Syrosingopine and UK5099 synergistically suppress non-small cell lung cancer by activating the integrated stress response.

Non-small cell lung cancer (NSCLC) presents a global health challenge due to its low five-year survival rates, underscoring the need for novel therapeutic strategies. Our research explored the synergistic mechanisms of syrosingopine and UK-5099 in treating NSCLC. In vitro experiments showed that the combination of syrosingopine and UK-5099 significantly synergized to suppress NSCLC proliferation. Further experiments revealed that this combination induced cell cycle arrest and promoted apoptosis in NSCLC cells. In vivo experiments demonstrated that the combination of syrosingopine and UK-5099 markedly inhibited tumor growth. Mechanistic studies revealed that this drug combination promoted mitochondrial damage by inducing lactate accumulation and oxidative stress. Additionally, the combination triggered an integrated stress response (ISR) through the activation of heme-regulated inhibitor kinase (HRI). Importantly, our findings suggested that the synergistic suppression of NSCLC by syrosingopine and UK-5099 was dependent on ISR activation. In summary, our study proposed a promising therapeutic approach that involved the combination of Syrosingopine and UK-5099 to activate ISR, significantly hindering NSCLC growth and proliferation.

Relationship between BUN/Cr and Prognosis of HF Across the Full Spectrum of Ejection Fraction. / Relação entre a Razão Nitrogênio Ureico/Creatinina e Prognóstico de Insuficiência Cardíaca em Todo o Espectro da Fração de Ejeção.

BACKGROUND: In patients with heart failure (HF), due to the relative deficiency of blood volume, neurohormone system activation leads to renal vasoconstriction, which affects the content of blood urea nitrogen (BUN) and creatinine (Cr) in the body, while BUN and Cr are easily affected by other factors. Therefore, BUN/Cr can be used as another marker for the prognosis of HF. OBJECTIVE: Explore the prognosis of adverse outcome of HF in the high BUN/Cr group compared with the low BUN/Cr group across the full spectrum of ejection fraction. METHODS: From 2014 to 2016, symptomatic hospitalized HF patients were recruited and followed up to observe adverse cardiovascular outcomes. Logistic analysis and COX analysis were performed to determine significance. p-values <0.05 were considered statistically significant. RESULTS: In the univariate logistic regression analysis, the high BUN/Cr group had a higher risk of adverse outcome in heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Multivariate logistic regression analysis showed that the risk of cardiac death in the HFrEF group was higher than that in the low BUN/Cr group, while the risk of all-cause death was significant only in 3 months (p<0.05) (Central Illustration). The risk of all-cause death in the high BUN/Cr in the HFpEF group was significantly higher than that in the low BUN/Cr group at two years. CONCLUSION: The high BUN/Cr group is related to the risk of poor prognosis of HFpEF, and is not lower than the predictive value of left ventricular ejection fraction (LVEF).

FUNDAMENTO: Em pacientes com insuficiência cardíaca (IC), devido à relativa deficiência do volume sanguíneo, a ativação do sistema neuro-hormonal leva à vasoconstrição renal, que afeta o teor de nitrogênio ureico (NU) e creatinina (C) no organismo, sendo que NU e C são facilmente afetados por outros fatores. Portanto, a razão NU/C pode ser utilizada como mais um marcador para o prognóstico da IC. OBJETIVO: Explorar o prognóstico do desfecho adverso da IC no grupo NU/C alta em comparação com o grupo NU/C baixa em todo o espectro da fração de ejeção. MÉTODOS: De 2014 a 2016, pacientes sintomáticos hospitalizados com IC foram recrutados e acompanhados para observar desfechos cardiovasculares adversos. Foram realizadas análise logística e a análise COX para determinar a significância. Valores de p<0,05 foram considerados estatisticamente significativos. RESULTADOS: Na análise de regressão logística univariada, o grupo NU/C alta apresentou maior risco de desfecho adverso na insuficiência cardíaca com fração de ejeção reduzida (ICFEr) e insuficiência cardíaca com fração de ejeção preservada (ICFEp). A análise de regressão logística multivariada mostrou que o risco de morte cardíaca no grupo ICFEr foi maior do que no grupo NU/C baixa, enquanto o risco de morte por todas as causas foi significativo apenas em 3 meses (p<0,05) (Ilustração Central). O risco de morte por todas as causas no grupo NU/C alta no grupo ICFEP foi significativamente maior do que no grupo NU/C baixa em dois anos. CONCLUSÃO: O grupo NU/C alta está relacionado ao risco de mau prognóstico da ICFEP, não sendo inferior ao valor preditivo da fração de ejeção do ventrículo esquerdo (FEVE).

