Thiosemicarbazone N-Heterocyclic Cu(II) complexes inducing nuclei DNA and mitochondria damage in hepatocellular carcinoma cells.

The α-N-Heterocyclic thiosemicarbazones and their metal complexes have been widely investigated as anticancer and antibacterial agents for their broad spectrum of pharmacological properties. Thus, two thiosemicarbazone-based Cu(II) complexes, [Cu2(ptpc)I2] (1) and [Cu(qtpc)I] (2) with thiosemicarbazone ligand (ptpc = 2-(di(pyridin-2-yl)methylene)-N-(2-(trifluoromethyl)phenyl)-hydrazine-1-carbothioamide, qtpc = 2-(quinolin-8-ylmethylene)-N-(2-(trifluoromethyl)phenyl)hydrazine-1-carbothioamide) were synthesized and evaluated for their biological activities. Complexes 1 and 2 are superior to cisplatin in vitro antiproliferative activities toward hepatocellular carcinoma cell line with the half maximal inhibitory concentration value of 0.2 and 2 µM, respectively. A series of spectroscopic assays and the DNA cleavage experiments showed that both complexes can change and distort the conformation of DNA. Molecular docking experiment further demonstrated that complex 1 binds to DNA mainly in groove mode. Meanwhile, benefiting from their good liposolubility, complexes 1 and 2 could easily enter cells, which further triggers cell cycle arrest and apoptosis. Moreover, complexes 1 and 2 caused serious mitochondrial damage, associating with increased the level of reactive oxygen species (ROS) and Ca2+, decreased adenosine triphosphate (ATP) content and mitochondrial membrane potential (Δψm), and transformed mitochondrial morphology. These findings indicated that complexes 1 and 2 might exert their anticancer activity by inducing DNA and mitochondrial damage simultaneously.

The Association Between FT3 With the Outcome and Inflammation/Coagulopathy/Fibrinolysis of COVID-19.

Background: The coronavirus disease 2019 (COVID-19) pandemic has caused substantial threats to people's physical health and lives, claiming the lives of over 5 million people worldwide. It is imperative to identify the disease severity and intervene with effective therapy as early as possible. Previous studies have shown that low free triiodothyronine (FT3) may possess the predictive value on COVID-19 prognosis. Methods: In this retrospective cohort study, 15-day clinical and laboratory data of 186 hospitalized patients of COVID-19 after admission were analyzed. Groups were based on the disease severity of COVID-19, survival or non-survival, and presence or absence of euthyroid sick syndrome (ESS). Categorical variables were compared with the chi-square test or Fisher's exact test. Continuous variables were tested by Wilcoxon rank-sum test for the non-normal distribution. Spearman correlations were used to assess the correlations between FT3 with clinic parameters of multiple time points. Results: The non-survival patients had significant lower levels of FT3 (3.24 ± 0.42 vs. 4.19 ± 0.08 pmol/L, p < 0.05) and thyroid-stimulating hormone (TSH) (0.69 ± 0.19 vs. 2.32 ± 0.2 uIU/ml, p < 0.05), and the FT3 of severe patients was significantly lower than that of non-severe patients (3.67 ± 0.14 vs. 4.33 ± 0.09 pmol/L, p < 0.05). Fifty-nine cases of COVID-19 patients were diagnosed with ESS. Compared with non-ESS patients, those with ESS were older and had higher proportions of fever, shortness of breath, hypertension, diabetes, severe disease, and mortality. In addition, the correlation analysis between FT3 and clinical parameters showed that FT3 were positively related to the lymphocyte count and albumin and negatively correlated with C-reactive protein, erythrocyte sedimentation rate, and D-dimer at all time points in the first 15 days after admission. Conclusion: Low FT3 had a significant predictive value on the prognosis of COVID-19 patients, and FT3 was significantly related with clinic parameters of inflammation/coagulopathy/fibrinolysis.

Association between non-alcoholic fatty liver disease with the susceptibility and outcome of COVID-19: A retrospective study.

