Tao Yao

Depression is a serious mental illness affecting millions of people worldwide. This study investigates the effects of gentiopicroside, a compound found in traditional Chinese medicine, on depression-like animal models and its potential mechanism of action. The study utilized rat models with corticosterone-induced depression and treated them with various concentrations of gentiopicroside. The effects on hippocampal cells, serum 5-HT levels, inflammation, autophagy, and oxidative stress markers were observed. The role of Cyclooxygenase-2 (COX-2) expression and mitophagy was also examined using in vitro neuron cell models. Gentiopicroside demonstrated dose-dependent effects on alleviating hippocampal cell damage, restoring serum 5-HT levels, and inhibiting inflammation and oxidative stress markers. It also promoted autophagy and modulated COX-2 expression in the rat models. The in vitro study revealed that gentiopicroside could regulate COX-2 expression, reduce mitochondrial membrane potential loss and cell apoptosis, and inhibit NLRP3 (NOD-like receptor family, pyrin domain-containing 3) inflammatory complex-related proteins and cytokines. Overexpression of COX-2 significantly reversed the positive effects of gentiopicroside, while PINK1 (PTEN-induced kinase 1) overexpression promoted mitophagy, inhibited NLRP3 inflammatory complex activation, and reduced oxidative stress. Gentiopicroside ameliorates depression-like symptoms in animal models by suppressing COX-2 expression. This suppression is necessary for the subsequent enhancement of PINK1-mediated mitophagy, which helps to re-establish mitochondrial homeostasis and attenuate neuroinflammation and oxidative stress. This novel mechanism may potentially lead to the development of new therapies for depression treatment. Graphical Abstract

Circular RNA is crucial for the development of multiple malignant tumors including colorectal cancer. Circular RNA lamin B1 has recently been verified to accelerate colorectal cancer progression. However, it is not clear whether circular RNA lamin B1 can be regulated by the main methylase (methyltransferaselike 3) in colorectal cancer. This study was to explore the mechanism of methyltransferase-like 3-mediated epigenetic reactivation of circular RNA lamin B1 in colorectal cancer. We first analyzed the expression and correlation between methyltransferase-like 3 and circular RNA lamin B1 in colorectal cancer tissues, and then assessed the effects of methyltransferase-like 3 and circular RNA lamin B1 on the malignant properties of colorectal cancer cells by conducting loss-of-function and restoration studies. We also examined the growth and pathological structures in colorectal cancer xenograft tumors, as well as the levels of methyltransferase-like 3, circular RNA lamin B1 and caspase 3 expression in colorectal cancer xenograft tumors by reverse transcription-quantitative polymerase chain reaction, western blotting, hematoxylin and eosin staining and immunohistochemistry. Our results showed that the levels of circular RNA lamin B1 and methyltransferase-like 3 expressions were elevated and positively correlated in colorectal cancer tissues. Functionally, methyltransferase-like 3 silencing could prevent colorectal cancer cell proliferation, migration and invasion, and facilitate apoptosis in colorectal cancer cells by downregulating circular RNA lamin B1. Moreover, we found that knockdown of methyltransferase-like 3 could prevent tumor growth and disrupt the histological structure of colorectal cancer xenograft tumors by reducing circular RNA lamin B1 expression. Our data confirmed that methyltransferase-like 3 knockdown could attenuate the development of colorectal cancer cells by lowering circular RNA lamin B1 expression. This suggests circular RNA lamin B1 as a novel oncogene in colorectal cancer, which could be regulated by methyltransferaselike 3. Methyltransferase-like 3 silencing and circular RNA lamin B1 might be of great significance in colorectal cancer therapy.

Background: With the widespread outbreak of novel coronavirus diseases 2019(COVID-19), more and more death cases were reported, however, limited data are available for the patients who died. We aimed to explore the clinical characteristics of deaths with COVID-19 pneumonia. Methods: We abstracted and analyzed epidemiological, demographic, clinical, and laboratory data from 83 death cases with COVID-19 pneumonia in East Hospital of Wuhan University Renmin Hospital, between January 26, 2020, and February 28, 2020. Results: Of the 83 deaths, none was the medical staff. The mean age was 71.8 years (SD 13.2; range, 34–97 years) and 53(63.9%) were male. The median from onset to admission was 10 days (IQR 7–14: range, 2–43 days), to death was 17 days (IQR 14–21: range, 6–54 days). Most deaths (66[80%]) had underlying comorbid diseases, the most of which was hypertension [47(57%)]. The main initial symptoms of these 83 deaths were shortness of breath(98.8%), fever(94%), and myalgia or fatigue(90.4%). Laboratory analyses showed the lymphocytopenia in 69(83%) deaths, hypoalbuminemia in 77(93%) deaths, the elevation of lactate dehydrogenase in 79(95%) deaths, procalcitonin in 69(83%) deaths and C-reactive protein in 79(95%) deaths. All 83 patients received antiviral treatment, 81(97.6%) deaths received antibiotic therapy, 54(65.1%) deaths received glucocorticoid therapy, and 20(24.1%) patients received invasive mechanical ventilation. Conclusion: Most of the deaths with COVID-19 pneumonia were elderly patients with underlying comorbid diseases, especially those over 70 years of age. The time of death after the onset of the disease was mostly 15–21 days. More care should be given to the elderly in further prevention and control strategies of COVID-19.

