-0.86, I2 = 47%). Moreover, the use of PH-TQ showed the decreasing trend of utilization of blood products, such as packed red blood cells (mean difference [MD]: -2.1 [unit], 95% CI: -5.0 to 0.8, I2 = 99%) or fresh frozen plasma (MD: -1.0 [unit], 95% CI: -4.0 to 2.0, I2 = 98%); however, both are not statistically significant. No significant differences were observed in the lengths of hospital and intensive care unit stays. For the safety outcomes, PH-TQ use did not significantly increase risk of amputation (OR: 0.85, 95% CI: 0.43 to 1.68, I2 = 60%) or compartment syndrome (OR: 0.94, 95% CI: 0.37 to 2.35, I2 = 0%). The certainty of the evidence was very low across all outcomes. CONCLUSION: The current data suggest that, in the pre-hospital settings, PH-TQ use for civilian patients with vascular traumatic injury of the extremities decreased mortality and tended to decrease blood transfusions. This did not increase the risk of amputation or compartment syndrome significantly.


Assuntos
Torniquetes , Lesões do Sistema Vascular , Humanos , Lesões do Sistema Vascular/mortalidade , Extremidades/lesões , Extremidades/irrigação sanguínea , Serviços Médicos de Emergência/métodos
13.
Health Care Manag Sci ; 27(2): 254-267, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38345674

RESUMO

Nowadays, emergency medical technicians (EMTs) decide to send a suspected stroke patient to a primary stroke center (PSC) or to an endovascular thrombectomy (EVT)-capable hospital, based on the Cincinnati Prehospital Stroke Scale (CPSS) and the number of symptoms a patient presents at the scene. Based on existing studies, the patient is likely to have a better functional outcome after three months if the time between the onset of symptoms and receiving EVT treatment is shorter. However, if an acute ischemic stroke (AIS) patient with large vessel occlusion (LVO) is first sent to a PSC, and then needs to be transferred to an EVT-capable hospital, the time to get definitive treatment is significantly increased. For this purpose, We formulate an integer programming model to minimize the expected time to receive a definitive treatment for stroke patients. We then use real-world data to verify the validity of the model. Also, we expand our model to find the optimal redistribution and centralization of EVT resources. It will enable therapeutic teams to increase their experience and skills more efficiently within a short period of time.


Assuntos
Procedimentos Endovasculares , Acidente Vascular Cerebral , Trombectomia , Humanos , Trombectomia/métodos , Procedimentos Endovasculares/métodos , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/cirurgia , Tempo para o Tratamento , Serviços Médicos de Emergência/métodos , AVC Isquêmico/cirurgia , AVC Isquêmico/terapia , Fatores de Tempo
14.
Environ Toxicol ; 39(4): 2417-2428, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38197544

RESUMO

The prevalence of oral squamous cell carcinoma (OSCC) is increasing worldwide mainly due to poor oral hygiene and unrestricted lifestyle. Advanced-stage OSCC is associated with poor prognosis and a 5-year survival rate of only 30%-50%. The present study was designed to investigate the anticancer effect and mode of action of Glycyrrhiza-derived semilicoisoflavone B (SFB) in 5-fluorourasil (5FU)-resistant human OSCC cell lines. The study findings revealed that SFB significantly reduces OSCC cell viability and colony formation ability by arresting cell cycle at the G2/M and S phases and reducing the expressions of key cell cycle regulators including cyclin A, cyclin B, CDC2, and CDK2. The compound caused a significant induction in the percentage of nuclear condensation and apoptotic cells in OSCC. Regarding pro-apoptotic mode of action, SFB was found to increase Fas-associated death domain and death receptor 5 expressions and reduce decoy receptor 2 expression, indicating involvement of extrinsic pathway. Moreover, SFB was found to increase pro-apoptotic Bim expression and reduce anti-apoptotic Bcl-2 and Bcl-xL expressions, indicating involvement of intrinsic pathway. Moreover, SFB-mediated induction in cleaved caspases 3, 8, and 9 and cleaved poly(ADP-ribose) polymerase confirmed the induction of caspase-mediated apoptotic pathways. Regarding upstream signaling pathway, SFB was found to reduce extracellular signal regulated kinase 1/2 (ERK) phosphorylation to execute its pro-apoptotic activity. The Human Apoptotic Array findings revealed that SFB suppresses claspin expression, which in turn caused reduced phosphorylation of ATR, checkpoint kinase 1 (Chk1), Wee1, and CDC25C, indicating disruption of ATR-Chk1 signaling pathway by SFB. Taken together, these findings indicate that SFB acts as a potent anticancer compound against 5FU-resistant OSCC by modulating mitogen-activated protein kinase (MAPK) and ATR-Chk1 signaling pathways.