This study aims to evaluate the effect of non-alcoholic fatty liver disease (NAFLD) on the susceptibility and consequences of coronavirus disease 2019 (COVID-19). We retrospectively collected data from 218 adult COVID-19 patients who showed no evidence of excessive alcohol consumption and underwent abdominal ultrasound examinations. Of these patients, 39.4% patients had been diagnosed with NAFLD, which indicates a much higher prevalence of NAFLD than that reported in the general population. Significantly elevated white blood cell count (p = 0.008), alanine aminotransferase (p = 0.000), aspartate aminotransferase (p = 0.006) and C reactive protein (p = 0.012) were found in the patients with NAFLD. These patients also had significantly higher proportions of hypertension (p = 0.006) and diabetes (p = 0.049) than the non-NAFLD cases. No significant differences existed in the severity, mortality, viral shedding time and length of hospital stay between patients with or without NAFLD in the sample population. However, subgroup analyses found that in patients with normal body mass index (BMI), NAFLD sufferers were more likely to experience a severe event (30.0% vs 11.5%, p = 0.021). Kaplan-Meier curve (log-rank p = 0.017) and Cox regression (HR = 3.26, 95% CI: 1.17-9.04, p = 0.023) analyses confirmed that before and after adjusting for gender, age and comorbidities, NAFLD patients with normal BMI had a higher incidence of suffering severe events. People with NAFLD may have a higher proportion of COVID-19. NAFLD may be correlated with the severity of COVID-19 patients in the normal BMI group.

Association Between Respiratory Alkalosis and the Prognosis of COVID-19 Patients.

Aim: The aim of the study was to describe the clinical characteristics of patients with or without respiratory alkalosis, and analyze the relationship of respiratory alkalosis and the outcome of adult coronavirus disease 2019 (COVID-19) patients. Methods: Clinical and laboratory data of adult COVID-19 patients in a single center in China, were retrospectively collected and analyzed. The Kaplan-Meier (KM) curve and cox regression were adopted to analyze the association between respiratory alkalosis and prognosis of COVID-19 patients. Results: Of 230 adult COVID-19 patients, 66 patients (28.7%) had respiratory alkalosis on admission. Of 66 patients, the median age was 53 years old (range, 21-84 years), and 43 (65.2%) were female. Compared with those without respiratory alkalosis, patients with respiratory alkalosis were significantly older (P = 0.002), had a higher proportion of female (P = 0.004), and showed higher ratios of underlying diseases including hypertension (P = 0.023) and cardiovascular disease (P = 0.028). Moreover, they demonstrated higher proportion of severe events (P = 0.001). Patients with respiratory alkalosis had a higher possibility of developing severe events compared with those without respiratory alkalosis (Log Rank P = 0.001). After adjusting for gender, age, and comorbidities, patients with respiratory alkalosis still showed significantly elevated risks of developing to severe cases (HR 2.445, 95% CI 1.307-4.571, P = 0.005) using cox regression analyses. Conclusions: Respiratory alkalosis as a common acid-base disorder in COVID-19 patients, was associated with a higher risk of developing severe event.

Impact of renin-angiotensin system inhibitors use on mortality in severe COVID-19 patients with hypertension: a retrospective observational study.

OBJECTIVE: Association of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) use with coronavirus disease 2019 (COVID-19) remains controversial. We aimed to investigate the impact of ACEI/ARB use on all-cause mortality in severe COVID-19 patients with hypertension. METHODS: We enrolled 650 COVID-19 patients from Changsha and Wuhan city between 17 January 2020 and 8 March 2020. Demographic, clinical characteristics, and outcomes were collected. Multivariable analysis and propensity-score matching were performed to assess the impact of ACEI/ARB therapy on mortality. RESULTS: Among the 650 patients, 126 who had severe COVID-19 concomitant with hypertension were analyzed. The average age was 66 years and 56 (44.4%) were men. There were 37 ACEI/ARB users and 21 in-hospital deaths (mortality rate, 16.7%). Male sex (odds ratio [OR], 5.13; 95% confidence interval [CI], 1.75 to 17.8), but not ACEI/ARB use (OR, 1.09; 95%CI, 0.31 to 3.43), was an independent risk factor for mortality in severe COVID-19 patients with hypertension. After propensity-score matching, 60 severe COVID-19 patients were included and no significant correlation between use of ACEI/ARB and mortality was observed. CONCLUSIONS: There was no significant association of ACEI/ARB use with mortality in severe COVID-19 patients with hypertension. These findings support the continuation of ACEI/ARB therapy for such patients.

