Int J Med Sci
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Sorafenib is the standard systemic treatment for advanced hepatocellular carcinoma (HCC), and improving its therapeutic effects is crucial for addressing cancer aggression. We previously reported that epalrestat, an aldo-keto reductase 1B10 inhibitor, enhanced sorafenib's inhibitory effects on HCC xenograft in nude mice. This study aimed to elucidate the mechanism of epalrestat's anti-tumour enhancing effects on sorafenib. ⋯ Treatment with a specific mTOR activator MHY-1485 increased mTOR phosphorylation, while suppressing apoptosis and autophagy. Consistent with in vitro results, data from the HCC-xenograft nude mouse model also indicated that combined treatment inhibited the mTOR pathway and promoted apoptosis and autophagy. In conclusion, epalrestat heightens sorafenib's anti-cancer effects via blocking the mTOR pathway, thus inducing cell cycle arrest, apoptosis, and autophagy.
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Background: A proportion of women with pregnancies complicated by gestational hypertension/preeclampsia (GH-PE) will have persistent postpartum chronic hypertension (CHTN). Common risk factors for postpartum CHTN include older age, pre-existing CHTN, smoking, pre-pregnancy obesity (elevated BMI), and co-morbidities such as thyroid disorders. However, most of explored risk factors are pre-pregnancy factors, and were mainly based on studies with small sample size. ⋯ After adjustment, logistic regression analysis revealed excessive pregnant weight gain (≥10 kgw at 28 weeks' gestation) (OR: 14.50, 95% CI: 11.02-19.08) and gestational diabetes mellitus (GDM) (OR: 6.25, 95% CI: 4.98-7.85) were major risk factors for developing CHTN, other than age (OR: 1.80, 95% CI: 1.68-1.93), pre-pregnancy BMI (OR: 3.15, 95% CI: 2.75-3.60), severity of GH-PE (OR: 2.46, 95% CI: 1.97-3.07), smoking (OR: 1.79, 95% CI: 1.35-2.38), and overt DM (OR: 2.30, 95% CI: 1.73-3.06). Conclusion: Excessive pregnant weight gain and GDM are major intra-pregnancy risk factors for postpartum CHTN in women with preceding GH-PE. Future studies should investigate interventions such as a healthy diet, appropriate physical exercise and avoidance of excessive pregnant weight gain as a means to reduce the frequency of CHTN following pregnancy.
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Background: The association between metformin and amiodarone-induced adverse events was examined using spontaneous adverse event database. Additionally, the association between other antidiabetic drugs and amiodarone-induced adverse events were also examined. Methods: A total of 6,153,696 reports from the first quarter of 2004 through the fourth quarter of 2015 were downloaded from the US Food and Drug Administration adverse event reporting system. ⋯ Additionally, metformin (ROR 0.43, 95%CI 0.33-0.57; IC -1.09, 95%CI -1.49 to -0.69), sulfonylureas (ROR 0.64, 95%CI 0.48-0.86; IC -0.59, 95%CI -1.00 to -0.17), and DPP-4 inhibitors (ROR 0.47, 95%CI 0.27-0.81; IC -0.99, 95%CI -1.76 to -0.22) were inversely associated with interstitial lung disease. In the logistic regression analyses, DPP-4 inhibitors (adjusted ROR 0.32, 95% CI 0.10-1.00) and metformin (adjusted ROR 0.46, 95% CI 0.34-0.62) were inversely associated with amiodarone-associated hyperthyroidism and interstitial lung disease, respectively. Conclusion: Metformin is a candidate drug to reduce the risk of amiodarone-induced hyperthyroidism and interstitial lung disease.
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Whether the abnormal circadian rhythm of urinary sodium excretion is associated with hypertension in chronic kidney disease (CKD) is poorly understood. In this study, we assessed the relationship between the circadian rhythm of urinary sodium excretion and hypertension. Urinary samples were collected during both the day (07:00 to 22:00) and night (22:00 to 07:00) to estimate night/day urinary sodium excretion ratios. ⋯ In addition, tertile 3 was also independently associated with eGFR ≤ 60 mL/min/1.73 m2 and left ventricular hypertrophy. These data suggested that an abnormal circadian rhythm of urinary sodium excretion was independently associated with hypertension and target-organ damage. Individualized salt intake and therapeutic strategies should be used to normalize the natriuretic dipping profile in CKD patients.
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Background: Corona Virus Disease 2019 (COVID-19) has become a global pandemic. This study established prognostic scoring models based on comorbidities and other clinical information for severe and critical patients with COVID-19. Material and Methods: We retrospectively collected data from 51 patients diagnosed as severe or critical COVID-19 who were admitted between January 29, 2020, and February 18, 2020. ⋯ There were significant trends for increasing hospital LOS with increasing CCI, ASCCI, and ASECI scores (OR 57.500, P = 0.001, 95%CI 5.687-581.399; OR 71.500, P = 0.001, 95%CI 5.689-898.642; and OR 19.556, P = 0.001, 95%CI 3.315-115.372, respectively). The result was similar for the outcome of critical illness (OR 21.333, P = 0.001, 95%CI 3.565-127.672; OR 13.000, P = 0.009, 95%CI 1.921-87.990; OR 11.333, P = 0.008, 95%CI 1.859-69.080, respectively). Conclusions: This study established prognostic scoring models based on comorbidities and clinical information, which may help with the graded management of patients according to prognosis score and remind physicians to pay more attention to patients with high scores.