Assuntos
Carcinoma de Células Escamosas , Flavonoides , Neoplasias Bucais , Humanos , Quinase 1 do Ponto de Checagem , Apoptose , Transdução de Sinais , Fosforilação , Fluoruracila , Linhagem Celular Tumoral , Proteínas Mutadas de Ataxia Telangiectasia
15.
J Clin Nurs ; 33(4): 1387-1397, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38240043

RESUMO

AIM AND OBJECTIVES: To develop a Delirium Care Critical-Thinking Scale for nurses caring for patients in the intensive care unit and examine the scale's psychometric properties. BACKGROUND: There is a tool to evaluate nurses' critical thinking skills to determine nursing competency when delirium care is required. DESIGN: This cross-sectional, mixed-methods study. METHODS: The Delphi method was applied for collection and analysis of data during conceptualization and item generation of the tool (Phase I). Item analysis, assessment of validity and reliability of the scale (Phase II) involved 318 nurses recruited by convenience sampling from nine adult intensive care units in medicine and surgery at one medical centre. Confirmatory factor analysis assessed construct validity. Internal consistency and 2-week test-retest stability measured reliability. A Critical Thinking Disposition Inventory Scale examined concurrent validity. RESULTS: After three rounds, the Delphi method resulted in 31 scale items. Item analysis demonstrated construct reliability ranged from 9.23 to 16.18. Confirmatory factor analysis eliminated one item and extracted five factors: applying knowledge, confirming the problem and accuracy of information, reasoning logically, choosing appropriate strategies and remaining open-minded. Average variance extracted values of all factors indicated good convergent validity. Cronbach's α for internal consistency was .96 with good test-retest reliability. The correlation coefficient for concurrent validity was .301. CONCLUSION: The new Delirium Care Critical-Thinking Scale for intensive care nurses was demonstrated to be a reliable and valid tool for evaluating their ability to assess patients with delirium. RELEVANCE TO CLINICAL PRACTICE: This new scale could be used to assess outcomes of education interventions and the effectiveness of nursing care quality involving patients with delirium in intensive and critical care units. REPORTING METHOD: The COSMIN checklist was used as the reporting guideline for this study. PATIENT OR PUBLIC CONTRIBUTION: None.


Assuntos
Delírio , Unidades de Terapia Intensiva , Adulto , Humanos , Estudos Transversais , Reprodutibilidade dos Testes , Inquéritos e Questionários , Pensamento , Psicometria , Delírio/diagnóstico
16.
Int J Mol Sci ; 25(2)2024 Jan 16.
Artigo em Inglês | MEDLINE | ID: mdl-38256171

RESUMO

Most disease single nucleotide polymorphisms (SNPs) are regulatory and approximately half of heritability is occupied by the top 1% of genes, with the gene-level structure varying with the number of variants associated with the most common alleles. Cancer occurrence and progression are significantly affected by Claspin (CLSPN) gene polymorphism present in the population, which alters the expression, function, and regulation of the gene. CLSPN genotypes are associated with oral cancer, but the literature on this association is limited. As a result, the goal of this study is to investigate the correlation between CLSPN genotypes and oral cancers' development. This study will explore the presence of four CLSPN SNPs including rs12058760, rs16822339, rs535638 and rs7520495 gene polymorphisms, and analyze the expression of these genes in 304 cancer-free controls and 402 oral squamous cell carcinoma (OSCC) cases. Attempts have been made to obtain insight into the role of CLSPN gene polymorphisms in oral cancer through the analysis of this study. We demonstrated that the OSCC risk of individuals with four CLSPN SNPs relative to the wild type did not differ significantly from that of the wild type when the polymorphisms are analyzed according to individual habits. We further studied the mechanism by which CLSPN polymorphisms affect the progression of clinicopathological features in OSCC patients. The results of the degree of cell differentiation showed that compared with patients of rs7520495 SNP carrying the CC genotype, the incidence of poor cell differentiation in patients carrying the CC + GG genotype was higher (AOR: 1.998-fold; 95% CI, 1.127-3.545; p = 0.018). In particular, patients with the G genotype of rs7520495 had increased poor cell differentiation compared with patients with the C genotype (AOR: 4.736-fold; 95% CI, 1.306-17.178; p = 0.018), especially in the drinking group. On the basis of our analysis of the Cancer Genome Atlas dataset, we found that higher CLSPN levels were associated with poorer cell differentiation in oral cancers. In this study, we provide the first evidence showing that CLSPN SNPs contribute to oral cancer. Whether or not rs7520495 can be used as a confirmatory factor in the future is uncertain, but it seems likely that it can be used as an important factor in predicting recurrence, response to treatment and medication toxicity to patients with oral cancer.