Euthyroid Sick Syndrome in Patients With COVID-19.

Background: Coronavirus disease 2019 (COVID-19) has been shown to affect almost every organ throughout the body. However, it is not clear whether the thyroid gland is impaired in COVID-19 patients. Euthyroid sick syndrome (ESS) is usually associated with the disease severity and deterioration prognosis in critical illness. In this study, the thyroid function of COVID-19 patients was assessed and factors associated with outcomes were analyzed to determine the potential predictive value of ESS. Methods: Clinical and laboratory data of COVID-19 patients with or without ESS in Changsha, China, were collected and analyzed on admission. Kaplan-Meier curve and cox regression model were utilized to determine the correlation between ESS and the endpoints. Subsequently, a receiver operating characteristic (ROC) curve was plotted to evaluate the predictive performances of FT3 and C-reactive protein (CRP) in the disease severity. Results: Forty-one (27.52%) cases of COVID-19 patients diagnosed with ESS. ESS patients had higher proportions of fever, shortness of breath, hypertension, diabetes, and severe events than those of non-ESS patients. The levels of erythrocyte sedimentation rate and C-reactive protein, and the positive rate of procalcitonin were significantly higher, whereas the lymphocyte count was apparently lower in ESS patients than in non-ESS patients. The regression analysis showed that ESS was significantly associated with the disease severity of COVID-19 (HR = 2.515, 95% CI: 1.050-6.026, P = 0.039). The areas under the curve (AUCs) for predicting the severe disease were [0.809 (95% CI 0.727-0.892), P < 0.001] and [0.792 (95% CI 0.689-0.895), P < 0.001] for FT3 and CRP, respectively. Conclusion: ESS was significantly associated with the disease severity and inflammatory parameters in COVID-19 patients.

Low high-density lipoprotein level is correlated with the severity of COVID-19 patients: an observational study.

BACKGROUND: The purpose of the study is to describe the blood lipid levels of patients diagnosed with coronavirus disease 2019 (COVID-19) and to analyze the correlation between blood lipid levels and the prognosis of COVID-19 patients. METHODS: In the clinical retrospective analysis, a total of 228 adults infected with COVID-19 were enrolled between January 17, 2020 and March 14, 2020, in Changsha, China. One thousand one hundred and forty healthy participants with matched age and gender were used as control. Median with interquartile range and Mann-Whitney test were adopted to describe and analyze clinical data. The Kaplan-Meier (KM) curve and Cox regression analysis were used to analyze the correlation between high-density lipoprotein cholesterol (HDL-C) and the severity of COVID-19. RESULTS: Compared with control, COVID-19 patients showed significantly lower levels of total cholesterol (TC) [median, 3.76 vs 4.65 mmol/L, P = 0.031], triglyceride [median, 1.08 vs 1.21 mmol/L, P <  0.001], low-density lipoprotein cholesterol (LDL-C) [median, 2.63 vs 2.83 mmol/L, P <  0.001], and HDL-C [median, 0.78 vs 1.37 mmol/L, P <  0.001], while compared with non-severe patients, severe COVID-19 patients only presented lower levels of HDL-C [median, 0.69 vs 0.79 mmol/L, P = 0.032]. In comparison with patients with high HDL-C, patients with low HDL-C showed a higher proportion of male (69.57% vs 45.60%, P = 0.004), higher levels of C-reactive protein (CRP) (median, 27.83 vs 12.56 mg/L, P <  0.001) and higher proportion of severe events (36.96% vs 14.84%, P = 0.001). Moreover, patients with low HDL-C at admission showed a higher risk of developing severe events compared with those with high HDL-C (Log Rank P = 0.009). After adjusting for age, gender and underlying diseases, they still had elevated possibility of developing severe cases than those with high HDL-C (HR 2.827, 95% CI 1.190-6.714, P = 0.019). CONCLUSIONS: HDL-C level was lower in COVID-19 adult patients, and low HDL-C in COVID-19 patients was correlated with a higher risk of developing severe events.