Objective To evaluate the predictive value of fasting blood glucose (FBG) on unfavourable outcomes and mortality in diabetes mellitus (DM) patients after acute ischaemic stroke (AIS). Study design A hospital-based observational cohort study was conducted. Clinical data, including sex, age, body mass index, vascular risk factors and systolic/diastolic blood pressure, were routinely collected. National Institutes of Health Stroke Scale score was used to assess stroke severity on admission. FBG was determined on the first day after fasting for at least 8 hours. The modified Rankin Scale was used to assess functional outcome at 90 days: 3–6, unfavourable outcome and 6, death. Setting Renmin Hospital of Wuhan University, Wuhan, China. Participants Patients who had AIS with DM, who were consecutively admitted within 24 hours of onset from January 2018 to June 2019. Results For the 568 patients, the median age was 65 years (IQR, 55–74 years). There were 377 (66.4%) men. The median FBG values were 7.37 mmol/L (IQR, 5.99–10.10 mmol/L), and the median glycated haemoglobin (HbA1c) values were 6.6 (IQR, 5.8–8.3). Multivariable logistic and Cox regression analysis of confounding factors showed that FBG at the time of admission was an independent predictor of unfavourable outcome (OR, 1.25 (1.14–1.37); pConclusions Higher FBG levels are associated with unfavourable outcomes and mortality in Chinese patients who had AIS with DM. Our data contribute to the knowledge regarding the relationship between FBG and prognosis in patients with DM who had AIS.

Intracranial artery calcification (IAC) is an important risk factor for cerebral infarction and a key biomarker for intracranial artery stenosis. Small dense low-density lipoprotein cholesterol (sd-LDL-c) was independently associated with increased cardiovascular events and coronary calcification. Our study assessed whether sd-LDL-c is an independent factor for IAC in acute ischemic stroke (AIS) patients. This cross-sectional study involved a total of 754 patients with AIS (mean age: 65 ± 13.2 years). All the patients had received brain computed tomography angiography (CTA) examination to evaluate IAC. Serum sd-LDL-c levels and other biochemical parameters were analyzed. Admission NIHSS score and mRS score at discharge were collected. After 60-days 85 patients died during hospitalization and follow-up. Partial correlation analysis showed that serum sd-LDL-c levels were associated with admission NIHSS score and IAC score after adjusted age and gender. Logistic regression analysis showed that serum sd-LDL-c levels independently predicted NIHSS scores (β = 1.537, 95%CI: 0.134-2.878, p = 0.042) and IAC scores (β = 1.355, 95%CI: 0.319-2.446, p = 0.015). The average level of sd-LDL-c in patients who died was also significantly increased compared to survival patients (1.04 ± 0.59 vs 0.88 ± 0.44 mmol/L, p = 0.017). However, multivariate logistic regression analysis showed serum sd-LDL-c levels could not predict all-cause mortality and prognosis in AIS patients. Our study found that sd-LDL-c as a strong atherogenic lipid particle can independently predict admission NIHSS scores and the severity of cerebral artery calcification in AIS patients. However, its prognostic value in AIS patients still needs further study in the future.