Assuntos
Proteínas Adaptadoras de Transdução de Sinal , Neoplasias Bucais , Carcinoma de Células Escamosas de Cabeça e Pescoço , Humanos , Proteínas Adaptadoras de Transdução de Sinal/genética , Consumo de Bebidas Alcoólicas/genética , Neoplasias Bucais/genética , Polimorfismo de Nucleotídeo Único , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética
17.
Eur J Radiol ; 172: 111322, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38295549

RESUMO

INTRODUCTION: In the era of lung cancer screening, more and more sub-centimeter indeterminate lung lesions are being identified. It is difficult to approach these lesions and obtain tissue to confirm diagnosis. CT-guided navigation followed by surgical resection is the best way to overcome this difficulty. The aim of this study is to compare the safety and feasibility of wire and dye-tattoo CT-guided localization techniques. MATERIALS AND METHODS: From September 2019 to August 2021, 418 patients who presented with single lung lesion and received single CT-guided localization were included in this study. Procedure details, navigation results, and related complications were compared. RESULTS: For patients who received wire localization, majority (98.3 %) had perihilar lesions. In addition, 68 (57.1 %) patients received tangential approach because of lesions were blocked by bony or vital structure, abutting major fissure, or previous approach failure. The characteristics of lesion location was quite different than dye-tattooing technique (p = 0.033). As regards persistence of the target lesion localization, the interval between localization and surgery using ICG tattooing was 829.0 ± 552.9 min; much longer than the other two navigation techniques (p < 0.0001). As regards safety, patients who received wire localization had a higher rate of pneumothorax (p = 0.042) and pulmonary hemorrhage (p < 0.001) than the dye-tattooing techniques. DISCUSSION: CT-guided navigation techniques are safe and feasible. Wire localization is suitable for centrally located lesions but the wire needs to be fixed properly and symptomatic pneumothorax monitored for. Dye-tattooing is more suitable for peripheral lesions, while ICG localization persists longer than other techniques.


Assuntos
Neoplasias Pulmonares , Pneumotórax , Nódulo Pulmonar Solitário , Humanos , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Estudos de Viabilidade , Detecção Precoce de Câncer , Cirurgia Torácica Vídeoassistida/métodos , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos
18.
J Formos Med Assoc ; 123(3): 340-346, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37996322

RESUMO

BACKGROUND: Information on the protein-based severe acute respiratory syndrome (SARS-CoV-2) vaccine-NVX-CoV2373 (Novavax), as a heterologous booster remains limited. We investigated the immunogenicity and adverse events of NVX-CoV2373 as a second booster and compared them with those of mRNA vaccines in healthy adults. METHODS: Healthcare workers who had received an mRNA vaccine (mRNA-1273 or BNT-162b2) as the first booster (third dose) 12 weeks prior were recruited. Participants voluntarily received either NVX-CoV2373 or an mRNA vaccine as a second booster. Participants with a history of SARS-CoV-2 infection were excluded. The primary outcomes included serum anti-SARS-CoV-2 spike protein (SP) and neutralizing antibody titers against B.1.1.7 (Alpha), B.1.1.529 (Omicron) BA2, and BA5 variants on the 28th day after the boost. Secondary outcomes included new SARS-CoV-2 infections and adverse events reported during the study period. RESULTS: A total of 160 participants were enrolled in this study. Compared with the mRNA vaccination group (n = 59), the NVX-CoV2373 vaccination group (n = 101) had significantly lower anti-SARS-CoV-2 SP antibody titers and neutralizing antibody titers against all variants tested after the boost. During the study period, higher rates of new SARS-CoV-2 infections and a lower incidence of adverse events were observed in the NVX-CoV2373 vaccination group. No significant differences in cellular immune responses were observed between the two groups. CONCLUSION: Compared to a homologous mRNA booster vaccination, heterologous boosters with NVX-CoV2373 showed lower antibody responses, a higher incidence of new SARS-CoV-2 infections, and fewer adverse events.