Clinical characteristics and the risk factors for severe events of elderly coronavirus disease 2019 patients. / 2019å† çŠ¶ç— æ¯’ç— è€å¹´æ‚£è€ çš„ä¸´åºŠç‰¹ç‚¹åŠé‡ç—‡çš„å±é™©å› ç´ .

OBJECTIVES: To investigate the clinical characteristics and risk factors for severe events of coronavirus disease 2019 (COVID-19) in elderly patients. METHODS: Retrospective analysis was performed on the clinical data of all elderly COVID- 19 patients treated in Changsha Public Health Treatment Center from January 17, 2020 to March 15, 2020, which included basic diseases, symptoms, test results, and other clinical characteristics, and prognostic indicators such as severity of illness, length of hospital stay, virus shedding time and mortality rate. The differences in clinical characteristics and prognostic indicators between elderly, middle-aged, and young COVID-19 patients were also analyzed. Logistic regression model was used to conduct univariate and multivariate analysis of risk factors for developing severe events in elderly COVID-19 patients; receiver operating characteristic (ROC) curve analysis was used to evaluate the prediction efficacy. RESULTS: Of the 230 COVID-19 adult patients, 34 were young patients (14.8%), 136 were middle-aged patients (59.1%), and 60 were elderly (26.1%). Among the 60 elderly patients, 23 were male (38.3%) and 37 were female (61.7%), with a medium age of 66 years old. Common symptoms were fever (66.7%), cough (50.0%), and fatigue (41.7%). C reactive protein (CRP) was increased significantly. The proportion of severe cases was 31.7%, and mortality was 1.7%. The median length of hospitalization and median virus shedding time were 18.5 days and 21 days, respectively. Compared with the young and the middle-aged patients, the elderly had a higher proportion of hypertension, diabetes, and cardiovascular diseases, more common shortness of breath, higher proportions of pneumonia and severe cases (all P<0.05), and the decreased lymphocyte count and lymphocyte percentage (both P<0.05), as well as higher CRP and erythrocyte sedimentation rate (ESR) levels (both P<0.05). Compared with non-severe cases, severe elderly patients demonstrated higher CRP and aspartate aminotransferase (AST) levels (all P<0.05), the reduced lymphocyte count (P<0.05), and the prolonged length of hospitalization and virus shedding duration (both P<0.05). Univariate logistic regression analysis indicated that the lymphocytes proportion, CRP and AST levels were significantly correlated with the risk for developing severe events in elderly COVID-19 patients (all P<0.05). Multivariate logistic regression found that severe events in elderly patients with COVID-19 were significantly correlated with CRP level (OR=1.041, P=0.013). ROC curve analysis revealed that the area under the curve (AUC) for CRP to diagnose severe events in elderly COVID 19 patients was 0.851. CONCLUSIONS: The proportion of severe cases in elderly COVID-19 patients is higher than that in young and middle-aged patients. CRP level has a good predictive value for the possibility of severe events in elderly COVID-19 patients.

Clinical Characteristics of Adult Fevered COVID-19 Patients and Predictors for Developing Severe Events.