Relação entre a Razão Nitrogênio Ureico/Creatinina e Prognóstico de Insuficiência Cardíaca em Todo o Espectro da Fração de Ejeção / Relationship between BUN/Cr and Prognosis of HF Across the Full Spectrum of Ejection Fraction

Resumo Fundamento Em pacientes com insuficiência cardíaca (IC), devido à relativa deficiência do volume sanguíneo, a ativação do sistema neuro-hormonal leva à vasoconstrição renal, que afeta o teor de nitrogênio ureico (NU) e creatinina (C) no organismo, sendo que NU e C são facilmente afetados por outros fatores. Portanto, a razão NU/C pode ser utilizada como mais um marcador para o prognóstico da IC. Objetivo Explorar o prognóstico do desfecho adverso da IC no grupo NU/C alta em comparação com o grupo NU/C baixa em todo o espectro da fração de ejeção. Métodos De 2014 a 2016, pacientes sintomáticos hospitalizados com IC foram recrutados e acompanhados para observar desfechos cardiovasculares adversos. Foram realizadas análise logística e a análise COX para determinar a significância. Valores de p<0,05 foram considerados estatisticamente significativos. Resultados Na análise de regressão logística univariada, o grupo NU/C alta apresentou maior risco de desfecho adverso na insuficiência cardíaca com fração de ejeção reduzida (ICFEr) e insuficiência cardíaca com fração de ejeção preservada (ICFEp). A análise de regressão logística multivariada mostrou que o risco de morte cardíaca no grupo ICFEr foi maior do que no grupo NU/C baixa, enquanto o risco de morte por todas as causas foi significativo apenas em 3 meses (p<0,05) (Ilustração Central). O risco de morte por todas as causas no grupo NU/C alta no grupo ICFEP foi significativamente maior do que no grupo NU/C baixa em dois anos. Conclusão O grupo NU/C alta está relacionado ao risco de mau prognóstico da ICFEP, não sendo inferior ao valor preditivo da fração de ejeção do ventrículo esquerdo (FEVE).

Abstract Background In patients with heart failure (HF), due to the relative deficiency of blood volume, neurohormone system activation leads to renal vasoconstriction, which affects the content of blood urea nitrogen (BUN) and creatinine (Cr) in the body, while BUN and Cr are easily affected by other factors. Therefore, BUN/Cr can be used as another marker for the prognosis of HF. Objective Explore the prognosis of adverse outcome of HF in the high BUN/Cr group compared with the low BUN/Cr group across the full spectrum of ejection fraction. Methods From 2014 to 2016, symptomatic hospitalized HF patients were recruited and followed up to observe adverse cardiovascular outcomes. Logistic analysis and COX analysis were performed to determine significance. p-values <0.05 were considered statistically significant. Results In the univariate logistic regression analysis, the high BUN/Cr group had a higher risk of adverse outcome in heart failure with reduced ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF). Multivariate logistic regression analysis showed that the risk of cardiac death in the HFrEF group was higher than that in the low BUN/Cr group, while the risk of all-cause death was significant only in 3 months (p<0.05) (Central Illustration). The risk of all-cause death in the high BUN/Cr in the HFpEF group was significantly higher than that in the low BUN/Cr group at two years. Conclusion The high BUN/Cr group is related to the risk of poor prognosis of HFpEF, and is not lower than the predictive value of left ventricular ejection fraction (LVEF).

Application of hospital-community-family health education to family caregivers of nasal fed patients under the background of a regional medical association.

BACKGROUND: Patients with nasogastric tube (NTG) nutrition after discharge still need to be transferred to community hospitals for continued care. Effective health education is conducive to raising the level of knowledge of caregivers to promote the rehabilitation of patients. METHODS: Clinical data of 65 caregivers of stroke patients in Putuo Hospital affiliated to Shanghai University of Traditional Chinese Medicine from June 2020 to December 2020 were retrospectively analyzed. These caregivers were divided into an observation group (33 cases, hospital-community-family education model) and a control group (32 cases, routine nursing health education). We used questionnaires to assess the knowledge, attitudes, and practice levels of caregivers before and after education, and recorded the occurrence of complications in patients within 12 weeks. RESULTS: The scores of the knowledge questionnaire and practice questionnaire of caregivers in the observation group were higher than those in the control group at 2, 4 and 12 weeks after intervention (P<0.05). The scores of caregivers' attitudes questionnaire were higher in the observation group than in the control group at 4 and 12 weeks after intervention (P<0.05). But 2 weeks after intervention, there was no significant difference between the two groups (P>0.05). Within 12 weeks after intervention, the probability of complications in observation group was lower than that in the control group (P<0.05). Logistic regression analysis showed that the hospital-community-family health education helped the outcome. CONCLUSION: For the main caregivers of NTG nutrition patients, the implementation of a hospital-community-family health education model based on regional medical consortium can improve the level of knowledge, attitude and practice of caregivers' NTG nutrition skills and reduce complications in patients.

WITHDRAWN: The clinical application of an innovative tracheotomy fixation belt in critically ill patients.

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