Background: With the widespread outbreak of novel coronavirus diseases 2019(COVID-19), more and more death cases were reported, however, limited data are available for the patients who died. We aimed to explore the clinial characteristics of deaths with COVID-19 pneumonia Methods: We abstracted and analyzed epidemiological, demographic, clinical, and laboratory data from 83 death cases with COVID-19 pneumonia in East hospital of Wuhan university Renmin hospital,between January 26, 2020, and February 28, 2020.Results: Of the 83 deaths, none was the medical staff. The mean age was 71.8 years (SD 13.2; range, 34-97 years) and 53(63.9%) were male. The median from onset to admission was 10 days (IQR 7-14: range, 2-43 days), to death was 17days (IQR 14-21: range, 6-54 days). Most deaths (66[80%]) had underlying comorbid diseases, the most of which was hypertension [47(57%)]. The main initial symptoms of these 83 deaths were shortness of breath(98.8%), fever(94%) and myalgia or fatigue(90.4%). Laboratory analyses showed the lymphocytopenia in 69(83%) deaths, hypoalbuminemia in 77(93%) deaths, the elevation of lactate dehydrogenase in 79(95%) deaths, procalcitonin in 69(83%) deaths and C-reactive protein in 79(95%) deaths. All 83 patients received antiviral treatment, 81(97.6%) deaths received antibiotic therapy, and 54(65.1%) deaths received glucocorticoid therapy and 20(24.1%) patients received invasive mechanical ventilation.Conclusion: Most of the deaths with COVID-19 pneumonia were elderly patients with underlying comorbid diseases, especially those over 70 years of age. The time of death was mostly 15-21 days after the onset of the disease. More care should be given to the elderly in the further prevention and control strategies of COVID-19.

Intracranial artery calcification (IAC) is an important risk factor for cerebral infarction and a key biomarker for intracranial artery stenosis. Gamma-glutamyl transferase (GGT) has been independently associated with increased cardiovascular events and coronary calcification. Our study assessed whether GGT is an independent factor for IAC in acute ischemic stroke (AIS) patients. This cross-sectional study involved a total of 754 patients with AIS (mean age: 65 ± 13.2 years). All the patients had received brain computed tomography angiography (CTA) examination to evaluate IAC. Further, serum GGT levels and other biochemical parameters were analyzed. The average GGT level in patients who died was also significantly increased (37.0 ± 26.8 vs 29.0 ± 21.5 U/L, p = 0.012). Partial correlation analysis showed that serum GGT levels were associated with NIHSS score at admission after adjustment for age and gender was considered (r = 0.150, p = 0.001). Logistic regression analysis showed that serum GGT levels independently predicted all-cause mortality (OR = 1.036, 95% CI: 1.014–1.060, p = 0.002), NIHSS scores (β = 0.051, 95% CI: 0.020–0.082, p = 0.001) and IAC scores (β = 0.006, 95% CI: 0.003–0.014, p = 0.005) in male patients. Each SD (standard deviation) increase of serum GGT levels was also associated with risk of all-cause mortality (OR = 2.272, 95% CI: 1.364–3.787, P = 0.002). GGT levels in patients with severe IAC were significantly elevated (37.6 ± 33.6 vs 28.6 ± 19.2, p < 0.001). However, serum GGT levels could not independently predict the severity of IAC in AIS patients. Our study identified that serum GGT levels were significantly elevated in patients who died, and the GGT levels had a certain association with the risk of death and IAC in male patients.

Elevated levels of plasma D-dimer increase the risk of ischemic stroke, stroke severity, and the progression of stroke status, but the association between plasma D-dimer level and functional outcome is unclear. The aim of this study is to investigate whether plasma D-dimer level is a determinant of short-term poor functional outcome in patients with acute ischemic stroke (AIS). This prospective study included 877 Chinese patients with AIS admitted to Renmin Hospital of Wuhan University within 72 h of symptom onset. Patients were categorized by plasma D-dimer level: Quartile 1(≤0.24 mg/L), Quartile 2 (0.25–0.56 mg/L), Quartile 3 (0.57–1.78 mg/L), and Quartile 4 (> 1.78 mg/L). The medical record of each patient was reviewed, and demographic, clinical, laboratory and neuroimaging information was abstracted. Functional outcome at 90 days was assessed with the modified Rankin Scale. Poor outcome was present in 302 (34.4%) of the 877 patients that were included in the study (mean age, 64 years; male, 68.5%). After adjustment for potential confounding variables, higher plasma D-dimer level on admission was associated with poor outcome (adjusted odds ratio 2.257, 95% confidence interval 1.349–3.777 for Q4:Q1; P trend = 0.004). According to receiver operating characteristic (ROC) analysis, the best discriminating factor for poor outcome was a plasma D-dimer level ≥ 0.315 mg/L (area under the ROC curve 0.657; sensitivity 83.8%; specificity 41.4%). Elevated plasma D-dimer levels on admission are significantly associated with poor outcome after admission for AIS, suggesting the potential role of plasma D-dimer level as a predictive marker for short-term poor outcome in patients with AIS.