Aim: Clinical findings indicated that a fraction of coronavirus disease 2019 (COVID-19) patients did not show fever. However, the difference between the clinical characteristics of fevered and non-fevered patients is still unclear. The aim of the present study was to describe the clinical characteristics of these patients and analyze the predictors for severe events of adult fevered COVID-19 patients. Methods: Clinical and laboratory data of fevered and non-fevered COVID-19 patients in Changsha, China, were collected and analyzed. Logistic regression analysis and Receiver Operating Characteristic Curve (ROC Curve) analysis were adopted to analyze risk factors and evaluate the effectiveness of the predictors for severe events in adult fevered COVID-19 patients. Results: Of the 230 adult COVD-19 patients in this study, 175 patients (76.1%) had fever and 55 patients (23.9%) did not have fever. Compared with non-fevered patients, the fevered patients showed a lower lymphocyte proportion (P = 0.000) and lymphocyte count (P = 0.000) as well as higher levels of C-reactive protein (CRP) (P = 0.000) and erythrocyte sedimentation rate (P = 0.000). The proportion of severe cases was significantly elevated in adult fevered patients (P = 0.000). Compared to non-severe fevered patients, severe fevered patients showed a lower lymphocyte count (P = 0.000), a lower lymphocyte proportion (P = 0.000), and higher levels of CRP (P = 0.000). As determined by the multivariate analysis, CRP (OR 1.026, P = 0.018) and lymphocyte proportion (OR 0.924, P = 0.009) were significantly associated with the risk of developing severe events in fevered adult COVID-19 patients. Furthermore, ROC Curve analysis revealed that the area under the curve (AUC) for CRP combined with lymphocyte proportion to diagnose severe events in fevered adult COVID-19 patients was 0.874 (95% CI 0.820-0.927). Conclusions: Adult fevered COVID-19 patients were more likely to progress into severe cases, while CRP and lymphocyte proportion were effective predictors for developing severe events in these patients.

C-Reactive Protein Level May Predict the Risk of COVID-19 Aggravation.

BACKGROUND: Clinical findings indicated that a fraction of coronavirus disease 2019 (COVID-19) patients diagnosed as mild early may progress to severe cases. However, it is difficult to distinguish these patients in the early stage. The present study aimed to describe the clinical characteristics of these patients, analyze related factors, and explore predictive markers of the disease aggravation. METHODS: Clinical and laboratory data of nonsevere adult COVID-19 patients in Changsha, China, were collected and analyzed on admission. A logistic regression model was adopted to analyze the association between the disease aggravation and related factors. The receiver operating characteristic curve (ROC) was utilized to analyze the prognostic ability of C-reactive protein (CRP). RESULTS: About 7.7% (16/209) of nonsevere adult COVID-19 patients progressed to severe cases after admission. Compared with nonsevere patients, the aggravated patients had much higher levels of CRP (median [range], 43.8 [12.3-101.9] mg/L vs 12.1 [0.1-91.4] mg/L; P = .000). A regression analysis showed that CRP was significantly associated with aggravation of nonsevere COVID-19 patients, with an area under the curve of 0.844 (95% confidence interval, 0.761-0.926) and an optimal threshold value of 26.9 mg/L. CONCLUSIONS: CRP could be a valuable marker to anticipate the possibility of aggravation of nonsevere adult COVID-19 patients, with an optimal threshold value of 26.9 mg/L.

Risk Factors of Ventilator-Associated Pneumonia in Critically III Patients.

Ventilator-associated pneumonia (VAP), a hospital acquired pneumonia that occurs more than 48 h after mechanical ventilation, is a common complication of mechanical ventilation with a high mortality rate. VAP can cause patients to have difficulty weaning off the ventilator and to stay in the hospital longer, which results in a huge financial burden to patients and a huge demand for medical resources. Several strategies, such as drugs including chlorhexidine, ß-lactam antibiotics and probiotics, have been used to prevent VAP in clinic. The incidence and the mortality rate of VAP have been decreased with the development of preventative strategies in the past decades, but VAP remains one of the most common causes of nosocomial infections and death in the intensive care unit. Current challenges in the management of VAP involved the lack of a gold standard for diagnosis, the absence of effective preventative strategies, and the rise in antibiotic resistance. Therefore, in order to reduce the incidence of VAP and improve the outcome of patients with mechanical ventilation, it is necessary to clarify the risk factors of VAP for clinical prevention and control of VAP. This paper reviews the international risk factors of VAP occurrence reported in recent years, including patient characteristics, increased mechanical ventilation time and prolonged length of hospital stay, disorders of consciousness, burns, comorbidities, prior antibiotic therapy, invasive operations, gene polymorphisms, and mentions the corresponding preventive measures. Each factor is not only an independent risk factor of VAP, but also has an influence on each other. A better understanding of risk factors for VAP is helpful for predicting the occurrence of VAP, improving the prevention and control of VAP, and reducing the morbidity and mortality rates of patients with VAP.