Assuntos
Vacinas contra COVID-19 , COVID-19 , Adulto , Humanos , Vacinas contra COVID-19/efeitos adversos , Vacinas de mRNA , SARS-CoV-2 , COVID-19/prevenção & controle , RNA Mensageiro , Anticorpos Neutralizantes , Anticorpos Antivirais
19.
J Cell Mol Med ; 28(2): e18071, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38044583

RESUMO

Oral squamous cell carcinoma (OSCC), which accounts for 90% of all oral cancers, has become a public health crisis worldwide. despite advances in therapeutic interventions, the prognosis remains poor for advanced-stage OSCC. In this study, we investigate the anticancer activity and the mode of action of hellebrigenin in human OSCC. The findings demonstrated that hellebrigenin exerted cytotoxic effects in OSCC cells through cell cycle arrest at the G2/M phase and downregulation of cell cycle-related proteins (cyclins A2, B1 and D3, Cdc2, CDK4 and CDK6). Moreover, hellebrigenin caused activation of PARP and caspase 3, 8 and 9, followed by downregulation of antiapoptotic proteins (Bcl-2 and Bcl-xL) and upregulation of pro-apoptotic proteins (Bax and Bak). The hellebrigenin treatment also increased Fas, DR5, DcR2 and DcR3 expressions in oral cancer cells, indicating the compound causes oral cancer cell apoptosis through both intrinsic and extrinsic pathways. Regarding upstream signalling, hellebrigenin was found to reduce the phosphorylation of ERK, p38, and JNK, indicating that hellebrigenin triggers caspase-mediated apoptosis by downregulating MAPK signalling pathway. Finally, the human apoptosis array findings revealed that hellebrigenin specifically suppressed the expression of XIAP to execute its pro-apoptotic activities. Taken together, the study suggests that hellebrigenin can act as a potent anticancer compound in human OSCC.


Assuntos
Bufanolídeos , Carcinoma de Células Escamosas , Neoplasias Bucais , Humanos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/genética , Neoplasias Bucais/patologia , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Transdução de Sinais , Apoptose/fisiologia , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Proliferação de Células , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/genética , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo
20.
J Formos Med Assoc ; 2023 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-37996323

RESUMO

BACKGROUND/PURPOSE: Blended learning offers the advantages of both instructor-led and self-instruction methods in basic life support (BLS). Our study aims to compare the effects of blended learning with those of traditional instructor-led methods on the performance of laypersons taking BLS courses. METHODS: A total of 108 participants were randomly assigned to three groups: traditional instruction (group A, n = 36), blended learning with two rounds of practice (group B, n = 36), and blended learning with three rounds of practice (group C, n = 36). Group A received a 90-min lecture and a 30-min hands-on practice session using a manikin and a metronome. Participants in groups B and C received 18-min standardized online video lessons and performed hands-on practice twice and thrice, respectively. The primary outcome was chest compression at a correct speed (100-120 compressions per min) after the training course. Secondary outcomes included knowledge test scores, attitudes and confidence, and individual skill performance after training. RESULTS: Patient characteristics were similar between the groups. Blended learning with practicing thrice resulted in the highest compressions at a correct speed (group A vs. B vs. C, 68.09 vs 80.03 vs 89.42, p = 0.015) and the shortest average hands-off time (group A vs. B vs. C, 1.12 vs 0.86 vs 0.17 s, p = 0.015). Both blended groups performed better in confirming environmental safety (p < 0.001). No differences in scores of the knowledge test, attitude, or confidence were noted among the three groups. CONCLUSION: Blended learning with three rounds of hands-on practice may be considered an alternative teaching method.

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